Phenotypic diversity in patients with lipodystrophy associated with LMNA mutations.

PubMed

Mory, Patricia B; Crispim, Felipe; Freire, Maria Beatriz S; Salles, João Eduardo N; Valério, Cynthia M; Godoy-Matos, Amelio F; Dib, Sérgio A; Moisés, Regina S

2012-09-01

Mutations in LMNA have been linked to diverse disorders called laminopathies, which display heterogeneous phenotypes and include diseases affecting muscles, axonal neurons, progeroid syndromes, and lipodystrophies. Among the lipodystrophies, LMNA mutations have been reported most frequently in patients with familial partial lipodystrophy (FPLD) of the Dunnigan variety; however, phenotypic heterogeneity in the pattern of body fat loss has been observed. In this study, we searched for LMNA mutations in patients with various forms of lipodystrophy. We studied 21 unrelated individuals with lipodystrophy. Subjects underwent a complete clinical evaluation and were classified as typical FPLD (n=12), atypical partial lipodystrophy (n=7), or generalized lipodystrophy (n=2). Molecular analysis of LMNA gene, analysis of body fat by dual-energy X-ray absorptiometry, and biochemical measurements were performed. ALL PATIENTS WITH TYPICAL FPLD WERE FOUND TO CARRY LMNA MUTATIONS: seven patients harbored the heterozygous p.R482W (c.1444C>T), two patients harbored the p.R482Q (c.1445G>A), and two individuals harbored the novel heterozygous variant p.N466D (c.1396A>G), all in exon 8. Also, a homozygous p.R584H (c.1751 G>A) mutation in exon 11 was found. Among patients with atypical partial lipodystrophy, two of them were found to have LMNA mutations: a novel heterozygous p.R582C variation (c.1744 C>T) in exon 11 and a heterozygous substitution p.R349W (c.1045C>T) in exon 6. Among patients with generalized lipodystrophy, only one harbored LMNA mutation, a heterozygous p.T10I (c.29C>T) in exon 1. We have identified LMNA mutations in phenotypically diverse lipodystrophies. Also, our study broadens the spectrum of LMNA mutations in lipodystrophy.

The effectiveness and safety of topical PhotoActif phosphatidylcholine-based anti-cellulite gel and LED (red and near-infrared) light on Grade II-III thigh cellulite: a randomized, double-blinded study.

PubMed

Sasaki, Gordon H; Oberg, Kerby; Tucker, Barbara; Gaston, Margaret

2007-06-01

Cellulite of the upper lateral and posterior thighs and lower buttocks represents a common, physiological and unwanted condition whose etiologies and effective management are subjects of continued debate. The purpose of this controlled, double-blinded study is to evaluate the efficacy and safety of a novel phosphatidylcholine-based, cosmeceutical anti-cellulite gel combined with a light-emitting diode (LED) array at the wavelengths of red (660 nm) and near-infrared (950 nm), designed to counter the possible mechanisms that purportedly accentuate the presence of thigh cellulite. Nine healthy female volunteers with Grade II-III thigh cellulite were randomly treated twice daily with an active gel on one thigh and a placebo gel on the control thigh for 3 months. Twice weekly, each thigh was exposed for a 15-minute treatment with LED light for a total of 24 treatments. At 0, 6, and 12 weeks of the study the following clinical determinants were obtained: standardized digital photography, height and weight measurements, standardized thigh circumference tape measurements, pinch testing, body mass index (kg/m2), body fat analysis (Futrex-5500/XL near-infrared analyzer), and digital high-resolution ultrasound imaging of the dermal-adiposal border. In selected patients, full-thickness biopsies of the placebo and active-treated sites were obtained. At 18 months, repeat standardized digital photography, height and weight measurements, and body mass index measurements were obtained. At the end of 3 months, eight of nine thighs treated with the phosphatidylcholine-based, anti-cellulite gel and LED treatments were downgraded to a lower cellulite grade by clinical examination, digital photography, and pinch test assessment. Digital ultrasound at the dermal-adiposal interface demonstrated not only a statistically significant reduction of immediate hypodermal depth, but also less echo-like intrusions into the dermal layer. Three of six biopsies from thighs treated for 3 months with

Thermographic mapping of the skin surface in biometric evaluation of cellulite treatment effectiveness.

PubMed

Wilczyński, S; Koprowski, R; Deda, A; Janiczek, M; Kuleczka, N; Błońska-Fajfrowska, B

2017-02-01

Cellulite is one of the worst tolerated aesthetic imperfections. Edema that accompanies cellulite causes disorders of blood flow what may be observed as changes in the skin surface temperature. The aim of this paper was to develop a new method based on the analysis and processing of thermal images of the skin for biometric evaluation of severity of cellulite and monitoring its treatment. The observations of the treatment effects were conducted on 10 females (33.4 ± 6.4 years). Thermal images of the volunteers' thighs were captured before starting the therapy (T 0 ). In the following stages: T 1 , T 2 , and T 3 , thermal images were captured 2 weeks after the first, second and third Alidya treatment administration, respectively. Profiled algorithms were developed to determine the mean Grey Level Co-occurrence Matrix (GLCM) contrast in the acquired thermograms. The mean GLCM contrast for the phase T 0 was 70.91, and for the stages T 1 , T 2 , and T 3 : 57.78, 41.80, and 38.53, respectively. The use of proposed method (GLCM contrast) enables biometric evaluation of the effectiveness of cellulite treatment. Traditionally used parameters of infrared analysis such as local points of the maximum and minimum temperature or the median temperatures are not useful in thermal, biometric evaluation of anti-cellulite preparations. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Circumference reduction and cellulite treatment with a TriPollar radiofrequency device: a pilot study.

PubMed

Manuskiatti, W; Wachirakaphan, C; Lektrakul, N; Varothai, S

2009-07-01

A wide variety of treatments for circumference reduction and cellulite are available, but most procedures offer suboptimal clinical effect and/or delayed therapeutic outcome. Objective To determine the safety and efficacy of the TriPollar radiofrequency device for cellulite treatment and circumference reduction. Thirty-nine females with cellulite received eight weekly TriPollar treatments. Treatment areas included the abdomen, thighs, buttocks and arms. Subjects were evaluated using standardized photographs and measurements of body weight, circumference, subcutaneous thickness, and skin elasticity of the treatment sites at baseline, immediately after and 4 weeks after the final treatment. Physicians' evaluation of clinical improvement scores using a quartile grading scale was recorded. Thirty-seven patients (95%) completed the treatment protocol. There was significant circumference reduction of 3.5 and 1.7 cm at the abdomen (P = 0.002) and thigh (P = 0.002) regions, respectively. At 4 weeks after the last treatment, the average circumferential reductions of the abdomen and thighs were sustained. No significant circumferential reductions of the buttocks and arms at the last treatment visit compared to baseline were demonstrated (P = 0.138 and 0.152, respectively). Quartile grading scores correlating to approximately 50% improvement in cellulite appearance were noted. Tripollar radiofrequency provided beneficial effects on the reduction of abdomen and thigh circumference and cellulite appearance.

Case report: unicameral bone cysts in a young patient with acquired generalized lipodystrophy.

PubMed

Gregory, James M; Arkader, Alexandre; Bokhari, Aqiba; Bothari, Aqiba; Dormans, John P

2010-05-01

We report the case of a 13-year-old boy with bilateral distal femoral unicameral bone cysts (UBCs) associated with acquired generalized lipodystrophy. As opposed to congenital generalized lipodystrophy, cystic bone lesions in acquired generalized lipodystrophy are rare. After radiographic and histologic confirmation of the UBCs, we performed percutaneous intramedullary decompression, curettage, and grafting. UBCs can be an important manifestation of acquired generalized lipodystrophy. Cystic bone lesions appear to be less common in acquired generalized lipodystrophy than in congenital generalized lipodystrophy, and intramedullary adipose tissue loss may be a predisposing factor for the development of bone lesions in patients with acquired generalized lipodystrophy. When evaluating a patient with lipodystrophy, doctors should recognize the clinical course may include the development of UBCs.

Case Report: Unicameral Bone Cysts in a Young Patient with Acquired Generalized Lipodystrophy

PubMed Central

Gregory, James M.; Arkader, Alexandre; Bothari, Aqiba

2009-01-01

We report the case of a 13-year-old boy with bilateral distal femoral unicameral bone cysts (UBCs) associated with acquired generalized lipodystrophy. As opposed to congenital generalized lipodystrophy, cystic bone lesions in acquired generalized lipodystrophy are rare. After radiographic and histologic confirmation of the UBCs, we performed percutaneous intramedullary decompression, curettage, and grafting. UBCs can be an important manifestation of acquired generalized lipodystrophy. Cystic bone lesions appear to be less common in acquired generalized lipodystrophy than in congenital generalized lipodystrophy, and intramedullary adipose tissue loss may be a predisposing factor for the development of bone lesions in patients with acquired generalized lipodystrophy. When evaluating a patient with lipodystrophy, doctors should recognize the clinical course may include the development of UBCs. PMID:19924491

Microfocused Ultrasound with Visualization and Calcium Hydroxylapatite for Improving Skin Laxity and Cellulite Appearance

PubMed Central

Pereira, Gregório

2017-01-01

Background: Age-associated skin laxity contributes to worsening of cellulite appearance. This study evaluated the effects of microfocused ultrasound with visualization (MFU-V; Ultherapy) in combination with diluted calcium hydroxylapatite (CaHA; Radiesse) on cellulite appearance and on neocollagenesis. Methods: Twenty women (18–55 years old) with skin laxity and moderate-to-severe cellulite on the buttocks and thighs were retrospectively enrolled. MFU-V was applied using 4 and 7 MHz transducers (25 lines/transducer/site) and immediately followed by subdermal CaHA injection (1 ml/buttock or thigh). Photographs at baseline and 90 days were assessed by 2 independent, blinded evaluators using a 5-item cellulite severity scale. One subject scheduled for thighplasty received treatment with 6 different CaHA dilutions (0.3 ml/5 cm2) followed by MFU-V. Tissue specimens from each dilution site were examined under polarized light microscopy to assess neocollagenesis. Results: Both evaluators reported statistically significant improvements compared with baseline for each item on the cellulite severity scale (P < 0.001) with a 4.5-point improvement in mean overall score (P < 0.001) after a single MFU-V/CaHA treatment. At 90 days, histologic analysis showed peak neocollagenesis in samples treated with the 1:1 dilution, whether with CaHA alone or in combination with MFU-V. The highest conversion of collagen type III into collagen type I at month 3 occurred in samples injected with 1:1 and 1:0.6 CaHA dilutions without subsequent MFU-V treatment. Both procedures were well tolerated, and subject satisfaction was high. Conclusions: Combination treatment with MFU-V and diluted CaHA is effective for improving skin laxity and the appearance of cellulite on the buttocks and upper thighs. PMID:28831339

Treatment of abdominal cellulite and circumference reduction with radiofrequency and dynamic muscle activation.

PubMed

Wanitphakdeedecha, Rungsima; Iamphonrat, Thanawan; Thanomkitti, Kanchalit; Lektrakul, Nittaya; Manuskiatti, Woraphong

2015-01-01

Cellulite is a frequent skin condition for which treatment remains a challenge. A wide variety of treatments are available but most procedures offer suboptimal clinical effect and/or delayed therapeutic outcome. Only few therapeutic options have proven efficacy in the treatment of cellulite. To determine the efficacy and the safety profiles of radiofrequency and dynamic muscle activation technology in treatment of abdominal cellulite and circumference reduction. Twenty-five females with abdominal cellulite received 6 weekly radiofrequency and dynamic muscle activation treatments. Treatment areas included the abdomen and both sides of flanks. Subjects were evaluated using standardized photographs, and measurements of body weight and abdominal circumference at baseline, before every treatment visit, and 1 week and four weeks after the final treatment. Subcutaneous tissue thickness was recorded by ultrasound at baseline and 4 weeks after completion of treatment protocol. Physicians' evaluation and patient's satisfaction of clinical improvement were also measured. All subjects completed the treatment protocol and attended every follow-up visits. There was significant abdominal circumference reduction of 2.96 and 2.52 cm at 1-, and 4-week follow-up visits (p < 0.05), respectively. At four weeks after the last treatment, the average circumferential reduction was sustained. Most of the patients were rated to have 25-49% improvement at 5th treatment, and 1- and 4-week follow-up visits. Ninety-two percent of the patients were satisfied with the treatment outcome. Radiofrequency provided beneficial effects on the reduction of abdomen and cellulite appearance. The benefit of muscle activation is yet to be determined.

Human lipodystrophies: genetic and acquired diseases of adipose tissue

PubMed Central

Capeau, Jacqueline; Magré, Jocelyne; Caron-Debarle, Martine; Lagathu, Claire; Antoine, Bénédicte; Béréziat, Véronique; Lascols, Olivier; Bastard, Jean-Philippe; Vigouroux, Corinne

2010-01-01

Human lipodystrophies represent a heterogeneous group of diseases characterized by generalized or partial fat loss, with fat hypertrophy in other depots when partial. Insulin resistance, dyslipidemia and diabetes are generally associated, leading to early complications. Genetic forms are uncommon: recessive generalized congenital lipodystrophies result in most cases from mutations in the genes encoding seipin or the 1-acyl-glycerol-3-phosphate-acyltransferase 2 (AGPAT2). Dominant partial familial lipodystrophies result from mutations in genes encoding the nuclear protein lamin A/C or the adipose transcription factor PPARγ. Importantly, lamin A/C mutations are also responsible for metabolic laminopathies, resembling the metabolic syndrome and progeria, a syndrome of premature aging. A number of lipodystrophic patients remain undiagnosed at the genetic level. Acquired lipodystrophy can be generalized, resembling congenital forms, or partial, as the Barraquer-Simons syndrome, with loss of fat in the upper part of the body contrasting with accumulation in the lower part. Although their aetiology is generally unknown, they could be associated with signs of auto-immunity. The most common forms of lipodystrophies are iatrogenic. In human immunodeficiency virus-infected patients, some first generation antiretroviral drugs were strongly related with peripheral lipoatrophy and metabolic alterations. Partial lipodystrophy also characterize patients with endogenous or exogenous long-term corticoid excess. Treatment of fat redistribution can sometimes benefit from plastic surgery. Lipid and glucose alterations are difficult to control leading to early occurrence of diabetic, cardio-vascular and hepatic complications. PMID:20551664

Adipocytokines, neuropeptide Y and insulin resistance in overweight women with gynoid and android type of adipose tissue distribution.

PubMed

Orbetzova, Maria M; Koleva, Daniela I; Mitkov, Mitko D; Atanassova, Iliana B; Nikolova, Julia G; Atanassova, Pepa K; Genchev, Gencho D

2012-01-01

The AIM of the study was to compare the levels of certain adipose tissue hormones in women with the two main morphological types of obesity - android and gynoid obesity. The study included 2 groups of age- and weight-matched women with android (n = 32) and gynoid (n = 27) type of obesity, and a group of age-matched healthy women (n = 24) with normal weight and body constitution. Leptin, resistin, tumour necrosis factor alpha (TNFalpha), neuropeptide Y (NPY), glucose and insulin were measured. HOMA index was calculated. Leptin levels in the women with gynoid obesity did not differ significantly from those in the controls and the women with android obesity. The controls had significantly lower leptin levels compared with the android obesity women. NPY was significantly higher in the control women compared to the women with android obesity and did not differ significantly between the two groups of obese women. TNFalpha levels in all groups were very similar. Resistin did not show significant differences between all groups but tended to have the lowest levels in the controls. In the women with android obesity, insulin was significantly higher than that in the women with gynoid obesity and the controls. Insulin resistance was found in the women with android obesity only. Basal insulin and HOMA index in the women with gynoid obesity did not differ significantly from the values in the control group. The results from this study contribute to understanding the association of adipose tissue hormones and insulin resistance in obesity. When adipose tissue is predominantly distributed in the abdominal area at similar amount and percentage of body fats, leptin production is higher and insulin resistance develops. In the gynoid type of adipose tissue predisposition, overt insulin resistance is not found, leptin levels does not differ significantly from those in the control group.

Importance of Android/Gynoid Fat Ratio in Predicting Metabolic and Cardiovascular Disease Risk in Normal Weight as well as Overweight and Obese Children

PubMed Central

Regier, Michael

2014-01-01

Numerous studies have shown that android or truncal obesity is associated with a risk for metabolic and cardiovascular disease, yet there is evidence that gynoid fat distribution may be protective. However, these studies have focused on adults and obese children. The purpose of our study was to determine if the android/gynoid fat ratio is positively correlated with insulin resistance, HOMA2-IR, and dislipidemia in a child sample of varying body sizes. In 7–13-year-old children with BMI percentiles ranging from 0.1 to 99.6, the android/gynoid ratio was closely associated with insulin resistance and combined LDL + VLDL-cholesterol. When separated by sex, it became clear that these relationships were stronger in boys than in girls. Subjects were stratified into BMI percentile based tertiles. For boys, the android/gynoid ratio was significantly related to insulin resistance regardless of BMI tertile with and LDL + VLDL in tertiles 1 and 3. For girls, only LDL + VLDL showed any significance with android/gynoid ratio and only in tertile 2. We conclude that the android/gynoid fat ratio is closely associated with insulin resistance and LDL + VLDL-, “bad,” cholesterol in normal weight boys and may provide a measurement of metabolic and cardiovascular disease risk in that population. PMID:25302115

Importance of android/gynoid fat ratio in predicting metabolic and cardiovascular disease risk in normal weight as well as overweight and obese children.

PubMed

Samsell, Lennie; Regier, Michael; Walton, Cheryl; Cottrell, Lesley

2014-01-01

Numerous studies have shown that android or truncal obesity is associated with a risk for metabolic and cardiovascular disease, yet there is evidence that gynoid fat distribution may be protective. However, these studies have focused on adults and obese children. The purpose of our study was to determine if the android/gynoid fat ratio is positively correlated with insulin resistance, HOMA2-IR, and dislipidemia in a child sample of varying body sizes. In 7-13-year-old children with BMI percentiles ranging from 0.1 to 99.6, the android/gynoid ratio was closely associated with insulin resistance and combined LDL + VLDL-cholesterol. When separated by sex, it became clear that these relationships were stronger in boys than in girls. Subjects were stratified into BMI percentile based tertiles. For boys, the android/gynoid ratio was significantly related to insulin resistance regardless of BMI tertile with and LDL + VLDL in tertiles 1 and 3. For girls, only LDL + VLDL showed any significance with android/gynoid ratio and only in tertile 2. We conclude that the android/gynoid fat ratio is closely associated with insulin resistance and LDL + VLDL-, "bad," cholesterol in normal weight boys and may provide a measurement of metabolic and cardiovascular disease risk in that population.

The Diagnosis and Management of Lipodystrophy Syndromes: A Multi-Society Practice Guideline

PubMed Central

Araujo-Vilar, David; Cheung, Pik To; Dunger, David; Garg, Abhimanyu; Jack, Michelle; Mungai, Lucy; Oral, Elif A.; Patni, Nivedita; Rother, Kristina I.; von Schnurbein, Julia; Sorkina, Ekaterina; Stanley, Takara; Vigouroux, Corinne; Wabitsch, Martin; Williams, Rachel; Yorifuji, Tohru

2016-01-01

Objective: Lipodystrophy syndromes are extremely rare disorders of deficient body fat associated with potentially serious metabolic complications, including diabetes, hypertriglyceridemia, and steatohepatitis. Due to their rarity, most clinicians are not familiar with their diagnosis and management. This practice guideline summarizes the diagnosis and management of lipodystrophy syndromes not associated with HIV or injectable drugs. Participants: Seventeen participants were nominated by worldwide endocrine societies or selected by the committee as content experts. Funding was via an unrestricted educational grant from Astra Zeneca to the Pediatric Endocrine Society. Meetings were not open to the general public. Evidence: A literature review was conducted by the committee. Recommendations of the committee were graded using the system of the American Heart Association. Expert opinion was used when published data were unavailable or scarce. Consensus Process: The guideline was drafted by committee members and reviewed, revised, and approved by the entire committee during group meetings. Contributing societies reviewed the document and provided approval. Conclusions: Lipodystrophy syndromes are heterogeneous and are diagnosed by clinical phenotype, supplemented by genetic testing in certain forms. Patients with most lipodystrophy syndromes should be screened for diabetes, dyslipidemia, and liver, kidney, and heart disease annually. Diet is essential for the management of metabolic complications of lipodystrophy. Metreleptin therapy is effective for metabolic complications in hypoleptinemic patients with generalized lipodystrophy and selected patients with partial lipodystrophy. Other treatments not specific for lipodystrophy may be helpful as well (eg, metformin for diabetes, and statins or fibrates for hyperlipidemia). Oral estrogens are contraindicated. PMID:27710244

Membranous lipodystrophy: case report and review of the literature.

PubMed

Akpinar, Fatma; Demir, Ektan; Apa, Duygu Dusmez

2015-01-01

Membranous lipodystrophy is a distinct type of membranocystic fat necrosis. It is associated with many local and systemic diseases, including vascular disorders. The histopathological changes which characterize this phenomenon are variably sized cysts in the fat lobules of the subcutaneous tissue, which are surrounded by eosinophilic membranes projecting into the cystic space. We report a case of secondary membranous lipodystrophy associated with both hypertension and venous insufficiency.

[Lipodystrophy and metabolic disturbances as complications of antiretroviral therapy].

PubMed

Bociaga-Jasik, Monika; Kieć-Wilk, Beata; Kalinowska-Nowak, Anna; Mach, Tomasz; Garlicki, Aleksander

2010-01-01

Effective treatment of HIV infection with antiretroviral drugs significantly improve prognosis. Reduction of mortality and life prolongations in patients receiving such therapy have been also connected with the risk of side effects development. Among these complications metabolic disturbances such as lipodystrophy, dyslipidaemia, and insulin resistance which are present according some authors in up to 50% of patients receiving HAART play an important role. In spite of different investigations molecular basis of lipodystrophy development during HAART have not be fully understood, and the latest research revealed a lot of new aspects connected w adipocyte tissue pathophysiology, which were not taken up to know into consideration. In the presented publication the most important information about pathogenesis of lipodystrophy development in HIV infected patients treated with ARV drugs have been presented.

High-frequency ultrasound evaluation of cellulite treated with the 1064 nm Nd:YAG laser.

PubMed

Bousquet-Rouaud, Regine; Bazan, Marie; Chaintreuil, Jean; Echague, Agustina Vila

2009-03-01

To investigate non-invasive laser treatment for cellulite using the 1064 nm Nd:YAG laser and to correlate clinical results with high-frequency skin ultrasound images. Twelve individuals of normal weight were treated on either the left or right posterior side of the thigh with the following parameters: fluence 30 J/cm, 18 mm spot size and dynamic cooling device pulse duration of 30 ms. Three treatments were performed at intervals of 3-4 weeks, and followed-up 1 and 3 months after the last session. Photographs and ultrasound imaging were assessed before each session. The 1064 nm Nd:YAG laser resulted in a tightening of the skin and an improvement in cellulite. No side effects were reported. High-resolution ultrasound imaging showed a significant improvement in dermis density and a reduction of dermis thickness. The method is described in detail in Appendix 1. Infra-red lasers may constitute a safe and effective treatment for cellulite and high-frequency ultrasound imaging provides a quantitative and objective measurement of the treatment efficacy.

Current concepts of metabolic abnormalities in HIV patients: focus on lipodystrophy.

PubMed

Kolter, Donald P

2003-12-01

HIV infection is associated with a number of metabolic abnormalities, including lipodystrophy, a difficult-to-define disorder whose characteristics include hyperlipidemia, insulin resistance, and fat redistribution. Current data suggest that lipodystrophy is caused by multiple factors. Dual-nucleoside reverse transcriptase inhibitor therapy combined with protease inhibitor therapy has been shown to increase the risk of metabolic abnormalities, but susceptibility independent of drug effects has also been shown. While many of the treatments for the broad range of signs and symptoms of lipodystrophy bring about improvements in patient status, none have been demonstrated to bring about a return to baseline levels.

Hepatic Lipodystrophy in Galloway Calves.

PubMed

Wieland, M; Mann, S; Hafner-Marx, A; Ignatius, A; Metzner, M

2017-05-01

Hepatic lipodystrophy in Galloway calves is a fatal liver disease affecting a small proportion of the Galloway breed described in different parts of Europe and North America during the past decades. The clinical findings include a diversity of neurological signs. Clinical pathology findings frequently indicate hepatobiliary disease. Postmortem examination reveals an enlarged, pale yellow, and firm liver. Histologic lesions include hepatic fibrosis, hepatic lipidosis, and bile duct hyperplasia. To date, the etiopathogenesis remains obscure. Infectious causes, intoxications, and a hereditary origin have been considered. We describe hepatic lipodystrophy in Galloway calves from an extensively farmed cow-calf operation in southern Germany. Main clinical findings in 6 calves were consistent with hepatic encephalopathy. Clinical pathology findings in 5 of 6 tested animals revealed increased concentration of total bilirubin (maximum value [MV], 54 μmol/l; reference range [RR], <8.5 μmol/l), direct bilirubin (MV, 20 μmol/l; RR, <3.4 μmol/l), increased activity of gamma glutamyl transferase (MV, 162 U/l; RR, <36 U/l) and glutamate dehydrogenase (MV, 420 U/l; RR, <16 U/l). In addition, activity of glutathione peroxidase was decreased in all tested ( n = 5) animals (MV, 61 U/g hemoglobin [Hb]; RR, >250 U/g Hb). Postmortem examination in 6 calves revealed a firm, diffusely enlarged yellow liver with a finely nodular surface. Histologic lesions included hepatic fibrosis, hepatic lipidosis, and bile duct hyperplasia. Our findings add to the existing data on hepatic lipodystrophy in the Galloway breed and outline a protocol to aid in the diagnosis of this disorder.

Evaluation of a noninvasive, dual-wavelength laser-suction and massage device for the regional treatment of cellulite.

PubMed

Kulick, Michael I

2010-06-01

Cellulite is a condition usually limited to women. The most common location for this surface irregularity is the thigh. Evaluation of treatment efficacy is difficult because of the reliance on patient satisfaction surveys and flash photography, which can "flatten" surface texture. Reproducibility of photographs is also difficult, as subtle changes in body position can affect appearance. Twenty women with mild to moderate cellulite of their lateral thighs were enrolled. Pretreatment and posttreatment assessment included patient weight, body mass index, percentage body fat, standard digital photographs, VECTRA three-dimensional images, and patient questionnaire. Patients received two treatments per week for 4 weeks. Treatment time was 15 minutes per thigh using the SmoothShapes device. Patients were evaluated 1, 3, and 6 months after their last treatment. To be considered improved after treatment, both thighs needed clear improvement in contour as determined by the "untextured" images obtained with the VECTRA camera system. This device depicts skin contour independent of incident lighting. There were no complications. Seventeen patients had complete data for analysis. Ninety-four percent of the patients felt their cellulite was improved. VECTRA analysis showed 82 percent improvement at 1 month, 76 percent improvement at 3 months, and 76 percent improvement at 6 months. Initial cellulite irregularities and improvement were more difficult to discern using standard digital photographs. There was an average increase in patient weight, body mass index, and percentage body fat at 6 months. The SmoothShapes device provided improvement in surface contour (cellulite) 6 months after the last treatment in the majority of the patients based on patient survey and VECTRA analysis.

Genetics Home Reference: familial partial lipodystrophy

MedlinePlus

... adulthood. Many people with familial partial lipodystrophy develop insulin resistance, a condition in which the body's tissues cannot ... that normally helps to regulate blood sugar levels. Insulin resistance may worsen to become a more serious disease ...

"We're stuck with what we've got": The impact of lipodystrophy on body image.

PubMed

Adams, Claire; Stears, Anna; Savage, David; Deaton, Christi

2018-05-01

To evaluate the impact of lipodystrophy on body image and how this affects patients' daily lives. Lipodystrophy refers to a group of rare conditions characterised by generalised or partial lack of body fat and is associated with severe metabolic problems, for example, severe insulin resistance, diabetes and pancreatitis. In addition to its metabolic effect, lack of adipose tissue may have a major impact on appearance and cause distressing physical changes. While global research has focused on diagnosis and management, there is no published work investigating the psychological effects of lipodystrophy on body image. Following ethical approval, participants with lipodystrophy were purposively sampled from the National Severe Insulin Resistance Service in Cambridge, UK, and invited to take part in a semi-structured interview. Eleven (10 female, one male) interviews were conducted and digitally recorded. Data were analysed using an inductive thematic approach. Four main themes were identified in the data set; "Always feeling appearance was different," "a better understanding of lipodystrophy is needed," "feeling accepted" and "there's more to lipodystrophy than managing symptoms." Participants spoke of distressing cosmetic effects related to lack of fat tissue and other changes related to lipodystrophy, contributing to negative body image. For some, negative body image led to feelings of worthlessness impacting daily life and adherence to treatment. Psychological support was lacking but desired by participants. Lipodystrophy contributes to negative body image affecting patients' daily lives. Patients wanted psychological support alongside medical management. Further research is needed to determine how best to deliver psychological support and to evaluate its impact on well-being and metabolic management. The effects of rare diseases such as lipodystrophy on appearance can be distressing for patients. Support beyond medical management is needed to improve patients

Berardinelli-Seip congenital lipodystrophy in two siblings

PubMed Central

Rao, T. S. Mohana; Chennamsetty, Kavya

2014-01-01

Berardinelli-Seip congenital lipodystrophy (BSCL) is a very rare autosomal recessive disorder characterized by various dermatological and systemic manifestations such as lipoatrophy, hypertriglyceridemia, hepatomegaly, acanthosis nigricans, and acromegaloid features. BSCL type 2 is more common and severe, with onset in the neonatal period or in early infancy. The locus for BSCL2 has been identified on chromosome 11q13. Early recognition and differentiation from other congenital generalized lipodystrophies help in the initiation of appropriate preventive and therapeutic measures such as lifestyle modification and pharmacotherapy that helps postpone the onset of metabolic syndrome. We report BSCL type 2 in two siblings with several cutaneous manifestations like acanthosis nigricans, hypertrichosis, prominent subcutaneous veins, and increased lanugo hair. PMID:25506557

Liposuction for lower limb lipodystrophy in congenital analbuminaemia: a case report.

PubMed

Kandamany, Nanda; Munnoch, Alex

2014-02-01

Congenital analbuminaemia is a very rare autosomal dominant disorder in which patients have no serum albumin and markedly low serum total protein concentration. Clinically patients present with mild oedema, hypotension, fatigue and lipodystrophy often with abnormal body habitus. With only around 50 reported cases in the literature worldwide, management of the resulting lipodystrophy remains unclear. A 42-year-old male who was diagnosed with congenital analbuminaemia presented with bilateral lower limb lipodystrophy disproportionately affecting his thighs. This was associated with concerns over appearance, difficulties with mobility and finding clothing. He successfully underwent bilateral lower leg liposuction and has had no recurrence of his symptoms after 12 months. We have demonstrated that liposuction along with controlled compression therapy is a safe and effective treatment for managing lipodystrophy secondary to congenital analbuminaemia. Although rare, clinicians need to be aware that liposuction is a successful treatment modality, which should be made available to this select group of patients. Copyright © 2013 British Association of Plastic, Reconstructive and Aesthetic Surgeons. Published by Elsevier Ltd. All rights reserved.

HIV-associated lipodystrophy syndrome: A review of clinical aspects

PubMed Central

Baril, Jean-Guy; Junod, Patrice; LeBlanc, Roger; Dion, Harold; Therrien, Rachel; Laplante, François; Falutz, Julian; Côté, Pierre; Hébert, Marie-Nicole; Lalonde, Richard; Lapointe, Normand; Lévesque, Dominic; Pinault, Lyse; Rouleau, Danielle; Tremblay, Cécile; Trottier, Benoît; Trottier, Sylvie; Tsoukas, Chris; Weiss, Karl

2005-01-01

Approximately two years after the introduction of highly active antiretroviral therapy for the treatment of HIV infection, body shape changes and metabolic abnormalities were increasingly observed. Initially, these were ascribed to protease inhibitors, but it is now clear that nucleoside reverse transcriptase inhibitors also contribute to lipodystrophy syndrome. The syndrome groups together clinical conditions describing changes in body fat distribution that include lipoatrophy, lipoaccumulation or both. However, there does not appear to be a direct link between lipoatrophy and lipoaccumulation that would support a single mechanism for the redistribution of body fat. Currently, there is no clear definition of lipodystrophy, which explains the difficulty in determining its prevalence and etiology. There are no current guidelines for the treatment of fat distribution abnormalities that occur in the absence of other metabolic complications. The present article reviews the current state of knowledge of the definition, symptoms, risk factors, pathogenesis, diagnosis and treatment of the morphological changes associated with lipodystrophy syndrome. PMID:18159551

HIV/AIDS and lipodystrophy: implications for clinical management in resource-limited settings.

PubMed

Finkelstein, Julia L; Gala, Pooja; Rochford, Rosemary; Glesby, Marshall J; Mehta, Saurabh

2015-01-01

Lipodystrophy is a term used to describe a metabolic complication of fat loss, fat gain, or a combination of fat loss and gain, which is associated with some antiretroviral (ARV) therapies given to HIV-infected individuals. There is limited research on lipodystrophy in low- and middle-income countries, despite accounting for more than 95% of the burden of HIV/AIDS. The objective of this review was to evaluate the prevalence, pathogenesis and prognosis of HIV-related lipoatrophy, lipohypertrophy and mixed syndrome, to inform clinical management in resource-limited settings. We conducted a structured literature search using MEDLINE electronic databases. Relevant MeSH terms were used to identify published human studies on HIV and lipoatrophy, lipohypertrophy, or mixed syndrome in low-, low-middle- and upper-middle-income countries through 31 March 2014. The search resulted in 5296 articles; after 1599 studies were excluded (958 reviews, 641 non-human), 3697 studies were extracted for further review. After excluding studies conducted in high-income settings (n=2808), and studies that did not meet inclusion criteria (n = 799), 90 studies were included in this review. Of the 90 studies included in this review, only six were from low-income countries and eight were from lower middle-income economies. These studies focused on lipodystrophy prevalence, risk factors and side effects of antiretroviral therapy (ART). In most studies, lipodystrophy developed after the first six months of therapy, particularly with the use of stavudine. Lipodystrophy is associated with increased risk of cardiometabolic complications. This is disconcerting and anticipated to increase, given the rapid scale-up of ART worldwide, the increasing number and lifespan of HIV-infected patients on long-term therapy, and the emergence of obesity and non-communicable diseases in settings with extensive HIV burden. Lipodystrophy is common in resource-limited settings, and has considerable implications for

Renal complications of lipodystrophy: A closer look at the natural history of kidney disease.

PubMed

Akinci, Baris; Unlu, Sadiye Mehtat; Celik, Ali; Simsir, Ilgin Yildirim; Sen, Sait; Nur, Banu; Keskin, Fatma Ela; Ozgen Saydam, Basak; Kutbay Ozdemir, Nilufer; Sarer Yurekli, Banu; Ergur, Bekir Ugur; Sonmez, Melda; Atik, Tahir; Arslan, Atakan; Demir, Tevfik; Altay, Canan; Tunc, Ulku Aybuke; Arkan, Tugba; Gen, Ramazan; Eren, Erdal; Akinci, Gulcin; Yilmaz, Aslihan Arasli; Bilen, Habib; Ozen, Samim; Celtik, Aygul; Savas Erdeve, Senay; Cetinkaya, Semra; Onay, Huseyin; Sarioglu, Sulen; Oral, Elif Arioglu

2018-07-01

Lipodystrophy syndromes are a group of heterogeneous disorders characterized by adipose tissue loss. Proteinuria is a remarkable finding in previous reports. In this multicentre study, prospective follow-up data were collected from 103 subjects with non-HIV-associated lipodystrophy registered in the Turkish Lipodystrophy Study Group database to study renal complications in treatment naïve patients with lipodystrophy. Main outcome measures included ascertainment of chronic kidney disease (CKD) by studying the level of proteinuria and the estimated glomerular filtration rate (eGFR). Kidney volume was measured. Percutaneous renal biopsies were performed in 9 patients. Seventeen of 37 patients with generalized and 29 of 66 patients with partial lipodystrophy had CKD characterized by proteinuria, of those 12 progressed to renal failure subsequently. The onset of renal complications was significantly earlier in patients with generalized lipodystrophy. Patients with CKD were older and more insulin resistant and had worse metabolic control. Increased kidney volume was associated with poor metabolic control and suppressed leptin levels. Renal biopsies revealed thickening of glomerular basal membranes, mesangial matrix abnormalities, podocyte injury, focal segmental sclerosis, ischaemic changes and tubular abnormalities at various levels. Lipid vacuoles were visualized in electron microscopy images. CKD is conspicuously frequent in patients with lipodystrophy which has an early onset. Renal involvement appears multifactorial. While poorly controlled diabetes caused by severe insulin resistance may drive the disease in some cases, inherent underlying genetic defects may also lead to cell autonomous mechanisms contributory to the pathogenesis of kidney disease. © 2018 John Wiley & Sons Ltd.

Review of the Mechanisms and Effects of Noninvasive Body Contouring Devices on Cellulite and Subcutaneous Fat

PubMed Central

Alizadeh, Zahra; Halabchi, Farzin; Mazaheri, Reza; Abolhasani, Maryam; Tabesh, Mastaneh

2016-01-01

Context Today, different kinds of non-invasive body contouring modalities, including cryolipolysis, radiofrequency (RF), low-level laser therapy (LLLT), and high-intensity focused ultrasound (HIFU) are available for reducing the volume of subcutaneous adipose tissue or cellulite. Each procedure has distinct mechanisms for stimulating apoptosis or necrosis adipose tissue. In addition to the mentioned techniques, some investigations are underway for analyzing the efficacy of other techniques such as whole body vibration (WBV) and extracorporeal shockwave therapy (ESWT). In the present review the mechanisms, effects and side effects of the mentioned methods have been discussed. The effect of these devices on cellulite or subcutaneous fat reduction has been assessed. Evidence Acquisition We searched pubmed, google scholar and the cochrane databases for systemic reviews, review articles, meta-analysis and randomized clinical trials up to February 2015. The keywords were subcutaneous fat, cellulite, obesity, noninvasive body contouring, cryolipolysis, RF, LLLT, HIFU, ESWT and WBV with full names and abbreviations. Results We included seven reviews and 66 original articles in the present narrative review. Most of them were applied on normal weight or overweight participants (body mass index < 30 kg/m2) in both genders with broad range of ages (18 to 50 years on average). In the original articles, the numbers of included methods were: 10 HIFU, 13 RF, 22 cryolipolysis, 11 LLLT, 5 ESWT and 4 WBV therapies. Six of the articles evaluated combination therapies and seven compared the effects of different devices. Conclusions Some of the noninvasive body contouring devices in animal and human studies such as cryolipolysis, RF, LLLT and HIFU showed statistical significant effects on body contouring, removing unwanted fat and cellulite in some body areas. However, the clinical effects are mild to moderate, for example 2 - 4 cm circumference reduction as a sign of subcutaneous fat

Review of the Mechanisms and Effects of Noninvasive Body Contouring Devices on Cellulite and Subcutaneous Fat.

PubMed

Alizadeh, Zahra; Halabchi, Farzin; Mazaheri, Reza; Abolhasani, Maryam; Tabesh, Mastaneh

2016-10-01

Today, different kinds of non-invasive body contouring modalities, including cryolipolysis, radiofrequency (RF), low-level laser therapy (LLLT), and high-intensity focused ultrasound (HIFU) are available for reducing the volume of subcutaneous adipose tissue or cellulite. Each procedure has distinct mechanisms for stimulating apoptosis or necrosis adipose tissue. In addition to the mentioned techniques, some investigations are underway for analyzing the efficacy of other techniques such as whole body vibration (WBV) and extracorporeal shockwave therapy (ESWT). In the present review the mechanisms, effects and side effects of the mentioned methods have been discussed. The effect of these devices on cellulite or subcutaneous fat reduction has been assessed. We searched pubmed, google scholar and the cochrane databases for systemic reviews, review articles, meta-analysis and randomized clinical trials up to February 2015. The keywords were subcutaneous fat, cellulite, obesity, noninvasive body contouring, cryolipolysis, RF, LLLT, HIFU, ESWT and WBV with full names and abbreviations. We included seven reviews and 66 original articles in the present narrative review. Most of them were applied on normal weight or overweight participants (body mass index < 30 kg/m 2 ) in both genders with broad range of ages (18 to 50 years on average). In the original articles, the numbers of included methods were: 10 HIFU, 13 RF, 22 cryolipolysis, 11 LLLT, 5 ESWT and 4 WBV therapies. Six of the articles evaluated combination therapies and seven compared the effects of different devices. Some of the noninvasive body contouring devices in animal and human studies such as cryolipolysis, RF, LLLT and HIFU showed statistical significant effects on body contouring, removing unwanted fat and cellulite in some body areas. However, the clinical effects are mild to moderate, for example 2 - 4 cm circumference reduction as a sign of subcutaneous fat reduction during total treatment sessions

HIV protease inhibitor-related lipodystrophy syndrome.

PubMed

Carr, A

2000-06-01

Human immunodeficiency virus (HIV) protease inhibitor (PI) therapy is frequently associated with a syndrome increasingly referred to as lipodystrophy syndrome, which is characterized by peripheral lipoatrophy, fat accumulation within the abdomen, in the breasts of women, and over the cervical vertebrae ("buffalo hump"), hyperlipidemia, and insulin resistance. In the largest study to date, peripheral lipoatrophy (an estimated 0.35-kg fat loss per month overall from the face, limbs, and upper trunk) was observed in association with all licensed PIs after a median 10 months of PI therapy. Diabetes mellitus type II appears to be a related, but less common, adverse effect. The lipodystrophy syndrome may be a result of the inhibition of 2 proteins involved in lipid metabolism that have significant homology to the catalytic site of HIV protease-namely, cytoplasmic retinoic acid binding protein type 1 and low density lipoprotein-receptor-related protein.

A prospective clinical study to evaluate the efficacy and safety of cellulite treatment using the combination of optical and RF energies for subcutaneous tissue heating.

PubMed

Sadick, Neil S; Mulholland, R Stephen

2004-12-01

There have not been any published studies on the use of radiofrequency (RF)-light-based technologies for the treatment of cellulite. Only preliminary results have recently been reported (ASDS Proceedings, September 2004). This two-center study investigated the safety and effectiveness of combined energies for cellulite treatment using the VelaSmoothtrade mark system. Thirty-five female subjects with cellulite and/or skin irregularities on the thighs and/or buttocks were treated with the VelaSmooth device. Patients received from eight to 16 treatments twice weekly. All patients maintained their normal lifestyle, and diet and fluid consumption. The circumference of the right and left medial thighs was measured at both baseline and approximately 4 weeks after the last treatment. During the last follow-up visit, the physician graded the level of improvement in skin smoothing and/or cellulite improvement using pre- and post-treatment photographs. Three patients provided biopsy specimens for histological assessment. All study patients showed some level of reduction in thigh circumference after 8 weeks of treatment; indeed, 70% of all patients showed such a reduction after 4 weeks of treatment. Also, 100% of all patients showed some level of improvement in skin texture and cellulite. The mean decrease in circumference was 0.8 inches. Some patients demonstrated reductions of more than 2 inches. There were minimal complications associated with treatment. This preliminary study demonstrates that the VelaSmooth system can have a beneficial effect on cellulite appearance. Further studies are needed to better define the mechanisms by which RF and light energies affect subdermal tissues and develop a method of quantified cellulite analysis.

Impact of extracorporeal shock waves on the human skin with cellulite: A case study of an unique instance

PubMed Central

Kuhn, Christoph; Angehrn, Fiorenzo; Sonnabend, Ortrud; Voss, Axel

2008-01-01

In this case study of an unique instance, effects of medium-energy, high-focused extracorporeal generated shock waves (ESW) onto the skin and the underlying fat tissue of a cellulite afflicted, 50-year-old woman were investigated. The treatment consisted of four ESW applications within 21 days. Diagnostic high-resolution ultrasound (Collagenoson) was performed before and after treatment. Directly after the last ESW application, skin samples were taken for histopathological analysis from the treated and from the contra-lateral untreated area of skin with cellulite. No damage to the treated skin tissue, in particular no mechanical destruction to the subcutaneous fat, could be demonstrated by histopathological analysis. However an astounding induction of neocollageno- and neoelastino-genesis within the scaffolding fabric of the dermis and subcutis was observed. The dermis increased in thickness as well as the scaffolding within the subcutaneous fat-tissue. Optimization of critical application parameters may turn ESW into a noninvasive cellulite therapy. PMID:18488890

Gender difference in the impact of gynoid and android fat masses on the progression of hepatic steatosis in Japanese patients with type 2 diabetes.

PubMed

Bouchi, Ryotaro; Fukuda, Tatsuya; Takeuchi, Takato; Nakano, Yujiro; Murakami, Masanori; Minami, Isao; Izumiyama, Hajime; Hashimoto, Koshi; Yoshimoto, Takanobu; Ogawa, Yoshihiro

2017-01-01

Increased visceral adiposity is strongly associated with non-alcoholic fatty liver disease (NAFLD). However, little attention has been paid to the association between the change in subcutaneous adipose mass and the progression of non-alcoholic fatty liver disease (NAFLD). We aimed to investigate whether increased subcutaneous adipose tissue (gynoid fat mass) could be protective against the progression of NAFLD in Japanese patients with type 2 diabetes. This is a retrospective observational study of 294 Japanese patients with type 2 diabetes (65 ± 10 years old, 40% female). Liver attenuation index (LAI) measured by abdominal computed tomography was used for the assessment of hepatic steatosis. Both gynoid (kg) and android (kg) fat masses were measured by the whole body dual-energy X-ray absorptiometry. One-year changes in LAI, gynoid, and android fat masses were evaluated in both male and female patients. Linear regression analysis with a stepwise procedure was used for the statistical analyses to investigate the association of the changes in gynoid and android fat masses with the change in LAI. LAI levels at baseline were 1.15 ± 0.31 and 1.10 ± 0.34 in female and male patients ( p  = 0.455). The change in gynoid fat mass was significantly and positively associated with the change in LAI in both univariate (standardized β 0.331, p  = 0.049) and multivariate (standardized β 0.360, p  = 0.016) models in the female patients. However, no significant association was observed in males. In contrast, the increase in android fat mass was significantly associated with the reduced LAI in both genders in the multivariate models (standardized β -0.651, p  < 0.001 in females and standardized β -0.519, p  = 0.042 in males). This study provides evidence that increased gynoid fat mass may be protective against the progression of NAFLD in female Japanese patients with type 2 diabetes.

A Standardized Composition Comprised of Extracts from Rosmarinus officinalis, Annona squamosa and Zanthoxylum clava-herculis for Cellulite

PubMed Central

Yimam, Mesfin; Lee, Young-Chul; Jiao, Ping; Hong, Mei; Brownell, Lidia; Jia, Qi

2017-01-01

Background: Cellulite, characterized by changes in the skin morphology presented as dimpled or puckered skin appearance, is highly prevalent among postadolescent women. Cellulite management ranges from topical cream applications to invasive procedures. While some interventions showed improvements in physical appearances of affected areas, so far, none have reversed the condition to a full recovery. These unsuccessful measures signify the intricate nature of cellulite etiology highlighting its complexity leading to the possibility for a combination treatment approach to target multiple mechanisms. Materials and Methods: We screened our plant library for extracts that reduce cellular lipid accumulation, improve microcirculation, possess high total antioxidant capacity, significant anti-platelet aggregation, and anti-inflammatory activities using lipid accumulation assay in 3T3-L1 cells, Croton oil-induced hemorrhoid test in rats as a model for microcirculation, anti-platelet aggregation assay, nitric oxide (NO) inhibition assay, and 1,1-diphenyl-2-picrylhydrazyl assay. Results: Three known botanicals such as Rosemary officinalis, Annona squamosa and Zanthoxylum clava-herculis were identified as lead extracts in these tests. Treatment of 3T3 cell with A. squamosa at 1 μg/ml resulted in 68.8% reduction in lipid accumulation. In croton oil-induced hemorrhoid study, Z. clava-herculis reduced the recto-anus coefficient by 79.6% at 6 mg/kg indicating improvement in microcirculations. Similarly, R. officinalis caused inhibition of 82%, 71.8%, and 91.8% in platelet aggregation, NO production and free radical generation at 31.25 μg/ml, 6.2 μg/ml, and 40 μg/ml concentrations suggesting its anti-oxidant, and anti-inflammatory activities. Conclusions: Data depicted here suggest that formulation of these well-known botanicals at a specific ratio perhaps may yield a composition with a much wider spectrum of mechanisms of actions to impact the multiple pathways involved in

Clinical features and management of non-HIV related lipodystrophy in children: A systematic review

USDA-ARS?s Scientific Manuscript database

Lipodystrophy syndromes are characterized by generalized or partial absence of adipose tissue. We conducted a systematic review to synthesize data on clinical and metabolic features of lipodystrophy (age at onset, < 18 years). Sources included Medline, Embase, Cochrane Library, Scopus and Non-Indexe...

The human lipodystrophy gene product Berardinelli-Seip congenital lipodystrophy 2/seipin plays a key role in adipocyte differentiation.

PubMed

Chen, Weiqin; Yechoor, Vijay K; Chang, Benny Hung-Junn; Li, Ming V; March, Keith L; Chan, Lawrence

2009-10-01

Mutations in the Berardinelli-Seip congenital lipodystrophy 2 gene (BSCL2) are the underlying defect in patients with congenital generalized lipodystrophy type 2. BSCL2 encodes a protein called seipin, whose function is largely unknown. In this study, we investigated the role of Bscl2 in the regulation of adipocyte differentiation. Bscl2 mRNA is highly up-regulated during standard hormone-induced adipogenesis in 3T3-L1 cells in vitro. However, this up-regulation does not occur during mesenchymal stem cell (C3H10T1/2 cells) commitment to the preadipocyte lineage. Knockdown of Bscl2 by short hairpin RNA in C3H10T1/2 cells has no effect on bone morphogenetic protein-4-induced preadipocyte commitment. However, knockdown in 3T3-L1 cells prevents adipogenesis induced by a standard hormone cocktail, but adipogenesis can be rescued by the addition of peroxisome proliferator-activated receptor-gamma agonist pioglitazone at an early stage of differentiation. Interestingly, pioglitazone-induced differentiation in the absence of standard hormone is not associated with up-regulated Bscl2 expression. On the other hand, short hairpin RNA-knockdown of Bscl2 largely blocks pioglitazone-induced adipose differentiation. These experiments suggest that Bscl2 may be essential for normal adipogenesis; it works upstream or at the level of peroxisome proliferator-activated receptor-gamma, enabling the latter to exert its full activity during adipogenesis. Loss of Bscl2 function thus interferes with the normal transcriptional cascade of adipogenesis during fat cell differentiation, resulting in near total loss of fat or lipodystrophy.

Side Effects of HIV Medicines: HIV and Lipodystrophy

MedlinePlus

... may help. Other ways to manage lipodystrophy include liposuction (surgical removal of fat) and injections of fat ... unless your health care provider tells you to. Liposuction (surgical removal of fat) is sometimes used to ...

Cellulite treatment: evidence and ethics, brief history, and emphasis on current practices including liposuction

NASA Astrophysics Data System (ADS)

de Riese, Cornelia

2005-04-01

According to Taber's Cyclopedic Medical Dictionary "cellulite" is defined as: "a non-technical term for subcutaneous deposits of fat, especially in the buttocks, legs, and thighs." These deposits result in puckered, dimply skin and they are a cause for major aesthetic concerns in affected patients. The etiology of this condition is still unclear. Female predilection is witnessed in clinical practice as it is reported in the literature. It remains a subject for further studies whether it is a structural problem of connective tissue or as suggested probably related to hormonal causes. Magnetic resonance imaging may provide some answers to these questions. Not knowing what is causing this nuisance makes it almost impossible to treat. No wonder that there is little scientific validation to support any of the many treatments that are advertised on the Internet or in women's magazines. This review focuses on mechanical and microinvasive interventions that claim to alleviate "cellulite": lipoplasty, liposcultpure, liposuction, subcision, and laser. Among the parameters analyzed are the proposed modes of action of these techniques as well as adverse events and complications that may occur. Of special interest will be the evidence that backs these procedures. Extracting reliable data is hampered by methodical problems with the design of most of the published trials. In essence, at this time there is no "cure" for cellulite. Safe treatment recommendations are related to healthy life style choices that include toning exercises, dietary changes, and weight loss.

Lipid regulation in lipodystrophy versus the obesity-associated metabolic syndrome: the dissociation of HDL-C and triglycerides.

PubMed

Joseph, Jalaja; Shamburek, Robert D; Cochran, Elaine K; Gorden, Phillip; Brown, Rebecca J

2014-09-01

There is an inverse relationship between triglycerides and high-density lipoprotein cholesterol (HDL-C) in insulin resistance, such that improvement in insulin resistance decreases triglycerides and increases HDL-C. Patients with lipodystrophy have extreme insulin resistance with high triglycerides and low HDL-C. Leptin replacement in lipodystrophy leads to a marked decrease in triglycerides (∼60%). Our objective was to study the effects of metreleptin on triglycerides and HDL-C in lipodystrophy in contrast to changes in triglycerides and HDL-C in interventions for the obesity-associated metabolic syndrome. This open-label nonrandomized study at the National Institutes of Health included 82 patients with various forms of lipodystrophy. Metreleptin (0.06-0.24 mg/kg/d) was administered for 24 months in lipodystrophy. Serum triglycerides and HDL-C were measured. At baseline, lipodystrophy patients had low HDL-C (30 ± 1 mg/dL) and high triglycerides (961 ± 220 mg/dL) with an inverse relationship between the two (R = -0.37, P = .0006). There was no change in HDL-C with metreleptin despite major improvement in triglycerides, and individual changes in triglycerides only weakly predicted HDL-C change. On linear regression, in obesity, a decrease of 0.1 mg/dL in log(triglycerides) was associated with a 4.2 mg/dL rise in HDL-C, whereas in lipodystrophy, a decrease of 0.1 mg/dL in log(triglycerides) was associated with only a 0.6 mg/dL rise in HDL-C. The normal reciprocal relationship between triglyceride and HDL-C change seen in response to interventions for the obesity-associated metabolic syndrome is quantitatively different from that seen in lipodystrophy in response to metreleptin. Further work is needed to understand HDL-C regulation in this condition.

Lipid Regulation in Lipodystrophy Versus the Obesity-Associated Metabolic Syndrome: The Dissociation of HDL-C and Triglycerides

PubMed Central

Joseph, Jalaja; Shamburek, Robert D.; Cochran, Elaine K.; Gorden, Phillip

2014-01-01

Context: There is an inverse relationship between triglycerides and high-density lipoprotein cholesterol (HDL-C) in insulin resistance, such that improvement in insulin resistance decreases triglycerides and increases HDL-C. Patients with lipodystrophy have extreme insulin resistance with high triglycerides and low HDL-C. Leptin replacement in lipodystrophy leads to a marked decrease in triglycerides (∼60%). Objective: Our objective was to study the effects of metreleptin on triglycerides and HDL-C in lipodystrophy in contrast to changes in triglycerides and HDL-C in interventions for the obesity-associated metabolic syndrome. Design, Setting, and Patients: This open-label nonrandomized study at the National Institutes of Health included 82 patients with various forms of lipodystrophy. Intervention: Metreleptin (0.06–0.24 mg/kg/d) was administered for 24 months in lipodystrophy. Main Outcome Measures: Serum triglycerides and HDL-C were measured. Results: At baseline, lipodystrophy patients had low HDL-C (30 ± 1 mg/dL) and high triglycerides (961 ± 220 mg/dL) with an inverse relationship between the two (R = −0.37, P = .0006). There was no change in HDL-C with metreleptin despite major improvement in triglycerides, and individual changes in triglycerides only weakly predicted HDL-C change. On linear regression, in obesity, a decrease of 0.1 mg/dL in log(triglycerides) was associated with a 4.2 mg/dL rise in HDL-C, whereas in lipodystrophy, a decrease of 0.1 mg/dL in log(triglycerides) was associated with only a 0.6 mg/dL rise in HDL-C. Conclusions: The normal reciprocal relationship between triglyceride and HDL-C change seen in response to interventions for the obesity-associated metabolic syndrome is quantitatively different from that seen in lipodystrophy in response to metreleptin. Further work is needed to understand HDL-C regulation in this condition. PMID:24926953

HIV lipodystrophy etiology and pathogenesis. Body composition and metabolic alterations: etiology and pathogenesis.

PubMed

Kotler, Donald P

2003-04-01

The results of epidemiologic investigations have clearly indicated that the development of lipodystrophy is multifactorial. Factors related to HIV infection, hormonal influences, mitochondrial dysfunction, cytokine activation related to immune reconstitution, and individual genetic predisposition all have been hypothesized as etiologic. Recent studies suggest that immune dysregulation rather than HIV infection per se may be the predominant factor in the development of lipodystrophy.

Effects of transcutaneous electrical nerve stimulation on pain intensity during application of carboxytherapy in patients with cellulite: A randomized placebo-controlled trial.

PubMed

Sadala, Adria Y; Machado, Aline F P; Liebano, Richard E

2018-01-16

Carboxytherapy may generate local pain that is considered the main limiting factor in clinical practice. Transcutaneous electric nerve stimulation (TENS) is widely used in the control of acute pain; however, the effect of TENS on pain relief during carboxytherapy has not been studied to date. To assess the effect of TENS on pain intensity during carboxytherapy in patients with cellulite in the gluteal region. This randomized clinical trial was conducted with 84 patients, 18-44 years of age, who had moderate cellulite in the gluteal region, according to Cellulite Severity Scale, but never received carboxytherapy. Patients were randomized into 3 groups: active TENS, placebo TENS, and control group. For the intervention, skin depressions with cellulite were outlined, and the gluteal area to be treated was defined. The subcutaneous injection of CO 2 was performed using 0.30 × 13 mm-needles at a 45° angle, with a controlled flow rate of 100 mL/min maintained for 1 minute at each puncture site. The parameters for TENS were as follows: frequency of 100 Hz and pulse duration of 200 μs; TENS intensity was adjusted until the patient reported strong paresthesia. The visual numeric pain rating scale was used to assess pain intensity after each puncture. The active TENS group reported lower pain intensity compared to the placebo TENS (P < .0001) and control (P < .0001) groups. Transcutaneous electric nerve stimulation (TENS) was effective in reducing pain intensity during carboxytherapy in patients with cellulite in the gluteal region. © 2018 Wiley Periodicals, Inc.

Painless, safe, and efficacious noninvasive skin tightening, body contouring, and cellulite reduction using multisource 3DEEP radiofrequency.

PubMed

Harth, Yoram

2015-03-01

In the last decade, Radiofrequency (RF) energy has proven to be safe and highly efficacious for face and neck skin tightening, body contouring, and cellulite reduction. In contrast to first-generation Monopolar/Bipolar and "X -Polar" RF systems which use one RF generator connected to one or more skin electrodes, multisource radiofrequency devices use six independent RF generators allowing efficient dermal heating to 52-55°C, with no pain or risk of other side effects. In this review, the basic science and clinical results of body contouring and cellulite treatment using multisource radiofrequency system (Endymed PRO, Endymed, Cesarea, Israel) will be discussed and analyzed. © 2015 Wiley Periodicals, Inc.

Associations Between Sedentary Time, Physical Activity, and Dual-Energy X-ray Absorptiometry Measures of Total Body, Android, and Gynoid Fat Mass in Children.

PubMed

McCormack, Lacey; Meendering, Jessica; Specker, Bonny; Binkley, Teresa

2016-01-01

Negative health outcomes are associated with excess body fat, low levels of physical activity (PA), and high sedentary time (ST). Relationships between PA, ST, and body fat distribution, including android and gynoid fat, assessed using dual-energy X-ray absorptiometry (DXA) have not been measured in children. The purpose of this study was to test associations between levels of activity and body composition in children and to evaluate if levels of activity predict body composition by DXA and by body mass index percentile in a similar manner. PA, ST, and body composition from 87 children (8.8-11.8 yr, grades 3-5, 44 boys) were used to test the association among study variables. Accelerometers measured PA and ST. Body composition measured by DXA included bone mineral content (BMC) and fat and lean mass of the total body (TB, less head), android, and gynoid regions. ST (range: 409-685 min/wk) was positively associated with TB percent fat (0.03, 95% confidence interval [CI]: 0.00-0.05) and android fat mass (1.5 g, 95% CI: 0.4-3.0), and inversely associated with the lean mass of the TB (-10.7 g, 95% CI: -20.8 to -0.63) and gynoid regions (-2.2 g, 95% CI: -4.3 to -0.2), and with BMC (-0.43 g, 95% CI: 0.77-0.09). Moderate-to-vigorous PA was associated with lower TB (-53 g, 95% CI: -87 to -18), android (-5 g, 95% CI: -8 to -2]), and gynoid fat (-6 g, 95% CI: -11 to -0.5). Vigorous activity results were similar. Light PA was associated with increased TB (17.1 g, 95% CI: 3.0-31.3) and gynoid lean mass (3.9 g, 95% CI: 1.0-6.8) and BMC (0.59 g, 95% CI: 0.10-1.07). In boys, there were significant associations between activity and DXA percent body fat measures that were not found with the body mass index percentile. Objective measures of PA were inversely associated with TB, android, and gynoid fat, whereas ST was directly associated with TB percent fat and, in particular, android fat. Activity levels predict body composition measures by DXA and, in

CASE REPORT OF SEVERE PROLIFERATIVE RETINOPATHY IN A PATIENT WITH CONGENITAL LIPODYSTROPHY.

PubMed

Rosin, Boris; Jaouni, Tareq

2017-08-21

A case report of a patient with severe proliferative retinopathy due to congenital lipodystrophy. We reviewed the medical history, imaging, and surgical procedures of a 25-year-old woman with a history of congenital lipodystrophy, presenting with bilateral combined tractional and exudative retinal detachment, poorly controlled diabetes mellitus, and extreme dislipidemia. The patient underwent retinal detachment repair surgery both eyes. On the last follow-up, both retinae were flat, and visual acuity had improved in the right eye to J3 for near and finger counting 3 m for distance. Surgery combining pars plana vitrectomy and scleral bucking successfully flattened both retinae and significantly improved visual acuity in one eye in this case of bilateral retinal detachment with combined tractional and exudative components in a patient with congenital lipodystrophy. Surgical control of retinal complications is thus possible, provided there is adequate control of the underlying risk factors.

Prediction of android and gynoid body adiposity via a three-dimensional stereovision body imaging system and dual-energy x-ray absorptiometry

PubMed Central

Lee, Jane J.; Freeland-Graves, Jeanne H.; Pepper, M. Reese; Stanforth, Philip R.; Xu, Bugao

2017-01-01

Objective Current methods for measuring regional body fat are expensive and inconvenient compared to the relative cost-effectiveness and ease-of-use of a stereovision body imaging (SBI) system. The primary goal of this research is to develop prediction models for android and gynoid fat by body measurements assessed via SBI and dual-energy x-ray absorptiometry (DXA). Subsequently, mathematical equations for prediction of total and regional (trunk, leg) body adiposity were established via parameters measured by SBI and DXA. Methods A total of 121 participants were randomly assigned into primary and cross-validation groups. Body measurements were obtained via traditional anthropometrics, SBI, and DXA. Multiple regression analysis was conducted to develop mathematical equations by demographics and SBI assessed body measurements as independent variables and body adiposity (fat mass and percent fat) as dependent variables. The validity of the prediction models was evaluated by a split sample method and Bland-Altman analysis. Results The R2 of the prediction equations for fat mass and percent body fat were 93.2% and 76.4% for android, and 91.4% and 66.5% for gynoid, respectively. The limits of agreement for the fat mass and percent fat were − 0.06 ± 0.87 kg and − 0.11 ± 1.97 % for android and − 0.04 ± 1.58 kg and − 0.19 ± 4.27 % for gynoid. Prediction values for fat mass and percent fat were 94.6% and 88.9% for total body, 93.9% and 71.0% for trunk, and 92.4% and 64.1% for leg, respectively. Conclusions The three-dimensional (3D) SBI produces reliable parameters that can predict android and gynoid, as well as total and regional (trunk, leg) fat mass. PMID:25915106

Prediction of Android and Gynoid Body Adiposity via a Three-dimensional Stereovision Body Imaging System and Dual-Energy X-ray Absorptiometry.

PubMed

Lee, Jane J; Freeland-Graves, Jeanne H; Pepper, M Reese; Stanforth, Philip R; Xu, Bugao

2015-01-01

Current methods for measuring regional body fat are expensive and inconvenient compared to the relative cost-effectiveness and ease of use of a stereovision body imaging (SBI) system. The primary goal of this research is to develop prediction models for android and gynoid fat by body measurements assessed via SBI and dual-energy x-ray absorptiometry (DXA). Subsequently, mathematical equations for prediction of total and regional (trunk, leg) body adiposity were established via parameters measured by SBI and DXA. A total of 121 participants were randomly assigned into primary and cross-validation groups. Body measurements were obtained via traditional anthropometrics, SBI, and DXA. Multiple regression analysis was conducted to develop mathematical equations by demographics and SBI assessed body measurements as independent variables and body adiposity (fat mass and percentage fat) as dependent variables. The validity of the prediction models was evaluated by a split sample method and Bland-Altman analysis. The R(2) of the prediction equations for fat mass and percentage body fat were 93.2% and 76.4% for android and 91.4% and 66.5% for gynoid, respectively. The limits of agreement for the fat mass and percentage fat were -0.06 ± 0.87 kg and -0.11% ± 1.97% for android and -0.04 ± 1.58 kg and -0.19% ± 4.27% for gynoid. Prediction values for fat mass and percentage fat were 94.6% and 88.9% for total body, 93.9% and 71.0% for trunk, and 92.4% and 64.1% for leg, respectively. The three-dimensional (3D) SBI produces reliable parameters that can predict android and gynoid as well as total and regional (trunk, leg) fat mass.

A novel paraneoplastic syndrome with acquired lipodystrophy and chronic inflammatory demyelinating polyneuropathy in an adolescent male with craniopharyngioma.

PubMed

Lockemer, Hillary Elizabeth; Sumpter, Kathryn Maria; Cope-Yokoyama, Sandy; Garg, Abhimanyu

2018-03-28

Acquired lipodystrophy, craniopharyngioma and chronic inflammatory demyelinating polyneuropathy (CIDP) are individually rare disorders, and have never before been reported in a single patient. A 15-year-7 month old Caucasian male presented with lower extremity weakness, frequent falls and abnormal fat distribution occurring over the previous 1 year. He was diagnosed with CIDP, craniopharyngioma and acquired lipodystrophy. The patient underwent tumor debulking and cranial irradiation for the craniopharyngioma, and received monthly intravenous immunoglobulin for the CIDP. The patient initially had some resolution of the lipodystrophy phenotype, but subsequently the abnormal fat distribution recurred and the patient developed additional systemic abnormalities, including mild pancytopenia and hepatic fibrosis. Our patient represents a novel association of acquired lipodystrophy, craniopharyngioma, and CIDP, possibly due to an as yet unidentified paraneoplastic autoantibody.

Metabolic abnormalities and cardiovascular disease risk factors in adults with human immunodeficiency virus infection and lipodystrophy.

PubMed

Hadigan, C; Meigs, J B; Corcoran, C; Rietschel, P; Piecuch, S; Basgoz, N; Davis, B; Sax, P; Stanley, T; Wilson, P W; D'Agostino, R B; Grinspoon, S

2001-01-01

We evaluated metabolic and clinical features of 71 HIV-infected patients with lipodystrophy by comparing them with 213 healthy control subjects, matched for age and body mass index, from the Framingham Offspring Study. Thirty HIV-infected patients without fat redistribution were compared separately with 90 matched control subjects from the Framingham Offspring Study. Fasting glucose, insulin, and lipid levels; glucose and insulin response to standard oral glucose challenge; and anthropometric measurements were determined. HIV-infected patients with lipodystrophy demonstrated significantly increased waist-to-hip ratios, fasting insulin levels, and diastolic blood pressure compared with controls. Patients with lipodystrophy were more likely to have impaired glucose tolerance, diabetes, hypertriglyceridemia, and reduced levels of high-density lipoprotein (HDL) cholesterol than were controls. With the exception of HDL cholesterol level, these risk factors for cardiovascular disease (CVD) were markedly attenuated in patients without lipodystrophy and were not significantly different in comparison with controls. These data demonstrate a metabolic syndrome characterized by profound insulin resistance and hyperlipidemia. CVD risk factors are markedly elevated in HIV-infected patients with fat redistribution.

Non-ionic surfactant based vesicular drug delivery system for topical delivery of caffeine for treatment of cellulite: design, formulation, characterization, histological anti-cellulite activity, and pharmacokinetic evaluation.

PubMed

Teaima, Mahmoud H; Abdelhalim, Sally A; El-Nabarawi, Mohamed A; Attia, Dalia A; Helal, Doaa A

2018-01-01

Cellulite is a common topographical alteration where skin acquires an orange peel or mattress appearance with alterations in adipose tissue and microcirculation. This work aims to develop and evaluate a topical niosomal gel formulae with good permeation to reach the subcutaneous fat layer. Several caffeine niosomal dispersions were prepared and incorporated into gel formulae using Carbopol 940 polymer, chemical penetration enhancers, and iontophoresis, then the prepared gels were applied onto the skin of rats and anticellulite activity of caffeine from the prepared gels compared to that of the commercial product Cellu Destock ® was evaluated by histological study of the skin and measurement of plasma level of caffeine passing through the skin using liquid chromatography (LC/MS-MS). Results of histology revealed reduction of size and thickness of fatty layer of rat skin in the following order: FVII > FXIV > Cellu Destock ®  > FVII + Iontophoresis > FXIV + Iontophoresis. Pharmacokinetic results of caffeine in plasma revealed that C max , T max , and AUC 0-12h decreased in the following order: FXIV > FVII > Cellu Destock ® . These results conclude that incorporation of caffeine niosomal dispersion into gel matrix with penetration enhancers and iontophoresis resulted in improvement in penetration of caffeine through the skin into the underlying fatty layer in treatment of cellulite.

[Polyalkylimide filler in human immunodeficiency virus-associated facial lipodystrophy: ophthalmic complications].

PubMed

García-Pacheco, S A; Blanco-Rivas, R; Campos-García, S

2014-10-01

A 54 year old male, who consulted for acute inflammatory palpebral edema. The patient has HIV infection (on antiretroviral treatment) and an associated facial lipodystrophy that was filled with polyalkylimide in both frontotemporal regions one year before. MRI revealed subcutaneous abscesses in the filled areas, which led to preseptal cellulitis. Complete remission was achieved with antibiotic therapy and monitoring. Polyalkylimide is a hydrogel that is recently used as facial filler without FDA approval. Although it was believed to be safe and useful for treating HIV lipodystrophy, it is not exempt from adverse effects (infection, abscesses, granulomas) that can compromise the eye area. Copyright © 2010 Sociedad Española de Oftalmología. Published by Elsevier Espana. All rights reserved.

The successful use of lipectomy in the management of airway obstruction in a woman with HIV-associated lipodystrophy

PubMed Central

Tsui, Edison; Bogdasarian, Ronald; Blomain, Eric

2015-01-01

Lipodystrophy is a common complication of highly active antiretroviral therapy and is associated with significant comorbidities. Altered fat distribution, particularly lipohypertrophy of the dorsal cervical fat pad is associated with reduced quality of life as well as medical complications. We report the rare case of a patient with airway obstruction secondary to HIV-associated lipodystrophy. Ultrasound-assisted liposuction was successfully performed to relieve her airway obstruction and to facilitate a tracheostomy. To the best of our knowledge, this is the first documented case of its kind. We also provide a brief review of the literature on the current management options for HIV-associated lipodystrophy. PMID:25694636

Human immunodeficiency virus-associated lipodystrophy: an objective definition based on dual-energy x-ray absorptiometry-derived regional fat ratios in a South Asian population.

PubMed

Asha, Hesarghatta Shyamasunder; Seshadri, Mandalam Subramaniam; Paul, Thomas Vizhalil; Abraham, Ooriapadickal Cherian; Rupali, Priscilla; Thomas, Nihal

2012-01-01

To develop an objective definition of human immunodeficiency virus (HIV)-associated lipodystrophy by using regional fat mass ratios and to assess the utility of anthropometric and skinfold measurements in the initial screening for lipodystrophy. Male patients between 25 and 50 years old with proven HIV infection (highly active antiretroviral therapy [HAART]-naïve subjects and those receiving successful HAART) were studied and compared with body mass index (BMI)-matched HIV-negative control subjects. Anthropometric variables, body composition, dual-energy x-ray absorptiometry findings, and metabolic variables were compared among the 3 study groups and between those patients with and those without lipodystrophy. Trunk fat/lower limb fat mass ratio >2.28 identified 54.3% of patients with HIV receiving HAART as having lipodystrophy and had the highest odds ratio for predicting metabolic syndrome. The "clinical diagnosis of lipodystrophy" and the "clinical scoring system" had too many false-positive and false-negative results. Triceps skinfold thickness (SFT)/BMI ratio ≤0.49 and abdominal SFT/triceps SFT ratio >1.385 have good sensitivity but poor specificity in identifying lipodystrophy. In comparison with HAART-naïve patients with HIV, those receiving HAART had significantly higher insulin resistance, and a significantly greater proportion had impaired glucose tolerance and dyslipidemia. Among patients receiving HAART, those with lipodystrophy had a greater degree of insulin resistance, higher triglyceride levels, and lower levels of high-density lipoprotein cholesterol. The trunk fat/lower limb fat mass ratio in BMI-matched normal subjects can be used to derive cutoff values to define lipodystrophy objectively in HIV-infected patients. Defining lipodystrophy in this way is better than other methods of identifying those patients with increased cardiovascular risk. Triceps SFT/BMI and abdominal SFT/triceps SFT ratios may be useful as screening tools in resource

[Congenital generalized lipodystrophy in a patient with Dandy Walker anomaly].

PubMed

Luna, Cecilia Inés; Fernández Cordero, Marisa; Escruela, Romina; Sierra, Valeria; Córdoba, Antonela; Goñi, Ignacio María; Berridi, Ricardo

2014-10-01

The objective of this study is to describe the unexpected association between the congenital generalized lipodystrophy (CGL) and Dandy Walker anomaly. We report the case of a 1-year-old infant who was hospitalized at her fourth month of life with Dandy Walker anomaly diagnosis and an increased social risk. During her hospitalization, she developed progressively: acromegaloid aspect, triangular fascia, hirsutism, lipoatrophy, muscle hypertrophy, clitoromegaly, abdominal distention, progressive hepatomegaly, and hypertriglyceridemia. This led to the clinical diagnosis of congenital generalized lipodystrophy. Importance should be given to the examination of clinical aspects as well as the interdisciplinary follow-up for proper detection of insulin resistance and diabetes, early puberty, cardiomyopathy, among others. In case of Dandy Walker anomaly, it should be checked the evolution to search intracranial hypertension signs. Due to its autosomal recessive nature, it is important to provide genetic counseling to the parents.

Iatrogenic lipodystrophy in HIV patients - the need for very-low-fat diets.

PubMed

McCarty, M F

2003-01-01

In HIV patients, chronic treatment with protease inhibitors often precipitates a peripheral lipodystrophy associated with insulin resistance syndrome and premature coronary disease. In vitro studies demonstrate that these drugs can compromise the ability of adipocytes to store triglycerides; in vivo, peripheral subcutaneous adipocytes appear to be most affected, such that body fat often redistributes to visceral or truncal adipose stores. Dysfunction of peripheral subcutaneous adipocytes - ordinarily quite efficient for storing fat - can be expected to give rise to an excessive flux of free fatty acids (FFAs) following fatty meals; chronic overexposure of tissues to FFAs is a likely explanation for the insulin resistance syndrome associated with lipodystrophy. These considerations suggest that a very-low-fat diet - less than 15% fat calories - may ameliorate the cardiovascular risk associated with lipodystrophy; such diets are known to have a favorable effect on the insulin sensitivity of healthy subjects. Very-low-fat whole-food vegan diets are particularly recommendable in this context, as they may help to shrink visceral fat depots while markedly reducing LDL cholesterol. Appropriate adjunctive measures may include aerobic exercise training - beneficial both for insulin sensitivity and weight control - as well as administration of statins or policosanol, and of fibrates or fish oil, to decrease LDL and triglycerides, respectively. Despite perceptions to the contrary, very-low-fat diets can meet with good compliance in well-motivated subjects given appropriate instruction.

Altered miRNA processing disrupts brown/white adipocyte determination and associates with lipodystrophy

PubMed Central

Mori, Marcelo A.; Thomou, Thomas; Boucher, Jeremie; Lee, Kevin Y.; Lallukka, Susanna; Kim, Jason K.; Torriani, Martin; Yki-Järvinen, Hannele; Grinspoon, Steven K.; Cypess, Aaron M.; Kahn, C. Ronald

2014-01-01

miRNAs are important regulators of biological processes in many tissues, including the differentiation and function of brown and white adipocytes. The endoribonuclease dicer is a major component of the miRNA-processing pathway, and in adipose tissue, levels of dicer have been shown to decrease with age, increase with caloric restriction, and influence stress resistance. Here, we demonstrated that mice with a fat-specific KO of dicer develop a form of lipodystrophy that is characterized by loss of intra-abdominal and subcutaneous white fat, severe insulin resistance, and enlargement and “whitening” of interscapular brown fat. Additionally, KO of dicer in cultured brown preadipocytes promoted a white adipocyte–like phenotype and reduced expression of several miRNAs. Brown preadipocyte whitening was partially reversed by expression of miR-365, a miRNA known to promote brown fat differentiation; however, introduction of other miRNAs, including miR-346 and miR-362, also contributed to reversal of the loss of the dicer phenotype. Interestingly, fat samples from patients with HIV-related lipodystrophy exhibited a substantial downregulation of dicer mRNA expression. Together, these findings indicate the importance of miRNA processing in white and brown adipose tissue determination and provide a potential link between this process and HIV-related lipodystrophy. PMID:24983316

Efficacy of Slimming Cream Containing 3.5% Water-Soluble Caffeine and Xanthenes for the Treatment of Cellulite: Clinical Study and Literature Review

PubMed Central

Byun, Sang-Young; Kwon, Soon-Hyo; Heo, Su-Hak; Shim, Jae-Seong; Du, Mi-Hee

2015-01-01

Background Cellulite is a 'cottage cheese-like' cutaneous change caused by subcutaneous fat bulging into the dermis that usually leads to cosmetic problems. Slimming cream containing 3.5% water-soluble caffeine and xanthenes exhibits a lipolytic effect with penetration into the dermis. Objective To evaluate the efficacy and safety of slimming cream for the treatment of cellulite. Methods Fifteen subjects with cellulite applied slimming cream to the thighs and inner side of the upper arms twice daily for 6 weeks. Efficacy was assessed using a standard visual scale, changes in the circumferences of the thighs and upper arms, and patient satisfaction by a questionnaire at baseline, week 3, and week 6. Safety was assessed by inquiring about adverse events through questionnaires. Results The standard visual scale score improved significantly by 0.49 points (19.8%) at week 6. Thigh and upper-arm circumferences decreased by 0.7 cm (1.7%) and 0.8 cm (2.3%), respectively, at week 6. Slight itching and transient flushing were commonly reported, but no serious adverse event occurred. Conclusion The slimming cream tested appears to be effective for the treatment of cellulitis without serious adverse effects. However, additional large clinical trials are required to confirm the efficacy and safety of slimming cream for the treatment of cellulitis. PMID:26082579

Long-term fundus changes in acquired partial lipodystrophy.

PubMed

Jansen, Joyce; Delaere, Lien; Spielberg, Leigh; Leys, Anita

2013-11-18

We describe long-term fundus changes in a patient with partial lipodystrophy (PL). Retinal pigment alterations, drusen and subretinal neovascularisation were seen without evidence for membranoproliferative glomerulonephritis. Fundus alterations similar to those seen in age-related macular degeneration can occur at an earlier age in patients with PL, even without renal disease. Dysregulation of an alternative complement pathway with low serum levels of C3 has been implicated as a pathogenetic mechanism.

Long-term fundus changes in acquired partial lipodystrophy

PubMed Central

Jansen, Joyce; Delaere, Lien; Spielberg, Leigh; Leys, Anita

2013-01-01

We describe long-term fundus changes in a patient with partial lipodystrophy (PL). Retinal pigment alterations, drusen and subretinal neovascularisation were seen without evidence for membranoproliferative glomerulonephritis. Fundus alterations similar to those seen in age-related macular degeneration can occur at an earlier age in patients with PL, even without renal disease. Dysregulation of an alternative complement pathway with low serum levels of C3 has been implicated as a pathogenetic mechanism. PMID:24248317

Do non-nucleoside reverse transcriptase inhibitors contribute to lipodystrophy?

PubMed

Nolan, David

2005-01-01

Lipodystrophy complications, including lipoatrophy (pathological fat loss) and metabolic complications, have emerged as important long-term toxicities associated with antiretroviral therapy in the current era. The wealth of data that has accumulated over the past 6 years has now clarified the contribution of specific antiretroviral drugs to the risk of these clinical endpoints, with evidence that lipoatrophy is strongly associated with the choice of nucleoside reverse transcriptase inhibitor therapy (specifically, stavudine and to a lesser extent zidovudine). The aetiological basis of metabolic complications of antiretroviral therapy has proven to be complex, in that the risk appears to be modulated by a number of lifestyle factors that have made the metabolic syndrome highly prevalent in the general population, with additional contributions from HIV disease status itself, as well as from individual drugs within the HIV protease inhibitor class. The currently licensed non-nucleoside reverse transcriptase inhibitor (NNRTI) drugs, efavirenz and nevirapine, have been proven to have a favourable safety profile in terms of lipodystrophy complications. However, it must be noted that NNRTI drugs also have individual toxicity profiles that must be accounted for when considering and/or monitoring their use in the treatment of HIV infection.

Hypotension, lipodystrophy, and insulin resistance in generalized PPARγ-deficient mice rescued from embryonic lethality

PubMed Central

Duan, Sheng Zhong; Ivashchenko, Christine Y.; Whitesall, Steven E.; D’Alecy, Louis G.; Duquaine, Damon C.; Brosius, Frank C.; Gonzalez, Frank J.; Vinson, Charles; Pierre, Melissa A.; Milstone, David S.; Mortensen, Richard M.

2007-01-01

We rescued the embryonic lethality of global PPARγ knockout by breeding Mox2-Cre (MORE) mice with floxed PPARγ mice to inactivate PPARγ in the embryo but not in trophoblasts and created a generalized PPARγ knockout mouse model, MORE-PPARγ knockout (MORE-PGKO) mice. PPARγ inactivation caused severe lipodystrophy and insulin resistance; surprisingly, it also caused hypotension. Paradoxically, PPARγ agonists had the same effect. We showed that another mouse model of lipodystrophy was hypertensive, ruling out the lipodystrophy as a cause. Further, high salt loading did not correct the hypotension in MORE-PGKO mice. In vitro studies showed that the vasculature from MORE-PGKO mice was more sensitive to endothelial-dependent relaxation caused by muscarinic stimulation, but was not associated with changes in eNOS expression or phosphorylation. In addition, vascular smooth muscle had impaired contraction in response to α-adrenergic agents. The renin-angiotensin-aldosterone system was mildly activated, consistent with increased vascular capacitance or decreased volume. These effects are likely mechanisms contributing to the hypotension. Our results demonstrated that PPARγ is required to maintain normal adiposity and insulin sensitivity in adult mice. Surprisingly, genetic loss of PPARγ function, like activation by agonists, lowered blood pressure, likely through a mechanism involving increased vascular relaxation. PMID:17304352

Focused Ultrasound Lipolysis in the Treatment of Abdominal Cellulite: An Open-Label Study

PubMed Central

Moravvej, Hamideh; Akbari, Zahra; Mohammadian, Shahrzad; Razzaghi, Zahra

2015-01-01

Introduction: Despite a growing popularity of noninvasive ultrasonic lipolysis procedure, there is a lack of evidence about the efficacy of this method. This study was performed to evaluate the efficacy of focused ultrasonic lipolysis on abdominal cellulite treatment. Methods: Twenty-eight consecutive subjects (age: 37.8 ± 8 years) underwent weekly transdermal focused ultrasonic lipolysis (Med Contour, General Project Ltd., Florence, Italy) and vacuum drainage for a maximum of eight sessions. Largest abdominal girth and 2 lines at 4 cm to 7 cm distance above and under it were located as fixed points of measurements. The mean value of the three fixed lines was considered as the abdominal circumference. Subjects were evaluated using measurements of circumference, immediately after and 3 weeks after the final treatment and compared using paired t test. Results: One hundred ninety-four ultrasonic lipolysis procedures were performed on 28 subjects. A statistically significant (P < .001) average of 1.89 cm (95% CI: 1.63-2.02 cm) decrease of circumference value was observed in each session of ultrasonic lipolysis. The mean pretreatment to posttreatment circumference reduction was 8.21 cm (95% CI: 6.38-10.04, P < .001) that declined to 7 cm (95% CI: 3.2-10.8, P < .001) at the 3-month follow-up visit. Conclusion: Focused ultrasonic lipolysis appears to be an effective method for reduction of abdominal cellulite, although some amount of circumference reduction reversal may be observed in long term follow-up visit. PMID:26464776

Treatment of cellulite with a bipolar radiofrequency, infrared heat, and pulsatile suction device: a pilot study.

PubMed

Wanitphakdeedecha, Rungsima; Manuskiatti, Woraphong

2006-12-01

Very few therapeutic options have proven effective in the treatment of cellulite. To evaluate the effectiveness and adverse effects of a bipolar radiofrequency (RF), infrared (IR) heat and pulsatile suction device for the treatment of cellulite. Twelve subjects were treated with the RF-light-based device. All subjects were treated twice weekly for a total number of eight to nine treatments. Subjects were evaluated using standardized photographs, and measurements of body weight and circumference of treatment sites at baseline, immediately after the last treatment, and four weeks and one year after the last treatment. Clinical improvement scores of comparable photographs using a quartile grading scale (0 = <25%, 1 = 25-50%, 2 = 51-75%, 3 = >75% improvement) were judged independently by two non-treating dermatologists after the series of treatment. The average body weights at baseline, immediately after the last treatment, and four weeks and one year after the complete treatment were 56.30, 56.05, 56.23, and 56.53 kg, respectively. The average circumferential reductions of the abdomen and thigh at the last treatment visit were 5.17 +/- 1.04 cm (6.32%+/- 1.82%) and 3.50 +/- 2.16 cm (6.23 +/- 3.58%), respectively. At four weeks after the last treatment, the average circumferential reductions of the abdomen and thigh were sustained at 3.17 +/- 2.75 cm (4.04%+/- 3.69%) and 3.50 +/- 2.04 cm (6.26%+/- 3.52%), respectively. At one year follow-up visit, the average circumferential reductions of the abdomen and thigh were maintained at 3.83 +/- 0.76 cm (4.64%+/- 1.15%) and 3.13 +/- 3.54 (5.50%+/- 6.12%), respectively. Average clinical improvement scores of the abdomen and thigh after the series of treatments were 0.75 (corresponding to approximately 25% improvement), and 1.75 (corresponding to approximately 50% improvement), respectively. A bipolar RF, IR heat and pulsatile suction device provides a beneficial effect on reduction of abdomen and thigh circumference, and

Lipodystrophy, lipid profile changes, and low serum retinol and carotenoid levels in children and adolescents with acquired immunodeficiency syndrome.

PubMed

Battistini, Tânia Regina Beraldo; Sarni, Roseli Oselka Saccardo; de Souza, Fabíola Isabel Suano; Pitta, Tassiana Sacchi; Fernandes, Ana Paula; Hix, Sonia; Fonseca, Fernando Luiz Affonso; Tardini, Priscila Chemiotti; dos Santos, Valter Pinho; Lopez, Fábio Ancona

2010-06-01

To assess serum retinol and levels of carotenoids in children and adolescents with acquired immunodeficiency syndrome (AIDS) and to correlate low serum retinol and carotenoid levels with the presence of lipodystrophy, lipid profile changes, lipid peroxidation, and insulin resistance. A cross-sectional, controlled observational study was carried out with 30 children and adolescents with AIDS (mean age 9.1 y) receiving antiretroviral therapy (median length of treatment 28.4 mo), including 30 uninfected healthy controls matched for age and gender. Clinical and laboratory assessments were performed to determine nutritional status, presence of lipodystrophy, serum concentrations of retinol, beta-carotene, lycopene, lipid profile (high-density lipoprotein cholesterol, high-density lipoprotein cholesterol, triacylglycerols), lipid peroxidation (thiobarbituric acid-reactive substances), glycemia, and serum insulin (homeostasis model assessment for insulin resistance, cutoff point >3). Statistical analysis was done with chi-square test and Student's t test. Lipodystrophy was observed in 53.3% of patients with AIDS, and dyslipidemia was detected in 60% and 23% of subjects with human immunodeficiency virus and control subjects, respectively (P = 0.004). A higher prevalence of retinol deficiency (60% versus 26.7%, P = 0.009) and beta-carotene deficiency (23.3% versus 3.3%, P = 0.026) was found in the group with human immunodeficiency virus than in the control group. No correlation was found for low retinol and beta-carotene levels, changes in lipid and glucose metabolism, or lipodystrophy in children and adolescents with AIDS. Despite the high frequency of dyslipidemia, lipodystrophy, and retinol and beta-carotene deficiencies, it was not possible to demonstrate a correlation of these findings with lipid peroxidation and insulin resistance. More studies are needed to investigate the causes of retinol and beta-carotene deficiencies in this population and the clinical

Acquired partial lipodystrophy is associated with increased risk for developing metabolic abnormalities.

PubMed

Akinci, Baris; Koseoglu, Fatos Dilan; Onay, Huseyin; Yavuz, Sevgi; Altay, Canan; Simsir, Ilgin Yildirim; Ozisik, Secil; Demir, Leyla; Korkut, Meltem; Yilmaz, Nusret; Ozen, Samim; Akinci, Gulcin; Atik, Tahir; Calan, Mehmet; Secil, Mustafa; Comlekci, Abdurrahman; Demir, Tevfik

2015-09-01

Acquired partial lipodystrophy (APL) is a rare disorder characterized by progressive selective fat loss. In previous studies, metabolic abnormalities were reported to be relatively rare in APL, whilst they were quite common in other types of lipodystrophy syndromes. In this nationwide cohort study, we evaluated 21 Turkish patients with APL who were enrolled in a prospective follow-up protocol. Subjects were investigated for metabolic abnormalities. Fat distribution was assessed by whole body MRI. Hepatic steatosis was evaluated by ultrasound, MRI and MR spectroscopy. Patients with diabetes underwent a mix meal stimulated C-peptide/insulin test to investigate pancreatic beta cell functions. Leptin and adiponectin levels were measured. Fifteen individuals (71.4%) had at least one metabolic abnormality. Six patients (28.6%) had diabetes, 12 (57.1%) hypertrigylceridemia, 10 (47.6%) low HDL cholesterol, and 11 (52.4%) hepatic steatosis. Steatohepatitis was further confirmed in 2 patients with liver biopsy. Anti-GAD was negative in all APL patients with diabetes. APL patients with diabetes had lower leptin and adiponectin levels compared to patients with type 2 diabetes and healthy controls. However, contrary to what we observed in patients with congenital generalized lipodystrophy (CGL), we did not detect consistently very low leptin levels in APL patients. The mix meal test suggested that APL patients with diabetes had a significant amount of functional pancreatic beta cells, and their diabetes was apparently associated with insulin resistance. Our results show that APL is associated with increased risk for developing metabolic abnormalities. We suggest that close long-term follow-up is required to identify and manage metabolic abnormalities in APL. Copyright © 2015 Elsevier Inc. All rights reserved.

Improvement in skin elasticity in the treatment of cellulite and connective tissue weakness by means of extracorporeal pulse activation therapy.

PubMed

Christ, Christophe; Brenke, Rainer; Sattler, Gerhard; Siems, Werner; Novak, Pavel; Daser, A

2008-01-01

Extracorporeal pulse activation therapy (EPAT), also called extracorporeal acoustic wave therapy, seeks to achieve effective and long-lasting improvement of age-related connective tissue weakness in the extremities, especially in the treatment of unsightly cosmetic skin defects referred to as cellulite. The objective of this study was to stimulate metabolic activity in subcutaneous fat tissue by means of EPAT in order evaluate its effectiveness in enhancing connective tissue firmness and improving skin texture and structure. Fifty-nine women with advanced cellulite were divided into 2 groups; one group of 15 patients received planar acoustic wave treatment for 6 therapy sessions within 3 weeks; a second group of 44 patients received 8 therapy sessions within 4 weeks. Changes in connective tissue were evaluated using the DermaScan C ultrasound system (Cortex Technology, Hadsund, Denmark). Skin elasticity measurements were performed using the DermaLab system (Cortex Technology). Photographs of treated areas were taken at each therapy session and at follow-up sessions. Skin elasticity values gradually improved over the course of EPAT therapy and revealed a 73% increase at the end of therapy. At 3- and 6-month follow-ups, skin elasticity had even improved by 95% and 105%, respectively. Side effects included minor pain for 3 patients during therapy and slight skin reddening. This study confirmed the effects of acoustic wave therapy on biologic tissue, including stimulation of microcirculation and improvement of cell permeability. Ultrasound evaluation demonstrated increased density and firmness in the network of collagen/elastic fibers in the dermis and subcutis. Treatment was most effective in older patients with a long history of cellulite.

In vivo evidence of impaired peripheral fatty acid trapping in patients with human immunodeficiency virus-associated lipodystrophy.

PubMed

van Wijk, J P H; Cabezas, M Castro; de Koning, E J P; Rabelink, T J; van der Geest, R; Hoepelman, I M

2005-06-01

The use of antiretroviral combination therapy in HIV has been associated with lipodystrophy and several metabolic risk factors. We postulated that patients with HIV-lipodystrophy have impaired adipose tissue free fatty acid (FFA) trapping and, consequently, increased hepatic FFA delivery. We investigated FFA, hydroxybutyric acid (HBA; reflecting hepatic FFA oxidation), and triglyceride (TG) changes after a high fat meal in HIV-infected males with (LIPO; n = 26) and without (NONLIPO; n = 12) lipodystrophy and in healthy males (n = 35). Because defective peripheral FFA trapping has been associated with impaired action of complement component 3 (C3), we also determined postprandial C3 concentrations. The LIPO group had higher homeostasis model assessment scores compared with the other groups. Areas under the curve (AUCs) for FFA, HBA, and TG were higher in the LIPO group than in the NONLIPO group or the controls. No differences in TG-AUC, FFA-AUC, and HBA-AUC were observed between the NONLIPO group and controls. In HIV-infected patients, FFA-AUC and HBA-AUC were inversely related to sc adipose tissue area. Plasma C3 showed a postprandial increase in healthy controls, but not in the HIV-infected groups. C3 was not related to body fat distribution, postprandial FFA, or HBA. The present data suggest disturbed postprandial FFA metabolism in patients with HIV-lipodystrophy, most likely due to inadequate incorporation of FFA into TG in sc adipose tissue, but do not support a major role for C3 in these patients. The higher postprandial HBA levels reflect increased hepatic FFA delivery and may aggravate insulin resistance and dyslipidemia, leading to increased cardiovascular risk.

Placebo controlled, prospectively randomized, double-blinded study for the investigation of the effectiveness and safety of the acoustic wave therapy (AWT(®)) for cellulite treatment.

PubMed

Russe-Wilflingseder, Katharina; Russe-Wilfingsleder, Katharina; Russe, Elisabeth; Vester, Johannes C; Haller, Gerd; Novak, Pavel; Krotz, Alexander

2013-06-01

Placebo controlled double-blinded, prospectively randomized clinical trial with 17 patients (11 verum, 5 placebo) for evaluation of cellulite treatment with Acoustic Wave Therapy, (AWT(®)) was performed. The patients were treated once a week for 7 weeks, a total of 8 treatments with the D-ACTOR(®) 200 by Storz Medical AG. Data were collected at baseline, before 8th treatment, at 1 month (follow-up 1) and at 3 months (follow-up 2) after the last treatment with a patients' questionnaire, weight control, measurement of circumference and standardized photography. Treatment progress was further documented using a specially designed 3D imaging system (SkinSCAN(3D), 3D-Shape GmbH) providing an objective measure of cellulite (primary efficacy criteria). Patient's questionnaire in the verum group revealed an improvement in number and depth of dimples, skin firmness and texture, in shape and in reduction of circumference. The overall result (of skin waviness, Sq and Sz, surface and volume of depressions and elevations, Vvv and Vmp) at two follow-up visits indicates a more than medium sized superiority (MW = 0.6706) and is statistically significant (pWei-Lachin = 0.0106). The placebo group revealed no statistical significance. No side effects were seen. This indicates the efficacy and safety of AWT(®) for patients with cellulite.

Effects of cellulite treatment with RF, IR light, mechanical massage and suction treating one buttock with the contralateral as a control.

PubMed

Romero, Carmen; Caballero, Natalia; Herrero, Montse; Ruíz, Raquel; Sadick, Neil S; Trelles, Mario A

2008-12-01

A system that combines bipolar radio frequency (RF) and intense infrared light (IR) together with mechanical massage and suction has recently been reported as being efficient for cellulite treatment. The present split study was designed to evaluate the efficacy of such a system through various treatments of cellulite located on the buttocks. Ten patients were enrolled for 12 sessions of 30 minutes each performed over one buttock, the other buttock serving as an untreated control. Sessions were conducted twice a week for a period of 12 weeks. Clinical photography and profilometry were carried out to assess textural changes before (baseline) and 2 months after the final treatment. Histopathology was performed at baseline, 2 hours after the first session, and just before the 12th session and 2 months thereafter. All patients noted improvement in the treated buttock before the final session, which was maintained at the 2-month assessment. Improved skin appearance was noticed after the first session and was maintained throughout the study. All patients were satisfied with the results and requested further treatment in order to balance the results in both buttocks. Random histological analyses suggested dermal firmness, fibre compaction and tightening of skin layers, including the subcutis, as possible reasons for the effects achieved. The authors recognize that the small number of participants limits the statistical power of the study. Treatment sessions with the combined RF, IR light and mechanical massage and suction system were complication free, produced improvements in the overall cellulite appearance and skin condition, suggesting that further treatment sessions for maintenance could sustain patient satisfaction index (SI) and lead to lasting results. Based on the good results in the limited trial population, further studies with larger patient populations are warranted.

Potential roles for uncoupling proteins in HIV lipodystrophy.

PubMed

Nolan, David; Pace, Craig

2004-07-01

The 'HIV lipodystrophy syndrome' consists of several distinct components, including lipoatrophy (pathological subcutaneous fat loss), lipohypertrophy (abdominal/visceral adiposity), and metabolic complications including insulin resistance and dyslipidemia. Lipoatrophy appears to represent an adipose tissue-specific form of mitochondrial toxicity associated strongly with stavudine NRTI therapy, whilst the 'metabolic syndrome' phenotype is associated with HIV protease inhibitor therapy. In this context, the role of uncoupling proteins (UCPs) in modulating resting energy expenditure in response to elevated fatty acid flux associated with the 'metabolic syndrome' is supported by clinical data as well as findings of elevated adipose tissue UCP expression. The role of UCPs in this syndrome therefore exemplifies the multifactorial nature of these antiretroviral therapy complications.

Substituting Abacavir for Stavudine in Children Who Are Virally Suppressed Without Lipodystrophy: Randomized Clinical Trial in Johannesburg, South Africa.

PubMed

Strehlau, Renate; Shiau, Stephanie; Arpadi, Stephen; Patel, Faeezah; Pinillos, Francoise; Tsai, Wei-Yann; Coovadia, Ashraf; Abrams, Elaine; Kuhn, Louise

2018-01-24

Abacavir has replaced stavudine in antiretroviral therapy (ART) regimens because it has largely been phased out as a result of toxicity concerns; this loss has reduced further the already-limited drug options for children. Few data regarding virologic and metabolic outcomes among children who undergo substitution of stavudine exist. We evaluated the effects of preemptive substitution of abacavir for stavudine in children initially without lipodystrophy and virally suppressed on a stavudine-containing regimen. At Rahima Moosa Mother and Child Hospital in Johannesburg, South Africa, virally suppressed human immunodeficiency virus (HIV)-infected children ≥36 months of age without lipodystrophy were randomly assigned to continue taking stavudine as part of their ART regimen (n = 106) or to have abacavir substituted for stavudine (n = 107). The children were followed for 56 weeks after randomization in the context of a larger trial of treatment options for ART-experienced children. The mean age of the children was 4.3 years, and the mean duration of ART before random assignment was 3.5 years. No differences in virological outcomes, CD4 response, growth, or dyslipidemia were noted between the stavudine and abacavir groups. By 56 weeks, children in the abacavir group had less clinically detected lipodystrophy (4.7% vs 16%, respectively), a higher proportion of leg fat relative to total fat (0.243 vs 0.230, respectively; P = .006), and a lower trunk/leg-skinfold ratio (0.547 vs 0.569, respectively; P = .003) than the children in the stavudine group. Substituting abacavir for stavudine did not compromise virological response to treatment and was associated with significantly less lipodystrophy. These results support recommendations that favor abacavir in this population. © The Author(s) 2018. Published by Oxford University Press on behalf of The Journal of the Pediatric Infectious Diseases Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

[Eucaloric substitution of medium chain triglycerides for dietary long chain fatty acids improves body composition and lipid profile in a patient with human immunodeficiency virus lipodystrophy].

PubMed

Vázquez, C; Reyes, R; Alcaraz, F; Balsa, J A; Botella-Carretero, J I

2006-01-01

Lipodystrophy is a frequent disorder among patients with human immunodeficiency virus (HIV) infection, characterized by a loss of adipose tissue from the extremities, gluteal region and face, with excess fat in the neck and abdominal region. Metabolic abnormalities such as hyperlipidaemia and diabetes mellitus frequently coexist, posing these patients to an increased cardiovascular risk. Drug therapy may improve some of these metabolic disturbances, but to date there are no treatments for lipodystrophy with proven benefit. A 42-year-old man with HIV lipodystrophy was started on a standard low caloric diet with <30% of total fat and <10% of saturated fat, together with rosiglitazone 8 mg daily. After five months of treatment, given that lipodystrophic features and dyslipidaemia were still present in our patient, we tried to further improve therapeutic results by eucaloric substitution of medium chain triglycerides for dietary long chain fatty acids. Three months later, a dramatic change in body composition was shown with an increase in lean mass and a decrease in fat mass, together with an improvement in lipid profile. Eucaloric substitution of medium chain triglycerides for dietary long chain fatty acids may produce therapeutic benefits in HIV lipodystrophy.

Myostatin inhibition prevents diabetes and hyperphagia in a mouse model of lipodystrophy.

PubMed

Guo, Tingqing; Bond, Nichole D; Jou, William; Gavrilova, Oksana; Portas, Jennifer; McPherron, Alexandra C

2012-10-01

Lipodystrophies are characterized by a loss of white adipose tissue, which causes ectopic lipid deposition, peripheral insulin resistance, reduced adipokine levels, and increased food intake (hyperphagia). The growth factor myostatin (MSTN) negatively regulates skeletal muscle growth, and mice with MSTN inhibition have reduced adiposity and improved insulin sensitivity. MSTN inhibition may therefore be efficacious in ameliorating diabetes. To test this hypothesis, we inhibited MSTN signaling in a diabetic model of generalized lipodystrophy to analyze its effects on glucose metabolism separate from effects on adipose mass. A-ZIP/F1 lipodystrophic mice were crossed to mice expressing a dominant-negative MSTN receptor (activin receptor type IIB) in muscle. MSTN inhibition in A-ZIP/F1 mice reduced blood glucose, serum insulin, triglyceride levels, and the rate of triglyceride synthesis, and improved insulin sensitivity. Unexpectedly, hyperphagia was normalized by MSTN inhibition in muscle. Blood glucose and hyperphagia were reduced in double mutants independent of the adipokine leptin. These results show that the effect of MSTN inhibition on insulin sensitivity is not secondary to an effect on adipose mass and that MSTN inhibition may be an effective treatment for diabetes. These results further suggest that muscle may play a heretofore unappreciated role in regulating food intake.

Myostatin Inhibition Prevents Diabetes and Hyperphagia in a Mouse Model of Lipodystrophy

PubMed Central

Guo, Tingqing; Bond, Nichole D.; Jou, William; Gavrilova, Oksana; Portas, Jennifer; McPherron, Alexandra C.

2012-01-01

Lipodystrophies are characterized by a loss of white adipose tissue, which causes ectopic lipid deposition, peripheral insulin resistance, reduced adipokine levels, and increased food intake (hyperphagia). The growth factor myostatin (MSTN) negatively regulates skeletal muscle growth, and mice with MSTN inhibition have reduced adiposity and improved insulin sensitivity. MSTN inhibition may therefore be efficacious in ameliorating diabetes. To test this hypothesis, we inhibited MSTN signaling in a diabetic model of generalized lipodystrophy to analyze its effects on glucose metabolism separate from effects on adipose mass. A-ZIP/F1 lipodystrophic mice were crossed to mice expressing a dominant-negative MSTN receptor (activin receptor type IIB) in muscle. MSTN inhibition in A-ZIP/F1 mice reduced blood glucose, serum insulin, triglyceride levels, and the rate of triglyceride synthesis, and improved insulin sensitivity. Unexpectedly, hyperphagia was normalized by MSTN inhibition in muscle. Blood glucose and hyperphagia were reduced in double mutants independent of the adipokine leptin. These results show that the effect of MSTN inhibition on insulin sensitivity is not secondary to an effect on adipose mass and that MSTN inhibition may be an effective treatment for diabetes. These results further suggest that muscle may play a heretofore unappreciated role in regulating food intake. PMID:22596054

Serum retinol binding protein 4 in patients with familial partial lipodystrophy.

PubMed

Godoy-Matos, Amélio F; Moreira, Rodrigo O; MacDowell, Renata; Bendet, Izidro; Mory, Patrícia B; Moises, Regina S

2009-07-01

To determine Retinol Binding Protein 4 (RBP4) levels in patients with Familial Partial Lipodystrophy (FPLD). Ten patients with FPLD and a control group (9 patients) were selected to participate in the study. RBP4-log levels were lower in patients with FPLD in comparison to control group (1.52 +/- 0.32 vs 1.84+/-0.25, p=0.029). A statistical trend was observed between Waist-to-Hip Ratio and RBP4-log (r=-0.44, p=0.054). RBP4 levels are decreased in FPLD.

Truncated C-terminus of fibrillin-1 induces Marfanoid-progeroid-lipodystrophy (MPL) syndrome in rabbit.

PubMed

Chen, Mao; Yao, Bing; Yang, Qiangbing; Deng, Jichao; Song, Yuning; Sui, Tingting; Zhou, Lina; Yao, HaoBing; Xu, Yuanyuan; Ouyang, Hongsheng; Pang, Daxin; Li, Zhanjun; Lai, Liangxue

2018-04-09

Various clinical differences have been observed between patients with the FBN1 gene mutation and those with the classical Marfan phenotype. Although FBN1 knockout (KO) or dominant-negative mutant mice are widely used as an animal model for Marfan syndrome (MFS), these mice cannot recapitulate the genotype/phenotype relationship of Marfanoid-progeroid-lipodystrophy (MPL) syndrome, which is caused by a mutation in the C-terminus of fibrillin-1, the penultimate exon of the FBN1 gene. Here, we describe the generation of a rabbit MPL model with C-terminal truncation of fibrillin-1 using a CRISPR/Cas9 system. FBN1 heterozygous ( FBN1 Het) rabbits faithfully recapitulated the phenotypes of MFS, including muscle wasting and impaired connective tissue, ocular syndrome and aortic dilation. Moreover, skin symptoms, lipodystrophy, growth retardation and dysglycemia were also seen in these FBN1 Het rabbits, and have not been reported in other animal models. In conclusion, this novel rabbit model mimics the histopathological changes and functional defects of MPL syndrome, and could become a valuable model for studies of pathogenesis and drug screening for MPL syndrome. © 2018. Published by The Company of Biologists Ltd.

Effects of mechanical massage, manual lymphatic drainage and connective tissue manipulation techniques on fat mass in women with cellulite.

PubMed

Bayrakci Tunay, V; Akbayrak, T; Bakar, Y; Kayihan, H; Ergun, N

2010-02-01

To evaluate and compare the effectiveness of three different noninvasive treatment techniques on fat mass and regional fat thickness of the patients with cellulites. Sixty subjects were randomized into three groups. Group 1 (n = 20) treated with mechanical massage (MM), group 2 (n = 20) treated with manual lymphatic drainage (MLD) and group 3 (n = 20) treated with connective tissue manipulation (CTM) techniques. Subjects were evaluated by using standardized photographs, body composition analyzer (TBF 300) (body weight (BW), body mass index (BMI), fat %, fat mass (FM), fat free mass (FFM), total body water (TBW)), circumference measurement from thigh, waist-hip ratio (WHR), fat thickness measurements from abdomen, suprailium and thigh regions with skin fold caliper. All groups had an improvement in thinning of the subcutaneous fat after the treatment (P < 0.05). Thigh circumference decreased by an average of 0.5 cm in all groups and thigh fat thickness decreased 1.66 mm in Group 1, 2.21 mm in Group 2 and 3.03 mm in Group 3. Abdomen and suprailium fat thicknesses decreased 2.4 and 2.58 mm in Group 1, 1.78 and 2 mm in Group 2 and 1.23 and 0.64 mm in Group 3, respectively. The mean difference in waist-hip ratio was 0.1 cm in all groups. All the treatment techniques are effective in decreasing the regional fat values of the patients with cellulites.

Partial lipodystrophy and insulin resistant diabetes in a patient with a homozygous nonsense mutation in CIDEC

PubMed Central

Rubio-Cabezas, Oscar; Puri, Vishwajeet; Murano, Incoronata; Saudek, Vladimir; Semple, Robert K; Dash, Satya; Hyden, Caroline S S; Bottomley, William; Vigouroux, Corinne; Magré, Jocelyne; Raymond-Barker, Philippa; Murgatroyd, Peter R; Chawla, Anil; Skepper, Jeremy N; Chatterjee, V Krishna; Suliman, Sara; Patch, Ann-Marie; Agarwal, Anil K; Garg, Abhimanyu; Barroso, Inês; Cinti, Saverio; Czech, Michael P; Argente, Jesús; O'Rahilly, Stephen; Savage, David B

2009-01-01

Lipodystrophic syndromes are characterized by adipose tissue deficiency. Although rare, they are of considerable interest as they, like obesity, typically lead to ectopic lipid accumulation, dyslipidaemia and insulin resistant diabetes. In this paper we describe a female patient with partial lipodystrophy (affecting limb, femorogluteal and subcutaneous abdominal fat), white adipocytes with multiloculated lipid droplets and insulin-resistant diabetes, who was found to be homozygous for a premature truncation mutation in the lipid droplet protein cell death-inducing Dffa-like effector C (CIDEC) (E186X). The truncation disrupts the highly conserved CIDE-C domain and the mutant protein is mistargeted and fails to increase the lipid droplet size in transfected cells. In mice, Cidec deficiency also reduces fat mass and induces the formation of white adipocytes with multilocular lipid droplets, but in contrast to our patient, Cidec null mice are protected against diet-induced obesity and insulin resistance. In addition to describing a novel autosomal recessive form of familial partial lipodystrophy, these observations also suggest that CIDEC is required for unilocular lipid droplet formation and optimal energy storage in human fat. PMID:20049731

Partial lipodystrophy and insulin resistant diabetes in a patient with a homozygous nonsense mutation in CIDEC.

PubMed

Rubio-Cabezas, Oscar; Puri, Vishwajeet; Murano, Incoronata; Saudek, Vladimir; Semple, Robert K; Dash, Satya; Hyden, Caroline S S; Bottomley, William; Vigouroux, Corinne; Magré, Jocelyne; Raymond-Barker, Philippa; Murgatroyd, Peter R; Chawla, Anil; Skepper, Jeremy N; Chatterjee, V Krishna; Suliman, Sara; Patch, Ann-Marie; Agarwal, Anil K; Garg, Abhimanyu; Barroso, Inês; Cinti, Saverio; Czech, Michael P; Argente, Jesús; O'Rahilly, Stephen; Savage, David B

2009-08-01

Lipodystrophic syndromes are characterized by adipose tissue deficiency. Although rare, they are of considerable interest as they, like obesity, typically lead to ectopic lipid accumulation, dyslipidaemia and insulin resistant diabetes. In this paper we describe a female patient with partial lipodystrophy (affecting limb, femorogluteal and subcutaneous abdominal fat), white adipocytes with multiloculated lipid droplets and insulin-resistant diabetes, who was found to be homozygous for a premature truncation mutation in the lipid droplet protein cell death-inducing Dffa-like effector C (CIDEC) (E186X). The truncation disrupts the highly conserved CIDE-C domain and the mutant protein is mistargeted and fails to increase the lipid droplet size in transfected cells. In mice, Cidec deficiency also reduces fat mass and induces the formation of white adipocytes with multilocular lipid droplets, but in contrast to our patient, Cidec null mice are protected against diet-induced obesity and insulin resistance. In addition to describing a novel autosomal recessive form of familial partial lipodystrophy, these observations also suggest that CIDEC is required for unilocular lipid droplet formation and optimal energy storage in human fat.

Comparison of Dorsocervical With Abdominal Subcutaneous Adipose Tissue in Patients With and Without Antiretroviral Therapy–Associated Lipodystrophy

PubMed Central

Sevastianova, Ksenia; Sutinen, Jussi; Greco, Dario; Sievers, Meline; Salmenkivi, Kaisa; Perttilä, Julia; Olkkonen, Vesa M.; Wågsäter, Dick; Lidell, Martin E.; Enerbäck, Sven; Eriksson, Per; Walker, Ulrich A.; Auvinen, Petri; Ristola, Matti; Yki-Järvinen, Hannele

2011-01-01

OBJECTIVE Combination antiretroviral therapy (cART) is associated with lipodystrophy, i.e., loss of subcutaneous adipose tissue in the abdomen, limbs, and face and its accumulation intra-abdominally. No fat is lost dorsocervically and it can even accumulate in this region (buffalo hump). It is unknown how preserved dorsocervical fat differs from abdominal subcutaneous fat in HIV-1–infected cART-treated patients with (cART+LD+) and without (cART+LD−) lipodystrophy. RESEARCH DESIGN AND METHODS We used histology, microarray, PCR, and magnetic resonance imaging to compare dorsocervical and abdominal subcutaneous adipose tissue in cART+LD+ (n = 21) and cART+LD− (n = 11). RESULTS Albeit dorsocervical adipose tissue in cART+LD+ seems spared from lipoatrophy, its mitochondrial DNA (mtDNA; copies/cell) content was significantly lower (by 62%) than that of the corresponding tissue in cART+LD−. Expression of CD68 mRNA, a marker of macrophages, and numerous inflammatory genes in microarray were significantly lower in dorsocervical versus abdominal subcutaneous adipose tissue. Genes with the greatest difference in expression between the two depots were those involved in regulation of transcription and regionalization (homeobox genes), irrespective of lipodystrophy status. There was negligible mRNA expression of uncoupling protein 1, a gene characteristic of brown adipose tissue, in either depot. CONCLUSIONS Because mtDNA is depleted even in the nonatrophic dorsocervical adipose tissue, it is unlikely that the cause of lipoatrophy is loss of mtDNA. Dorsocervical adipose tissue is less inflamed than lipoatrophic adipose tissue. It does not resemble brown adipose tissue. The greatest difference in gene expression between dorsocervical and abdominal subcutaneous adipose tissue is in expression of homeobox genes. PMID:21602514

Surgical management of HIV-associated lipodystrophy: role of ultrasonic-assisted liposuction and suction-assisted lipectomy in the treatment of lipohypertrophy.

PubMed

Hultman, C Scott; McPhail, Lindsee E; Donaldson, Jeffrey H; Wohl, David A

2007-03-01

HIV-associated lipodystrophy is a frequent consequence of highly active antiretroviral therapy and has been associated with several metabolic disorders (increased triglycerides, hypercholesterolemia, insulin resistance) as well as altered fat distribution, including lipohypertrophy (neck, trunk, breasts) and lipoatrophy (nasolabial fold, cheek, extremities). Medical treatment of fat redistribution is usually ineffective. We evaluated the efficacy and safety of the surgical management of HIV lipodystrophy. We performed a retrospective review of 12 consecutive patients (3 female, 9 male; mean age, 44.4 years; mean CD4+ cell count, 554/mm3; mean body mass index, 28.9 kg/m2; mean triglycerides, 421 mg/dL; no active opportunistic infections; mean duration of HIV infection, 11.4 years) who underwent surgical management of HIV lipodystrophy at a university hospital from 2001 to 2006. Surgical intervention included a combination of ultrasonic-assisted liposuction (UAL) and suction-assisted lipectomy (SAL) of the anterior neck (7 patients), posterior neck (10 patients), and trunk (2 patients); direct excision of mastoid fat pads (1 patient); direct excision of thigh lipomata (1 patient); facelift/necklift (1 patient); browlift (1 patient); fat injections (1 patient); and blepharoplasty (2 patients). Mean lipoaspirate volume was 701 mL (range, 270-1400 mL). Complications and sequelae included seroma (1 patient), ecchymosis (1 patient), need for revision (2 patients), and recurrence (3 patients) but did not include nerve injury, fat necrosis, skin loss, or infection. Although all patients reported improvement in form and function, UAL/SAL of the anterior neck had limited efficacy in 3 of 7 patients. UAL/SAL of the cervicodorsal fat pad was initially successful in 10 of 10 patients, but 3 patients developed partial late (>1 year) recurrence, all associated with weight gain. Mean follow up was 30 months (range, 1-66 months). Despite the potential for recurrence, surgical

People living with HIV on ART have accurate perception of lipodystrophy signs: a cross-sectional study.

PubMed

Alencastro, Paulo R; Barcellos, Nemora T; Wolff, Fernando H; Ikeda, Maria Letícia R; Schuelter-Trevisol, Fabiana; Brandão, Ajácio B M; Fuchs, Sandra C

2017-01-13

The prevalence of lipodystrophy ranges from 31 to 65%, depending on the criteria adopted for diagnosis. The usual methods applied in the diagnosis vary from self-perception, medical examination, skinfolds measurements, or even imaging assessment for confirmation of fat distribution changes. Although several methods have been developed, there is no gold standard for characterization of LA and LH, or mixed forms. This study aimed to compare self-reported signs of lipodystrophy with objective measures by skinfolds and circumferences, and to evaluate the prevalence of lipoatrophy (LA) and lipohypertrophy (LH) among subjects living with HIV/AIDS on ART. A cross-sectional study enrolled participants living with HIV/AIDS receiving ART, aged 18 years or older from an outpatient health care center, in Southern Brazil. Self-reported body fat enlargement in the abdomen, chest or breasts, and dorsocervical fat pad were used to determine LH, while LA was identified by self-reported fat wasting of the face, neck, legs, arms or buttocks. Measurements were obtained with a scientific caliper for infraorbital, buccal, and submandibular skinfolds, and using an inelastic tape to measure circumferences of waist, hip, neck, and arm. LH and LA were established by the presence of at least one self-reported sign. Comparisons of self-reported signs with objective measurements for men and women were carried out in 815 participants on ART, out of 1240 participants with HIV infection. Self-report of decreased facial fat and sunken cheeks was associated with lower infraorbital, buccal, and submandibular skinfolds. Participants who reported buffalo hump had, on average, greater neck circumference, as well as those who have increased waist circumference also reported abdominal enlargement, but no buttock wasting. Men were most commonly affected by lipoatrophy (73 vs. 53%; P < 0.001), and women by lipohypertrophy (79 vs. 56%; P < 0.001). In conclusion, self-reported signs of lipodystrophy and

Metabolic Abnormalities and Clinical Lipodystrophy in Children With Human Immunodeficiency Virus Infection: A Report From a Tertiary Care Center in India.

PubMed

Kumar, Prasanna; Suri, Deepti; Vignesh, Pandiarajan; Verma Attri, Savita; Kumar Bhalla, Anil; Singh, Surjit

2017-12-01

A cross-sectional study from a tertiary care center in India was undertaken to assess and compare the prevalence of blood glucose and lipid profile aberrations in children who received first-line antiretroviral therapy (ART; n = 63) and in children who were naïve to ART (n = 46). Impaired fasting blood glucose values were found in 7 children in ART-experienced group but none in ART-naïve group (P = 0.02). Low concentrations of high-density lipoprotein cholesterol were more prevalent in the ART-naïve group compared with ART-experienced group (54.3% vs. 22.2%; P = 0.001). Hypertriglyceridemia was noted in a significant proportion of both ART-naïve (43.5%) and ART-experienced children (39.7%). Incidence of clinical lipodystrophy was 47.7%, and there was no significant association noted between lipid profile abnormalities and lipodystrophy.

Severity of Lipodystrophy Is Associated with Decreased Health-Related Quality of Life

PubMed Central

Murri, Rita; Orlando, Gabriella; Giovanardi, Chiara; Squillace, Nicola; Vandelli, Marcella; Beghetto, Barbara; Nardini, Giulia; De Paola, Maria; Esposito, Roberto; Wu, Albert W.

2008-01-01

Abstract The impact of lipodystrophy (LD) on quality of life is high, but it has not been demonstrated in literature. The objective of the study was to assess the impact of LD on the health–related quality of life (HRQOL) in HIV-infected people on highly active antiretroviral therapy (HAART). Patients with LD phenotype defined by the Multicenter AIDS Cohort Study (MACS) were included. Three different methods were used to define LD severity: both patient and physician evaluation using the HIV Outpatient Study (HOPS) severity scales and the Lipodystrophy Case Definition (LDCD). The HRQOL was evaluated by MOS-HIV Health Survey. Four hundred one patients on HAART for a mean of 108 ± 52 months were evaluated for LD at the Metabolic Clinic of Modena and Reggio Emilia University were enrolled from January 2003 to July 2006. According to self-perceived or physician-based HOPS, 106 (26.5%) and 122 (30.4%) patients had severe LD. Females had significantly more severe LD. Few HRQOL scores correlated to LD severity using the physician-based score (both HOPSph and LDCD), while all the HRQOL scores correlated with LD severity when a patient-based score was used (HOPSpt). In multiple linear regression analysis, Mental Health HRQOL score, gender, body mass index, age, body image satisfaction were independent predictors of patient-based (HOPSpt) LD, while none of the HRQOL scores, but female gender, age, waist-to-hip ratio, limb fat, and body image satisfaction were correlated with physician-estimated HOPSph LD severity. HRQOL was strongly correlated with LD severity when a patient-based score was used. For an overall assessment of the impact of LD on HIV-infected people, both patient-based and physician-based measures are required. PMID:18647097

Beneficial effects of physical activity in an HIV-infected woman with lipodystrophy: a case report

PubMed Central

2011-01-01

Introduction Lipodystrophy is common in patients infected with human immunodeficiency virus receiving highly active antiretroviral therapy, and presents with morphologic changes and metabolic alterations that are associated with depressive behavior and reduced quality of life. We examined the effects of exercise training on morphological changes, lipid profile and quality of life in a woman with human immunodeficiency virus presenting with lipodystrophy. Case presentation A 31-year-old Latin-American Caucasian woman infected with human immunodeficiency virus participated in a 12-week progressive resistance exercise training program with an aerobic component. Her weight, height, skinfold thickness, body circumferences, femur and humerus diameter, blood lipid profile, maximal oxygen uptake volume, exercise duration, strength and quality of life were assessed pre-exercise and post-exercise training. After 12 weeks, she exhibited reductions in her total subcutaneous fat (18.5%), central subcutaneous fat (21.0%), peripheral subcutaneous fat (10.7%), waist circumference (WC) (4.5%), triglycerides (9.9%), total cholesterol (12.0%) and low-density lipoprotein cholesterol (8.6%). She had increased body mass (4.6%), body mass index (4.37%), humerus and femur diameter (3.0% and 2.3%, respectively), high-density lipoprotein cholesterol (16.7%), maximal oxygen uptake volume (33.3%), exercise duration (37.5%) and strength (65.5%). Quality of life measures improved mainly for psychological and physical measures, independence and social relationships. Conclusions These findings suggest that supervised progressive resistance exercise training is a safe and effective treatment for evolving morphologic and metabolic disorders in adults infected with HIV receiving highly active antiretroviral therapy, and improves their quality of life. PMID:21892961

Beneficial effects of physical activity in an HIV-infected woman with lipodystrophy: a case report.

PubMed

Mendes, Edmar Lacerda; Ribeiro Andaki, Alynne Christian; Brito, Ciro José; Córdova, Cláudio; Natali, Antônio José; Santos Amorim, Paulo Roberto Dos; de Oliveira, Leandro Licursi; de Paula, Sérgio Oliveira; Mutimura, Eugene

2011-09-05

Lipodystrophy is common in patients infected with human immunodeficiency virus receiving highly active antiretroviral therapy, and presents with morphologic changes and metabolic alterations that are associated with depressive behavior and reduced quality of life. We examined the effects of exercise training on morphological changes, lipid profile and quality of life in a woman with human immunodeficiency virus presenting with lipodystrophy. A 31-year-old Latin-American Caucasian woman infected with human immunodeficiency virus participated in a 12-week progressive resistance exercise training program with an aerobic component. Her weight, height, skinfold thickness, body circumferences, femur and humerus diameter, blood lipid profile, maximal oxygen uptake volume, exercise duration, strength and quality of life were assessed pre-exercise and post-exercise training. After 12 weeks, she exhibited reductions in her total subcutaneous fat (18.5%), central subcutaneous fat (21.0%), peripheral subcutaneous fat (10.7%), waist circumference (WC) (4.5%), triglycerides (9.9%), total cholesterol (12.0%) and low-density lipoprotein cholesterol (8.6%). She had increased body mass (4.6%), body mass index (4.37%), humerus and femur diameter (3.0% and 2.3%, respectively), high-density lipoprotein cholesterol (16.7%), maximal oxygen uptake volume (33.3%), exercise duration (37.5%) and strength (65.5%). Quality of life measures improved mainly for psychological and physical measures, independence and social relationships. These findings suggest that supervised progressive resistance exercise training is a safe and effective treatment for evolving morphologic and metabolic disorders in adults infected with HIV receiving highly active antiretroviral therapy, and improves their quality of life.

The first Japanese patient with mandibular hypoplasia, deafness, progeroid features and lipodystrophy diagnosed via POLD1 mutation detection

PubMed Central

Okada, Asami; Kohmoto, Tomohiro; Naruto, Takuya; Yokota, Ichiro; Kotani, Yumiko; Shimada, Aki; Miyamoto, Yoko; Takahashi, Rizu; Goji, Aya; Masuda, Kiyoshi; Kagami, Shoji; Imoto, Issei

2017-01-01

Mandibular hypoplasia, deafness, progeroid features and lipodystrophy (MDPL) syndrome is a rare autosomal dominant disorder caused by heterozygous POLD1 mutations. To date, 13 patients affected by POLD1 mutation-caused MDPL have been described. We report a clinically undiagnosed 11-year-old male who noted joint contractures at 6 years of age. Targeted exome sequencing identified a known POLD1 mutation [NM_002691.3:c.1812_1814del, p.(Ser605del)] that diagnosed him as the first Japanese/East Asian MDPL case. PMID:28791128

The first Japanese patient with mandibular hypoplasia, deafness, progeroid features and lipodystrophy diagnosed via POLD1 mutation detection.

PubMed

Okada, Asami; Kohmoto, Tomohiro; Naruto, Takuya; Yokota, Ichiro; Kotani, Yumiko; Shimada, Aki; Miyamoto, Yoko; Takahashi, Rizu; Goji, Aya; Masuda, Kiyoshi; Kagami, Shoji; Imoto, Issei

2017-01-01

Mandibular hypoplasia, deafness, progeroid features and lipodystrophy (MDPL) syndrome is a rare autosomal dominant disorder caused by heterozygous POLD1 mutations. To date, 13 patients affected by POLD1 mutation-caused MDPL have been described. We report a clinically undiagnosed 11-year-old male who noted joint contractures at 6 years of age. Targeted exome sequencing identified a known POLD1 mutation [NM_002691.3:c.1812_1814del, p.(Ser605del)] that diagnosed him as the first Japanese/East Asian MDPL case.

Progranulin is increased in human and murine lipodystrophy.

PubMed

Miehle, Konstanze; Ebert, Thomas; Kralisch, Susan; Hoffmann, Annett; Kratzsch, Jürgen; Schlögl, Haiko; Stumvoll, Michael; Fasshauer, Mathias

2016-10-01

Lipodystrophies (LD) are genetic or acquired disorders sharing the symptom of partial or complete adipose tissue deficiency and a dysregulation of adipokines including leptin and adiponectin. Progranulin, an adipokine with proinflammatory and insulin resistance-inducing characteristics, has not been investigated in LD so far. Circulating progranulin was determined in LD patients (N=37) and in age-, gender-, and body mass index-matched healthy control subjects (N=37). Additionally, we investigated progranulin expression in an LD mouse model as compared to wild-type mice. Moreover, we elucidated circulating progranulin before and during metreleptin supplementation in 10 patients with LD. Median [interquartile range] circulating progranulin was increased in patients with LD (82.9 [25.9] μg/l) as compared to controls (73.6 [22.8] μg/l) (p=0.005). C-reactive protein (CRP) remained an independent and positive predictor of progranulin in multivariate analysis. Progranulin mRNA was significantly upregulated in all adipose tissue depots, i.e. visceral, subcutaneous, and brown adipose tissue, and in muscle of LD animals versus wild-type mice. Progranulin levels did not significantly change during metreleptin supplementation. Progranulin serum concentration is increased in patients with LD, and shows an independent and positive correlation with CRP. Different adipose tissue depots and muscle might be potential origins of elevated progranulin. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

[Bezafibrate in an infant with congenital generalized lipodystrophy and severe hypertriglyceridemia].

PubMed

Araújo, Rogério Santiago; Ramos, André de Paula Silva; Borges, Máriton de Araújo Sousa

2013-11-01

Congenital generalized lipodystrophy (CGL) with severe hypertriglyceridemia in a children less than 1 year of age is associated with worse metabolic risk. We used data from patient records, as well as extensive literature research to write the manuscript. We report the case of an infant with typical phenotype of CGL and hypertriglyceridemia of 1,360 mg/dL who was treated with bezafibrate at a dose of 30 to 60 mg/day from age 11 months to 5.5 years old, with a measurement of nadir of triglycerides of 55 mg/dL. Clinical evolution and clinical laboratory tests before and after bezafibrate were carried out over 5 years and 6 months. Phenotype was classified as CGL type 2. Despite the efficient control of hypertriglyceridemia and absence of development of diabetes mellitus, the use of bezafibrate did not prevent the onset of hepatic steatosis during evolution. Hypolipidemic therapy with bezafibrate proved effective in maintaining the levels of triglycerides, cholesterol and its fractions at normal levels, and its use was not correlated with severe side effects during the described period.

4th International Workshop on Adverse Drug Reactions and Lipodystrophy in HIV. San Diego, California, USA 22-25 September 2002.

PubMed

Nolan, David; Christiansen, Frank

2003-01-01

Highlights are presented from this annual workshop, which was devoted to the investigation of adverse effects associated with antiretroviral therapy for HIV infection. Topics covered included the lipodystrophy syndrome, which encompasses body composition changes (subcutaneous fat wasting, visceral fat accumulation) and metabolic abnormalities (insulin resistance and dyslipidaemia). The relevance of HIV protease inhibitor-induced metabolic abnormalities to cardiovascular disease is discussed. Research in the areas of hyperlactataemia, abacavir hypersensitivity, and bone mineral density in the context of HIV infection is also briefly reviewed.

Lipodystrophy in HIV patients: its challenges and management approaches.

PubMed

Singhania, Rohit; Kotler, Donald P

2011-01-01

HIV-associated lipodystrophy is a term used to describe a constellation of body composition (lipoatrophy and lipohypertrophy) and metabolic (dyslipidemia and insulin resistance) alterations that accompany highly active antiretroviral therapy. These changes, which resemble metabolic syndrome, have been associated with a variety of adverse outcomes including accelerated cardiovascular disease. The body composition and metabolic changes appear to cluster in HIV infection, although they are distinct alterations and do not necessarily coexist. Epidemiological studies have demonstrated multiple pathogenic influences associated with host, disease, and treatment-related factors. The adverse treatment effects were more prominent in early regimens; continued drug development has led to the application of metabolically safer regimens with equal or greater potency than the regimens being replaced. Disease-related factors include HIV infection as well as inflammation, immune activation, and immune depletion. The body composition changes promote anxiety and depression in patients and may affect treatment adherence. Treatment of dyslipidemia and alterations in glucose metabolism is the same as in non-HIV-infected individuals. Lipoatrophy is managed by strategic choice of antivirals or by antiviral switching, and in some cases by plastic/reconstructive surgery. Lipohypertrophy has been managed mainly by lifestyle modification, ie, a hypocaloric diet and increased exercise. A growth hormone releasing factor, which reduces central fat, has recently become available for clinical use.

Lipodystrophy in HIV patients: its challenges and management approaches

PubMed Central

Singhania, Rohit; Kotler, Donald P

2011-01-01

HIV-associated lipodystrophy is a term used to describe a constellation of body composition (lipoatrophy and lipohypertrophy) and metabolic (dyslipidemia and insulin resistance) alterations that accompany highly active antiretroviral therapy. These changes, which resemble metabolic syndrome, have been associated with a variety of adverse outcomes including accelerated cardiovascular disease. The body composition and metabolic changes appear to cluster in HIV infection, although they are distinct alterations and do not necessarily coexist. Epidemiological studies have demonstrated multiple pathogenic influences associated with host, disease, and treatment-related factors. The adverse treatment effects were more prominent in early regimens; continued drug development has led to the application of metabolically safer regimens with equal or greater potency than the regimens being replaced. Disease-related factors include HIV infection as well as inflammation, immune activation, and immune depletion. The body composition changes promote anxiety and depression in patients and may affect treatment adherence. Treatment of dyslipidemia and alterations in glucose metabolism is the same as in non-HIV-infected individuals. Lipoatrophy is managed by strategic choice of antivirals or by antiviral switching, and in some cases by plastic/reconstructive surgery. Lipohypertrophy has been managed mainly by lifestyle modification, ie, a hypocaloric diet and increased exercise. A growth hormone releasing factor, which reduces central fat, has recently become available for clinical use. PMID:22267946

Mutations disrupting the Kennedy phosphatidylcholine pathway in humans with congenital lipodystrophy and fatty liver disease.

PubMed

Payne, Felicity; Lim, Koini; Girousse, Amandine; Brown, Rebecca J; Kory, Nora; Robbins, Ann; Xue, Yali; Sleigh, Alison; Cochran, Elaine; Adams, Claire; Dev Borman, Arundhati; Russel-Jones, David; Gorden, Phillip; Semple, Robert K; Saudek, Vladimir; O'Rahilly, Stephen; Walther, Tobias C; Barroso, Inês; Savage, David B

2014-06-17

Phosphatidylcholine (PC) is the major glycerophospholipid in eukaryotic cells and is an essential component in all cellular membranes. The biochemistry of de novo PC synthesis by the Kennedy pathway is well established, but less is known about the physiological functions of PC. We identified two unrelated patients with defects in the Kennedy pathway due to biallellic loss-of-function mutations in phosphate cytidylyltransferase 1 alpha (PCYT1A), the rate-limiting enzyme in this pathway. The mutations lead to a marked reduction in PCYT1A expression and PC synthesis. The phenotypic consequences include some features, such as severe fatty liver and low HDL cholesterol levels, that are predicted by the results of previously reported liver-specific deletion of murine Pcyt1a. Both patients also had lipodystrophy, severe insulin resistance, and diabetes, providing evidence for an additional and essential role for PCYT1A-generated PC in the normal function of white adipose tissue and insulin action.

Mutations disrupting the Kennedy phosphatidylcholine pathway in humans with congenital lipodystrophy and fatty liver disease

PubMed Central

Payne, Felicity; Lim, Koini; Girousse, Amandine; Brown, Rebecca J.; Kory, Nora; Robbins, Ann; Xue, Yali; Sleigh, Alison; Cochran, Elaine; Adams, Claire; Dev Borman, Arundhati; Russel-Jones, David; Gorden, Phillip; Semple, Robert K.; Saudek, Vladimir; O’Rahilly, Stephen; Walther, Tobias C.; Barroso, Inês; Savage, David B.

2014-01-01

Phosphatidylcholine (PC) is the major glycerophospholipid in eukaryotic cells and is an essential component in all cellular membranes. The biochemistry of de novo PC synthesis by the Kennedy pathway is well established, but less is known about the physiological functions of PC. We identified two unrelated patients with defects in the Kennedy pathway due to biallellic loss-of-function mutations in phosphate cytidylyltransferase 1 alpha (PCYT1A), the rate-limiting enzyme in this pathway. The mutations lead to a marked reduction in PCYT1A expression and PC synthesis. The phenotypic consequences include some features, such as severe fatty liver and low HDL cholesterol levels, that are predicted by the results of previously reported liver-specific deletion of murine Pcyt1a. Both patients also had lipodystrophy, severe insulin resistance, and diabetes, providing evidence for an additional and essential role for PCYT1A-generated PC in the normal function of white adipose tissue and insulin action. PMID:24889630

Uridine Metabolism in HIV-1-Infected Patients: Effect of Infection, of Antiretroviral Therapy and of HIV-1/ART-Associated Lipodystrophy Syndrome

PubMed Central

Domingo, Pere; Torres-Torronteras, Javier; Pomar, Virginia; Giralt, Marta; Domingo, Joan Carles; Gutierrez, Maria del Mar; Gallego-Escuredo, José M.; Mateo, Maria Gracia; Cano-Soldado, Pedro; Fernandez, Irene; Pastor-Anglada, Marçal; Vidal, Francesc; Villarroya, Francesc; Andreu, Antoni; Marti, Ramon

2010-01-01

Background Uridine has been advocated for the treatment of HIV-1/HAART-associated lipodystrophy (HALS), although its metabolism in HIV-1-infected patients is poorly understood. Methods Plasma uridine concentrations were measured in 35 controls and 221 HIV-1-infected patients and fat uridine in 15 controls and 19 patients. The diagnosis of HALS was performed following the criteria of the Lipodystrophy Severity Grading Scale. Uridine was measured by a binary gradient-elution HPLC method. Analysis of genes encoding uridine metabolizing enzymes in fat was performed with TaqMan RT-PCR. Results Median plasma uridine concentrations for HIV-1-infected patients were 3.80 µmol/l (interquartile range: 1.60), and for controls 4.60 µmol/l (IQR: 1.8) (P = 0.0009). In fat, they were of 6.0 (3.67), and 2.8 (4.65) nmol/mg of protein, respectively (P = 0.0118). Patients with a mixed HALS form had a median plasma uridine level of 4.0 (IC95%: 3.40–4.80) whereas in those with isolated lipoatrophy it was 3.25 (2.55–4.15) µmol/l/l (P = 0.0066). The expression of uridine cytidine kinase and uridine phosphorylase genes was significantly decreased in all groups of patients with respect to controls. A higher expression of the mRNAs for concentrative nucleoside transporters was found in HIV-1-infected patients with respect to healthy controls. Conclusions HIV-1 infection is associated with a decrease in plasma uridine and a shift of uridine to the adipose tissue compartment. Antiretroviral therapy was not associated with plasma uridine concentrations, but pure lipoatrophic HALS was associated with significantly lower plasma uridine concentrations. PMID:21085568

Factors associated with severe impact of lipodystrophy on the quality of life of patients infected with HIV-1.

PubMed

Blanch, Jordi; Rousaud, Araceli; Martinez, Esteban; De Lazzari, Elisa; Milinkovic, Ana; Peri, Josep-Maria; Blanco, José-Luis; Jaen, Jesús; Navarro, Victor; Massana, Guillem; Gatell, Josep-Maria

2004-05-15

A standardized questionnaire was used to assess the impact of lipodystrophy (LD) on quality of life (QoL). Eighty-four consecutive asymptomatic human immunodeficiency virus type 1 (HIV-1)-infected outpatients with clinical LD completed a modified version of the Dermatology Life Quality Index (DLQI) survey to measure the impact of body fat changes on their QoL. Body changes influenced dressing for 55 patients (65%), produced feelings of shame for 41 (49%), and disrupted sexual life for 23 (27%). There was a greater impact on the DLQI due to body changes among women, injection drug users, patients with abdominal or breast lipoaccumulation, and patients with a high number of non-LD side effects. Multivariate proportional odds model analysis showed that the severity of non-LD-associated side effects and the presence of breast lipoaccumulation were associated with impaired psychosocial functioning. Specific characteristics of patients, antiretroviral-based side effects, and breast lipoaccumulation exert a greater impact on QoL in HIV-1-infected patients with LD.

HIV-1/HAART-Related Lipodystrophy Syndrome (HALS) Is Associated with Decreased Circulating sTWEAK Levels

PubMed Central

López-Dupla, Miguel; Maymó-Masip, Elsa; Martínez, Esteban; Domingo, Pere; Leal, Manuel; Peraire, Joaquim; Viladés, Consuelo; Veloso, Sergi; Arnedo, Mireia; Ferrando-Martínez, Sara; Beltrán-Debón, Raúl; Alba, Verónica; Gatell, Josep Mª; Vendrell, Joan; Vidal, Francesc; Chacón, Matilde R.

2015-01-01

Background and Objectives Obesity and HIV-1/HAART–associated lipodystrophy syndrome (HALS) share clinical, pathological and mechanistic features. Tumor necrosis factor-like weak inducer of apoptosis (TWEAK) is a multifunctional cytokine that plays an important role in obesity and related diseases. We sought to explore the relationship between HALS and circulating levels of soluble (s) TWEAK and its scavenger receptor sCD163. Methods This was a cross-sectional multicenter study of 120 HIV-1-infected patients treated with a stable HAART regimen; 56 with overt HALS and 64 without HALS. Epidemiological and clinical variables were determined. Serum levels of sTWEAK and sCD163 levels were measured by ELISA. Results were analyzed with Student’s t-test, Mann-Whitney U and χ2 test. Pearson and Spearman correlation were used to estimate the strength of association between variables. Results Circulating sTWEAK was significantly decreased in HALS patients compared with non-HALS patients (2.81±0.2 vs. 2.94±0.28 pg/mL, p = 0.018). No changes were observed in sCD163 levels in the studied cohorts. On multivariate analysis, a lower log sTWEAK concentration was independently associated with the presence of HALS (OR 0.027, 95% CI 0.001–0.521, p = 0.027). Conclusions HALS is associated with decreased sTWEAK levels. PMID:26658801

HIV-1/HAART-Related Lipodystrophy Syndrome (HALS) Is Associated with Decreased Circulating sTWEAK Levels.

PubMed

López-Dupla, Miguel; Maymó-Masip, Elsa; Martínez, Esteban; Domingo, Pere; Leal, Manuel; Peraire, Joaquim; Viladés, Consuelo; Veloso, Sergi; Arnedo, Mireia; Ferrando-Martínez, Sara; Beltrán-Debón, Raúl; Alba, Verónica; Gatell, Josep Ma; Vendrell, Joan; Vidal, Francesc; Chacón, Matilde R

2015-01-01

Obesity and HIV-1/HAART-associated lipodystrophy syndrome (HALS) share clinical, pathological and mechanistic features. Tumor necrosis factor-like weak inducer of apoptosis (TWEAK) is a multifunctional cytokine that plays an important role in obesity and related diseases. We sought to explore the relationship between HALS and circulating levels of soluble (s) TWEAK and its scavenger receptor sCD163. This was a cross-sectional multicenter study of 120 HIV-1-infected patients treated with a stable HAART regimen; 56 with overt HALS and 64 without HALS. Epidemiological and clinical variables were determined. Serum levels of sTWEAK and sCD163 levels were measured by ELISA. Results were analyzed with Student's t-test, Mann-Whitney U and χ2 test. Pearson and Spearman correlation were used to estimate the strength of association between variables. Circulating sTWEAK was significantly decreased in HALS patients compared with non-HALS patients (2.81±0.2 vs. 2.94±0.28 pg/mL, p = 0.018). No changes were observed in sCD163 levels in the studied cohorts. On multivariate analysis, a lower log sTWEAK concentration was independently associated with the presence of HALS (OR 0.027, 95% CI 0.001-0.521, p = 0.027). HALS is associated with decreased sTWEAK levels.

Identification of a novel nonsense mutation and a missense substitution in the AGPAT2 gene causing congenital generalized lipodystrophy type 1

PubMed Central

Haghighi, Amirreza; Razzaghy-Azar, Maryam; Talea, Ali; Sadeghian, Mahnaz; Ellard, Sian; Haghighi, Alireza

2012-01-01

Congenital generalized lipodystrophy (CGL) is an autosomal recessive disease characterized by the generalized scant of adipose tissue. CGL type 1 is caused by mutations in gene encoding 1-acylglycerol-3-phosphate O-acyltransferase-2 (AGPAT2). A clinical and molecular genetic investigation was performed in affected and unaffected members of two families with CGL type 1. The AGPAT2 coding region was sequenced in index cases of the two families. The presence of the identified mutations in relevant parents was tested. We identified a novel nonsense mutation (c.685G>T, p.Glu229*) and a missense substitution (c.514G>A, p.Glu172Lys). The unaffected parents in both families were heterozygous carrier of the relevant mutation. The results expand genotype–phenotype spectrum in CGL1 and will have applications in prenatal and early diagnosis of the disease. This is the first report of Persian families identified with AGPAT2 mutations. PMID:22902344

Acoustic Wave Treatment For Cellulite—A New Approach

NASA Astrophysics Data System (ADS)

Russe-Wilflingseder, Katharina; Russe, Elisabeth

2010-05-01

Background and Objectives: Cellulite is a biological caused modification of the female connective tissue. In extracorporeal shockwave therapy (ESWT) pulses are penetrating into the tissue without causing a thermal effect or micro lesions, but leading to a stimulation of tissue metabolism and blood circulation, inducing a natural repair process with cell activation and stem cells proliferation. Recently ESWT treatment showed evidence of remodelling collagen within the dermis and of stimulating microcirculation in fatty tissue. Study Design and Methods: The study was designed to assess acoustic wave treatment for cellulite by comparison treated vs. untreated side (upper-leg and buttock). Each individual served as its own control. 11 females with a BMI less then 30 and an age over 18 years were included. 6 treatments were given weekly with radial acoustic waves. Documentation was done before and 1, 4, 12 weeks after last treatment by standardized photo documentation, relaxed and with muscle contraction, measurement of body weight and circumference of the thigh, pinch test, and evaluation of hormonal status and lifestyle. The efficacy of AWT/EPAT was evaluated before and 1, 4, 12 weeks after last treatment. Patients rated the improvement of cellulite, overall satisfaction and acceptance. The therapist assessed improvement of cellulite, side effects and photo documentation treated vs. untreated side, before vs. after treatment. The blinded investigator evaluated the results using photo documentation right vs. left leg, before vs. after treatment in a frontal, lateral and dorsal view, relaxed and with muscle contraction. Results: The improvement of cellulite at the treated side was rated by patients with 27,3% at week 4 and 12, by the therapist with 34,1% at week 4 and 31,2% at week 12 after the last treatment The blinded investigator could verify an improvement of cellulite in an increasing number of patients with increasing time interval after treatment. No side

Treatment of altered body composition in HIV-associated lipodystrophy: comparison of rosiglitazone, pravastatin, and recombinant human growth hormone.

PubMed

Macallan, Derek C; Baldwin, Christine; Mandalia, Sundihya; Pandol-Kaljevic, Vjera; Higgins, Nadine; Grundy, Alan; Moyle, Graeme J

2008-01-01

Treatment options for HIV-associated lipodystrophy syndrome (HALS) remain limited. The objective of this randomized open-label study was to compare three emerging therapies, rosiglitazone, pravastatin, and growth hormone alone and together, in men and women with HALS. Sixty-four subjects received daily rosiglitazone (4 mg, n = 14), pravastatin (40 mg, n = 11), or rosiglitazone plus pravastatin (n = 13) for 48 weeks or recombinant human growth hormone (rhGH; Serostim 2 mg, 12 weeks, n = 13) alone or combined with rosiglitazone (n = 13). Primary endpoint was body composition change by dual X-ray absorptiometry (DXA) and computed tomography (CT). Rosiglitazone resulted in slow accrual of limb fat detected by DXA (+444 +/- 186 g; p < .05) but not CT. Pravastatin had no consistent significant effects on body composition, although it reduced total and LDL cholesterol. Negative interactions were observed between pravastatin and rosiglitazone. rhGH reduced abdominal fat by CT (-31 +/- 15 cm2, 26%; p < .05) and DXA (-1597 +/- 383 g, 27%; p < .05) and increased trunk and limb lean mass (+10% and +12%, respectively). However, effects largely disappeared within 12 weeks post treatment. rhGH alone impaired insulin sensitivity but not when combined with rosiglitazone. Prolonged rosiglitazone treatment slowly improves lipoatrophy. rhGH rapidly and selectively reduces visceral fat, although effects are short-lived; co-administered rosiglitazone abrogates rhGH-related insulin resistance.

Comparing Efficacy and Costs of Four Facial Fillers in Human Immunodeficiency Virus-Associated Lipodystrophy: A Clinical Trial.

PubMed

Vallejo, Alfonso; Garcia-Ruano, Angela A; Pinilla, Carmen; Castellano, Michele; Deleyto, Esther; Perez-Cano, Rosa

2018-03-01

The objective of this study was to evaluate and compare the safety and effectiveness of four different dermal fillers in the treatment of facial lipoatrophy secondary to human immunodeficiency virus. The authors conducted a clinical trial including 147 patients suffering from human immunodeficiency virus-induced lipoatrophy treated with Sculptra (poly-L-lactic acid), Radiesse (calcium hydroxylapatite), Aquamid (polyacrylamide), or autologous fat. Objective and subjective changes were evaluated during a 24-month follow-up. Number of sessions, total volume injected, and overall costs of treatment were also analyzed. A comparative cost-effectiveness analysis of the treatment options was performed. Objective improvement in facial lipoatrophy, assessed by the surgeon in terms of changes from baseline using the published classification of Fontdevila, was reported in 53 percent of the cases. Patient self-evaluation showed a general improvement after the use of facial fillers. Patients reported being satisfied with the treatment and with the reduced impact of lipodystrophy on their quality of life. Despite the nonsignificant differences observed in the number of sessions and volume, autologous fat showed significantly lower costs than all synthetic fillers (p < 0.05). Surgical treatment of human immunodeficiency virus-associated facial lipoatrophy using dermal fillers is a safe and effective procedure that improves the aesthetic appearance and the quality of life of patients. Permanent fillers and autologous fat achieve the most consistent results over time, with lipofilling being the most cost-effective procedure.

Insulin resistance and diabetes mellitus in transgenic mice expressing nuclear SREBP-1c in adipose tissue: model for congenital generalized lipodystrophy

PubMed Central

Shimomura, Iichiro; Hammer, Robert E.; Richardson, James A.; Ikemoto, Shinji; Bashmakov, Yuriy; Goldstein, Joseph L.; Brown, Michael S.

1998-01-01

Overexpression of the nuclear form of sterol regulatory element-binding protein-1c (nSREBP-1c/ADD1) in cultured 3T3-L1 preadipocytes was shown previously to promote adipocyte differentiation. Here, we produced transgenic mice that overexpress nSREBP-1c in adipose tissue under the control of the adipocyte-specific aP2 enhancer/promoter. A syndrome with the following features was observed: (1) Disordered differentiation of adipose tissue. White fat failed to differentiate fully, and the size of white fat depots was markedly decreased. Brown fat was hypertrophic and contained fat-laden cells resembling immature white fat. Levels of mRNA encoding adipocyte differentiation markers (C/EBPα, PPARγ, adipsin, leptin, UCP1) were reduced, but levels of Pref-1 and TNFα were increased. (2) Marked insulin resistance with 60-fold elevation in plasma insulin. (3) Diabetes mellitus with elevated blood glucose (>300 mg/dl) that failed to decline when insulin was injected. (4) Fatty liver from birth and elevated plasma triglyceride levels later in life. These mice exhibit many of the features of congenital generalized lipodystrophy (CGL), an autosomal recessive disorder in humans. PMID:9784493

The effectiveness of anticellulite treatment using tripolar radiofrequency monitored by classic and high-frequency ultrasound.

PubMed

Mlosek, R K; Woźniak, W; Malinowska, S; Lewandowski, M; Nowicki, A

2012-06-01

  Cellulite affects nearly 85% of the female population. Given the size of the phenomenon, we are continuously looking for effective ways to reduce cellulite. Reliable monitoring of anticellulite treatment remains a problem.   The main aim of the study was to evaluate the effectiveness of anticellulite treatment carried out using radiofrequency (RF), which was monitored by classical and high-frequency ultrasound.   Twenty-eight women underwent anticellulite treatment using RF, 17 women were in the placebo group. The therapy was monitored by classical and high-frequency ultrasound. The examinations evaluated the thickness of the epidermal echo, dermis thickness, dermis echogenicity, the length of the subcutaneous tissue bands growing into the dermis, the presence or absence of oedema, the thickness of subcutaneous tissue as well as thigh circumference and the stage of cellulite (according to the Nürnberger-Müller scale).   Cellulite was reduced in 89.286% of the women who underwent RF treatment. After the therapy, the following observations were made: a decrease in the thickness of the dermis and subcutaneous tissue, an increase in echogenicity reflecting on the increase in the number of collagen fibres, decreased subcutaneous tissue growing into bands in the dermis, and the reduction of oedema. In the placebo group, no statistically significant changes of the above parameters were observed.   Radiofrequency enables cellulite reduction. A crucial aspect is proper monitoring of the progress of such therapy, which ultrasound allows. © 2011 The Authors. Journal of the European Academy of Dermatology and Venereology © 2011 European Academy of Dermatology and Venereology.

A new method for body fat evaluation, body adiposity index, is useful in women with familial partial lipodystrophy.

PubMed

Godoy-Matos, Amélio F; Moreira, Rodrigo O; Valerio, Cynthia M; Mory, Patricia B; Moises, Regina S

2012-02-01

BMI is a widely used method to evaluate adiposity. However, it has several limitations, particularly an inability to differentiate lean from fat mass. A new method, body adiposity index (BAI), has been recently proposed as a new measurement capable to determine fat excess better than BMI. The aim of this study was to investigate BAI as a mean to evaluate adiposity in a group of women with familial partial lipodystrophy (FPLD) and compare it with BMI. Thirteen women with FLPD Dunnigan type (FPLD2) and 13 healthy volunteers matched by age and BMI were studied. Body fat content and distribution were analyzed by dual X-ray absorptiometry (DXA). Plasma leptin was also measured. BAI was significantly lower in FPLD2 in comparison to control group (24.6 ± 1.5 vs. 30.4 ± 4.3; P < 0.001) and presented a more significant correlation with total fat (%) (r = 0.71; P < 0.001) and fat Mass (g) (r = 0.80; P < 0.001) than BMI (r = 0.27; P = 0.17 for total fat and r = 0.52; P = 0.006 for fat mass). There was a correlation between leptin and BAI (r = 0.57; P = 0.01), [corrected] but not between leptin and BMI. In conclusion, BAI was able to catch differences in adiposity in a sample of FPLD2 patients. It also correlated better with leptin levels than BMI. Therefore, we provide further evidence that BAI may become a more reliable indicator of fat mass content than the currently available measurements.

Radial extracorporeal shock wave treatment harms developing chicken embryos

PubMed Central

Kiessling, Maren C.; Milz, Stefan; Frank, Hans-Georg; Korbel, Rüdiger; Schmitz, Christoph

2015-01-01

Radial extracorporeal shock wave treatment (rESWT) has became one of the best investigated treatment modalities for cellulite, including the abdomen as a treatment site. Notably, pregnancy is considered a contraindication for rESWT, and concerns have been raised about possible harm to the embryo when a woman treated with rESWT for cellulite is not aware of her pregnancy. Here we tested the hypothesis that rESWT may cause serious physical harm to embryos. To this end, chicken embryos were exposed in ovo to various doses of radial shock waves on either day 3 or day 4 of development, resembling the developmental stage of four- to six-week-old human embryos. We found a dose-dependent increase in the number of embryos that died after radial shock wave exposure on either day 3 or day 4 of development. Among the embryos that survived the shock wave exposure a few showed severe congenital defects such as missing eyes. Evidently, our data cannot directly be used to draw conclusions about potential harm to the embryo of a pregnant woman treated for cellulite with rESWT. However, to avoid any risks we strongly recommend applying radial shock waves in the treatment of cellulite only if a pregnancy is ruled out. PMID:25655309

Ex vivo human skin evaluation of localized fat reduction and anti-aging effect by TriPollar radio frequency treatments.

PubMed

Boisnic, Sylvie; Branchet, Marie Christine

2010-02-01

A wide variety of radio frequency (RF) treatments for localized fat and cellulite reduction as well as anti-aging are available nowadays, but only a few have shown the biological mechanism responsible for the clinical results. To determine the biological mechanism of the TriPollar RF device for localized fat and cellulite reduction as well as the collagen remodeling effect. Human skin samples were collected from abdominoplasty surgery and facial lifts, in order to evaluate the lipolytic and anti-aging effects of the apollo device powered by TriPollar RF technology using an ex vivo human skin model. The anti-cellulite effect was evaluated by the dosage of released glycerol and histological analysis of the hypodermis. Skin tightening was evaluated by morphometric analysis of collagen fibers and the dosage of collagen synthesis. Following TriPollar treatment, a significant increase of glycerol release by skin samples was found. The structure of fat cells was altered in shape and a modification of the fibrous tract was also detected in the fat layer. Additional findings indicated stimulation of the dermal fibroblasts with increased collagen synthesis. The detected alteration in the hypodermal layer is manifested by fat and cellulite reduction accompanied by structural and biochemical improvement of dermal collagen, which result in overall skin tightening.

Atypical generalized lipoatrophy and severe insulin resistance due to a heterozygous LMNA p.T10I mutation.

PubMed

Mory, Patricia B; Crispim, Felipe; Kasamatsu, Teresa; Gabbay, Monica A L; Dib, Sergio A; Moisés, Regina S

2008-11-01

Lipodystrophies are a group of heterogeneous disorders characterized by the loss of adipose tissue and metabolic complications. The main familial forms of lipodystrophy are Congenital Generalized Lipodystrophy and Familial Partial Lipodystrophy (FPLD). FPLD may result from mutations in the LMNA gene. Besides FPLD, mutations in LMNA have been shown to be responsible for other inherited diseases called laminopathies. Here we describe the case of a 15-year-old girl who was referred to our service due to diabetes mellitus and severe hypertriglyceridemia. Physical examination revealed generalized loss of subcutaneous fat, confirmed by DEXA (total body fat 8.6%). As the patient presented with pubertal-onset of generalized lipodystrophy and insulin resistance, molecular analysis of the LMNA gene was performed. We identified a heterozygous substitution in exon 1 (c.29C>T) predicting a p.T10I mutation. In summary, we describe an atypical phenotype of lipodistrophy associated with a de novo appearance of the p.T10I mutation in LMNA gene.

The role of diet, exercise and smoking in dyslipidaemia in HIV-infected patients with lipodystrophy.

PubMed

Shah, M; Tierney, K; Adams-Huet, B; Boonyavarakul, A; Jacob, K; Quittner, C; Dinges, Wl; Peterson, D; Garg, A

2005-07-01

Lipodystrophy in HIV-infected (LDHIV) patients receiving protease inhibitors (PIs) is associated with dyslipidaemia. Whether lifestyle factors play a role in dyslipidaemia in LDHIV subjects on PIs is not well characterized. A total of 45 LDHIV male and six LDHIV female patients on PIs were recruited, and data were collected on smoking, exercise, diet (by 3-day food record), and fasting levels of serum lipids and lipoproteins. The relationships between lifestyle factors and metabolic variables were analysed in male patients by Spearman's correlation test and the significant relationships were further analysed by adjusting for age, PI duration, and waist circumference by Spearman's partial correlation test. In men, mean (+/-standard deviation) serum concentrations of total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), triglycerides (TG), and non-HDL-C were 212+/-70, 35+/-7.3, 325+/-230 and 169+/-44 mg/dL, respectively. Sixty-seven percent of the men exercised regularly and 31.1% smoked. The reported diet was high in cholesterol (390+/-212 mg) and percentage energy from saturated (12.2+/-3.3%) and trans (2.4+/-1.2%) fats, and low in soluble fibre (6.9+/-2.3 g) compared with recent dietary guidelines. Following adjustments for the confounding variables, percentage energy intake from total protein and animal protein was positively related to TC (r=0.44, P<0.01 and r=0.37, P<0.05, respectively), TG (r=0.40, P<0.01 and r=0.46, P<0.01, respectively) and non-HDL-C (r=0.56, P<0.001 and r=0.49, P<0.01, respectively), that from trans fat was positively related to TG (r=0.34, P<0.05), and soluble fibre was negatively related to non-HDL-C (r=-0.41, P<0.01). Moderate to heavy aerobic exercise tended to be associated with higher HDL-C (r=0.30, P=0.07) whereas smoking was not associated with any of the metabolic variables. Increased intake of total protein, animal protein and trans fat, and reduced soluble fibre consumption contribute to dyslipidaemia in LDHIV

Regulation of adiponectin in adipocytes upon exposure to HIV-1

USDA-ARS?s Scientific Manuscript database

Adipose dysregulation, dyslipidemia, and insulin resistance are hallmarks of HIV-related lipodystrophy. The precise mechanisms behind these disturbances are unknown. In HIV-infected patients, we previously demonstrated a strong relationship between lipodystrophy and levels of adiponectin, an adipose...

Diphlorethohydroxycarmalol of Ishige okamurae and Caffeine Modified the Expression of Extracellular Fibrillars during Adipogenesis of Mouse Subcutaneous Adipose Derived Stem Cell

PubMed Central

Jeon, Younmi; Song, Siyoung; Kim, Hagju; Cheon, Yong-Pil

2013-01-01

Although, one of the etiologies of localized lipodystrophy of the subcutaneous connective tissue (cellulite) is the histological alternation of adipose tissue, the characteristics of expression of the components of extracellular matrix (ECM) components during adipogenesis are not uncovered. In this study, the effects of caffeine and Ishige okamurae originated diphlorethohydroxycarmalol (DPHC) on the expression of extracellualr fibers was analyzed with quantitative RT-PCR during differentiation induction of mouse subcutaneous adipose derived stem cells (msADSC) into adipocyte. The expression levels of Col1a, Col3a1, and Col61a were decreased by the adipogenci induction in a time-dependent manners. However, Col2a mRNA and Col4a1 mRNA expressions were oposit to them. Caffeine and DPHC stimulated the changes of the expression of these collagens. Eln mRNA expression was increased by induction. DPHC stimulated the expression of it. Mfap5 mRNA expression was deceased in both adipogenic cell and matured adipocytes. Caffeine suppressed the expression of Mfap5 but the effect of DPHC was different by the concentration. The expression of bioglycan, decorin, and lumican were also modified by caffeine and DPHC in a concentration-dependent manner. Based on this study, we revealed firstly the effects of caffeine and DPHC on the expression of collagens, elastin, and glycoproteins during adipogenesis of msADSCs. Those results suggest that DPHC may have antiadipogenic effect and has more positive effets on normal adipose tissue generation and work as suppressor the abnormality of ECM structure. Such results indicate that DPHC can be applied in keeping the stability of the ECM of adipogenic tissues. PMID:25949143

Leptin replacement therapy for the treatment of non-HAART associated lipodystrophy syndromes: a meta-analysis into the effects of leptin on metabolic and hepatic endpoints.

PubMed

Rodríguez, Alexander J; Neeman, Teresa; Giles, Aaron G; Mastronardi, Claudio A; Paz Filho, Gilberto

2014-11-01

The clinical manifestations of lipodystrophy syndromes (LS) are hypoleptinemia, hyperglycemia, insulin resistance, dyslipidemia and hepatic steatosis. Leptin replacement therapy (LRT) is effective at improving these pathologies. Currently, there are no data compiling the evidence from the literature, and demonstrating the effect of LRT in LS patients. A systematic review of the MEDLINE and Cochrane Library databases was conducted to identify studies assessing the effect of LRT on metabolic and hepatic endpoints in patients with LS not associated with highly active antiretroviral therapy (HAART) use. Standardized mean differences (SMD) and 95% confidence intervals of pooled results were calculated for overall changes in glucose homeostasis, lipid profile, and hepatic physiology, using an inverse-variance random-effects model. After screening, 12 studies were included for review. Meta-analysis of results from 226 patients showed that LRT decreased fasting glucose [0.75 SMD units (range 0.36-1.13), p=0.0001], HbA1c [0.49 (0.17-0.81), p=0.003], triglycerides [1.00 (0.69-1.31), p<0.00001], total cholesterol [0.62 (0.21-1.02), p=0.003], liver volume [1.06 (0.51-1.61), p=0.0002] and AST [0.41 (0.10-0.73) p=0.01]. In patients with non-HAART LS, LRT improves the outcome of several metabolic and hepatic parameters. Studies were limited by small populations and therefore large prospective trials are needed to validate these findings.

Berardinelli Seip syndrome with insulin-resistant diabetes mellitus and stroke in an infant.

PubMed

Indumathi, C K; Lewin, S; Ayyar, Vageesh

2011-07-01

Berardinelli Seip congenital lipodystrophy (BSCL) is a rare metabolic disorder characterized by severe generalized lipodystrophy, insulin resistance, and dyslipedemia since infancy, and onset of overt diabetes mellitus in adolescence. Here we report a 5-month-old infant with clinical and metabolic manifestations of Berardinelli Seip syndrome including overt diabetes mellitus and stroke, which are very rare at this age.

Dyslipidemia in HIV Infected Children Receiving Highly Active Antiretroviral Therapy.

PubMed

Mandal, Anirban; Mukherjee, Aparna; Lakshmy, R; Kabra, Sushil K; Lodha, Rakesh

2016-03-01

To assess the prevalence of dyslipidemia and lipodystrophy in Indian children receiving non-nucleoside reverse transcriptase inhibitor (NNRTI) based highly active antiretroviral therapy (HAART) and to determine the associated risk factors for the same. The present cross-sectional study was conducted at a Pediatric Clinic of a tertiary care teaching center in India, from May 2011 through December 2012. HIV infected children aged 5-15 y were enrolled if they did not have any severe disease or hospital admission within last 3 mo or receive any medications known to affect the lipid profile. Eighty-one children were on highly active antiretroviral therapy (HAART) for at least 6 mo and 16 were receiving no antiretroviral therapy (ART). Participants' sociodemographic, nutritional, clinical, and laboratory data were recorded in addition to anthropometry and evidence of lipodystrophy. Fasting lipid profile, apolipoprotein A1 and B levels were done for all the children. Among the children on highly active antiretroviral therapy (HAART), 38.3 % had dyslipidemia and 80.2 % had lipodystrophy, while 25 % antiretroviral therapy (ART) naïve HIV infected children had dyslipidemia. No clinically significant risk factors could be identified that increased the risk of dyslipidemia or lipodystrophy in children on highly active antiretroviral therapy (HAART). There is a high prevalence of dyslipidemia and lipodystrophy in Indian children with HIV infection with an imminent need to establish facilities for testing and treatment of these children for metabolic abnormalities.

Benefit of a topical slimming cream in conjunction with dietary advice

PubMed Central

Escudier, B; Fanchon, C; Labrousse, E; Pellae, M

2011-01-01

Synopsis The aim of this study was to determine how worthwhile it would be to combine a newly developed topical slimming product with customized dietary habits not based on calorie restriction, so as to improve the cellulite appearance of the skin. At the beginning of the study, a nutritionist recorded the dietary habits of each participant and gave recommendations to each of them according to their food consumption. The chosen methodology was a right/left comparison, one thigh and hip being treated with the new topical slimming product and the other one left untreated to serve as a random control. Objective evaluations were performed by blind assessors. Control of food intake improved the cellulite score after 4 weeks when compared with the base value, but this reduction was significantly greater and earlier on the treated side than on the untreated side, indicating an objective additional benefit derived from the new slimming cream. This result corroborated the slimming effect assessed by measurement in centimetres of the circumference of the upper thighs and the reconstructed volume of the thigh between two fixed horizontal slices. Furthermore, skin tonicity, a major component of cellulite visibility, was also significantly improved on the treated side after only 2 weeks. This new topical cream thus enhances the benefit of a dietetic control for the treatment of the visible aspect of cellulite on the skin. Résumé Cette étude avait pour objectif d’étudier l'intérêt éventuel d'associer une nouvelle crème amincissante à des conseils nutritionnels personnalisés, non basés sur la restriction calorique mais sur un meilleur équilibre alimentaire afin d'améliorer l'aspect cellulitique de la peau. Au début de l’étude un médecin nutritionniste a enregistré les habitudes alimentaires de chaque sujet et a donné des recommandations à chacun en fonction de leur consommation alimentaire. La méthodologie contrôlée en hémi corps, gauche/droite a �

Berardinelli Seip syndrome with insulin-resistant diabetes mellitus and stroke in an infant

PubMed Central

Indumathi, C. K.; Lewin, S.; Ayyar, Vageesh

2011-01-01

Berardinelli Seip congenital lipodystrophy (BSCL) is a rare metabolic disorder characterized by severe generalized lipodystrophy, insulin resistance, and dyslipedemia since infancy, and onset of overt diabetes mellitus in adolescence. Here we report a 5-month-old infant with clinical and metabolic manifestations of Berardinelli Seip syndrome including overt diabetes mellitus and stroke, which are very rare at this age. PMID:21847459

The Role of a Novel Myosin Isoform in Prostate Cancer Metastasis

DTIC Science & Technology

2013-10-01

of unconventional myosin function and targeting, Annu. Rev. Cell Dev. Biol. 27 (2011) 133–155. [42] W. Kliche, S. Fujita- Becker , M. Kollmar, D.J...tissue-specific diseases (laminopathies), including Emery–Dreifuss muscular dystrophy , Dunnigan-type familial partial lipodystrophy (FPLD), and...structure of the C-terminal domain of lamin A/C, mutated in muscular dystrophies , cardiomyopathy, and partial lipodystrophy. Structure 10, 811–823

Photobiomodulation with non-thermal lasers: Mechanisms of action and therapeutic uses in dermatology and aesthetic medicine.

PubMed

Nestor, Mark; Andriessen, Anneke; Berman, Brian; Katz, Bruce E; Gilbert, Dore; Goldberg, David J; Gold, Michael H; Kirsner, Robert S; Lorenc, Paul Z

2017-08-01

Non-thermal laser therapy in dermatology, is a growing field in medical technology by which therapeutic effects are achieved by exposing tissues to specific wavelengths of light. The purpose of this review was to gain a better understanding of the science behind non-thermal laser and the evidence supporting its use in dermatology. A group of dermatologists and surgeons recently convened to review the evidence supporting the use of non-thermal laser for body sculpting, improving the appearance of cellulite, and treating onychomycosis. The use of non-thermal laser for body sculpting is supported by three randomized, double-blind, sham-controlled studies (N = 161), one prospective open-label study (N = 54), and two retrospective studies (N = 775). Non-thermal laser application for improving the appearance of cellulite is supported by one randomized, double-blind, sham-controlled study (N = 38). The use of non-thermal laser for the treatment of onychomycosis is supported by an analysis of three non-randomized, open-label studies demonstrating clinical improvement of nails (N = 292). Non-thermal laser is steadily moving into mainstream medical practice, such as dermatology. Although present studies have demonstrated the safety and efficacy of non-thermal laser for body sculpting, cellulite reduction and onychomycosis treatment, studies demonstrating the efficacy of non-thermal laser as a stand-alone procedure are still inadequate.

A controlled-release mitochondrial protonophore reverses hypertriglyceridemia, nonalcoholic steatohepatitis, and diabetes in lipodystrophic mice.

PubMed

Abulizi, Abudukadier; Perry, Rachel J; Camporez, João Paulo G; Jurczak, Michael J; Petersen, Kitt Falk; Aspichueta, Patricia; Shulman, Gerald I

2017-07-01

Lipodystrophy is a rare disorder characterized by complete or partial loss of adipose tissue. Patients with lipodystrophy exhibit hypertriglyceridemia, severe insulin resistance, type 2 diabetes, and nonalcoholic steatohepatitis (NASH). Efforts to ameliorate NASH in lipodystrophies with pharmacologic agents have met with limited success. We examined whether a controlled-release mitochondrial protonophore (CRMP) that produces mild liver-targeted mitochondrial uncoupling could decrease hypertriglyceridemia and reverse NASH and diabetes in a mouse model (fatless AZIP/F-1 mice) of severe lipodystrophy and diabetes. After 4 wk of oral CRMP (2 mg/kg body weight per day) or vehicle treatment, mice underwent hyperinsulinemic-euglycemic clamps combined with radiolabeled glucose to assess liver and muscle insulin responsiveness and tissue lipid measurements. CRMP treatment reversed hypertriglyceridemia and insulin resistance in liver and skeletal muscle. Reversal of insulin resistance could be attributed to reductions in diacylglycerol content and reduced PKC-ε and PKC-θ activity in liver and muscle respectively. CRMP treatment also reversed NASH as reflected by reductions in plasma aspartate aminotransferase and alanine aminotransferase concentrations; hepatic steatosis; and hepatic expression of IL-1α, -β, -2, -4, -6, -10, -12, CD69, and caspase 3 and attenuated activation of the IRE-1α branch of the unfolded protein response. Taken together, these results provide proof of concept for the development of liver-targeted mitochondrial uncoupling agents as a potential novel therapy for lipodystrophy-associated hypertriglyceridemia, NASH and diabetes.-Abulizi, A., Perry, R. J., Camporez, J. P. G., Jurczak, M. J., Petersen, K. F., Aspichueta, P., Shulman, G. I. A controlled-release mitochondrial protonophore reverses hypertriglyceridemia, nonalcoholic steatohepatitis, and diabetes in lipodystrophic mice. © FASEB.

Leptin applications in 2015: What have we learned about leptin and obesity?

PubMed Central

Farr, Olivia M.; Gavrieli, Anna; Mantzoros, Christos S.

2015-01-01

Purpose of review To summarize previous and current advancements for leptin therapeutics, we described how leptin may be useful in leptin deficient states such as lipodystrophy, for which leptin was recently approved, and how it may be useful in the future for typical obesity. Recent findings The discovery of leptin in 1994 built the foundation for understanding the pathophysiology and treatment of obesity. Leptin therapy reverses morbid obesity related to congenital leptin deficiency and appears to effectively treat lipodystrophy, a finding which has led to the approval of leptin for the treatment of lipodystrophy in the USA and Japan. Typical obesity, on the other hand, is characterized by hyperleptinemia and leptin resistance. Thus, leptin administration has proven ineffective for inducing weight loss on its own but may be useful in combination with other therapies or for weight loss maintenance. Summary Leptin is not yet able to treat typical obesity, however, it is effective for reversing leptin deficiency-induced obesity and lipodystrophy. New mechanisms and pathways involved in leptin resistance are continuously discovered, while the development of new techniques and drug combinations which may improve leptin’s efficacy and safety regenerate the hope for its use as an effective treatment for typical obesity. PMID:26313897

Birth weight and growth from infancy to late adolescence in relation to fat and lean mass in early old age: findings from the MRC National Survey of Health and Development.

PubMed

Bann, D; Wills, A; Cooper, R; Hardy, R; Aihie Sayer, A; Adams, J; Kuh, D

2014-01-01

High birth weight and greater weight gain in infancy have been associated with increased risk of obesity as assessed using body mass index, but few studies have examined associations with direct measures of fat and lean mass. This study examined associations of birth weight and weight and height gain in infancy, childhood and adolescence with fat and lean mass in early old age. A total of 746 men and 812 women in England, Scotland and Wales from the MRC National Survey of Health and Development whose heights and weights had been prospectively ascertained across childhood and adolescence and who had dual energy X-ray absorptiometry measures at age 60-64 years. Associations of birth weight and standardised weight and height (0-2 (weight only), 2-4, 4-7, 7-11, 11-15, 15-20 years) gain velocities with outcome measures were examined. Higher birth weight was associated with higher lean mass and lower android/gynoid ratio at age 60-64 years. For example, the mean difference in lean mass per 1 standard deviation increase in birth weight was 1.54 kg in males (95% confidence interval=1.04, 2.03) and 0.78 kg in females (0.41, 1.14). Greater weight gain in infancy was associated with higher lean mass, whereas greater gains in weight in later childhood and adolescence were associated with higher fat and lean mass, and fat/lean and android/gynoid ratios. Across growth intervals greater height gain was associated with higher lean but not fat mass, and with lower fat/lean and android/gynoid ratios. Findings suggest that growth in early life may have lasting effects on fat and lean mass. Greater weight gain before birth and in infancy may be beneficial by leading to higher lean mass, whereas greater weight gain in later childhood and adolescence may be detrimental by leading to higher fat/lean and android/gynoid ratios.

Exploring channeling optimized radiofrequency energy: a review of radiofrequency history and applications in esthetic fields.

PubMed

Belenky, Inna; Margulis, Ariel; Elman, Monica; Bar-Yosef, Udi; Paun, Silviu D

2012-03-01

Because of its high efficiency and safety, radiofrequency (RF) energy is widely used in the dermatological field for heating biological tissue in various esthetic applications, including skin tightening, skin lifting, body contouring, and cellulite reduction. This paper reviews the literature on the use of nonablative RF energy in the esthetic field and its scientific background. The purpose of this article is to describe in detail the extensive use of medical devices based on RF technology, the development of these medical devices over the years, and recent developments and trends in RF technology. The authors conducted a systematic search of publications that address safety and efficacy issues, technical system specifications, and clinical techniques. Finally, the authors focused on their own clinical experiences with the use of patented Channeling Optimized RF Energy technique and mechanical massage. An in-vivo study was conducted in domestic pigs, with a thermal video camera. Twenty-seven female patients participated in a cellulite and body shaping study. The treatments were conducted according to a three-phase protocol. An additional 16 females participated in a skin tightening case study. All of the patients underwent three treatment sessions at 3-week intervals, each according to a protocol specific to the area being treated. The review of the literature on RF-based systems revealed that these systems are safe, with low risks for potential side effects, and effective for cellulite, body contouring, and skin tightening procedures. The in-vivo measurements confirmed the theory that the penetration depth of RF is an inverse function of its frequency, and using a vacuum mechanism makes an additional contribution to the RF energy penetration. The heating effect of RF was also found to increase blood circulation and to induce collagen remodeling. The results from the cellulite and body shaping treatments showed an overall average improvement of 55% in the

Reep1 null mice reveal a converging role for hereditary spastic paraplegia proteins in lipid droplet regulation.

PubMed

Renvoisé, Benoît; Malone, Brianna; Falgairolle, Melanie; Munasinghe, Jeeva; Stadler, Julia; Sibilla, Caroline; Park, Seong H; Blackstone, Craig

2016-12-01

Hereditary spastic paraplegias (HSPs; SPG1-76 plus others) are length-dependent disorders affecting long corticospinal axons, and the most common autosomal dominant forms are caused by mutations in genes that encode the spastin (SPG4), atlastin-1 (SPG3A) and REEP1 (SPG31) proteins. These proteins bind one another and shape the tubular endoplasmic reticulum (ER) network throughout cells. They also are involved in lipid droplet formation, enlargement, or both in cells, though mechanisms remain unclear. Here we have identified evidence of partial lipoatrophy in Reep1 null mice in addition to prominent spastic paraparesis. Furthermore, Reep1-/- embryonic fibroblasts and neurons in the cerebral cortex both show lipid droplet abnormalities. The apparent partial lipodystrophy in Reep1 null mice, although less severe, is reminiscent of the lipoatrophy phenotype observed in the most common form of autosomal recessive lipodystrophy, Berardinelli-Seip congenital lipodystrophy. Berardinelli-Seip lipodystrophy is caused by autosomal recessive mutations in the BSCL2 gene that encodes an ER protein, seipin, that is also mutated in the autosomal dominant HSP SPG17 (Silver syndrome). Furthermore, REEP1 co-immunoprecipitates with seipin in cells. This strengthens the link between alterations in ER morphogenesis and lipid abnormalities, with important pathogenic implications for the most common forms of HSP. Published by Oxford University Press 2016. This work is written by US Government employees and is in the public domain in the US.

One-year metreleptin improves insulin secretion in patients with diabetes linked to genetic lipodystrophic syndromes.

PubMed

Vatier, C; Fetita, S; Boudou, P; Tchankou, C; Deville, L; Riveline, Jp; Young, J; Mathivon, L; Travert, F; Morin, D; Cahen, J; Lascols, O; Andreelli, F; Reznik, Y; Mongeois, E; Madelaine, I; Vantyghem, Mc; Gautier, Jf; Vigouroux, C

2016-07-01

Recombinant methionyl human leptin (metreleptin) therapy was shown to improve hyperglycaemia, dyslipidaemia and insulin sensitivity in patients with lipodystrophic syndromes, but its effects on insulin secretion remain controversial. We used dynamic intravenous (i.v.) clamp procedures to measure insulin secretion, adjusted to insulin sensitivity, at baseline and after 1 year of metreleptin therapy, in 16 consecutive patients with lipodystrophy, diabetes and leptin deficiency. Patients, with a mean [± standard error of the mean (s.e.m.)] age of 39.2 (±4) years, presented with familial partial lipodystrophy (n = 11, 10 women) or congenital generalized lipodystrophy (n = 5, four women). Their mean (± s.e.m.) BMI (23.9 ± 0.7 kg/m(2) ), glycated haemoglobin levels (8.5 ± 0.4%) and serum triglycerides levels (4.6 ± 0.9 mmol/l) significantly decreased within 1 month of metreleptin therapy, then remained stable. Insulin sensitivity (from hyperglycaemic or euglycaemic-hyperinsulinaemic clamps, n = 4 and n = 12, respectively), insulin secretion during graded glucose infusion (n = 12), and acute insulin response to i.v. glucose adjusted to insulin sensitivity (disposition index, n = 12), significantly increased after 1 year of metreleptin therapy. The increase in disposition index was related to a decrease in percentage of total and trunk body fat. Metreleptin therapy improves not only insulin sensitivity, but also insulin secretion in patients with diabetes attributable to genetic lipodystrophies. © 2015 John Wiley & Sons Ltd.

Exome sequencing reveals a de novo POLD1 mutation causing phenotypic variability in mandibular hypoplasia, deafness, progeroid features, and lipodystrophy syndrome (MDPL).

PubMed

Elouej, Sahar; Beleza-Meireles, Ana; Caswell, Richard; Colclough, Kevin; Ellard, Sian; Desvignes, Jean Pierre; Béroud, Christophe; Lévy, Nicolas; Mohammed, Shehla; De Sandre-Giovannoli, Annachiara

2017-06-01

Mandibular hypoplasia, deafness, progeroid features, and lipodystrophy syndrome (MDPL) is an autosomal dominant systemic disorder characterized by prominent loss of subcutaneous fat, a characteristic facial appearance and metabolic abnormalities. This syndrome is caused by heterozygous de novo mutations in the POLD1 gene. To date, 19 patients with MDPL have been reported in the literature and among them 14 patients have been characterized at the molecular level. Twelve unrelated patients carried a recurrent in-frame deletion of a single codon (p.Ser605del) and two other patients carried a novel heterozygous mutation in exon 13 (p.Arg507Cys). Additionally and interestingly, germline mutations of the same gene have been involved in familial polyposis and colorectal cancer (CRC) predisposition. We describe a male and a female patient with MDPL respectively affected with mild and severe phenotypes. Both of them showed mandibular hypoplasia, a beaked nose with bird-like facies, prominent eyes, a small mouth, growth retardation, muscle and skin atrophy, but the female patient showed such a severe and early phenotype that a first working diagnosis of Hutchinson-Gilford Progeria was made. The exploration was performed by direct sequencing of POLD1 gene exon 15 in the male patient with a classical MDPL phenotype and by whole exome sequencing in the female patient and her unaffected parents. Exome sequencing identified in the latter patient a de novo heterozygous undescribed mutation in the POLD1 gene (NM_002691.3: c.3209T>A), predicted to cause the missense change p.Ile1070Asn in the ZnF2 (Zinc Finger 2) domain of the protein. This mutation was not reported in the 1000 Genome Project, dbSNP and Exome sequencing databases. Furthermore, the Isoleucine1070 residue of POLD1 is highly conserved among various species, suggesting that this substitution may cause a major impairment of POLD1 activity. For the second patient, affected with a typical MDPL phenotype, direct sequencing

The frequency of low muscle mass and its overlap with low bone mineral density and lipodystrophy in individuals with HIV--a pilot study using DXA total body composition analysis.

PubMed

Buehring, Bjoern; Kirchner, Elizabeth; Sun, Zhiyuan; Calabrese, Leonard

2012-01-01

As a result of the advances in antiretroviral therapy, the life span of human immunodeficiency virus (HIV)-infected patients has increased dramatically. Attendant to these effects are signs of premature aging with notable changes in the musculoskeletal system. Although changes in bone and fat distribution have been studied extensively, far less is known about changes in muscle. This study examined the extent of low muscle mass (LMM) and its relationship with low bone mineral density (BMD) and lipodystrophy (LD) in HIV-positive males. As such, HIV-positive males on therapy or treatment naive underwent dual-energy X-ray absorptiometry total body composition measurements. Appendicular lean mass/(height)2 and lowest 20% of residuals from regression analysis were used to define LMM. BMD criteria defined osteopenia/osteoporosis, and the percent central fat/percent lower extremity ratio defined LD. Several potential risk factors were assessed through chart review. Sixty-six males (57 with treatment and 9 treatment naive) volunteered. Treated individuals were older than naive (44 vs 34 yr) and had HIV longer (108 vs 14 mo). When definitions for sarcopenia (SP) in elderly individuals were applied, the prevalence of LMM was 21.9% and 18.8% depending on the definition used. Low BMD was present in 68.2% of participants. LD with a cutoff of 1.5 and 1.961 was present in 54.7% and 42.2% of participants, respectively. LMM and LD were negatively associated. In conclusion, this study shows that LMM is common in males with HIV and that SP affecting muscle function could be present in a substantial number of individuals. Future research needs to examine what impact decreased muscle mass and function has on morbidity, physical function, and quality of life in individuals with HIV. Copyright © 2012 The International Society for Clinical Densitometry. Published by Elsevier Inc. All rights reserved.

Fetal and infant growth patterns associated with total and abdominal fat distribution in school-age children.

PubMed

Gishti, Olta; Gaillard, Romy; Manniesing, Rashindra; Abrahamse-Berkeveld, Marieke; van der Beek, Eline M; Heppe, Denise H M; Steegers, Eric A P; Hofman, Albert; Duijts, Liesbeth; Durmuş, Büşra; Jaddoe, Vincent W V

2014-07-01

Higher infant growth rates are associated with an increased risk of obesity in later life. We examined the associations of longitudinally measured fetal and infant growth patterns with total and abdominal fat distribution in childhood. We performed a population-based prospective cohort study among 6464 children. We measured growth characteristics in the second and third trimesters of pregnancy, at birth, and at 6, 12, and 24 months. Body mass index, fat mass index (body fat mass/height(2)), lean mass index (body lean mass/height(2)), android/gynoid fat ratio measured by dual-energy x-ray absorptiometry, and sc and preperitoneal abdominal fat measured by ultrasound at the median age of 6.0 years (90% range, 5.7-7.4). We observed that weight gain in the second and third trimesters of fetal life and in early, mid, and late infancy were independently and positively associated with childhood body mass index (P < .05). Only infant weight gain was associated with higher fat mass index, android/gynoid fat ratio, and abdominal fat in childhood (P < .05). Children with both fetal and infant growth acceleration had the highest childhood body mass index, fat mass index, and sc abdominal fat, whereas children with fetal growth deceleration and infant growth acceleration had the highest value for android/gynoid fat ratio and the lowest value for lean mass index (P < .05). Growth in both fetal life and infancy affects childhood body mass index, whereas only infant growth directly affects measured total body and abdominal fat. Fetal growth deceleration followed by infant growth acceleration may lead to an adverse body fat distribution in childhood.

Risk factors in human immunodeficiency virus/acquired immunodeficiency syndrome patients undergoing antiretroviral therapy in the state of Pernambuco, Brazil: a case-control study.

PubMed

Gelenske, Thais; e Farias, Francisco Alfredo Bandeira; de Alencar Ximenes, Ricardo Arraes; de Melo, Heloísa Ramos Lacerda; de Albuquerque, Maria de Fátima Pessoa Militão; de Carvalho, Erico Higino; de Medeiros Barros, Zoraya; Diniz, George Tadeu Nunes; Filho, Demócrito de Barros Miranda

2010-06-01

Although human immunodeficiency virus (HIV)-associated lipodystrophy has been reported for more than a decade, there is still considerable uncertainty regarding the mechanisms involved in its pathogenesis. A case-control study was performed that aimed to identify the risk factors for lipodystrophy in HIV/acquired immunodeficiency syndrome (AIDS) patients undergoing antiretroviral therapy in Pernambuco, Brazil. Between July and November, 2007, a total of 332 patients were enrolled in the study: 182 cases and 150 controls. The following factors were independently associated with lipodystrophy: Use of stavudine [odds ratio (OR), 4.0; 95% confidence interval (CI), 2.3-6.9], use of didanosine (OR, 1.8; 95% CI, 1.0-3.4), use of lopinavir/ritonavir for less than 3 years (OR, 0.5; 95% CI, 0.2-1.0) and use of nucleoside/nucleotide analogue reverse transcriptase inhibitors (NTRIs) for more than 3 years (OR, 2.9; 95% CI, 1.6-5.2). Other associated factors were: duration of antiretroviral therapy (OR, 4.3; 95% CI, 2.4-7.9) and duration of HIV infection (OR, 2.9; 95% CI, 1.8-4.7). There was no association with the use of protease inhibitor when it was adjusted for the use of NRTIs. In this study, factors related to antiretroviral therapy were the main risk factors for lipodystrophy, corroborating the literature, but the findings also point to the need for further exploration into some of these associations, especially with the use of didanosine and lopinavir/ritonavir, which are less frequently reported. Future studies with a larger number of patients and a prospective design could provide valuable information for understanding this disorder.

Leptin's Role in Lipodystrophic and Nonlipodystrophic Insulin-Resistant and Diabetic Individuals

PubMed Central

Moon, Hyun-Seuk; Dalamaga, Maria; Kim, Sang-Yong; Polyzos, Stergios A.; Hamnvik, Ole-Petter; Magkos, Faidon; Paruthi, Jason

2013-01-01

Leptin is an adipocyte-secreted hormone that has been proposed to regulate energy homeostasis as well as metabolic, reproductive, neuroendocrine, and immune functions. In the context of open-label uncontrolled studies, leptin administration has demonstrated insulin-sensitizing effects in patients with congenital lipodystrophy associated with relative leptin deficiency. Leptin administration has also been shown to decrease central fat mass and improve insulin sensitivity and fasting insulin and glucose levels in HIV-infected patients with highly active antiretroviral therapy (HAART)-induced lipodystrophy, insulin resistance, and leptin deficiency. On the contrary, the effects of leptin treatment in leptin-replete or hyperleptinemic obese individuals with glucose intolerance and diabetes mellitus have been minimal or null, presumably due to leptin tolerance or resistance that impairs leptin action. Similarly, experimental evidence suggests a null or a possibly adverse role of leptin treatment in nonlipodystrophic patients with nonalcoholic fatty liver disease. In this review, we present a description of leptin biology and signaling; we summarize leptin's contribution to glucose metabolism in animals and humans in vitro, ex vivo, and in vivo; and we provide insights into the emerging clinical applications and therapeutic uses of leptin in humans with lipodystrophy and/or diabetes. PMID:23475416

Abdominal elephantiasis: a case report.

PubMed

Hanna, Dominique; Cloutier, Richard; Lapointe, Roch; Desgagné, Antoine

2004-01-01

Elephantiasis is a well-known condition in dermatology usually affecting the legs and external genitalia. It is characterized by chronic inflammation and obstruction of the lymphatic channels and by hypertrophy of the skin and subcutaneous tissues. The etiology is either idiopathic or caused by a variety of conditions such as chronic filarial disease, leprosy, leishmaniasis, and chronic recurrent cellulites. Elephantiasis of the abdominal wall is very rare. A complete review of the English and French literature showed only two cases reported in 1966 and 1973, respectively. We report a third case of abdominal elephantiasis and we briefly review this entity. We present the case of a 51-year-old woman who had progressively developed an enormous pediculated abdominal mass hanging down her knees. The skin was thickened, hyperpigmented, and fissured. She had a history of multiple abdominal cellulites. She underwent an abdominal lipectomy. Histopathology of the specimen confirmed the diagnosis of abdominal elephantiasis. Abdominal elephantiasis is a rare disease that represents end-stage failure of lymph drainage. Lipectomy should be considered in the management of this condition.

Study and description of hydrogels and organogels as vehicles for cosmetic active ingredients.

PubMed

Morales, M E; Gallardo, V; Clarés, B; García, M B; Ruiz, M A

2009-01-01

Cellulite, a clinical syndrome mainly affecting women, involves specific changes in conjunctive dermic and subcutaneous tissue, leading to vascular and hypertrophic alterations in adipose tissues and the consequent alteration of tissue structure. This paper describes the design of hydrogels and pluronic-lecithin organogels elaborated as vehicles of Aloe vera (Aloe vera linné) and Hydrocotyle asiatica (Centella asiatica) for the treatment of cellulite. The objective of this work was to carry out a complete evaluation of the proposed formulae through the study of the organoleptic and rheological properties of the formulae. Our work revealed that, in appearance, hydrogels show better organoleptic characteristics than organogels. On the other hand, from a rheological point of view, both hydrogels and organogels display a plastic behavior. However, the main difference between the two is that the more complex internal structure of the organogel bestows it with more viscosity. Finally, in vitro tests with Franz-type diffusion cells revealed that the release of cosmetic active principle from the tested excipients was appropriate, both in terms of magnitude and velocity.

Indian girls have higher bone mineral content per unit of lean body than boys through puberty.

PubMed

Khadilkar, Anuradha V; Sanwalka, Neha; Mughal, M Zulf; Chiplonkar, Shashi; Khadilkar, Vaman

2018-05-01

Our aim is to describe changes in the muscle-bone unit assessed as a ratio of bone mineral content (BMC) to lean body mass (LBM) through puberty at total body and various skeletal sites in Indian boys and girls. A cross-sectional study was conducted (888 children, 480 boys, aged 5-17 years) in Pune, India. Pubertal staging was assessed. BMC, LBM and fat percentage at the arms, legs, android, gynoid and total body (less the head) were assessed by dual energy X-ray absorptiometry. The amount of BMC per unit LBM (BMC/LBM) was computed. Changes in mean BMC/LBM at 5 Tanner (pubertal) stages after adjustment for age and fat percentage were calculated. In boys, adjusted BMC/LBM was significantly higher with successive Tanner stages [legs (TS-II vs TS-I), android (TS-III vs TS-II, TS-IV vs TS-III) and gynoid region (TS-III vs TS-II and TS-II vs TS-I) (p < 0.05)]. In girls, adjusted BMC/LBM was significantly higher with successive Tanner stages at total body, legs and gynoid (TS-III vs TS-II; TS-II vs TS-I; TS-V vs TS-IV), arms (TS-I to TS-V) and android regions (TS-V vs TS-IV) (p < 0.05). Boys had significantly higher adjusted BMC/LBM than girls at earlier Tanner stages (TS-I to TS-III), whereas girls had significantly higher adjusted BMC/LBM than boys at later Tanner stages (TS-IV, TS-V) (p < 0.05). Indian boys and girls showed higher total and regional body, and age- and fat percentage-adjusted BMC/LBM with successive pubertal stages. Girls had higher BMC/LBM than boys which may possibly act as a reservoir for later demands of pregnancy and lactation.

Dietary variety is inversely associated with body adiposity among US adults using a novel food diversity index.

PubMed

Vadiveloo, Maya; Dixon, L Beth; Mijanovich, Tod; Elbel, Brian; Parekh, Niyati

2015-03-01

Consuming a variety (vs. monotony) of energy-poor, nutrient-dense foods may help individuals adhere to dietary patterns favorably associated with weight control. The objective of this study was to examine whether greater healthful food variety quantified using the US Healthy Food Diversity (HFD) index favorably influenced body adiposity. Men and nonpregnant, nonlactating women aged ≥20 y with two 24-h recalls from the cross-sectional NHANES 2003-2006 (n = 7470) were included in this study. Dietary recalls were merged with the MyPyramid Equivalent database to generate the US HFD index, which ranges from 0 to ∼1, with higher scores indicative of diets with a higher number and proportion of healthful foods. Multiple indicators of adiposity including BMI, waist-to-height ratio, android-to-gynoid fat ratio, fat mass index (FMI), and percentage body fat were assessed across US HFD index quintiles. ORs and 95% CIs were computed with use of multivariable logistic regression (SAS v. 9.3). The US HFD index was inversely associated with most adiposity indicators in both sexes. After multivariable adjustment, the odds of obesity, android-to-gynoid ratio >1, and high FMI were 31-55% lower (P-trend < 0.01) among women in quintile 5 vs. quintile 1 of the US HFD index. Among men, the odds of obesity, waist-to-height ratio ≥0.5, and android-to-gynoid ratio >1 were 40-48% lower (P-trend ≤ 0.01) in quintile 5 vs. quintile 1 of the US HFD index. Higher US HFD index values were inversely associated with indicators of body adiposity in both sexes, indicating that greater healthful food variety may protect against excess adiposity. This study explicitly recognizes the potential benefits of dietary variety in obesity management and provides the foundation to support its ongoing evaluation. © 2015 American Society for Nutrition.

Negative association between acrylamide exposure and body composition in adults: NHANES, 2003–2004

PubMed Central

Chu, P-L; Lin, L-Y; Chen, P-C; Su, T-C; Lin, C-Y

2017-01-01

Background/Objectives: Acrylamide is present in mainstream cigarette smoke and in some food prepared at high temperature. Animal studies have shown that acrylamide exposure reduces body weight. Prenatal exposure to acrylamide also has been linked to reduced birth weight in human. Whether acrylamide exposure is associated with altered body compositions in adults is not clear. Subjects/Methods: We selected 3623 subjects (aged ⩾20 years) from a National Health and Nutrition Examination Survey (NHANES) in 2003–2004 to determine the relationship among hemoglobin adducts of acrylamide (HbAA), hemoglobin adducts of glycidamide (HbGA) and body composition (body measures, bioelectrical impedance analysis (BIA), dual energy x-ray absorptiometry (DXA)). Data were adjusted for potential confounding variables. Results: The geometric means and 95% CI concentrations of HbAA and HbGA were 60.48 (59.32–61.65) pmol/g Hb and 55.64 (54.40–56.92) pmol/g Hb, respectively. After weighting for sampling strategy, we identified that one-unit increase in natural log-HbAA, but not HbGA, was associated with reduction in body measures (body weight, body mass index (BMI), subscapular/triceps skinfold), parameters of BIA (fat-free mass, fat mass, percent body fat, total body water) and parameters of DXA (android fat mass, android percent fat, gynoid fat/lean mass, gynoid percent mass, android to gynoid ratio). Subgroup analysis showed that these associations were more evident in subjects at younger age, male gender, whites, lower education level, active smokers and those with lower BMI. Conclusions: Higher concentrations of HbAA are associated with a decrease in body composition in the US general population. Further studies are warranted to clarify this association. PMID:28287631

Android fat depot is more closely associated with metabolic syndrome than abdominal visceral fat in elderly people.

PubMed

Kang, Seon Mee; Yoon, Ji Won; Ahn, Hwa Young; Kim, So Yeon; Lee, Kyoung Ho; Shin, Hayley; Choi, Sung Hee; Park, Kyong Soo; Jang, Hak Chul; Lim, Soo

2011-01-01

Fat accumulation in android compartments may confer increased metabolic risk. The incremental utility of measuring regional fat deposition in association with metabolic syndrome (MS) has not been well described particularly in an elderly population. As part of the Korean Longitudinal Study on Health and Aging, which is a community-based cohort study of people aged more than 65 years, subjects (287 male, 75.9±8.6 years and 278 female, 76.0±8.8 years) with regional body composition data using Dual energy X-ray absorptiometry for android/gynoid area, computed tomography for visceral/subcutaneous adipose tissue (VAT/SAT), and cardiometabolic markers including adiponectin and high-sensitivity CRP were enrolled. We investigated the relationship between regional body composition and MS in multivariate regression models. Mean VAT and SAT area was 131.4±65.5 cm(2) and 126.9±55.2 cm(2) in men (P = 0.045) and 120.0±46.7 cm(2) and 211.8±65.9 cm(2) in women (P<0.01). Mean android and gynoid fat amount was 1.8±0.8 kg and 2.5±0.8 kg in men and 2.0±0.6 kg and 3.3±0.8 kg in women, respectively (both P<0.01). VAT area and android fat amount was strongly correlated with most metabolic risk factors compared to SAT or gynoid fat. Furthermore, android fat amount was significantly associated with clustering of MS components after adjustment for multiple parameters including age, gender, adiponectin, hsCRP, a surrogate marker of insulin resistance, whole body fat mass and VAT area. Our findings are consistent with the hypothesized role of android fat as a pathogenic fat depot in the MS. Measurement of android fat may provide a more complete understanding of metabolic risk associated with variations in fat distribution.

75 FR 13559 - Endocrinologic and Metabolic Drugs Advisory Committee; Notice of Meeting

Federal Register 2010, 2011, 2012, 2013, 2014

2010-03-22

... to induce and maintain a reduction of excess visceral abdominal fat in human immunodeficiency virus (HIV)-infected patients with lipodystrophy (a condition in which abnormal deposits of fat are seen...

Compassionate Use Protocol for the Treatment of Autoinflammatory Syndromes

ClinicalTrials.gov

2018-04-17

Chronic Atypical Neutrophilic Dermatosis With Lipodystrophy and Elevated Temperature (CANDLE); Juvenile Dermatomyositis (JDM); Stimulator of Interferon Genes (STING)-Associated Vasculopathy With Onset During Infancy (SAVI); Aicardi-Goutières Syndrome (AGS)

Higher serum concentrations of betaine rather than choline is associated with better profiles of DXA-derived body fat and fat distribution in Chinese adults.

PubMed

Chen, Y-M; Liu, Y; Liu, Y-H; Wang, X; Guan, K; Zhu, H-L

2015-03-01

Animal studies have suggested that betaine, but not choline, may improve body composition, but little evidence is available in humans. We examined the association of serum concentrations of choline and betaine with body composition and fat distribution in adults. This community-based study recruited 1996 adults (women/men: 1380/616) aged 40-75 years in urban Guangzhou, China. General information and anthropometric measurements were taken, and serum choline and betaine levels were assessed by high-performance liquid chromatography-tandem mass spectrometry between July 2008 and June 2010. After 3.2 years, 1623 of the 1996 participants were measured for fat mass (FM and %FM) over the total body (TB), trunk, limbs, android (A) and gynoid (G) regions. The %FM ratios of the A/G regions and the trunk and limbs were determined by dual energy X-ray absorptiometry. Univariate analyses showed that higher serum betaine levels were significantly associated with lower values of adiposity indices (all P-trends<0.05), except in the case of the %FM at the gynoid area. After adjusting for potential covariates, similar associations were observed. The mean percentage differences between quartiles 4 and 1 of the serum betaine levels were -4.9% (weight), -4.7% (body mass index, BMI), -2.5% (waist circumference), -7.9% (TB FM) and -3.4% (TB %FM). The mean differences in the FM and %FM were much more pronounced at the trunk (-10.0 and -4.5%) or android areas (-10.7 and -4.7%) than those at the limbs (-0.8 and -2.3%) or gynoid areas (-0.6 and -1.4%). Such favorable associations were stronger in men than in women. No significant associations between serum choline and the adiposity indices were observed, except in the cases of body weight and BMI. Greater circulating betaine, but not choline, was dose-dependently associated with better body composition and fat distribution due to a lower FM in the trunk regions in this population.

Android Fat Depot Is More Closely Associated with Metabolic Syndrome than Abdominal Visceral Fat in Elderly People

PubMed Central

Kang, Seon Mee; Yoon, Ji Won; Ahn, Hwa Young; Kim, So Yeon; Lee, Kyoung Ho; Shin, Hayley; Choi, Sung Hee; Park, Kyong Soo; Jang, Hak Chul; Lim, Soo

2011-01-01

Background Fat accumulation in android compartments may confer increased metabolic risk. The incremental utility of measuring regional fat deposition in association with metabolic syndrome (MS) has not been well described particularly in an elderly population. Methods and Findings As part of the Korean Longitudinal Study on Health and Aging, which is a community-based cohort study of people aged more than 65 years, subjects (287 male, 75.9±8.6 years and 278 female, 76.0±8.8 years) with regional body composition data using Dual energy X-ray absorptiometry for android/gynoid area, computed tomography for visceral/subcutaneous adipose tissue (VAT/SAT), and cardiometabolic markers including adiponectin and high-sensitivity CRP were enrolled. We investigated the relationship between regional body composition and MS in multivariate regression models. Mean VAT and SAT area was 131.4±65.5 cm2 and 126.9±55.2 cm2 in men (P = 0.045) and 120.0±46.7 cm2 and 211.8±65.9 cm2 in women (P<0.01). Mean android and gynoid fat amount was 1.8±0.8 kg and 2.5±0.8 kg in men and 2.0±0.6 kg and 3.3±0.8 kg in women, respectively (both P<0.01). VAT area and android fat amount was strongly correlated with most metabolic risk factors compared to SAT or gynoid fat. Furthermore, android fat amount was significantly associated with clustering of MS components after adjustment for multiple parameters including age, gender, adiponectin, hsCRP, a surrogate marker of insulin resistance, whole body fat mass and VAT area. Conclusions Our findings are consistent with the hypothesized role of android fat as a pathogenic fat depot in the MS. Measurement of android fat may provide a more complete understanding of metabolic risk associated with variations in fat distribution. PMID:22096613

Parental smoking during pregnancy and total and abdominal fat distribution in school-age children: the Generation R Study.

PubMed

Durmuş, B; Heppe, D H M; Taal, H R; Manniesing, R; Raat, H; Hofman, A; Steegers, E A P; Gaillard, R; Jaddoe, V W V

2014-07-01

Fetal smoke exposure may influence growth and body composition later in life. We examined the associations of maternal and paternal smoking during pregnancy with total and abdominal fat distribution in school-age children. We performed a population-based prospective cohort study among 5243 children followed from early pregnancy onward in the Netherlands. Information about parental smoking was obtained by questionnaires during pregnancy. At the median age of 6.0 years (90% range: 5.7-7.4), we measured anthropometrics, total fat and android/gynoid fat ratio by dual-energy X-ray absorptiometry, and preperitoneal and subcutaneous abdominal fat were measured by ultrasound. The associations of maternal smoking during pregnancy were only present among girls (P-value for sex interaction<0.05). Compared with girls from mothers who did not smoke during pregnancy, those from mothers who smoked during the first trimester only had a higher android/gynoid fat ratio (difference 0.23 (95% confidence interval (CI): 0.09-0.37) s.d. scores (SDS). Girls from mothers who continued smoking throughout pregnancy had a higher body mass index (difference: 0.24 (95% CI: 0.14-0.35) SDS), total fat mass (difference: 0.23 (95% CI: 0.14-0.33) SDS), android/gynoid fat ratio (difference: 0.34 (95% CI: 0.22-0.46) SDS), subcutaneous abdominal fat (difference: 0.22 (95% CI: 0.11-0.33) SDS) and preperitoneal abdominal fat (difference: 0.20 (95% CI: 0.08-0.31) SDS). Similar associations with body fat distribution outcomes were observed for paternal smoking during pregnancy. Both continued maternal and paternal smoking during pregnancy may be associated with an increased risk of childhood overweight. The corresponding odds ratios were 1.19 (95% CI: 0.98-1.46) and 1.32 (1.10-1.58), respectively. Maternal and paternal smoking during pregnancy are associated with an adverse body and abdominal fat distribution and increased risk of overweight in children. Similar effects of maternal and paternal smoking

Maternal polyunsaturated fatty acid plasma levels during pregnancy and childhood adiposity. The Generation R Study

PubMed Central

Vidakovic, Aleksandra Jelena; Gishti, Olta; Voortman, Trudy; Felix, Janine F.; Williams, Michelle A.; Hofman, Albert; Demmelmair, Hans; Koletzko, Berthold; Tiemeier, Henning; Jaddoe, Vincent WV; Gaillard, Romy

2017-01-01

Background Maternal polyunsaturated fatty acid (PUFA) levels during pregnancy may have persistent effects on growth and adiposity in the offspring. Suboptimal maternal diet during pregnancy might lead to fetal cardio-metabolic adaptations with persistent consequences in the offspring. Objective We examined the associations of maternal PUFA levels during pregnancy with childhood general and abdominal fat distribution measures. Design In a population-based prospective cohort study among 4,830 mothers and their children, we measured maternal second trimester n-3 and n-6 PUFA plasma levels. At the median age of 6.0 years (95% range, 5.6–7.9), we measured childhood body mass index, fat mass percentage, android/gynoid fat ratio with dual-energy x-ray absorptiometry, and pre-peritoneal abdominal fat area with ultrasound. Analyses were adjusted for maternal and childhood socio-demographic and lifestyle related characteristics. Results We observed that higher maternal total n-3 PUFA levels, and specifically eicosapentaenoic acid (EPA), docosapentaenoic acid (DPA), docosahexaenoic acid (DHA) levels, were associated with lower childhood total body fat percentage and lower android/gynoid fat mass ratio (p-values<0.05), but not with childhood body mass index and abdominal pre-peritoneal fat mass area. Higher maternal total n-6 PUFA levels and specifically dihomo-gamma linolenic acid (DGLA) were associated with a higher childhood total body fat percentage, android/gynoid fat mass ratio and abdominal pre-peritoneal fat mass area (p-values<0.05), but not with childhood body mass index. In line with these findings, a higher maternal n-6/n-3 PUFA ratio was associated with higher childhood total body and abdominal fat mass levels. Conclusions Lower maternal n-3 PUFA levels and higher n-6 PUFA levels during pregnancy are associated with higher total body fat and abdominal fat levels in childhood. Further studies are needed to replicate these observations and to explore the causality

Campylobacter Immunity and Quantitative Excretion Rates in Thai Children

DTIC Science & Technology

1993-01-01

vitro studies suggest that other pathogens, in- excluded if the diarrhea had lasted >3 days or jfthe patient had C 0 ~~~~~~~recently received...antibiotics. Age.smtsadciclancluding Shigella and Salmonella species and Escherichia coli. . . symptoms. and clinical and treatment data were recorded, and...ubiq- static cellulitic lesions progressing to bullae formation, skin uitous in the estuarine environment. It can cause a syndrome necrosis, necrotizin

Haplotypes in the promoter region of the CIDEC gene associated with growth traits in Nanyang cattle

USDA-ARS?s Scientific Manuscript database

Cell death-inducing DFFA-like effector c (CIDEC, also known as Fsp27) has emerged as an important regulator of metabolism associated with lipodystrophy, diabetes, and hepatic steatosis. It is required for unilocular lipid droplet formation and optimal energy storage. The mechanism between this gene ...

Vitamin D and body composition in the elderly.

PubMed

Vitezova, Anna; Muka, Taulant; Zillikens, M Carola; Voortman, Trudy; Uitterlinden, Andre G; Hofman, Albert; Rivadeneira, Fernando; Kiefte-de Jong, Jessica C; Franco, Oscar H

2017-04-01

To investigate the association between vitamin D status and body composition in the elderly. This study was embedded in the Rotterdam Study, a population-based prospective study in Rotterdam, the Netherlands, including subjects aged 55 years and older. Serum 25-hydroxyvitamin D (25(OH)D) was measured between 1997 and 1999. Total body fat, android fat, gynoid fat and lean mass were assessed using dual-energy X-ray absorptiometry (DXA) during a follow-up visit after a median time of 5 years (2002-2004). We calculated body fat percentage, lean mass percentage, and android/gynoid fat ratio. We had 2158 participants included in our analysis. We used multivariable linear regression models. Serum 25(OH)D was analyzed continuously and after categorization according to cut-offs. Mean (±SD) serum 25(OH)D concentration of the study population was 52.6 ± 25.4 nmol/L. Compared to subjects with an adequate vitamin D status (25(OH)D ≥ 75 nmol/L), vitamin D deficient participants (25(OH)D < 50 nmol/L) had a higher body fat percentage (β = 1.29, 95% CI: 0.55, 2.04) whereas no association was found with lean mass (β = 0.01, 95%CI: -0.33, 0.35). Lower 25(OH)D was associated with higher total body fat percentage specifically in participants without cardio-metabolic disease. Each 10 unit increase in serum 25(OH)D was associated with 0.03 unit decrease in android fat (β = -0.03, 95%CI: -0.06, -0.01); after adjustment for BMI the association was no longer significant. Serum 25(OH)D was also associated with the android/gynoid fat ratio but this was also mainly explained by BMI. Lower serum 25(OH)D concentrations were associated with a higher fat mass percentage. The association between serum 25(OH)D and differential fat distribution in the elderly was mainly explained by BMI and deserves further study. Copyright © 2016 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.

Genetics Home Reference: congenital generalized lipodystrophy

MedlinePlus

... childhood. One of the most common features is insulin resistance, a condition in which the body's tissues are ... that normally helps to regulate blood sugar levels. Insulin resistance may develop into a more serious disease called ...

[The use of growth hormone to treat endocrine-metabolic disturbances in acquired immunodeficiency syndrome (AIDS) patients].

PubMed

Spinola-Castro, Angela Maria; Siviero-Miachon, Adriana A; da Silva, Marcos Tadeu Nolasco; Guerra-Junior, Gil

2008-07-01

Acquired Immunodeficiency Syndrome (Aids) was initially related to HIV-associated wasting syndrome, and its metabolic disturbances to altered body composition. After Highly Active Antiretroviral Therapy (HAART) was started, malnutrition has declined and HIV-associated lipodystrophy syndrome has emerged as an important metabolic disorder. Aids is also characterized by hormonal disturbances, principally in growth hormone/insulin-like growth factor 1 (GH/IGF-1) axis. The use of recombinant human GH (hrGH) was formerly indicated to treat wasting syndrome, in order to increase lean body mass. Even though the use of hrGH in lipodystrophy syndrome has been considered, the decrease in insulin sensitivity is a limitation for its use, which has not been officially approved yet. Diversity in therapeutic regimen is another limitation to its use in Aids patients. The present study has reviewed the main HIV-related endocrine-metabolic disorders as well as the use of hrGH in such conditions.

Lipodystrophic syndromes due to LMNA mutations: recent developments on biomolecular aspects, pathophysiological hypotheses and therapeutic perspectives

PubMed Central

Vigouroux, Corinne; Guénantin, Anne-Claire; Vatier, Camille; Le Dour, Caroline; Afonso, Pauline; Bidault, Guillaume; Béréziat, Véronique; Lascols, Olivier; Capeau, Jacqueline; Briand, Nolwenn; Jéru, Isabelle

2018-01-01

Abstract Mutations in LMNA, encoding A-type lamins, are responsible for laminopathies including muscular dystrophies, lipodystrophies, and premature ageing syndromes. LMNA mutations have been shown to alter nuclear structure and stiffness, binding to partners at the nuclear envelope or within the nucleoplasm, gene expression and/or prelamin A maturation. LMNA-associated lipodystrophic features, combining generalized or partial fat atrophy and metabolic alterations associated with insulin resistance, could result from altered adipocyte differentiation or from altered fat structure. Recent studies shed some light on how pathogenic A-type lamin variants could trigger lipodystrophy, metabolic complications, and precocious cardiovascular events. Alterations in adipose tissue extracellular matrix and TGF-beta signaling could initiate metabolic inflexibility. Premature senescence of vascular cells could contribute to cardiovascular complications. In affected families, metabolic alterations occur at an earlier age across generations, which could result from epigenetic deregulation induced by LMNA mutations. Novel cellular models recapitulating adipogenic developmental pathways provide scalable tools for disease modeling and therapeutic screening. PMID:29578370

Formulation and Evaluation of Organogels Containing Hyaluronan Microparticles for Topical Delivery of Caffeine.

PubMed

Simsolo, Erol Eli; Eroğlu, İpek; Tanrıverdi, Sakine Tuncay; Özer, Özgen

2018-04-01

Cellulite is a dermal disorder including the extracellular matrix, the lymphatic and microcirculatory systems and the adipose tissue. Caffeine is used as the active moiety depending its preventive effect on localization of fat in the cellular structure. Hyaluronic acid (hyaluronan-HA) is a natural constituent of skin that generates formation and poliferation of new cells having a remarkable moisturizing ability. The aim of this study is to formulate HA microparticles loaded with caffeine via spray-drying method. Resulting microparticle formulations (33.97 ± 0.3 μm, span < 2, 88.56 ± 0.42% encapsulation efficiency) were distributed in lecithin organogels to maintain the proper viscosity for topical application. Following the characterization and cell culture studies, in vitro drug release and ex vivo permeation studies were performed. The accumulated amount of caffeine was twice higher than the aqueous solution for the microparticle-loaded organogels at 24 h (8262,673 μg/cm 2 versus 4676,691 μg/cm 2 ). It was related to the sustained behaviour of caffeine release from the microparticles. As a result, lecithin organogel containing HA-encapsulated microparticles could be considered as suitable candidate formulations for efficient topical drug delivery system of caffeine. In addition to that, synergistic effect of this combination appears as a promising approach for long-acting treatment of cellulite.

Differences in regional adiposity, bone mineral density, and physical exercise participation based on exercise self-efficacy among senior adults.

PubMed

Glenn, J M; Gray, M; Vincenzo, J L

2015-10-01

The impact of exercise self-efficacy levels (ESE) on exercise participation, levels of body fat (BF), and bone mineral density (BMD) are unclear in senior-aged adults. The purpose of this study was to investigate effects of ESE on exercise participation, regional distribution of BF, and BMD among seniors. Senior adults (N.=76; 36 males, 40 females) were separated into tertiles (T1, age=60.4±1.4; T2, age=61.3±1.4; T3, age=60.4±1.5) based on self-reported levels of ESE. BMD and regional BF were measured using dual-energy x-ray absorptiometry and exercise participation levels were measured using the Rapid Physical-Activity Questionnaire. MANOVA revealed a significant Wilks Lambda (p < 0.001) and univariate analysis was completed for exercise participation levels, android BF, gynoid BF, and spinal BMD. ANOVA revealed T3 was significantly lower for android BF (p=0.002) than T1 and T2 (30% and 26%, respectively) while gynoid BF was significantly lower (p=0.012) for T3 (24%) compared to T1. When evaluating exercise participation levels, T3 was significantly higher (p < 0.001) than T1 or T2. Spinal BMD was significantly higher (p=0.030) between T2 (10%) and T1. ESE is an important factor in senior adults ability to maintain longitudinal health.

Mapping disease-related missense mutations in the immunoglobulin-like fold domain of lamin A/C reveals novel genotype-phenotype associations for laminopathies.

PubMed

Scharner, Juergen; Lu, Hui-Chun; Fraternali, Franca; Ellis, Juliet A; Zammit, Peter S

2014-06-01

Mutations in A-type nuclear lamins cause laminopathies. However, genotype-phenotype correlations using the 340 missense mutations within the LMNA gene are unclear: partially due to the limited availability of three-dimensional structure. The immunoglobulin (Ig)-like fold domain has been solved, and using bioinformatics tools (including Polyphen-2, Fold X, Parameter OPtimized Surfaces, and PocketPicker) we characterized 56 missense mutations for position, surface exposure, change in charge and effect on Ig-like fold stability. We find that 21 of the 27 mutations associated with a skeletal muscle phenotype are distributed throughout the Ig-like fold, are nonsurface exposed and predicted to disrupt overall stability of the Ig-like fold domain. Intriguingly, the remaining 6 mutations clustered, had higher surface exposure, and did not affect stability. The majority of 9 lipodystrophy or 10 premature aging syndrome mutations also did not disrupt Ig-like fold domain stability and were surface exposed and clustered in distinct regions that overlap predicted binding pockets. Although buried, the 10 cardiac mutations had no other consistent properties. Finally, most lipodystrophy and premature aging mutations resulted in a -1 net charge change, whereas skeletal muscle mutations caused no consistent net charge changes. Since premature aging, lipodystrophy and the subset of 6 skeletal muscle mutations cluster tightly in distinct, charged regions, they likely affect lamin A/C -protein/DNA/RNA interactions: providing a consistent genotype-phenotype relationship for mutations in this domain. Thus, this subgroup of skeletal muscle laminopathies that we term the 'Skeletal muscle cluster', may have a distinct pathological mechanism. These novel associations refine the ability to predict clinical features caused by certain LMNA missense mutations. © 2013 Wiley Periodicals, Inc.

Arabidopsis SEIPIN proteins modulate triacylglycerol accumulation and influence lipid droplet proliferation

USDA-ARS?s Scientific Manuscript database

The lipodystrophy protein SEIPIN is important for lipid droplet (LD) biogenesis in human and yeast cells. By contrast to the single SEIPIN genes in humans and yeast, there are three SEIPIN homologues in Arabidopsis thaliana, designated At-SEIPIN1, At-SEIPIN2 and At-SEIPIN3. Here, a yeast (Saccharomy...

Deiodinase 2 expression is increased in dorsocervical fat of patients with HIV-associated lipohypertrophy syndrome.

PubMed

Torriani, Martin; Fitch, Kathleen; Stavrou, Eleni; Bredella, Miriam A; Lim, Ruth; Sass, Christina A; Cypess, Aaron M; Grinspoon, Steven

2012-04-01

The pathogenesis and function of dorsocervical sc adipose tissue (DSAT) accumulation in HIV-infected patients is not known. Previous investigations using either UCP-1 expression or positron emission tomography have been inconclusive as to whether this depot represents brown adipose tissue (BAT). We investigated DSAT gene expression, including DIO2, a deiodinase that contributes to increased thermogenesis in brown fat, and simultaneously determined [¹⁸F]fluorodeoxyglucose ([¹⁸F]FDG) uptake in lipodystrophic HIV and healthy control subjects. Thirteen HIV-infected and three non-HIV-infected men were recruited. HIV-infected subjects had evidence of significant lipodystrophy, including fat atrophy of the face, arms, and legs, and/or fat accumulation of the neck and abdomen. Subjects were cooled, followed by [¹⁸F]FDG positron emission tomography/computed tomography, fat biopsy of DSAT, and measurement of resting energy expenditure (REE). HIV-infected subjects were characterized as lipohypertrophic and lipoatrophic and compared. Mean standardized uptake value of [¹⁸F]FDG and UCP-1 expression were not significantly different in DSAT among the groups. However, lipohypertrophic subjects demonstrated increased expression of DIO2 in DSAT compared with lipoatrophic subjects (P = 0.03). Among HIV-infected patients, DIO2 expression was strongly related to REE (r = 0.78, P = 0.002) and was a predictor of REE in multivariate modeling controlling for age, TSH, and lean body mass (r² = 0.79, P = 0.008). One control subject demonstrated typical BAT in the supraclavicular area. Adipose tissue accumulating in the dorsocervical area in HIV lipodystrophy does not appear to be classical BAT. However, DIO2 expression is increased in DSAT among patients with HIV lipodystrophy, particularly those with increased visceral adiposity, and is positively associated with energy expenditure.

Metabolic, Reproductive, and Neurologic Abnormalities in Agpat1-Null Mice.

PubMed

Agarwal, Anil K; Tunison, Katie; Dalal, Jasbir S; Nagamma, Sneha S; Hamra, F Kent; Sankella, Shireesha; Shao, Xinli; Auchus, Richard J; Garg, Abhimanyu

2017-11-01

Defects in the biosynthesis of phospholipids and neutral lipids are associated with cell membrane dysfunction, disrupted energy metabolism, and diseases including lipodystrophy. In these pathways, the 1-acylglycerol-3-phosphate O-acyltransferase (AGPAT) enzymes transfer a fatty acid to the sn-2 carbon of sn-1-acylglycerol-3-phosphate (lysophosphatidic acid) to form sn-1, 2-acylglycerol-3-phosphate [phosphatidic acid (PA)]. PA is a precursor for key phospholipids and diacylglycerol. AGPAT1 and AGPAT2 are highly homologous isoenzymes that are both expressed in adipocytes. Genetic defects in AGPAT2 cause congenital generalized lipodystrophy, indicating that AGPAT1 cannot compensate for loss of AGPAT2 in adipocytes. To further explore the physiology of AGPAT1, we characterized a loss-of-function mouse model (Agpat1-/-). The majority of Agpat1-/- mice died before weaning and had low body weight and low plasma glucose levels, independent of plasma insulin and glucagon levels, with reduced percentage of body fat but not generalized lipodystrophy. These mice also had decreased hepatic messenger RNA expression of Igf-1 and Foxo1, suggesting a decrease in gluconeogenesis. In male mice, sperm development was impaired, with a late meiotic arrest near the onset of round spermatid production, and gonadotropins were elevated. Female mice showed oligoanovulation yet retained responsiveness to gonadotropins. Agpat1-/- mice also demonstrated abnormal hippocampal neuron development and developed audiogenic seizures. In summary, Agpat1-/- mice developed widespread disturbances of metabolism, sperm development, and neurologic function resulting from disrupted phospholipid homeostasis. AGPAT1 appears to serve important functions in the physiology of multiple organ systems. The Agpat1-deficient mouse provides an important model in which to study the contribution of phospholipid and triacylglycerol synthesis to physiology and diseases. Copyright © 2017 Endocrine Society.

Microalbuminuria in obese patients with or without hypertension.

PubMed

Valensi, P; Assayag, M; Busby, M; Pariès, J; Lormeau, B; Attali, J R

1996-06-01

To evaluate the prevalence in obese patients of an increased urinary albumin excretion rate (UAER) and the factors involved in this parameter. Two hundred and seven nondiabetic obese patients with BMI = 34.7 +/- 5.7 (SD) kg/m2. None had proteinuria or a history of nephropathy or uropathy. Fifty-two had moderate hypertension. A control group of 22 lean healthy subjects was also studied. The UAER was determined from 24-h urine samples by means of immunonephelemetry laser method. Creatinine clearance was calculated. Glycemia and plasma C peptide at fasting and 120 mine after glucose oral administration, HbA1c, serum fructosamine, plasma total cholesterol and triglycerides, HDL and LDL cholesterol were measured. Food intakes were determined by dietary history. Compared with the control group, the UAER was significantly higher in the obese patients (18.0 +/- 20.1 mg/24 h vs 3.2 +/- 2.8 mg/24 h, P < 0.0001). It was elevated (> 30 mg/24 h) in 25 obese patients (12.1%) and in particular, in 19.2% of the obese patients with hypertension. It was significantly higher in the patients with android or mixed (both android and gynoid) obesity than in those with gynoid obesity (p = 0.050). Log UAER correlated negatively with the duration of hypertension (p = 0.038) and was higher in the patients with familial hypertension than in those without (p = 0.002). Log UAER correlated strongly with log creatinine clearance (p < 0.0001) and fractional albumin clearance (p < 0.0001). It correlated significantly with fasting and 120 min after glucose plasma C peptide concentrations (p = 0.018 and p = 0.046, respectively). Creatinine clearance was significantly higher in the patients with android or mixed obesity than in those with gynoid obesity (p = 0.001). Log creatinine clearance correlated negatively with age (p = 0.046), and log LDL cholesterol (p = 0.025) and positively with log lipid caloric intake (p = 0.014). These results show the high prevalence of microalbuminuria in nondiabetic

Long-Term Supplementation of Green Tea Extract Does Not Modify Adiposity or Bone Mineral Density in a Randomized Trial of Overweight and Obese Postmenopausal Women1234

PubMed Central

Dostal, Allison M; Arikawa, Andrea; Espejo, Luis; Kurzer, Mindy S

2016-01-01

Background: Green tea extract (GTE) consumption has been linked to favorable changes in adiposity and bone mineral density (BMD), although it is unknown if these effects are due to green tea catechins or caffeine. The catechol-O-methyltransferase (COMT) genotype may also modify these associations. Objective: We examined the impact of decaffeinated GTE on body composition (using dual-energy X-ray absorptiometry) and obesity-associated hormones. Methods: The Minnesota Green Tea Trial was a 12-mo randomized, double-blind, placebo-controlled clinical trial in 937 postmenopausal women (aged 50–70 y) assigned to receive either GTE containing 843 mg (−)-epigallocatechin-3-gallate or placebo. This substudy was conducted in 121 overweight/obese participants [body mass index (BMI) (kg/m2) ≥25.0]. Results: There were no differences in changes in BMI (−0.13 ± 0.11 compared with −0.05 ± 0.11; P = 0.61), total fat mass (−0.30 ± 0.16 compared with −0.12 ± 0.15 kg; P = 0.40), percentage of body fat (−0.15% ± 0.17% compared with −0.15% ± 0.16%; P = 0.99), or BMD (−0.006 ± 0.002 compared with −0.003 ± 0.002 g/cm2; P = 0.49) over 12 mo between women taking GTE (n = 61) and those taking a placebo (n = 60). Interactions were observed between treatment and time for gynoid percentage of fat (%fat) and tissue %fat. Gynoid %fat increased from baseline to month 12 in the placebo group as baseline BMI increased and decreased over time as baseline BMI increased in the GTE group (P-interaction = 0.02). Tissue %fat increased from baseline to month 12 in the placebo group as baseline BMI increased. In the GTE group, tissue %fat decreased during the intervention as baseline BMI increased (P-interaction = 0.04). No changes were seen in circulating leptin, ghrelin, adiponectin, or insulin concentrations. COMT genotype did not modify the effect of GTE on any variable. Conclusions: Decaffeinated GTE was not associated with overall reductions in adiposity or improvements

'Laminopathies': A wide spectrum of human diseases

DOE Office of Scientific and Technical Information (OSTI.GOV)

Worman, Howard J.; Bonne, Gisele; Universite Pierre et Marie Curie-Paris 6, Faculte de medecine, Paris F-75013

2007-06-10

Mutations in genes encoding the intermediate filament nuclear lamins and associated proteins cause a wide spectrum of diseases sometimes called 'laminopathies.' Diseases caused by mutations in LMNA encoding A-type lamins include autosomal dominant Emery-Dreifuss muscular dystrophy and related myopathies, Dunnigan-type familial partial lipodystrophy, Charcot-Marie-Tooth disease type 2B1 and developmental and accelerated aging disorders. Duplication in LMNB1 encoding lamin B1 causes autosomal dominant leukodystrophy and mutations in LMNB2 encoding lamin B2 are associated with acquired partial lipodystrophy. Disorders caused by mutations in genes encoding lamin-associated integral inner nuclear membrane proteins include X-linked Emery-Dreifuss muscular dystrophy, sclerosing bone dysplasias, HEM/Greenberg skeletal dysplasiamore » and Pelger-Huet anomaly. While mutations and clinical phenotypes of 'laminopathies' have been carefully described, data explaining pathogenic mechanisms are only emerging. Future investigations will likely identify new 'laminopathies' and a combination of basic and clinical research will lead to a better understanding of pathophysiology and the development of therapies.« less

Comparable Effects of High-Intensity Interval Training and Prolonged Continuous Exercise Training on Abdominal Visceral Fat Reduction in Obese Young Women.

PubMed

Zhang, Haifeng; Tong, Tom K; Qiu, Weifeng; Zhang, Xu; Zhou, Shi; Liu, Yang; He, Yuxiu

2017-01-01

This study compared the effect of prolonged moderate-intensity continuous training (MICT) on reducing abdominal visceral fat in obese young women with that of work-equivalent (300 kJ/training session) high-intensity interval training (HIIT). Forty-three participants received either HIIT ( n = 15), MICT ( n = 15), or no training (CON, n = 13) for 12 weeks. The abdominal visceral fat area (AVFA) and abdominal subcutaneous fat area (ASFA) of the participants were measured through computed tomography scans preintervention and postintervention. Total fat mass and the fat mass of the android, gynoid, and trunk regions were assessed through dual-energy X-ray absorptiometry. Following HIIT and MICT, comparable reductions in AVFA (-9.1, -9.2 cm 2 ), ASFA (-35, -28.3 cm 2 ), and combined AVFA and ASFA (-44.7, -37.5 cm 2 , p > 0.05) were observed. Similarly, reductions in fat percentage (-2.5%, -2.4%), total fat mass (-2.8, -2.8 kg), and fat mass of the android (-0.3, -0.3 kg), gynoid (-0.5, -0.7 kg), and trunk (-1.6, -1.2 kg, p > 0.05) regions did not differ between HIIT and MICT. No variable changed in CON. In conclusion, MICT consisting of prolonged sessions has no quantitative advantage, compared with that resulting from HIIT, in abdominal visceral fat reduction. HIIT appears to be the predominant strategy for controlling obesity because of its time efficiency.

[Some concerns and semantic confusions about feminine skin].

PubMed

Piérard, G E; Piérard-Franchimont, C

1999-04-01

Some characteristics of the skin are badly perceived by women living in a society where youth and idealized physical aspect are respected as a cult. Among the most frequent concerns, one should cite dry skin, wrinkles, striae distensae, cellulite, diffuse hair loss, hyperpilosity, as well as the unwanted effects of menopause and of the immoderate exposure to sun and sunbeds. Most of these concerns are subject to semantic confusions sustained by some medias. They are frequently targets of a worldwide ballyhoo conveyed to the general public without the support of sound physiopathological basis.

Low-level laser therapy for fat layer reduction: a comprehensive review.

PubMed

Avci, Pinar; Nyame, Theodore T; Gupta, Gaurav K; Sadasivam, Magesh; Hamblin, Michael R

2013-08-01

Low-level laser (light) therapy (LLLT) is a noninvasive, nonthermal approach to disorders requiring reduction of pain and inflammation and stimulation of healing and tissue regeneration. Within the last decade, LLLT started being investigated as an adjuvant to liposuction, for noninvasive body contouring, reduction of cellulite, and improvement of blood lipid profile. LLLT may also aid autologous fat transfer procedures by enhancing the viability of adipocytes. However the underlying mechanism of actions for such effects still seems to be unclear. It is important, therefore, to understand the potential efficacy and proposed mechanism of actions of this new procedure for fat reduction. A review of the literature associated with applications of LLLT related to fat layer reduction was performed to evaluate the findings from pre-clinical and clinical studies with respect to the mechanism of action, efficacy, and safety. The studies as of today suggest that LLLT has a potential to be used in fat and cellulite reduction as well as in improvement of blood lipid profile without any significant side effects. One of the main proposed mechanism of actions is based upon production of transient pores in adipocytes, allowing lipids to leak out. Another is through activation of the complement cascade which could cause induction of adipocyte apoptosis and subsequent release of lipids. Although the present studies have demonstrated safety and efficacy of LLLT in fat layer reduction, studies demonstrating the efficacy of LLLT as a stand-alone procedure are still inadequate. Moreover, further studies are necessary to identify the mechanism of action. Copyright © 2013 Wiley Periodicals, Inc.

Low-Level Laser Therapy for Fat Layer Reduction: A Comprehensive Review

PubMed Central

Avci, Pinar; Nyame, Theodore T.; Gupta, Gaurav K.; Sadasivam, Magesh; Hamblin, Michael R.

2013-01-01

Background and Objective Low-level laser (light) therapy (LLLT) is a noninvasive, nonthermal approach to disorders requiring reduction of pain and inflammation and stimulation of healing and tissue regeneration. Within the last decade, LLLT started being investigated as an adjuvant to liposuction, for noninvasive body contouring, reduction of cellulite, and improvement of blood lipid profile. LLLT may also aid autologous fat transfer procedures by enhancing the viability of adipocytes. However the underlying mechanism of actions for such effects still seems to be unclear. It is important, therefore, to understand the potential efficacy and proposed mechanism of actions of this new procedure for fat reduction. Materials and Methods A review of the literature associated with applications of LLLT related to fat layer reduction was performed to evaluate the findings from pre-clinical and clinical studies with respect to the mechanism of action, efficacy, and safety. Results The studies as of today suggest that LLLT has a potential to be used in fat and cellulite reduction as well as in improvement of blood lipid profile without any significant side effects. One of the main proposed mechanism of actions is based upon production of transient pores in adipocytes, allowing lipids to leak out. Another is through activation of the complement cascade which could cause induction of adipocyte apoptosis and subsequent release of lipids. Conclusion Although the present studies have demonstrated safety and efficacy of LLLT in fat layer reduction, studies demonstrating the efficacy of LLLT as a stand-alone procedure are still inadequate. Moreover, further studies are necessary to identify the mechanism of action. PMID:23749426

Soy sauce allergy.

PubMed

Sugiura, K; Sugiura, M

2010-07-01

Soy sauce is well-known as a Japanese traditional seasoning, namely shoyu. Usually, shoyu means sauce made from soy. Shoyu does have not only benefits but also adverse effects. Soy sauce allergy which is not caused by soy or wheat allergy is rare. Our four patients developed cellulites and dermatitis around lips with irritation after a meal with shoyu. The age of the patients was 10, 35, 46 and 51 years; they were all female. These inflammations can be developed by two causes; first it can be caused by allergic reactions to shoyu; the second, it can be caused by histamine poisoning. It is important to determine whether inflammation is caused by allergic reactions or histamine poisoning. We determined the volume of histamine in some sauces and performed prick test and laboratory tests. Four patients had positive reactions by prick test after using some sauces. We suspected that histamine caused their symptoms, but nine normal volunteers had negative reactions. Patient's specific IgE score to soy and wheat was class 0. The results showed that the sauce made from soybean and broad bean contained histamine, but histamine in other sauces was not detected. In this study, we confirmed by prick test, four cases of soy sauce allergy, which was caused by some products during brewing. When patients with inflammations around mouth, after a meal containing or using soy sauce, are examined, it should be considered whether dermatitis or cellulites were developed by allergic reaction or by histamine poisoning.

Associations of Dispositional Mindfulness with Obesity and Central Adiposity: the New England Family Study

PubMed Central

Britton, Willoughby B.; Howe, Chanelle J.; Gutman, Roee; Gilman, Stephen E.; Brewer, Judson; Eaton, Charles B.; Buka, Stephen L.

2016-01-01

Purpose To evaluate whether dispositional mindfulness (defined as the ability to attend nonjudgmentally to one’s own physical and mental processes) is associated with obesity and central adiposity. Methods Study participants (n=394) were from the New England Family Study, a prospective birth cohort, with median age 47 years. Dispositional mindfulness was assessed using the Mindful Attention Awareness Scale (MAAS). Central adiposity was assessed using dual-energy X-ray absorptiometry (DXA) scans with primary outcomes android fat mass and android/gynoid ratio. Obesity was defined as body mass index ≥30 kg/m2. Results Multivariable-adjusted regression analyses demonstrated that participants with low vs. high MAAS scores were more likely to be obese (prevalence ratio for obesity= 1.34 (95 % confidence limit (CL): 1.02, 1.77)), adjusted for age, gender, race/ethnicity, birth weight, childhood socioeconomic status, and childhood intelligence. Furthermore, participants with low vs. high MAAS level had a 448 (95 % CL 39, 857) g higher android fat mass and a 0.056 (95 % CL 0.003, 0.110) greater android/gynoid fat mass ratio. Prospective analyses demonstrated that participants who were not obese in childhood and became obese in adulthood (n=154) had −0.21 (95 % CL −0.41, −0.01; p=0.04) lower MAAS scores than participants who were not obese in childhood or adulthood (n=203). Conclusions Dispositional mindfulness may be inversely associated with obesity and adiposity. Replication studies are needed to adequately establish whether low dispositional mindfulness is a risk factor for obesity and adiposity. PMID:26481650

Comparable Effects of High-Intensity Interval Training and Prolonged Continuous Exercise Training on Abdominal Visceral Fat Reduction in Obese Young Women

PubMed Central

Zhang, Haifeng; Tong, Tom K.; Qiu, Weifeng; Zhang, Xu; Zhou, Shi

2017-01-01

This study compared the effect of prolonged moderate-intensity continuous training (MICT) on reducing abdominal visceral fat in obese young women with that of work-equivalent (300 kJ/training session) high-intensity interval training (HIIT). Forty-three participants received either HIIT (n = 15), MICT (n = 15), or no training (CON, n = 13) for 12 weeks. The abdominal visceral fat area (AVFA) and abdominal subcutaneous fat area (ASFA) of the participants were measured through computed tomography scans preintervention and postintervention. Total fat mass and the fat mass of the android, gynoid, and trunk regions were assessed through dual-energy X-ray absorptiometry. Following HIIT and MICT, comparable reductions in AVFA (−9.1, −9.2 cm2), ASFA (−35, −28.3 cm2), and combined AVFA and ASFA (−44.7, −37.5 cm2, p > 0.05) were observed. Similarly, reductions in fat percentage (−2.5%, −2.4%), total fat mass (−2.8, −2.8 kg), and fat mass of the android (−0.3, −0.3 kg), gynoid (−0.5, −0.7 kg), and trunk (−1.6, −1.2 kg, p > 0.05) regions did not differ between HIIT and MICT. No variable changed in CON. In conclusion, MICT consisting of prolonged sessions has no quantitative advantage, compared with that resulting from HIIT, in abdominal visceral fat reduction. HIIT appears to be the predominant strategy for controlling obesity because of its time efficiency. PMID:28116314

Effects of Different Resistance Training Frequencies on Fat in Overweight/Obese Older Women.

PubMed

Cavalcante, Edilaine F; Ribeiro, Alex S; do Nascimento, Matheus A; Silva, Analiza M; Tomeleri, Crisieli M; Nabuco, Hellen C G; Pina, Fábio L C; Mayhew, Jerry L; Da Silva-Grigoletto, Marzo E; da Silva, Danilo R P; Fleck, Steven J; Cyrino, Edilson S

2018-05-18

This study compared the effect of different resistance training (RT) frequencies on total, android, gynoid and trunk body fat in overweight/obese older women. Fifty-seven overweight/obese older women (66.9±5.3 years and 39.9±4.9% body fat) were randomly assigned to one of three groups: a group performing RT twice a week (G2X), a group performing RT three times a week (G3X), or a non-exercise control group (CG). Both training groups performed the same 12-week RT program consisting of 8 exercises that trained all major muscle groups. Dual-energy X-ray absorptiometry was used to assess body composition. After the intervention period, both G2X and G3X demonstrated significant (P<0.05) reductions in adiposity compared to the CG for total body fat (G2X=-1.7%, G3X=-2.7%, CG=+2.1%), android fat (G2X=-6.2%, G3X=-7.0%, CG=+8.6%), gynoid fat (G2X=-2.5%, G3X=-2.9%, CG=+1.0%), and trunk fat (G2X=-2.5%, G3X=-3.0%, CG=+2.9%), with no significant differences between training groups. These results demonstrate that a low-volume 12-week RT program performed two or three times per week causes decreases in total and regional fat deposition with the greatest reductions occurring in the android region. © Georg Thieme Verlag KG Stuttgart · New York.

Association of APOC3 polymorphisms with both dyslipidemia and lipoatrophy in HAART-receiving patients.

PubMed

Bonnet, Eric; Bernard, Jacques; Fauvel, Josette; Massip, Patrice; Ruidavets, Jean-Bernard; Perret, Bertrand

2008-02-01

The incidence and the magnitude of lipodystrophy and dyslipidemia in HIV-treated people reported in previous studies are very variable. Several predisposing factors have been identified, but there are few data on genetic factors. To search for a correlation between APOC3 polymorphisms and lipid disorders and lipodystrophy in HIV patients under d4T and protease inhibitors (PI)-containing HAART, we designed a monocenter, cross-sectional study in a University Hospital in Southern France during the period 2001-2004. Forty patients under HAART were included, with d4T for > or = 2 years and PI for > or = 1 year. We determined body mass composition by DXA, lipoprotein markers, and the -455/-482 apo C3 genotypes. Carriers of APOC3 variant alleles (-455 1/-482 1) displayed higher levels of triglycerides (3.72 vs. 2.57 mmol/liter), apo C3 (45.3 vs. 34.5 mg/liter), and apo E (130.2 vs. 66.5 mg/liter) and a lower fat mass (13.9 vs. 19.7%) than patients with nonvariant alleles (-455 0/-482 0). APOC3 polymorphisms might be associated with both dyslipidemia and lipoatrophy in HAART-treated patients.

Adipose tissue mitochondrial dysfunction triggers a lipodystrophic syndrome with insulin resistance, hepatosteatosis, and cardiovascular complications.

PubMed

Vernochet, Cecile; Damilano, Federico; Mourier, Arnaud; Bezy, Olivier; Mori, Marcelo A; Smyth, Graham; Rosenzweig, Anthony; Larsson, Nils-Göran; Kahn, C Ronald

2014-10-01

Mitochondrial dysfunction in adipose tissue occurs in obesity, type 2 diabetes, and some forms of lipodystrophy, but whether this dysfunction contributes to or is the result of these disorders is unknown. To investigate the physiological consequences of severe mitochondrial impairment in adipose tissue, we generated mice deficient in mitochondrial transcription factor A (TFAM) in adipocytes by using mice carrying adiponectin-Cre and TFAM floxed alleles. These adiponectin TFAM-knockout (adipo-TFAM-KO) mice had a 75-81% reduction in TFAM in the subcutaneous and intra-abdominal white adipose tissue (WAT) and interscapular brown adipose tissue (BAT), causing decreased expression and enzymatic activity of proteins in complexes I, III, and IV of the electron transport chain (ETC). This mitochondrial dysfunction led to adipocyte death and inflammation in WAT and a whitening of BAT. As a result, adipo-TFAM-KO mice were resistant to weight gain, but exhibited insulin resistance on both normal chow and high-fat diets. These lipodystrophic mice also developed hypertension, cardiac hypertrophy, and cardiac dysfunction. Thus, isolated mitochondrial dysfunction in adipose tissue can lead a syndrome of lipodystrophy with metabolic syndrome and cardiovascular complications. © FASEB.

Lifespan extension by dietary intervention in a mouse model of Cockayne syndrome uncouples early postnatal development from segmental progeria.

PubMed

Brace, Lear E; Vose, Sarah C; Vargas, Dorathy F; Zhao, Shuangyun; Wang, Xiu-Ping; Mitchell, James R

2013-12-01

Cockayne syndrome (CS) is a rare autosomal recessive segmental progeria characterized by growth failure, lipodystrophy, neurological abnormalities, and photosensitivity, but without skin cancer predisposition. Cockayne syndrome life expectancy ranges from 5 to 16 years for the two most severe forms (types II and I, respectively). Mouse models of CS have thus far been of limited value due to either very mild phenotypes, or premature death during postnatal development prior to weaning. The cause of death in severe CS models is unknown, but has been attributed to extremely rapid aging. Here, we found that providing mutant pups with soft food from as late as postnatal day 14 allowed survival past weaning with high penetrance independent of dietary macronutrient balance in a novel CS model (Csa(-/-) | Xpa(-/-)). Survival past weaning revealed a number of CS-like symptoms including small size, progressive loss of adiposity, and neurological symptoms, with a maximum lifespan of 19 weeks. Our results caution against interpretation of death before weaning as premature aging, and at the same time provide a valuable new tool for understanding mechanisms of progressive CS-related progeroid symptoms including lipodystrophy and neurodysfunction. © 2013 the Anatomical Society and John Wiley & Sons Ltd.

Noncosmetic applications of liposuction.

PubMed

Coleman, W P

1988-10-01

Noncosmetic applications of liposuction have continued to appear since its introduction into the United States in 1982. Although the most common use is in removing lipomas, liposuction has also been used for benign symmetric lipomatosis, flap undermining, flap defatting, gynecomastia, pseudogynecomastia, breast reduction, buffalo hump, hypertrophic insulin lipodystrophy, lymphedema, evacuating hematomas, emergency neck defatting for airway restoration, and axillary hyperhidrosis. Other uses remain to be discovered.

Effects of Weight Loss with and without Exercise on Regional Body Fat Distribution in Postmenopausal Women.

PubMed

Serra, Monica C; Blumenthal, Jacob B; Addison, Odessa R; Miller, Ann J; Goldberg, Andrew P; Ryan, Alice S

2017-01-01

The purpose was to determine whether lifestyle interventions have different effects on regional fat in women with normal glucose tolerance vs. impaired glucose tolerance (NGT vs. IGT). Changes in glucose metabolism (2-h oral glucose-tolerance tests), android to gynoid fat mass ratio (dual energy X-ray absorptiometry [DXA]), visceral to subcutaneous abdominal fat area ratio (CT), and abdominal to gluteal subcutaneous fat cell weight (FCW; adipose tissue biopsies) were determined in 60 overweight postmenopausal women (45-80 years) following 6 months of weight loss alone (WL; n = 28) or with aerobic exercise (AEX + WL; n = 32). The interventions led to ∼8% decrease in weight, but only the AEX + WL group improved fitness (↑11% in VO2max) and reduced the android-to-gynoid fat mass ratio (↓5%; p < 0.05). Both NGT and IGT groups reduced visceral and subcutaneous abdominal fat areas and abdominal and gluteal FCWs, which related to improvements in homeostatic model assessment (r = 0.34-0.42) and 2-h glucose (r = 0.34-0.35), respectively (p < 0.05). The decline in FCW was 2× greater in women with IGT following WL (p < 0.05). The ratios of abdominal-to-gluteal FCW did not change following either intervention. The mechanisms by which WL with and without exercise impact regional fat loss should be explored as reductions in abdominal fat area and subcutaneous FCW appear to influence glucose metabolism. This is a work of the U.S. Government and is not subject to copyright protection in the United States. Foreign copyrights may apply. Published by S. Karger AG, Basel.

Maternal haemoglobin levels and cardio-metabolic risk factors in childhood: the Generation R study.

PubMed

Welten, M; Gaillard, R; Hofman, A; de Jonge, L L; Jaddoe, V W V

2015-05-01

To assess whether variations in maternal haemoglobin levels during pregnancy are associated with cardio-metabolic risk factors in school age children. Population-based prospective cohort study. Rotterdam, The Netherlands, 2002-2012. Mothers and children (n = 5002) participating in the Generation R Study. We obtained maternal haemoglobin levels during early pregnancy (median gestational age 14.6 weeks [95% range 10.3, 25.3]) from venous blood samples. Maternal anaemia and elevated haemoglobin levels were based on World Health Organization criteria. We measured childhood cardio-metabolic risk factors at age 6 years. Cardio-metabolic risk factors included body mass index, total fat mass percentage, android/gynoid fat mass ratio, systolic and diastolic blood pressure, left ventricular mass, and blood levels of cholesterol, insulin and C-peptide. Maternal haemoglobin levels were not associated with childhood body mass index, total fat mass percentage, android/gynoid fat mass ratio, systolic blood pressure, cholesterol or insulin levels. Compared with children with normal maternal haemoglobin levels, children from anaemic mothers had slightly higher diastolic blood pressures (difference 0.70 mmHg, 95% CI 0.12, 1.29) and lower C-peptide levels (difference factor 0.93, 95% CI 0.88, 0.98), and children of mothers with elevated haemoglobin levels had lower left ventricular masses (difference -1.08 g, 95% CI -1.88, -0.29). These associations attenuated after adjustment for multiple testing and were not consistent within linear models. These results do not strongly support the hypothesis that variations in maternal haemoglobin levels during pregnancy influence cardio-metabolic risk factors in childhood. © 2014 Royal College of Obstetricians and Gynaecologists.

The role of body mass index, insulin, and adiponectin in the relation between fat distribution and bone mineral density.

PubMed

Zillikens, M Carola; Uitterlinden, André G; van Leeuwen, Johannes P T M; Berends, Anne L; Henneman, Peter; van Dijk, Ko Willems; Oostra, Ben A; van Duijn, Cornelia M; Pols, Huibert A P; Rivadeneira, Fernando

2010-02-01

Despite the positive association between body mass index (BMI) and bone mineral density (BMD) and content (BMC), the role of fat distribution in BMD/BMC remains unclear. We examined relationships between BMD/BMC and various measurements of fat distribution and studied the role of BMI, insulin, and adiponectin in these relations. Using a cross-sectional investigation of 2631 participants from the Erasmus Rucphen Family study, we studied associations between BMD (using dual-energy X-ray absorptiometry (DXA]) at the hip, lumbar spine, total body (BMD and BMC), and fat distribution by the waist-to-hip ratio (WHR), waist-to-thigh ratio (WTR), and DXA-based trunk-to-leg fat ratio and android-to-gynoid fat ratio. Analyses were stratified by gender and median age (48.0 years in women and 49.2 years in men) and were performed with and without adjustment for BMI, fasting insulin, and adiponectin. Using linear regression (adjusting for age, height, smoking, and use of alcohol), most relationships between fat distribution and BMD and BMC were positive, except for WTR. After BMI adjustment, most correlations were negative except for trunk-to-leg fat ratio in both genders. No consistent influence of age or menopausal status was found. Insulin and adiponectin levels did not explain either positive or negative associations. In conclusion, positive associations between android fat distribution and BMD/BMC are explained by higher BMI but not by higher insulin and/or lower adiponectin levels. Inverse associations after adjustment for BMI suggest that android fat deposition as measured by the WHR, WTR, and DXA-based android-to-gynoid fat ratio is not beneficial and possibly even deleterious for bone.

Associations of infant subcutaneous fat mass with total and abdominal fat mass at school-age. The Generation R Study

PubMed Central

Santos, Susana; Gaillard, Romy; Oliveira, Andreia; Barros, Henrique; Abrahamse-Berkeveld, Marieke; van der Beek, Eline M; Hofman, Albert; Jaddoe, Vincent WV

2017-01-01

Background Skinfold thickness enables the measurement of overall and regional subcutaneous fatness in infancy and may be associated with total and abdominal body fat in later childhood. We examined the associations of subcutaneous fat in infancy with total and abdominal fat at school-age. Methods In a population-based prospective cohort study among 821 children, we calculated total subcutaneous fat (sum of biceps, triceps, suprailiacal and subscapular skinfold thicknesses) and central-to-total subcutaneous fat ratio (sum of suprailiacal and subscapular skinfold thicknesses/total subcutaneous fat) at 1.5 and 24 months. At 6 years, we measured fat mass index (total fat/height3), central-to-total fat ratio (trunk fat/total fat) and android-to-gynoid fat ratio (android fat/gynoid fat) by dual-energy X-ray absorptiometry and preperitoneal fat mass area by abdominal ultrasound. Results Central-to-total subcutaneous fat ratio at 1.5 months was positively associated with fat mass index and central-to-total fat ratio at 6 years, whereas both total and central-to-total subcutaneous fat ratio at 24 months were positively associated with all childhood adiposity measures (p<0.05). A 1-standard-deviation scores higher total subcutaneous fat at 24 months was associated with an increased risk of childhood overweight (Odds Ratio 1.70 [95% Confidence Interval 1.36, 2.12]). These associations were weaker than those for body mass index and stronger among girls than boys. Conclusions Subcutaneous fat in infancy is positively associated with total and abdominal fat at school-age. Our results also suggest that skinfold thicknesses add little value to estimate later body fat, as compared to body mass index. PMID:27225335

Associations of Infant Subcutaneous Fat Mass with Total and Abdominal Fat Mass at School-Age: The Generation R Study.

PubMed

Santos, Susana; Gaillard, Romy; Oliveira, Andreia; Barros, Henrique; Abrahamse-Berkeveld, Marieke; van der Beek, Eline M; Hofman, Albert; Jaddoe, Vincent W V

2016-09-01

Skinfold thickness enables the measurement of overall and regional subcutaneous fatness in infancy and may be associated with total and abdominal body fat in later childhood. We examined the associations of subcutaneous fat in infancy with total and abdominal fat at school-age. In a population-based prospective cohort study among 821 children, we calculated total subcutaneous fat (sum of biceps, triceps, suprailiacal, and subscapular skinfold thicknesses) and central-to-total subcutaneous fat ratio (sum of suprailiacal and subscapular skinfold thicknesses/total subcutaneous fat) at 1.5 and 24 months. At 6 years, we measured fat mass index (total fat/height(3) ), central-to-total fat ratio (trunk fat/total fat), and android-to-gynoid fat ratio (android fat/gynoid fat) by dual-energy X-ray absorptiometry and preperitoneal fat mass area by abdominal ultrasound. Central-to-total subcutaneous fat ratio at 1.5 months was positively associated with fat mass index and central-to-total fat ratio at 6 years, whereas both total and central-to-total subcutaneous fat ratio at 24 months were positively associated with all childhood adiposity measures. A 1-standard-deviation scores higher total subcutaneous fat at 24 months was associated with an increased risk of childhood overweight (odds ratio 1.70, 95% confidence interval 1.36, 2.12). These associations were weaker than those for body mass index and stronger among girls than boys. Subcutaneous fat in infancy is positively associated with total and abdominal fat at school-age. Our results also suggest that skinfold thicknesses add little value to estimate later body fat, as compared with body mass index. © 2016 John Wiley & Sons Ltd.

PERCEPTIONS OF HIV AND PREVENTION EDUCATION AMONG INMATES OF ALABAMA PRISONS

PubMed Central

Ayanwale, Lekan; Moorer; Moorer, Ellis; Shaw, Habiba; Habtemariam, Tsegaye; Blackwell, Velma; Foster, Pamela; Findlay, Henry; Tameru, Berhanu; Nganwa, David; Ahmad, Anwar; Beyene, Gemechu; Robnett, Vinaida

2009-01-01

A 3-year interactive and passive training for HIV prevention education was conducted for 2,600 prisoners; 1,404 (54%) black, 1,092 (42%) white and 204 (4%) Hispanic. Less than 520 (20%) of inmates knew all the routes of HIV transmission. A post-presentation test showed that 96% became aware of HIV/AIDS transmission and can better protect themselves. Skin infections caused by Staphylococcus aereus were reported and manifested clinically as pustules, cellulites, boils, carbuncles or impetigo. Though no systemic infection was involved, staphylococcal infections suggest lowered immunity, an indicator to undiagnosed HIV. This study purposefully provides HIV prevention education model for prison health educators. PMID:20191111

Anti-sense oligonucleotide therapies for the treatment of hyperlipidaemia.

PubMed

Wierzbicki, Anthony S; Viljoen, Adie

2016-09-01

Anti-sense oligonucleotide (ASO) therapies are a new development in clinical pharmacology offering greater specificity compared to small molecule inhibitors and the ability to target intracellular process' not susceptible to antibody-based therapies. This article reviews the chemical biology of ASOs and related RNA therapeutics. It then reviews the data on their use to treat hyperlipidaemia. Data on mipomersen - an ASO to apolipoprotein B-100(apoB) licensed for treatment of homozygous familial hypercholesterolaemia (FH) is presented. Few effective therapies are available to reduce atehrogenic lipoprotein (a) levels. An ASO therapy to apolipoprotein(a) (ISIS Apo(a)Rx) specifically reduced lipoprotein (a) levels by up to 78%. Treatment options for patients with familial chylomicronaemia syndrome (lipoprotein lipase deficiency; LPLD) or lipodystrophies are highly limited and often inadequate. Volanesorsen, an ASO to apolipoprotein C-3, shows promise in the treatment of LPLD and severe hypertriglyceridaemia as it increases clearance of triglyceride-rich lipoproteins and can normalise triglycerides in these patients. The uptake of the novel ASO therapies is likely to be limited to selected niche groups or orphan diseases. These will include homozygous FH, severe heterozygous FH for mipomersen; LPLD deficiency and lipodystrophy syndromes for volanesorsen and treatment of patients with high elevated Lp(a) levels.

Immunology in clinic review series; focus on autoinflammatory diseases: update on monogenic autoinflammatory diseases: the role of interleukin (IL)-1 and an emerging role for cytokines beyond IL-1

PubMed Central

Goldbach-Mansky, R

2012-01-01

chronic atypical neutrophilic dermatitis with lipodystrophy and elevated temperatures (CANDLE), Japanese autoinflammatory syndrome with lipodystrophy (JASL), Nakajo–Nishimura syndrome (NNS) and joint contractures, muscle atrophy, panniculitis induced lipodystrophy (JMP), and urge the continued quest to characterize additional dysregulated innate immune pathways that cause autoinflammatory conditions. PMID:22288582

Incidence and predictors of regimen-modification from first-line antiretroviral therapy in Thailand: a cohort study.

PubMed

Tsuchiya, Naho; Pathipvanich, Panita; Wichukchinda, Nuanjun; Rojanawiwat, Archawin; Auwanit, Wattana; Ariyoshi, Koya; Sawanpanyalert, Pathom

2014-10-30

Antiretroviral therapy markedly reduced mortality in HIV-infected individuals. However, in the previous studies, up to 50% of patients are compelled to modify their regimen in middle and low-income countries where salvage drug is still limited. This cohort study aimed to investigate the incidence and predictors of regimen modification from the first-line antiretroviral regimen in northern Thailand. All HIV-infected patients starting antiretroviral therapy (ART) with generic drug (GPOvir®; stavudine, lamivudine and nevirapine) at a governmental hospital in northern Thailand from 2002 to 2007 were recruited. Baseline characteristics and detailed information of regimen modification until the end of 2010 were ascertained from cohort database and medical charts. As a potential genetic predictor of regimen modification, HLA B allele was determined by bead-based array hybridization (WAKFlow® HLA typing kit). We investigated predictors of the regimen modification using Cox's proportional hazard models. Of 979 patients, 914 were eligible for the analysis. The observed events of regimen modification was 377, corresponding to an incidence 13.8/100 person-year-observation (95% CI:12.5-15.3) over 2,728 person years (PY) follow up. The main reasons for regimen modification were adverse effects (73.5%), especially lipodystrophy (63.2%) followed by rash (17.7%). Sixty three patients (17.1%) changed the regimen due to treatment failure. 2% and 19% of patients had HLA-B*35:05 and B*4001, respectively. HLA-B*35:05 was independently associated with rash-related regimen modification (aHR 7.73, 95% CI:3.16-18.9) while female gender was associated with lipodystrophy (aHR 2.11, 95% CI:1.51-2.95). Female gender (aHR 0.54, 95% CI: 0.30-0.96), elder age (aHR 0.56, 95% CI: 0.32-0.99) and having HLA-B*40:01 (aHR 0.29, 95% CI: 0.10-0.82) were protective for treatment failure related modification. HLA-B*35:05 and female gender were strong predictors of regimen modification due to rash and

Synergistic effects of Combined Therapy: nonfocused ultrasound plus Aussie current for noninvasive body contouring.

PubMed

Canela, Vivianne Carvalho; Crivelaro, Cinthia Nicoletti; Ferla, Luciane Zacchi; Pelozo, Gisele Marques; Azevedo, Juliana; Liebano, Richard Eloin; Nogueira, Caroline; Guidi, Renata Michelini; Grecco, Clóvis; Sant'Ana, Estela

2018-01-01

Nowadays, there are several noninvasive technologies being used for improving of body contouring. The objectives of this pilot study were to verify the effectiveness of the Heccus ® device, emphasizing the synergism between nonfocused ultrasound plus Aussie current in the improvement of body contour, and to determine if the association of this therapy with whole-body vibration exercises can have additional positive effects in the results of the treatments. Twenty healthy women aged 20-40 years participated in the study. Ten patients received Combined Therapy treatment (G1) and the other 10 participants received Combined Therapy with additional vibratory platform treatment (G2). Anthropometric and standardized photography analysis, ultrasonography, cutometry and self-adminestered questionnaires of tolerance and satisfaction levels with the treatment were used. Compared with baseline values, reduction of fat thickness was observed by ultrasonography in the posterior thigh area in the G1 group ( P <0.05) and in the buttocks ( P <0.05) and the posterior thigh areas ( P <0.05) in the G2. All the treated areas in both groups showed reduction in cellulite degree in the buttocks, G1 ( P <0.05) and G2 ( P <0.05), and in posterior thigh areas, G1 ( P <0.05) and G2 ( P <0.05). Optimal improvement of skin firmness (G1, P <0.0001; G2, P =0.0034) in the treated areas was observed in both groups. We conclude that the synergistic effects of the Combined Therapy (nonfocused ultrasound plus Aussie current) might be a good option with noninvasive body contouring treatment for improving the aspect of the cellulite, skin firmness and localized fat. If used in association with the whole-body vibratory platform, the results can be better, especially in the treatment of localized fat. Further studies with larger sample size should be performed to confirm these results.

Associations of genetic risk scores based on adult adiposity pathways with childhood growth and adiposity measures.

PubMed

Monnereau, Claire; Vogelezang, Suzanne; Kruithof, Claudia J; Jaddoe, Vincent W V; Felix, Janine F

2016-08-18

Results from genome-wide association studies (GWAS) identified many loci and biological pathways that influence adult body mass index (BMI). We aimed to identify if biological pathways related to adult BMI also affect infant growth and childhood adiposity measures. We used data from a population-based prospective cohort study among 3,975 children with a mean age of 6 years. Genetic risk scores were constructed based on the 97 SNPs associated with adult BMI previously identified with GWAS and on 28 BMI related biological pathways based on subsets of these 97 SNPs. Outcomes were infant peak weight velocity, BMI at adiposity peak and age at adiposity peak, and childhood BMI, total fat mass percentage, android/gynoid fat ratio, and preperitoneal fat area. Analyses were performed using linear regression models. A higher overall adult BMI risk score was associated with infant BMI at adiposity peak and childhood BMI, total fat mass, android/gynoid fat ratio, and preperitoneal fat area (all p-values < 0.05). Analyses focused on specific biological pathways showed that the membrane proteins genetic risk score was associated with infant peak weight velocity, and the genetic risk scores related to neuronal developmental processes, hypothalamic processes, cyclicAMP, WNT-signaling, membrane proteins, monogenic obesity and/or energy homeostasis, glucose homeostasis, cell cycle, and muscle biology pathways were associated with childhood adiposity measures (all p-values <0.05). None of the pathways were associated with childhood preperitoneal fat area. A genetic risk score based on 97 SNPs related to adult BMI was associated with peak weight velocity during infancy and general and abdominal fat measurements at the age of 6 years. Risk scores based on genetic variants linked to specific biological pathways, including central nervous system and hypothalamic processes, influence body fat development from early life onwards.

Sex- and age-specific percentiles of body composition indices for Chinese adults using dual-energy X-ray absorptiometry.

PubMed

Xiao, Zeyu; Guo, Bin; Gong, Jian; Tang, Yongjin; Shang, Jingjie; Cheng, Yong; Xu, Hao

2017-10-01

The aims of the study were to develop sex- and age-specific percentiles for lean mass index (LMI), appendicular LMI (aLMI), fat mass index (FMI), and body fat distribution indices in Chinese adults using dual-energy X-ray absorptiometry (DXA), and to compare those indices with those of other ethnicities using the US NHANES data. Whole-body and regional lean mass and fat mass (FM) were measured using DXA in 5688 healthy males (n = 1693) and females (n = 3995) aged 20-90 years. Body fat distribution indices were expressed as % fat trunk/% fat legs, trunk/appendicular FM ratio (FMR), and android/gynoid FMR. Percentile curves of LMI, aLMI, FMI, and body fat distribution indices were obtained by the Lambda-Mu-Sigma method. The aLMI and LMI were negatively associated with age, decreasing from the fifth decade for males, but were not associated with age in females. Females had more total FM than males, whereas males had greater central adiposity (% fat trunk/% fat legs ratio, trunk/appendicular FMR, and android/gynoid FMR) than females. Moreover, FMI and body fat distribution indices consistently increased with age in both sexes, especially in women. In comparison with white, black, and Mexican populations in the USA, Chinese adults had lower total FM, but had greater central adiposity (% fat trunk/% fat legs ratio and trunk/appendicular FMR). Additionally, older white and Mexican populations showed greater decreases for aLMI and LMI than their Chinese counterparts. We present the sex- and age-specific percentiles for aLMI, LMI, FMI, and body fat distribution indices by DXA in Chinese adults, which may refine the individual assessment of the nutritional status of Chinese adults.

Abdominal obesity and circulating metabolites: A twin study approach.

PubMed

Bogl, Leonie H; Kaye, Sanna M; Rämö, Joel T; Kangas, Antti J; Soininen, Pasi; Hakkarainen, Antti; Lundbom, Jesper; Lundbom, Nina; Ortega-Alonso, Alfredo; Rissanen, Aila; Ala-Korpela, Mika; Kaprio, Jaakko; Pietiläinen, Kirsi H

2016-03-01

To investigate how obesity, insulin resistance and low-grade inflammation link to circulating metabolites, and whether the connections are due to genetic or environmental factors. Circulating serum metabolites were determined by proton NMR spectroscopy. Data from 1368 (531 monozygotic (MZ) and 837 dizygotic (DZ)) twins were used for bivariate twin modeling to derive the genetic (rg) and environmental (re) correlations between waist circumference (WC) and serum metabolites. Detailed examination of the associations between fat distribution (DEXA) and metabolic health (HOMA-IR, CRP) was performed among 286 twins including 33 BMI-discordant MZ pairs (intrapair BMI difference ≥3 kg/m(2)). Fat, especially in the abdominal area (i.e. WC, android fat % and android to gynoid fat ratio), together with HOMA-IR and CRP correlated significantly with an atherogenic lipoprotein profile, higher levels of branched-chain (BCAA) and aromatic amino acids, higher levels of glycoprotein, and a more saturated fatty acid profile. In contrast, a higher proportion of gynoid to total fat associated with a favorable metabolite profile. There was a significant genetic overlap between WC and several metabolites, most strongly with phenylalanine (rg=0.40), glycoprotein (rg=0.37), serum triglycerides (rg=0.36), BCAAs (rg=0.30-0.40), HDL particle diameter (rg=-0.33) and HDL cholesterol (rg=-0.30). The effect of acquired obesity within the discordant MZ pairs was particularly strong for atherogenic lipoproteins. A wide range of unfavorable alterations in the serum metabolome was associated with abdominal obesity, insulin resistance and low-grade inflammation. Twin modeling and obesity-discordant twin analysis suggest that these associations are partly explained by shared genes but also reflect mechanisms independent of genetic liability. Copyright © 2015 Elsevier Inc. All rights reserved.

TNFα blockade for inflammatory rheumatic diseases is associated with a significant gain in android fat mass and has varying effects on adipokines: a 2-year prospective study.

PubMed

Toussirot, Éric; Mourot, Laurent; Dehecq, Barbara; Wendling, Daniel; Grandclément, Émilie; Dumoulin, Gilles

2014-04-01

To evaluate the long-term consequences of TNFα inhibitors on body composition and fat distribution, as well as changes in serum adipokines in patients with rheumatoid arthritis (RA) or ankylosing spondylitis (AS). Eight patients with RA and twelve with AS requiring a TNFα inhibitor were prospectively followed for 2 years. Body composition was evaluated by dual X-ray absorptiometry and included measurements of total fat mass, lean mass, fat in the gynoid and android regions, and visceral fat. Serum leptin, total and high molecular weight (HMW) adiponectin, resistin, and ghrelin were also assessed. There was a significant gain in body mass index (p = 0.05) and a tendency for weight (p = 0.07), android fat (p = 0.07), and visceral fat (p = 0.059) increase in patients with RA, while in AS, total fat mass significantly increased (p = 0.02) with a parallel weight gain (p = 0.07). When examining the whole population of patients, we observed after 2 years a significant increase in body weight (+1.9%; p = 0.003), body mass index (+2.5%; p = 0.004), total fat mass (+11.1%; p = 0.007), and fat in the android region (+18.3%; p = 0.02). There was a substantial, albeit nonsignificant gain in visceral fat (+24.3%; p = 0.088). Lean mass and gynoid fat were not modified. No major changes were observed for serum leptin, total adiponectin, and ghrelin, while HMW adiponectin and the HMW/total adiponectin ratio tended to decrease (-15.2%, p = 0.057 and -9.3%, p = 0.067, respectively). Resistin decreased significantly (-22.4%, p = 0.01). Long-term TNFα inhibition in RA and AS is associated with a significant gain in fat mass, with a shift to the android (visceral) region. This fat redistribution raises questions about its influence on the cardiovascular profile of patients receiving these treatments.

Centella asiatica in cosmetology.

PubMed

Bylka, Wiesława; Znajdek-Awiżeń, Paulina; Studzińska-Sroka, Elżbieta; Brzezińska, Małgorzata

2013-02-01

Centella asiatica known as Gotu Kola is a medicinal plant that has been used in folk medicine for hundreds of years as well as in scientifically oriented medicine. The active compounds include pentacyclic triterpenes, mainly asiaticoside, madecassoside, asiatic and madecassic acids. Centella asiatica is effective in improving treatment of small wounds, hypertrophic wounds as well as burns, psoriasis and scleroderma. The mechanism of action involves promoting fibroblast proliferation and increasing the synthesis of collagen and intracellular fibronectin content and also improvement of the tensile strength of newly formed skin as well as inhibiting the inflammatory phase of hypertrophic scars and keloids. Research results indicate that it can be used in the treatment of photoaging skin, cellulite and striae.

Rare adipose disorders (RADs) masquerading as obesity

PubMed Central

Herbst, Karen L

2012-01-01

Rare adipose disorders (RADs) including multiple symmetric lipomatosis (MSL), lipedema and Dercum's disease (DD) may be misdiagnosed as obesity. Lifestyle changes, such as reduced caloric intake and increased physical activity are standard care for obesity. Although lifestyle changes and bariatric surgery work effectively for the obesity component of RADs, these treatments do not routinely reduce the abnormal subcutaneous adipose tissue (SAT) of RADs. RAD SAT likely results from the growth of a brown stem cell population with secondary lymphatic dysfunction in MSL, or by primary vascular and lymphatic dysfunction in lipedema and DD. People with RADs do not lose SAT from caloric limitation and increased energy expenditure alone. In order to improve recognition of RADs apart from obesity, the diagnostic criteria, histology and pathophysiology of RADs are presented and contrasted to familial partial lipodystrophies, acquired partial lipodystrophies and obesity with which they may be confused. Treatment recommendations focus on evidence-based data and include lymphatic decongestive therapy, medications and supplements that support loss of RAD SAT. Associated RAD conditions including depression, anxiety and pain will improve as healthcare providers learn to identify and adopt alternative treatment regimens for the abnormal SAT component of RADs. Effective dietary and exercise regimens are needed in RAD populations to improve quality of life and construct advanced treatment regimens for future generations. PMID:22301856

Adipose tissue mitochondrial dysfunction triggers a lipodystrophic syndrome with insulin resistance, hepatosteatosis, and cardiovascular complications

PubMed Central

Vernochet, Cecile; Damilano, Federico; Mourier, Arnaud; Bezy, Olivier; Mori, Marcelo A.; Smyth, Graham; Rosenzweig, Anthony; Larsson, Nils-Göran; Kahn, C. Ronald

2014-01-01

Mitochondrial dysfunction in adipose tissue occurs in obesity, type 2 diabetes, and some forms of lipodystrophy, but whether this dysfunction contributes to or is the result of these disorders is unknown. To investigate the physiological consequences of severe mitochondrial impairment in adipose tissue, we generated mice deficient in mitochondrial transcription factor A (TFAM) in adipocytes by using mice carrying adiponectin-Cre and TFAM floxed alleles. These adiponectin TFAM-knockout (adipo-TFAM-KO) mice had a 75–81% reduction in TFAM in the subcutaneous and intra-abdominal white adipose tissue (WAT) and interscapular brown adipose tissue (BAT), causing decreased expression and enzymatic activity of proteins in complexes I, III, and IV of the electron transport chain (ETC). This mitochondrial dysfunction led to adipocyte death and inflammation in WAT and a whitening of BAT. As a result, adipo-TFAM-KO mice were resistant to weight gain, but exhibited insulin resistance on both normal chow and high-fat diets. These lipodystrophic mice also developed hypertension, cardiac hypertrophy, and cardiac dysfunction. Thus, isolated mitochondrial dysfunction in adipose tissue can lead a syndrome of lipodystrophy with metabolic syndrome and cardiovascular complications.—Vernochet, C., Damilano, F., Mourier, A., Bezy, O., Mori, M. A., Smyth, G., Rosenzweig, A., Larsson, N.-G., Kahn, C. R. Adipose tissue mitochondrial dysfunction triggers a lipodystrophic syndrome with insulin resistance, hepatosteatosis, and cardiovascular complications. PMID:25005176

Fascian.

PubMed

Burres, Steve

2004-05-01

Fascian is preserved particulate fascia derived from the gastrocnemious fascia that extends from the Achilles tendon. Over 50,000 syringes of material have been sold to physicians over the past six years with an impeccable safety record. The material has been used for wrinkles, scars, fat atrophy, diffuse depressions, paralyzed lips and tongues, nasolabial folds, cellulite, and other problems. Solid fascia grafts are routinely replaced with native collagen and a similar effect may be achieved with Fascian, especially after repeat injections. The FDA classifies the material as a tissue product, so injections may be made anywhere in the human body at the physician's discretion. Injections may last from a few months to permanently, depending on the volume of material, location, particle size, skin layer, and technique.

Centella asiatica in cosmetology

PubMed Central

Znajdek-Awiżeń, Paulina; Studzińska-Sroka, Elżbieta; Brzezińska, Małgorzata

2013-01-01

Centella asiatica known as Gotu Kola is a medicinal plant that has been used in folk medicine for hundreds of years as well as in scientifically oriented medicine. The active compounds include pentacyclic triterpenes, mainly asiaticoside, madecassoside, asiatic and madecassic acids. Centella asiatica is effective in improving treatment of small wounds, hypertrophic wounds as well as burns, psoriasis and scleroderma. The mechanism of action involves promoting fibroblast proliferation and increasing the synthesis of collagen and intracellular fibronectin content and also improvement of the tensile strength of newly formed skin as well as inhibiting the inflammatory phase of hypertrophic scars and keloids. Research results indicate that it can be used in the treatment of photoaging skin, cellulite and striae. PMID:24278045

Mechanisms of insulin resistance in obesity

PubMed Central

Ye, Jianping

2014-01-01

Obesity increases the risk for type 2 diabetes through induction of insulin resistance. Treatment of type 2 diabetes has been limited by little translational knowledge of insulin resistance although there have been several well-documented hypotheses for insulin resistance. In those hypotheses, inflammation, mitochondrial dysfunction, hyperinsulinemia and lipotoxicity have been the major concepts and have received a lot of attention. Oxidative stress, endoplasmic reticulum (ER) stress, genetic background, aging, fatty liver, hypoxia and lipodystrophy are active subjects in the study of these concepts. However, none of those concepts or views has led to an effective therapy for type 2 diabetes. The reason is that there has been no consensus for a unifying mechanism of insulin resistance. In this review article, literature is critically analyzed and reinterpreted for a new energy-based concept of insulin resistance, in which insulin resistance is a result of energy surplus in cells. The energy surplus signal is mediated by ATP and sensed by adenosine monophosphate-activated protein kinase (AMPK) signaling pathway. Decreasing ATP level by suppression of production or stimulation of utilization is a promising approach in the treatment of insulin resistance. In support, many of existing insulin sensitizing medicines inhibit ATP production in mitochondria. The effective therapies such as weight loss, exercise, and caloric restriction all reduce ATP in insulin sensitive cells. This new concept provides a unifying cellular and molecular mechanism of insulin resistance in obesity, which may apply to insulin resistance in aging and lipodystrophy. PMID:23471659

A Novel Lamin A Mutant Responsible for Congenital Muscular Dystrophy Causes Distinct Abnormalities of the Cell Nucleus.

PubMed

Barateau, Alice; Vadrot, Nathalie; Vicart, Patrick; Ferreiro, Ana; Mayer, Michèle; Héron, Delphine; Vigouroux, Corinne; Buendia, Brigitte

2017-01-01

A-type lamins, the intermediate filament proteins participating in nuclear structure and function, are encoded by LMNA. LMNA mutations can lead to laminopathies such as lipodystrophies, premature aging syndromes (progeria) and muscular dystrophies. Here, we identified a novel heterozygous LMNA p.R388P de novo mutation in a patient with a non-previously described severe phenotype comprising congenital muscular dystrophy (L-CMD) and lipodystrophy. In culture, the patient's skin fibroblasts entered prematurely into senescence, and some nuclei showed a lamina honeycomb pattern. C2C12 myoblasts were transfected with a construct carrying the patient's mutation; R388P-lamin A (LA) predominantly accumulated within the nucleoplasm and was depleted at the nuclear periphery, altering the anchorage of the inner nuclear membrane protein emerin and the nucleoplasmic protein LAP2-alpha. The mutant LA triggered a frequent and severe nuclear dysmorphy that occurred independently of prelamin A processing, as well as increased histone H3K9 acetylation. Nuclear dysmorphy was not significantly improved when transfected cells were treated with drugs disrupting microtubules or actin filaments or modifying the global histone acetylation pattern. Therefore, releasing any force exerted at the nuclear envelope by the cytoskeleton or chromatin did not rescue nuclear shape, in contrast to what was previously shown in Hutchinson-Gilford progeria due to other LMNA mutations. Our results point to the specific cytotoxic effect of the R388P-lamin A mutant, which is clinically related to a rare and severe multisystemic laminopathy phenotype.

Fungal infections of the eye--laboratory diagnosis and treatment.

PubMed

Nayak, N

2008-03-01

Infections of the eye give rise to severe ocular morbidity and blindness include keratitis, orbital cellulites, endophthalmitis and dacryocystitis. Corneal blindness, in developing countries is predominantly associated with infections. In India, nearly 30-35% of all culture positive infectious keratitis are caused fungi. Laboratory diagnosis mainly depends upon proper collection and transport of clinical specimens. In fungal keratitis, corneal scraping is the ideal sample, but occasionally corneal biopsy or anterior chamber aspirate may also be needed. Corneal scraping is usually by Kimura spatula, under a slit lamp examination, after anaesthetizing the cornea with topical anaesthetic like 0.4% proparcaine. Corneal biopsy is done by a minor trephining and AC aspirate using a sterile tuberculin syringe. In case of endophthalmitis, 150-200 ìl of aqueous humour is collected. Vitreous fluid (500-1000 ìl), however, is collected by pars plana vitrectomy onto sterile tuberculin syringe, the needle is then fixed to a sterile rubber bung after expelling air from the syringe. The collected sample is immediately transported to the laboratory. Swabs from the regurgitating lacrimnal sacs and wound aspirate/swabs are the ideal specimens for dacryocystitis and orbital cellulites, respectively. These samples are cultured onto SDA slants following standard procedures. The main draw back of culture is its long incubation time (5 to 14 days), though it is indispensable from the view point of the specificity. Direct examination (KOH wet mount, Gram's, Giemsa or calcofluor fluorescent staining methods) of the specimen, however, is quick and immensely helpful for ophthalmologist. The newer rapid methods, such as molecular techniques are also available and the management of patients can be according to the results obtained. With the advent of novel antifungal agents such as newer azoles and cell wall acting antifungals like echinocandins, the clinician has the wider option of selecting

Synergistic effects of Combined Therapy: nonfocused ultrasound plus Aussie current for noninvasive body contouring

PubMed Central

Canela, Vivianne Carvalho; Crivelaro, Cinthia Nicoletti; Ferla, Luciane Zacchi; Pelozo, Gisele Marques; Azevedo, Juliana; Liebano, Richard Eloin; Nogueira, Caroline; Guidi, Renata Michelini; Grecco, Clóvis; Sant’Ana, Estela

2018-01-01

Background and objectives Nowadays, there are several noninvasive technologies being used for improving of body contouring. The objectives of this pilot study were to verify the effectiveness of the Heccus® device, emphasizing the synergism between nonfocused ultrasound plus Aussie current in the improvement of body contour, and to determine if the association of this therapy with whole-body vibration exercises can have additional positive effects in the results of the treatments. Subjects and methods Twenty healthy women aged 20–40 years participated in the study. Ten patients received Combined Therapy treatment (G1) and the other 10 participants received Combined Therapy with additional vibratory platform treatment (G2). Anthropometric and standardized photography analysis, ultrasonography, cutometry and self-adminestered questionnaires of tolerance and satisfaction levels with the treatment were used. Results Compared with baseline values, reduction of fat thickness was observed by ultrasonography in the posterior thigh area in the G1 group (P<0.05) and in the buttocks (P<0.05) and the posterior thigh areas (P<0.05) in the G2. All the treated areas in both groups showed reduction in cellulite degree in the buttocks, G1 (P<0.05) and G2 (P<0.05), and in posterior thigh areas, G1 (P<0.05) and G2 (P<0.05). Optimal improvement of skin firmness (G1, P<0.0001; G2, P=0.0034) in the treated areas was observed in both groups. Conclusion We conclude that the synergistic effects of the Combined Therapy (nonfocused ultrasound plus Aussie current) might be a good option with noninvasive body contouring treatment for improving the aspect of the cellulite, skin firmness and localized fat. If used in association with the whole-body vibratory platform, the results can be better, especially in the treatment of localized fat. Further studies with larger sample size should be performed to confirm these results. PMID:29731654

The Apparent Relation between Plasma 25-Hydroxyvitamin D and Insulin Resistance Is Largely Attributable to Central Adiposity in Overweight and Obese Adults12

PubMed Central

Wright, Christian S; Weinheimer-Haus, Eileen M; Fleet, James C; Peacock, Munro; Campbell, Wayne W

2015-01-01

Background: Research indicates that plasma 25-hydroxyvitamin D [25(OH)D] is associated with insulin resistance, but whether regional adiposity confounds this association is unclear. Objective: This study assessed the potential influence of adiposity and its anatomical distribution on the relation between plasma 25(OH)D and insulin resistance. Methods: A secondary analysis of data from middle-aged overweight and obese healthy adults [n = 336: 213 women and 123 men; mean ± SD (range); age: 48 ± 8 y (35–65 y); body mass index (BMI; in kg/m2): 30.3 ± 2.7 (26–35)] from West Lafayette, Indiana (40.4°N), were used for this cross-sectional analysis. Multiple linear regression analyses that controlled for multiple covariates were used as the primary statistical model. Results: Of all participants, 8.6% and 20.5% displayed moderate [20.1–37.5 nmol/L plasma 25(OH)D] to mild (37.6–49.9 nmol/L) vitamin D insufficiency, respectively. A regression analysis controlling for age, sex, race, plasma parathyroid hormone concentration, season of year, and supplement use showed that 25(OH)D was negatively associated with fasting insulin (P = 0.021). Additional regression analyses showed that total and central adiposity but not peripheral adiposity predicted low plasma 25(OH)D [total fat mass index (FMI): P = 0.018; android FMI: P = 0.052; gynoid FMI: P = 0.15; appendicular FMI: P = 0.07) and insulin resistance (homeostasis model assessment of insulin resistance: total and android FMI, P <0.0001; gynoid FMI, P = 0.94; appendicular FMI, P = 0.86). The associations of total and central adiposity with insulin resistance remained significant after adjusting for plasma 25(OH)D. However, adjusting for central adiposity but not other anatomical measures of fat distribution eliminated the association between plasma 25(OH)D and insulin resistance. Conclusion: Central adiposity drives the association between plasma 25(OH)D and insulin resistance in overweight and obese adults. The trial

Differentiating lipedema and Dercum's disease.

PubMed

Beltran, K; Herbst, K L

2017-02-01

People with lipedema or Dercum's disease (DD) can have a similar distribution of excess painful nodular subcutaneous adipose tissue (SAT), making them difficult to differentiate. Case series of 94 patients with DD, 160 with lipedema and 18 with both diagnoses (Lip+DD) from a single clinic in an academic medical center to improve identification and differentiation of these disorders by comparison of clinical findings, prevalence of type 2 diabetes (DM2), hypermobility by the Beighton score and assessment of a marker of inflammation, Total complement activity (CH50). Differences between groups were by Student's t-test with α of 0.05. The Lipedema Group had significantly greater weight, body mass index (BMI), gynoid distributed nodular SAT and fibrotic and heavy tissue than the DD Group. Hypermobility was significantly higher in the Lipedema (58±0.5%) than DD Group (23±0.4%; P<0.0001). DM2 was significantly greater in the DD (16±0.2%; P=0.0007) than the Lipedema Group (6±0.2%). Average pain by an analog scale was significantly higher in the DD (6±2.5%) than the Lipedema Group (4±2.1%; P<0.0001). Fatigue and swelling were common in both groups. Easy bruising was more common in the Lipedema Group, whereas abdominal pain, shortness of breath, fibromyalgia, migraines and lipomas were more prevalent in the DD Group. The percentage of patients with elevated CH50 was significantly positive in both groups. The significantly lower prevalence of DM2 in people with lipedema compared with DD may be due to the greater amount of gynoid fat known to be protective against metabolic disorders. The high percentage of hypermobility in lipedema patients indicates that it may be a comorbid condition. The location of fat, high average daily pain, presence of lipomas and comorbid painful disorders in DD patients may help differentiate from lipedema.

Factitious thyrotoxicosis induced by mesotherapy: a case report.

PubMed

Danilovic, Debora Lucia Seguro; Bloise, Walter; Knobel, Meyer; Marui, Suemi

2008-06-01

Mesotherapy consists of cutaneous injections of a mixture of compounds and has recently been used for cosmetic purposes to reduce local fat and cellulite. To date, several reports have described only local adverse events related to this therapy. We describe the first report of a female patient who developed thyrotoxicosis due to cosmetic mesotherapy with triiodothyroacetic acid in its formulation. Apart from mechanical rupture of the epidermal barrier, a disturbance of type III deiodinase activity or skin fibroblast paracrine function and vascular alterations related to simultaneously injected vasoactive compounds were observed. These findings could be related to thyroid hormone metabolite absorption and systemic consequences in the reported case. We describe factitious thyrotoxicosis induced by mesotherapy, to raise awareness of a systemic adverse effect resulting from this widespread cosmetic practice.

New Combinational Method for Noninvasive Treatments of Superficial Tissues for Body Aesthetics Applications

NASA Astrophysics Data System (ADS)

Rybyanets, A. N.; Naumenko, A. A.

The paper introduces an innovative combinational treatment method based on ultrasonic standing waves (USW) technology for noninvasive surgical, therapeutic, lypolitic or cosmetic treatment of tissues including subcutaneous adipose tissue, cellulite or skin on arbitrary body part of patient. The method is based on simultaneous or successive applying of constructively interfering physically and biologically sensed influences: USW, ultrasonic shear waves, radio-frequency (RF) heating, and vacuum massage. The paper provides basic physical principles of USW as well as critical comparison of USW and HIFU methods. The results of finite-elements and finite- difference modeling of USW transducer design and nodal pattern structure in tissue are presented. Biological effects of USW-tissue interaction and synergetic aspects of USW and RF combination are explored. Combinational treatment transducer designs and original in-vitro experiments on tissues are described.

Quantification of Liver Fat with Magnetic Resonance Imaging

PubMed Central

Reeder, Scott B.; Sirlin, Claude

2010-01-01

Intracellular fat accumulation is common feature of liver disease. Intracellular fat (steatosis) is the histological hallmark of non-alcoholic fatty liver disease (NAFLD) but also may occur with alcohol abuse, viral hepatitis, HIV and genetic lipodystrophies, and chemotherapy. This article reviews emerging magnetic resonance imaging techniques that attempt to quantify liver fat. The content provides an overview of fatty liver disease and diseases where fat is an important disease feature. Also discussed is the current use and limitation of non-targeted biopsy in diffuse liver disease, and why quantitative non-invasive biomarkers of liver fat would be beneficial. PMID:21094444

Physiology of leptin: energy homeostasis, neuroendocrine function and metabolism

PubMed Central

Park, Hyeong-Kyu; Ahima, Rexford S.

2014-01-01

Leptin is secreted by adipose tissue and regulates energy homeostasis, neuroendocrine function, metabolism, immune function and other systems through its effects on the central nervous system and peripheral tissues. Leptin administration has been shown to restore metabolic and neuroendocrine abnormalities in individuals with leptin-deficient states, including hypothalamic amenorrhea and lipoatrophy. In contrast, obese individuals are resistant to leptin. Recombinant leptin is beneficial in patients with congenital leptin deficiency or generalized lipodystrophy. However, further research on molecular mediators of leptin resistance is needed for the development of targeted leptin sensitizing therapies for obesity and related metabolic diseases. PMID:25199978

Histological study of subcutaneous fat at NIR laser treatment of the rat skin in vivo

NASA Astrophysics Data System (ADS)

Yanina, I. Y.; Svenskaya, Yu. I.; Navolokin, N. A.; Matveeva, O. V.; Bucharskaya, A. B.; Maslyakova, G. N.; Gorin, D. A.; Sukhorukov, G. B.; Tuchin, V. V.

2015-07-01

The goal of this work is to quantify impact of in vivo photochemical treatment using indocyanine green (ICG) or encapsulated ICG and NIR laser irradiation through skin of rat with obesity by the follow up tissue sampling and histochemistry. After 1 hour elapsed since 1-min light exposure samples of rat skin with subcutaneous tissue of thickness of 1.5-2.5 mm were taken by surgery from rats within marked 4-zones of the skin site. For hematoxylin-eosin histological examination of excised tissue samples, fixation was carried out by 10%-formaldehyde solution. For ICG and encapsulated ICG subcutaneous injection and subsequent 1-min diode laser irradiation with power density of 8 W/cm2, different necrotic regions with lipolysis of subcutaneous fat were observed. The obtained data can be used for safe layer-by-layer laser treatment of obesity and cellulite.

Hepatic fibrosis and factors associated with liver stiffness in HIV mono-infected individuals

PubMed Central

Ferenci, Tamás; Makara, Mihály; Horváth, Gábor; Szlávik, János; Rupnik, Zsófia; Kormos, Luca; Gerlei, Zsuzsanna; Sulyok, Zita; Vályi-Nagy, István

2017-01-01

Background Liver disease has become an important cause of morbidity and mortality even in those HIV-infected individuals who are devoid of hepatitis virus co-infection. The aim of this study was to evaluate the degree of hepatic fibrosis and the role of associated factors using liver stiffness measurement in HIV mono-infected patients without significant alcohol intake. Methods We performed a cross-sectional study of 101 HIV mono-infected patients recruited prospectively from March 1, 2014 to October 30, 2014 at the Center for HIV, St István and St László Hospital, Budapest, Hungary. To determine hepatic fibrosis, liver stiffness was measured with transient elastography. Demographic, immunologic and other clinical parameters were collected to establish a multivariate model. Bayesian Model Averaging (BMA) was performed to identify predictors of liver stiffness. Results Liver stiffness ranged from 3.0–34.3 kPa, with a median value of 5.1 kPa (IQR 1.7). BMA provided a very high support for age (Posterior Effect Probability-PEP: 84.5%), moderate for BMI (PEP: 49.3%), CD4/8 ratio (PEP: 44.2%) and lipodystrophy (PEP: 44.0%). For all remaining variables, the model rather provides evidence against their effect. These results overall suggest that age and BMI have a positive association with LS, while CD4/8 ratio and lipodystrophy are negatively associated. Discussion Our findings shed light on the possible importance of ageing, overweight and HIV-induced immune dysregulation in the development of liver fibrosis in the HIV-infected population. Nonetheless, further controlled studies are warranted to clarify causal relations. PMID:28097068

Long-term outcome and prognostic factors of juvenile dermatomyositis: a multinational, multicenter study of 490 patients.

PubMed

Ravelli, Angelo; Trail, Lucia; Ferrari, Cristina; Ruperto, Nicolino; Pistorio, Angela; Pilkington, Clarissa; Maillard, Susan; Oliveira, Sheila K; Sztajnbok, Flavio; Cuttica, Ruben; Beltramelli, Matilde; Corona, Fabrizia; Katsicas, Maria Martha; Russo, Ricardo; Ferriani, Virginia; Burgos-Vargas, Ruben; Magni-Manzoni, Silvia; Solis-Valleoj, Eunice; Bandeira, Marcia; Zulian, Francesco; Baca, Vicente; Cortis, Elisabetta; Falcini, Fernanda; Alessio, Maria; Alpigiani, Maria Giannina; Gerloni, Valeria; Saad-Magalhaes, Claudia; Podda, Rosanna; Silva, Clovis A; Lepore, Loredana; Felici, Enrico; Rossi, Federica; Sala, Elena; Martini, Alberto

2010-01-15

To investigate the long-term outcome and prognostic factors of juvenile dermatomyositis (DM) through a multinational, multicenter study. Patients consisted of inception cohorts seen between 1980 and 2004 in 27 centers in Europe and Latin America. Predictor variables were sex, continent, ethnicity, onset year, onset age, onset type, onset manifestations, course type, disease duration, and active disease duration. Outcomes were muscle strength/endurance, continued disease activity, cumulative damage, muscle damage, cutaneous damage, calcinosis, lipodystrophy, physical function, and health-related quality of life (HRQOL). A total of 490 patients with a mean disease duration of 7.7 years were included. At the cross-sectional visit, 41.2-52.8% of patients, depending on the instrument used, had reduced muscle strength/endurance, but less than 10% had severe impairment. Persistently active disease was recorded in 41.2-60.5% of the patients, depending on the activity measure used. Sixty-nine percent of the patients had cumulative damage. The frequency of calcinosis and lipodystrophy was 23.6% and 9.7%, respectively. A total of 40.7% of the patients had decreased functional ability, but only 6.5% had major impairment. Only a small fraction had decreased HRQOL. A chronic course, either polycyclic or continuous, consistently predicted a poorer outcome. Mortality rate was 3.1%. This study confirms the marked improvement in functional outcome of juvenile DM when compared with earlier literature. However, many patients had continued disease activity and cumulative damage at followup. A chronic course was the strongest predictor of poor prognosis. These findings highlight the need for treatment strategies that enable a better control of disease activity over time and the reduction of nonreversible damage.

Insulin resistance is a sufficient basis for hyperandrogenism in lipodystrophic women with polycystic ovarian syndrome.

PubMed

Lungu, Andreea O; Zadeh, Elika Safar; Goodling, Anne; Cochran, Elaine; Gorden, Phillip

2012-02-01

The lipodystrophies (LD) are characterized by metabolic abnormalities (insulin resistance, hypertriglyceridemia, and diabetes) and a polycystic ovarian syndrome (PCOS) phenotype. Therapeutic administration of leptin improves insulin sensitivity and the metabolic features. The objective of the study was to investigate whether the PCOS features are corrected by increasing insulin sensitivity as a function of leptin treatment. This was a prospective, open-label trial using leptin replacement in various forms of lipodystrophy. The study was performed at the Clinical Center at the National Institutes of Health. Twenty-three female patients with LD were enrolled in a leptin replacement trial from 2000 to the present. Different parameters were assessed at baseline and after 1 yr of therapy. Patients were treated with leptin for at least 1 yr. We evaluated free testosterone, SHBG, and IGF-I at baseline and after 1 yr of leptin. Testosterone levels decreased from 3.05 ±0.6 ng/ml at baseline to 1.7 ±0.3 ng/ml (P = 0.02). SHBG increased from 14.5 ±2 to 25 ±3.5 nmol/liter after 1 yr of leptin therapy. There were no significant changes in the levels of gonadotropins and ovarian size as a result of leptin replacement therapy. IGF-I increased significantly after leptin therapy from 150 ±14 to 195 ±17. There was a significant decrease in triglycerides and glycosylated hemoglobin in the context of reduced insulin requirements. In the present study, we show that LD may be a model for the common forms of PCOS and that the endocrine features are corrected by leptin therapy, which reduces insulin resistance.

Hypertriglyceridemia and Waist Circumference Predict Cardiovascular Risk among HIV Patients: A Cross-Sectional Study

PubMed Central

Janiszewski, Peter M.; Ross, Robert; Despres, Jean-Pierre; Lemieux, Isabelle; Orlando, Gabriella; Carli, Federica; Bagni, Pietro; Menozzi, Marianna; Zona, Stefano; Guaraldi, Giovanni

2011-01-01

Background Although half of HIV-infected patients develop lipodystrophy and metabolic complications, there exists no simple clinical screening tool to discern the high from the low-risk HIV-infected patient. Thus, we evaluated the associations between waist circumference (WC) combined with triglyceride (TG) levels and the severity of lipodystrophy and cardiovascular risk among HIV-infected men and women. Methods 1481 HIV-infected men and 841 HIV-infected women were recruited between 2005 and 2009 at the metabolic clinic of the University of Modena and Reggio Emilia in Italy. Within each gender, patients were categorized into 4 groups according to WC and TG levels. Total and regional fat and fat-free mass were assessed by duel-energy x-ray absorptiometry, and visceral adipose tissue (VAT) and abdominal subcutaneous AT (SAT) were quantified by computed tomography. Various cardiovascular risk factors were assessed in clinic after an overnight fast. Results The high TG/high WC men had the most VAT (208.0±94.4 cm2), as well as the highest prevalence of metabolic syndrome (42.2%) and type-2 diabetes (16.2%), and the highest Framingham risk score (10.3±6.5) in comparison to other groups (p<0.05 for all). High TG/high WC women also had elevated VAT (150.0±97.9 cm2) and a higher prevalence of metabolic syndrome (53.3%), hypertension (30.5%) and type-2 diabetes (12.0%), and Framingham risk score(2.9±2.8) by comparison to low TG/low WC women (p<0.05 for all). Conclusions A simple tool combining WC and TG levels can discriminate high- from low-risk HIV-infected patients. PMID:21966404

HIV or HIV-Therapy? Causal attributions of symptoms and their impact on treatment decisions among women and men with HIV

PubMed Central

2009-01-01

Objectives Among people with HIV, we examined symptom attribution to HIV or HIV-therapy, awareness of potential side effects and discontinuation of treatment, as well as sex/gender differences. Methods HIV-patients (N = 168, 46% female) completed a comprehensive symptom checklist (attributing each endorsed symptom to HIV, HIV-therapy, or other causes), reported reasons for treatment discontinuations and potential ART-related laboratory abnormalities. Results Main symptom areas were fatigue/sleep/energy, depression/mood, lipodystrophy, and gastrointestinal, dermatological, and neurological problems. Top HIV-attributed symptoms were lack of stamina/energy in both genders, night sweats, depression, mood swings in women; and fatigue, lethargy, difficulties concentrating in men. Women attributed symptoms less frequently to HIV than men, particularly fa-tigue(p < .01). Top treatment-attributed symptoms were lipodystrophy and gastrointestinal problems in both genders. Symptom attribution to HIV-therapy did not differ between genders. Over the past six months, 22% switched/interrupted ART due to side effects. In women, side effect-related treatment decisions were more complex, involving more side effects and substances. Remarkably, women took predominantly protease inhibitor-sparing regimens (p = .05). Both genders reported only 15% of potential ART-related laboratory abnormalities but more than 50% had laboratory abnormalities. Notably, women had fewer elevated renal parameters (p < .01). Conclusions Men may attribute symptoms more often to HIV and maintain a treatment-regimen despite side effects, whereas women may be more prudent in avoiding treatment side effects. Lacking awareness of laboratory abnormalities in both genders potentially indicates gaps in physician-patient communication. Gender differences in causal attributions of symptoms/side effects may influence treatment decisions. PMID:19380286

Type 1 diabetes: Syndromes in resource-challenged settings.

PubMed

Nagesh, V Sri; Kalra, Sanjay

2015-06-01

Type 1 Diabetes is a complex disorder that is made more complex by the myriad of co-morbid conditions associated with it. Mauriac Syndrome is a well-known but nowadays uncommon condition that presents with growth retardation secondary to poor glycaemic control. Limited Joint Mobility is an often-missed association of diabetes. Its importance lies in the fact that it can cause significant impairment of fine movements in T1DM children. It also indicates poor glycaemic control over a long period of time and can be used as a surrogate marker for development of diabetic microvascular complications. Anaemia in T1DM is protean and can develop due to a combination of nutritional factors, chronic renal disease, coeliac disease and worm infestation. Management is etiological. Vitamin deficiencies are ubiquitous in T1DM and if left untreated, can lead to neurological, haematological and skeletal dysfunction. The best-known co-morbid conditions are the local site reactions clubbed together under the moniker lipodystrophies. These can be either atrophic or hypertrophic and are usually due to repeated injections at the same site, improper technique and needle re-use. Management is often difficult and they are best prevented by appropriate diabetes education and emphasis on proper injection techniques at the time of T1DM diagnosis, with periodic reinforcement. Amyloidosis is a little known condition that shares a lot of features in common with the lipodystrophies and often needs to be differentiated from lipohypertrophy. T1DM is a disease which is often associated with a poor quality of life and these co-morbid conditions also need to be treated for effective general and psychological well-being.

From wasting to obesity, changes in nutritional concerns in HIV/AIDS.

PubMed

Mankal, Pavan K; Kotler, Donald P

2014-09-01

Optimal nutrition is an important part of human immunodeficiency virus (HIV) care; to support the immune system, limit HIV-associated complications as well as maintain better quality of life and survival. The presentation and nature of malnutrition in patients with HIV has changed dramatically over the past 30 years from predominantly a wasting syndrome to lipodystrophy and, now, frailty. Nevertheless, we continue to see all 3 presentations in patient care today. The pathogenesis of poor nutrition in HIV-infected patients depends on caloric intake, intestinal nutrient absorption/translocation, and resting energy expenditure, which are features seen in all chronic diseases. Copyright © 2014 Elsevier Inc. All rights reserved.

Leptin and Hormones: Energy Homeostasis.

PubMed

Triantafyllou, Georgios A; Paschou, Stavroula A; Mantzoros, Christos S

2016-09-01

Leptin, a 167 amino acid adipokine, plays a major role in human energy homeostasis. Its actions are mediated through binding to leptin receptor and activating JAK-STAT3 signal transduction pathway. It is expressed mainly in adipocytes, and its circulating levels reflect the body's energy stores in adipose tissue. Recombinant methionyl human leptin has been FDA approved for patients with generalized non-HIV lipodystrophy and for compassionate use in subjects with congenital leptin deficiency. The purpose of this review is to outline the role of leptin in energy homeostasis, as well as its interaction with other hormones. Copyright © 2016 Elsevier Inc. All rights reserved.

Physiology of leptin: energy homeostasis, neuroendocrine function and metabolism.

PubMed

Park, Hyeong-Kyu; Ahima, Rexford S

2015-01-01

Leptin is secreted by adipose tissue and regulates energy homeostasis, neuroendocrine function, metabolism, immune function and other systems through its effects on the central nervous system and peripheral tissues. Leptin administration has been shown to restore metabolic and neuroendocrine abnormalities in individuals with leptin-deficient states, including hypothalamic amenorrhea and lipoatrophy. In contrast, obese individuals are resistant to leptin. Recombinant leptin is beneficial in patients with congenital leptin deficiency or generalized lipodystrophy. However, further research on molecular mediators of leptin resistance is needed for the development of targeted leptin sensitizing therapies for obesity and related metabolic diseases. Copyright © 2015 Elsevier Inc. All rights reserved.

[Fasciae latae perforator flap for breast reconstruction: An attractive alternative in case of DIEP contraindication].

PubMed

Lefèvre, M; Sarfati, B; Honart, J-F; Alkashnam, H; Rimareix, F; Leymarie, N; Kolb, F

2017-02-01

The musculocutaneous tensor fascia latae flap was one of the first free flaps described. It is possible to harvest a flap with the same skin paddle, vascularized by a septo-cutaneous perforator running through the tensor fascia lata muscle septum and coming from the ascending branch of the lateral circumflex femoral artery. The DIEP is currently the workhorse of autologous breast reconstruction, but there are some contraindications. The septo-cutaneous tensor fascia latae perforator flap may be an alternative for women with lateral upper thigh lipodystrophy. Between 2010 and 2014, three flaps have been performed in two patients for delayed breast reconstruction (one case of unilateral reconstruction, and one bilateral). Perforators were identified by preoperative angiography. The intervention was performed in a two-team approach, in only one operative position. Perforators were located in the horizontal axis of the upper rim of the pubis bone. One perforator artery was dissected for each flap. The mean caliber of the pedicle was 2.8mm, and the mean length was 6.4cm. The operative time was 240minutes for unilateral flap, 375minutes for bilateral flap. There was no case of total or partial necrosis, or complications on the donor site. Cosmetic results were considered satisfying by patients and surgeons with the reconstructed breast as well as the donor site. Septo-cutaneous fascia lata perforator flap is an attractive flap for breast reconstruction in patients with DIEP contraindication and lateral upper thigh lipodystrophy. It has many advantages: easy to harvest, length and calibre of the pedicle, double team approach, only one operating position, quality of reconstruction. It is necessary to carry out a larger series of cases to study the complication rate in the donor site. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

Adipose tissue expandability and the early origins of PCOS.

PubMed

de Zegher, Francis; Lopez-Bermejo, Abel; Ibáñez, Lourdes

2009-11-01

The most prevalent phenotypes of polycystic ovary syndrome (PCOS) are characterized by insulin resistance and androgen excess. The adipose tissue (AT) expandability hypothesis explains the development of insulin resistance in obesity and in cases of AT deficit. In line with this hypothesis, we propose that hyperinsulinemic androgen excess in PCOS is often underpinned by exhaustion of the capacity to expand subcutaneous AT in a metabolically safe way. Such exhaustion might occur when a positive energy imbalance meets a normal fat-storage capacity and/or when a normal energy balance faces a low fat storage capacity. This concept thus explains how PCOS phenotypes might result from obesity, prenatal growth restraint or a genetic lipodystrophy, or, experimentally, from prenatal androgen excess.

[Antioxidant activity of hepatotropic preparations in the treatment of chronic diseases of the liver].

PubMed

Loginov, A S; Matiushin, B N; Sukhareva, G V; Tkachev, V D

1988-01-01

Hepatotropic drugs were shown to decrease blood lipid peroxidation activity (LPO) in patients with chronic diffuse liver diseases. A positive time course of LPO indices was noted in the treatment of chronic active hepatitis and liver cirrhosis of moderate activity. Comparison of antioxidant features of the drugs were suggestive of a noticeable effect of trophopar and essential in patients with chronic active hepatitis, trophopar in patients with liver lipodystrophy, and drugs of a silimarina series in patients with liver cirrhosis. Under clinical conditions the effect of the drugs on LPO processes was less noticeable than in experiments in vitro. It is assumed that the pharmacological effect of the hepatotropic drugs is associated with their antioxidant activity.

Diagnostic et traitement de la Maladie du charbon à localisation palpébrale: à propos d'un cas et revue de littérature

PubMed Central

Hafidi, Zouheir; Handor, Hanan; Laghmari, Mina; Handor, Najat; Cherkaoui, Lalla Ouafae; Tachfouti, Samira; Seffar, Myriame; Daoudi, Rajae

2013-01-01

L′anthrax est une zoonose causée par le Bacillus anthracis. les humains contractent généralement cette maladie dans des régions endémiques, par contact direct avec des animaux infectés ou avec leurs produits contaminés. Les localisations palpébrales sont rares dans la pratique clinique et posent des problèmes de diagnostic différentiel. Les auteurs rapportent l'observation d'un patient admis dans un tableau de cellulite préseptale, avec escarre noirâtre étendue de la paupière supérieure et œdème extensif de l′hémiface, faisant suspecter une localisation palpébrale de la maladie du charbon. L'examen bactériologique a permis de confirmer le diagnostic. Le patient a bénéficié d′une antibiothérapie à base de pénicilline G avec une bonne évolution. PMID:24171070

New-generation radiofrequency technology.

PubMed

Krueger, Nils; Sadick, Neil S

2013-01-01

Radiofrequency (RF) technology has become a standard treatment in aesthetic medicine with many indications due to its versatility, efficacy, and safety. It is used worldwide for cellulite reduction; acne scar revision; and treatment of hypertrophic scars and keloids, rosacea, and inflammatory acne in all skin types. However, the most common indication for RF technology is the nonablative tightening of tissue to improve skin laxity and reduce wrinkles. Radiofrequency devices are classified as unipolar, bipolar, or multipolar depending on the number of electrodes used. Additional modalities include fractional RF; sublative RF; phase-controlled RF; and combination RF therapies that apply light, massage, or pulsed electromagnetic fields (PEMFs). This article reviews studies and case series on these devices. Radiofrequency technology for aesthetic medicine has seen rapid advancements since it was used for skin tightening in 2003. Future developments will continue to keep RF technology at the forefront of the dermatologist's armamentarium for skin tightening and rejuvenation.

Noninvasive radio frequency for skin tightening and body contouring.

PubMed

Weiss, Robert A

2013-03-01

The medical use of radio frequency (RF) is based on an oscillating electrical current forcing collisions between charged molecules and ions, which are then transformed into heat. RF heating occurs irrespective of chromophore or skin type and is not dependent on selective photothermolysis. RF can be delivered using monopolar, bipolar, and unipolar devices, and each method has theoretical limits of depth penetration. A variant of bipolar delivery is fractional RF delivery. In monopolar configurations, RF will penetrate deeply and return via a grounding electrode. Multiple devices are available and are detailed later in the text. RF thermal stimulation is believed to result in a microinflammatory process that promotes new collagen. By manipulating skin cooling, RF can also be used for heating and reduction of fat. Currently, the most common uses of RF-based devices are to noninvasively manage and treat skin tightening of lax skin (including sagging jowls, abdomen, thighs, and arms), as well as wrinkle reduction, cellulite improvement, and body contouring.

Psychosocial aspects of beauty: how and why to look good.

PubMed

Koblenzer, Caroline S

2003-01-01

It is difficult to pick up a paper or magazine today or turn on the television without being reminded that ours is a culture of youth and beauty. Bookstore shelves sag under the weight of enticing tomes devoted to the subject. We are bombarded with advertisements for any one of thousands of different products, both prescription and over-the-counter, that claim to be able to restore our youthful appearance, banish wrinkles, tone skin, and remove cellulite, among other promises that often sound, and probably are, too good to be true. Health food stores and sales catalogs are replete with myriad products, so that one wonders how the average person, in face of such bombardment, can either resist the temptation to buy or make an informed selection from the veritable feast of goodies put before them. Billions of dollars are expended each year, and false claims abound, but fortunately, there are many preparations and procedures that, in skilled hands, can really make a difference.

Could metabolic syndrome, lipodystrophy, and aging be mesenchymal stem cell exhaustion syndromes?

PubMed

Mansilla, Eduardo; Díaz Aquino, Vanina; Zambón, Daniel; Marin, Gustavo Horacio; Mártire, Karina; Roque, Gustavo; Ichim, Thomas; Riordan, Neil H; Patel, Amit; Sturla, Flavio; Larsen, Gustavo; Spretz, Rubén; Núñez, Luis; Soratti, Carlos; Ibar, Ricardo; van Leeuwen, Michiel; Tau, José María; Drago, Hugo; Maceira, Alberto

2011-01-01

One of the most important and complex diseases of modern society is metabolic syndrome. This syndrome has not been completely understood, and therefore an effective treatment is not available yet. We propose a possible stem cell mechanism involved in the development of metabolic syndrome. This way of thinking lets us consider also other significant pathologies that could have similar etiopathogenic pathways, like lipodystrophic syndromes, progeria, and aging. All these clinical situations could be the consequence of a progressive and persistent stem cell exhaustion syndrome (SCES). The main outcome of this SCES would be an irreversible loss of the effective regenerative mesenchymal stem cells (MSCs) pools. In this way, the normal repairing capacities of the organism could become inefficient. Our point of view could open the possibility for a new strategy of treatment in metabolic syndrome, lipodystrophic syndromes, progeria, and even aging: stem cell therapies.

Could Metabolic Syndrome, Lipodystrophy, and Aging Be Mesenchymal Stem Cell Exhaustion Syndromes?

PubMed Central

Mansilla, Eduardo; Díaz Aquino, Vanina; Zambón, Daniel; Marin, Gustavo Horacio; Mártire, Karina; Roque, Gustavo; Ichim, Thomas; Riordan, Neil H.; Patel, Amit; Sturla, Flavio; Larsen, Gustavo; Spretz, Rubén; Núñez, Luis; Soratti, Carlos; Ibar, Ricardo; van Leeuwen, Michiel; Tau, José María; Drago, Hugo; Maceira, Alberto

2011-01-01

One of the most important and complex diseases of modern society is metabolic syndrome. This syndrome has not been completely understood, and therefore an effective treatment is not available yet. We propose a possible stem cell mechanism involved in the development of metabolic syndrome. This way of thinking lets us consider also other significant pathologies that could have similar etiopathogenic pathways, like lipodystrophic syndromes, progeria, and aging. All these clinical situations could be the consequence of a progressive and persistent stem cell exhaustion syndrome (SCES). The main outcome of this SCES would be an irreversible loss of the effective regenerative mesenchymal stem cells (MSCs) pools. In this way, the normal repairing capacities of the organism could become inefficient. Our point of view could open the possibility for a new strategy of treatment in metabolic syndrome, lipodystrophic syndromes, progeria, and even aging: stem cell therapies. PMID:21716667

Psychological morbidity and facial volume in HIV lipodystrophy: quantification of treatment outcome.

PubMed

Nelson, Lisa; Stewart, Kenneth J

2012-04-01

HIV lipoatrophy is a stigmatizing condition associated with significant psychological morbidity. The aim of this study was to evaluate change in facial volume and psychological morbidity following treatment with autologous fat, Sculptra and Bio-alcamid. HIV LD patients were treated based on a clinical assessment in a prospective, observational study. 3-D images were obtained pre-operatively then at 2, 6 and 12 months post-operatively using the DI3D system. Volume changes were measured using DI3D software. The DAS-24 and HADS were used to assess psychological morbidity at similar time intervals. Forty-eight patients with HIV LD were treated: 16 patients had Bio-alcamid, 20 patients received Sculptra and 12 patients underwent fat transfer. The mean injected volume of Bio-alcamid was 25.5 cc which was comparable to the measured volume change at follow-up. The mean injected volume of fat was 20.1 cc, which did not differ from the measured volumes at 2 months. There was a mean reduction in measured volume change to11.2 cc at 6 months and 10 cc at 12 months. For Sculptra, the mean volume change compared to baseline was 8.7 cc at 2 months, increasing to 12.6 cc at 6 months and 12.3 cc at 12 months. ANOVA tests demonstrated no difference in psychological outcomes between groups. There was a significant improvement in DAS-24 scores compared to baseline for all 3 groups. No correlation between change in facial volume and psychological measures was demonstrated. Change in 3-D measured facial volume for all 3 groups was seen. Treatment was associated with improved body image perception. Copyright © 2011 British Association of Plastic, Reconstructive and Aesthetic Surgeons. Published by Elsevier Ltd. All rights reserved.

Challenges to diagnosis of HIV-associated wasting.

PubMed

Kotler, Donald

2004-12-01

There is a wide variability in the clinical presentation of the protein energy malnutrition often characterized as wasting in patients infected with HIV. Moreover, the clinical presentation has evolved over time. Initially, protein energy malnutrition was characterized by profound weight loss and depletion of body cell mass (BCM). Recently, unrelated concurrent metabolic abnormalities, such as lipodystrophy, may complicate the diagnosis of HIV wasting. Although measures of BCM are relatively accurate for the diagnosis of HIV wasting, the optimal tools for assessing BCM are not necessarily available to the clinician. From the practical standpoint, HIV wasting may be a self-evident diagnosis in advanced stages, but effective interpretation of the early signs of HIV wasting requires familiarity with other complications included in the differential diagnosis.

Successful Treatment of an Unusual Case of FPLD2: The Role of Roux-en-Y Gastric Bypass-Case Report and Literature Review.

PubMed

Grundfest-Broniatowski, Sharon; Yan, JingLiang; Kroh, Matthew; Kilim, Holly; Stephenson, Andrew

2017-04-01

Familial partial lipodystrophy type 2 (FPLD2) is a rare disorder associated with LMNA gene mutations. It is usually marked by loss of subcutaneous fat on the limbs and trunk and severe insulin resistance. Scattered reports have indicated that Roux-en-Y bypass helps to control the diabetes mellitus in these patients. We present here a very unusual patient with FPLD2 who had life-threatening retroperitoneal and renal fat accumulation accompanied by bilateral renal cancers. Following cryotherapy of one renal cancer and a contralateral nephrectomy with debulking of the retroperitoneal fat, Roux-en-Y gastric bypass (RYGB) has successfully controlled the disease for 3 years. The clinical presentations and causes of FPLD are reviewed and the role of RYGB is discussed.

Dietary fat composition, total body fat and regional body fat distribution in two Caucasian populations of middle-aged and older adult women.

PubMed

Muka, Taulant; Blekkenhorst, Lauren C; Lewis, Joshua R; Prince, Richar L; Erler, Nicole S; Hofman, Albert; Franco, Oscar H; Rivadeneira, Fernando; Kiefte-de Jong, Jessica C

2017-10-01

We aimed to study whether dietary fat composition (n-3 and n-6 polyunsaturated fatty acids ratio (PUFAs) and PUFAs and saturated fatty acids (SFAs) ratio) is associated with total body fat (TF) and body fat distribution and whether this association was modified by the presence of chronic disease in middle-aged and elderly women in two population-based cohorts in the Netherlands and Australia. The study was performed in the Rotterdam Study (RS), a prospective cohort study among subjects aged 55 years and older (N = 1182 women) and the Calcium Intake Fracture Outcome Study (CAIFOS), a 5-year randomized controlled trial among women age 70+ (N = 891). At baseline, diet (i.e. PUFAs and SFAs) was measured by validated food frequency questionnaires. TF was assessed using Dual-energy X-ray absorptiometry in both studies and android abdominal fat (AF), gynoid fat (GF) and the android/gynoid ratio (A/G ratio) in the RS but not the CAIFOS. Chronic disease was defined as the presence of cardiovascular disease, diabetes mellitus and cancer. No association was found between dietary n-3/n-6 PUFAs ratio or SFA/PUFAs ratio with TF in both cohorts. In the RS, a high n-3/n-6 PUFAs ratio was associated with a higher AF (3rd vs. 2nd tertile (reference): β: 0.15; 95% CI: 0.05, 0.24) but not with the A/G ratio. A low SFA/PUFA ratio was associated with a lower AF (1st vs. 2nd tertile (reference): β: -0.12; 95% CI: -0.22, -0.06) but not with the A/G ratio. Presence of chronic disease was found to be a significant effect modifier in both cohorts with regard to n-3/n-6 PUFAs and TF (P < 0.05). In participants without chronic disease, a higher n-3/n-6 PUFAs ratio was associated with a higher TF in the RS cohort (3rd vs. 2nd tertile (reference): β: 0.94; 95% CI: 0.12, 1.76), but this was not replicated in CAIFOS. These findings do not support the hypothesis that dietary fat composition is consistently associated with TF and body fat distribution in women. Future studies should clarify

The effects of pre- and post-exercise consumption of multi-ingredient performance supplements on cardiovascular health and body fat in trained men after six weeks of resistance training: a stratified, randomized, double-blind study

PubMed Central

2013-01-01

Background The cardiovascular (CV) and metabolic health benefits or risks associated with consumption of multi-ingredient performance supplements (MIPS) in conjunction with periodized resistance training (RT) in resistance-trained men are unknown. This population is a major target audience for performance supplements, and therefore, the purpose of this study was to investigate the combined effect of RT and commercially available pre- and post-exercise performance supplements on CV health and body fat in resistance-trained men. Methods Twenty-four resistance-trained men completed six weeks (three times/week) of periodized RT while either ingesting SHOT 15-min pre-exercise and SYN immediately post-exercise (multi-ingredient performance supplement group: MIPS) or an isocaloric maltodextrin placebo 15-min pre-exercise and immediately post-exercise (Placebo group). Before and after six weeks of RT and supplementation, resting heart rate (HR), blood pressure (BP), total body fat, android fat, gynoid fat, fat-free mass (FFM) and fasting blood measures of glucose, lipids, nitrate/nitrite (NOx), cortisol and high sensitivity C-reactive protein (hs-CRP) were measured. Statistical analysis was conducted using a one-way ANOVA for baseline differences and a 2 × 2 (group × time) repeated measures ANOVA and Tukey post-hoc tests where appropriate. Significance was set at p < 0.05. Results There was no group × time interaction for HR, BP, blood glucose, lipids, NOx, hs-CRP, cortisol concentrations or body fat. However, there was a time effect where significant decreases in body fat (mean ± SD; MIPS: -1.2 ± 1.2%; Placebo: -0.9 ± 1.1%), android fat (MIPS: -1.8 ± 2.1%; Placebo: -1.6 ± 2.0%), and gynoid fat (MIPS: -1.3 ± 1.6%; Placebo: -1.0 ± 1.4%) for both groups were observed. FFM increased in both groups, and a group × time interaction was observed with MIPS increasing significantly more than the Placebo group (4.2% vs. 1

Prenatal pesticide exposure and PON1 genotype associated with adolescent body fat distribution evaluated by dual X-ray absorptiometry (DXA).

PubMed

Tinggaard, J; Wohlfahrt-Veje, C; Husby, S; Christiansen, L; Skakkebaek, N E; Jensen, T K; Grandjean, P; Main, K M; Andersen, H R

2016-07-01

Many modern pesticides have endocrine disrupting abilities and early-life exposure may affect growth and disease risk later in life. Previously, we reported associations between prenatal pesticide exposure and higher childhood body fat content measured by anthropometry. The associations were affected by child PON1 Q192R genotype. We aimed to study whether prenatal pesticide exposure was still associated with body fat content and distribution in the children at puberty and the potential impact of both maternal and child PON1 Q192R genotype. In this prospective cohort study of 247 children born by occupationally exposed or unexposed women (greenhouse workers and controls) two follow-up examinations (age 10-15 and 11-16 years) including simple anthropometry, skinfold measurements, pubertal staging and blood sampling were performed. Total and regional fat% was determined by dual X-ray absorptiometry (DXA) at age 10-15. Prenatal pesticide exposure was associated with increased total, android, and gynoid fat percentage (DXA) at age 10-15 years after adjustment for sex, socioeconomic status, and puberty (all β = 0.5 standard deviation score (SDS) p < 0.05). Stratified by sex, the associations were significant in girls (total fat: β = 0.7 SDS, android-gynoid ratio: β = 0.1, both p < 0.05), but not in boys. Carrying the R-allele (child or mother, separately, or both) augmented the differences between exposed and unexposed children (total fat: β = 1.0 SDS, β = 0.8 SDS, p < 0.05, respectively, and β = 1.2 SDS, p < 0.01). No exposure-related differences were found if either the child or mother had the QQ wild-type. At age 11-16, exposed children tended to have a higher total fat% estimated by skinfolds than unexposed children (p = 0.06). No significant associations between prenatal exposure and body mass index or waist circumference were found. Prenatal pesticide exposure was associated with higher adolescent body fat content, including android

The long road to leptin.

PubMed

Friedman, Jeffrey

2016-12-01

Leptin is an adipose tissue hormone that functions as an afferent signal in a negative feedback loop that maintains homeostatic control of adipose tissue mass. This endocrine system thus serves a critical evolutionary function by protecting individuals from the risks associated with being too thin (starvation) or too obese (predation and temperature dysregulation). Mutations in leptin or its receptor cause massive obesity in mice and humans, and leptin can effectively treat obesity in leptin-deficient patients. Leptin acts on neurons in the hypothalamus and elsewhere to elicit its effects, and mutations that affect the function of this neural circuit cause Mendelian forms of obesity. Leptin levels fall during starvation and elicit adaptive responses in many other physiologic systems, the net effect of which is to reduce energy expenditure. These effects include cessation of menstruation, insulin resistance, alterations of immune function, and neuroendocrine dysfunction, among others. Some or all of these effects are also seen in patients with constitutively low leptin levels, such as occur in lipodystrophy. Leptin is an approved treatment for generalized lipodystrophy, a condition associated with severe metabolic disease, and has also shown potential for the treatment of other types of diabetes. In addition, leptin restores reproductive capacity and increases bone mineral density in patients with hypothalamic amenorrhea, an infertility syndrome in females. Most obese patients have high endogenous levels of leptin, in some instances as a result of mutations in the neural circuit on which leptin acts, though in most cases, the pathogenesis of leptin resistance is not known. Obese patients with leptin resistance show a variable response to exogenous leptin but may respond to a combination of leptin plus amylin. Overall, the identification of leptin has provided a framework for studying the pathogenesis of obesity in the general population, clarified the nature of the

Nursing sickness in the mink--a metabolic mystery or a familiar foe?

PubMed

Rouvinen-Watt, Kirsti

2003-07-01

Nursing sickness, the largest single cause of mortality in adult female mink (Mustela vison), is an example of a metabolic disorder, which develops when the demands for lactation require extensive mobilization of body energy reserves. The condition is characterized by progressive weight loss, emaciation, and dehydration with high concentrations of glucose and insulin in the blood. Morbidity due to nursing sickness can be as high as 15% with mortality around 8%, but the incidence is known to vary from year to year. Stress has been shown to trigger the onset of the disease and old females and females with large litters are most often affected. Increasing demand for gluconeogenesis from amino acids due to heavy milk production may be a predisposing factor. Glucose metabolism is inextricably linked to that of protein and fats. In obesity (or lipodystrophy), the ability of adipose tissue to buffer the daily influx of nutrients is overwhelmed (or absent), interfering with insulin-mediated glucose disposal and leading to insulin resistance. Polyunsaturated fatty acids of the n-3 family play an important role in modulating insulin signalling and glucose uptake by peripheral tissue. The increasing demand on these fatty acids for milk fat synthesis towards late lactation may result in deficiency in the lactating female, thus impairing glucose disposal. It is suggested that the underlying cause of mink nursing sickness is the development of acquired insulin resistance with 3 contributing key elements: obesity (or lipodystrophy), n-3 fatty acid deficiency, and high protein oxidation rate. It is recommended that mink breeder females be kept in moderate body condition during fall and winter to avoid fattening or emaciation. A dietary n-3 fatty acid supplement during the lactation period may be beneficial for improved glycemic control. Lowering of dietary protein reduces (oxidative) stress and improves water balance in the nursing females and may, therefore, prevent the

Laminopathies and the long strange trip from basic cell biology to therapy

PubMed Central

Worman, Howard J.; Fong, Loren G.; Muchir, Antoine; Young, Stephen G.

2009-01-01

The main function of the nuclear lamina, an intermediate filament meshwork lying primarily beneath the inner nuclear membrane, is to provide structural scaffolding for the cell nucleus. However, the lamina also serves other functions, such as having a role in chromatin organization, connecting the nucleus to the cytoplasm, gene transcription, and mitosis. In somatic cells, the main protein constituents of the nuclear lamina are lamins A, C, B1, and B2. Interest in the nuclear lamins increased dramatically in recent years with the realization that mutations in LMNA, the gene encoding lamins A and C, cause a panoply of human diseases (“laminopathies”), including muscular dystrophy, cardiomyopathy, partial lipodystrophy, and progeroid syndromes. Here, we review the laminopathies and the long strange trip from basic cell biology to therapeutic approaches for these diseases. PMID:19587457

Human immunodeficiency virus endocrinopathy

PubMed Central

Sinha, Uma; Sengupta, Nilanjan; Mukhopadhyay, Prasanta; Roy, Keshab Sinha

2011-01-01

Human immunodeficiency virus (HIV) endocrinopathy encompasses a broad spectrum of disorders. Almost all the endocrine organs are virtually affected by HIV infection. HIV can directly alter glandular function. More commonly secondary endocrine dysfunction occurs due to opportunistic infections and neoplasms in immunocompromised state. The complex interaction between HIV infection and endocrine system may be manifested as subtle biochemical and hormonal perturbation to overt glandular failure. Antiretroviral therapy as well as other essential medications often result in adverse endocrinal consequences. Apart from adrenal insufficiency, hypogonadism, diabetes and bone loss, AIDS wasting syndrome and HIV lipodystrophy need special reference. Endocrinal evaluation should proceed as in other patients with suspected endocrine dysfunction. Available treatment options have been shown to improve quality of life and long-term mortality in AIDS patients. PMID:22028995

Morphology alterations of skin and subcutaneous fat at NIR laser irradiation combined with delivery of encapsulated indocyanine green

NASA Astrophysics Data System (ADS)

Yanina, Irina Yu.; Navolokin, Nikita A.; Svenskaya, Yulia I.; Bucharskaya, Alla B.; Maslyakova, Galina N.; Gorin, Dmitry A.; Sukhorukov, Gleb B.; Tuchin, Valery V.

2017-05-01

The goal of this study is to quantify the impact of the in vivo photochemical treatment of rats with obesity using indocyanine green (ICG) dissolved in saline or dispersed in an encapsulated form at NIR laser irradiation, which was monitored by tissue sampling and histochemistry. The subcutaneous injection of the ICG solution or ICG encapsulated into polyelectrolyte microcapsules, followed by diode laser irradiation (808 nm, 8 W/cm2, 1 min), resulted in substantial differences in lipolysis of subcutaneous fat. Most of the morphology alterations occurred in response to the laser irradiation if a free-ICG solution had been injected. In such conditions, membrane disruption, stretching, and even delamination in some cases were observed for a number of cells. The encapsulated ICG aroused similar morphology changes but with weakly expressed adipocyte destruction under the laser irradiation. The Cochran Q test rendered the difference between the treatment alternatives statistically significant. By this means, laser treatment using the encapsulated form of ICG seems more promising and could be used for safe layerwise laser treatment of obesity and cellulite.

Morphology alterations of skin and subcutaneous fat at NIR laser irradiation combined with delivery of encapsulated indocyanine green.

PubMed

Yanina, Irina Yu; Navolokin, Nikita A; Svenskaya, Yulia I; Bucharskaya, Alla B; Maslyakova, Galina N; Gorin, Dmitry A; Sukhorukov, Gleb B; Tuchin, Valery V

2017-05-01

The goal of this study is to quantify the impact of the in vivo photochemical treatment of rats with obesity using indocyanine green (ICG) dissolved in saline or dispersed in an encapsulated form at NIR laser irradiation, which was monitored by tissue sampling and histochemistry. The subcutaneous injection of the ICG solution or ICG encapsulated into polyelectrolyte microcapsules, followed by diode laser irradiation (808 nm, 8 ?? W / cm 2 , 1 min), resulted in substantial differences in lipolysis of subcutaneous fat. Most of the morphology alterations occurred in response to the laser irradiation if a free-ICG solution had been injected. In such conditions, membrane disruption, stretching, and even delamination in some cases were observed for a number of cells. The encapsulated ICG aroused similar morphology changes but with weakly expressed adipocyte destruction under the laser irradiation. The Cochran Q test rendered the difference between the treatment alternatives statistically significant. By this means, laser treatment using the encapsulated form of ICG seems more promising and could be used for safe layerwise laser treatment of obesity and cellulite.

The accordion gracilis muscle flap: a new design for coverage of recurrent and complicated ischeal pressure sores.

PubMed

El-Sabbagh, Ahmed H

2011-10-01

Management of patients with large or recurrent pressure ulcerations can be complicated by the lack of available local flap, whether already used or because adjacent lesions make such flap insufficient for complete coverage. In this article, the gracilis muscle was modified to cover large defects without help from its cutaneous territory. Twelve ischeal pressure sores were treated between August 2007 and 2009 with the modified gracilis muscle flap in a single-staged procedure. Five ulcers were recurrent and seven patients have associated pressure ulcers. All reconstructions were successful. Mean patient age was 35 years and nearly all patients had multiple significant comorbidities, including associated ulcers, diabetes and urethrocutaneous fistula. All flaps and donor sites healed uneventfully. There was one complication presented as cellulites at the donor site. Follow-up in some cases extend up to 1·5 years. No recurrence was observed. The accordion gracilis muscle flap is a handy, safe and fast flap for reconstruction of recurrent, difficult ischeal pressure sores. © 2011 The Author. © 2011 Blackwell Publishing Ltd and Medicalhelplines.com Inc.

Body fat distribution of overweight females with a history of weight cycling.

PubMed

Wallner, S J; Luschnigg, N; Schnedl, W J; Lahousen, T; Sudi, K; Crailsheim, K; Möller, R; Tafeit, E; Horejsi, R

2004-09-01

Weight cycling may cause a redistribution of body fat to the upper body fat compartments. We investigated the distribution of subcutaneous adipose tissue (SAT) in 30 overweight women with a history of weight-cycling and age-matched controls (167 normal weight and 97 overweight subjects). Measurements of SAT were performed using an optical device, the Lipometer. The SAT topography describes the thicknesses of SAT layers at 15 anatomically well-defined body sites from neck to calf. The overweight women with a history of weight cycling had significantly thicker SAT layers on the upper body compared to the overweight controls, but even thinner SAT layers on their legs than the normal weight women. An android fat pattern was attributed to overweight females and, even more pronounced, to the weight cyclers. The majority of normal weight women showed a gynoid fat pattern. Using stepwise discriminant analysis, 89.0% of all weight cyclers and overweight controls could be classified correctly into the two groups. These findings show the importance of normal weight maintenance as a health-promoting factor.

Contributions of fat mass and fat distribution to hip bone strength in healthy postmenopausal Chinese women.

PubMed

Shao, Hong Da; Li, Guan Wu; Liu, Yong; Qiu, Yu You; Yao, Jian Hua; Tang, Guang Yu

2015-09-01

The fat and bone connection is complicated, and the effect of adipose tissue on hip bone strength remains unclear. The aim of this study was to clarify the relative contribution of body fat accumulation and fat distribution to the determination of proximal femur strength in healthy postmenopausal Chinese women. This cross-sectional study enrolled 528 healthy postmenopausal women without medication history or known diseases. Total lean mass (LM), appendicular LM (ALM), percentage of lean mass (PLM), total fat mass (FM), appendicular FM (AFM), percentage of body fat (PBF), android and gynoid fat amount, android-to-gynoid fat ratio (AOI), bone mineral density (BMD), and proximal femur geometry were measured by dual energy X-ray absorptiometry. Hip structure analysis was used to compute some variables as geometric strength-related parameters by analyzing the images of the hip generated from DXA scans. Correlation analyses among anthropometrics, variables of body composition and bone mass, and geometric indices of hip bone strength were performed with stepwise linear regression analyses as well as Pearson's correlation analysis. In univariate analysis, there were significantly inverse correlations between age, years since menopause (YSM), hip BMD, and hip geometric parameters. Bone data were positively related to height, body weight, LM, ALM, FM, AFM, and PBF but negatively related to AOI and amount of android fat (all P < 0.05). AFM and AOI were significantly related to most anthropometric parameters. AFM was positively associated with height, body weight, and BMI. AFM was negatively associated with age and YSM. AOI was negatively associated with height, body weight, and BMI. AOI positively associated with age and YSM. LM, ALM, and FM had a positive relationship with anthropometric parameters (P < 0.05 for all). PLM had a negative relationship with those parameters. The correlation between LM, ALM, FM, PLM, ALM, age, and YSM was not significant. In multivariate

Exploring factors related to changes in body composition, insulin sensitivity and aerobic capacity in response to a 12-week exercise intervention in overweight and obese women with and without polycystic ovary syndrome

PubMed Central

Harrison, Cheryce L.; Hutchison, Samantha; de Courten, Barbora; Stepto, Nigel K.

2017-01-01

Objective To determine factors associated with differential changes in body fat, insulin resistance and aerobic capacity following a 12-week exercise intervention in overweight and obese women with and without polycystic ovary syndrome (PCOS). Methods 16 overweight and obese women (9 PCOS; 7 without PCOS) completed a supervised progressive 12-week exercise program. Primary outcomes included changes in indicators of insulin sensitivity (including glucose infusion rate relative to fat-free mass [GIR/FFM]), body composition, and aerobic capacity (VO2 peak; 12 participants only). Comparisons were made between women with and without PCOS, and between participants who lost ≥5% (classified as exercise responders) and <5% (non-responders) in body fat (assessed by dual-energy X-ray absorptiometry). Results Training decreased body fat percentage by (mean; 95% CI) -2.3%; -5.3, 0.7% in women with PCOS and by -6.4%; -10.9, -1.9% in women without PCOS (P = 0.08). Ten women (7 PCOS; 3 without PCOS) did not reduce body fat by ≥5%. All participants improved VO2 peak (mean change 27%; 16–39%) but four (2 PCOS; 2 without PCOS) demonstrated decreases in GIR/FFM (mean change for whole cohort: 37%; 3–71%). Android-gynoid fat ratio (0.58; 0.51, 0.66 vs 0.46; 0.40, 0.51; P<0.01) was significantly higher and GIR/FFM (6.69; 3.49, 9.90 vs 11.44; 9.15, 13.72 mg/kg/min; P = 0.01) was significantly lower in non-responders compared with responders at baseline, but non-responders had significant post-training decreases in android-gynoid ratio (-0.02; -0.04, -0.01; P = 0.03), and increases in VO2 peak (7.24; 2.28, 12.21 mL/kg/min; P = 0.01) and GIR/FFM (1.44; 0.27, 2.61 mg/kg/min; P = 0.02). In women with PCOS, pre-training VO2 peak was significantly negatively correlated with change in total body fat (r = -0.75; P = 0.02), and pre-training fasting glucose negatively correlated with changes in VO2 peak (r = -0.76; P = 0.04), but positively correlated with changes in GIR (r = 0.67; P = 0

Visceral fat mass: is it the link between uric acid and diabetes risk?

PubMed

Seyed-Sadjadi, Neda; Berg, Jade; Bilgin, Ayse A; Grant, Ross

2017-07-24

Uric acid (UA) has been suggested as a novel risk factor for diabetes. However, its definite role in this prevalent disease is still the subject of much discussion because it is always accompanied with other major risk factors such as obesity and high visceral adiposity. In order to clarify the role of UA in diabetes, this study aimed to investigate the associations between plasma UA and fasting plasma glucose, HbA1c, lipid profile and inflammatory markers after accounting for the contribution of other diabetes risk factors such as BMI and VAT fat mass. In the present cross-sectional study, 100 non-diabetic middle-aged males (n = 48) and females (n = 52) were recruited. Central fat distribution measures including android to gynoid fat ratio, VAT and subcutaneous adipose tissue (SAT) fat mass were determined using dual-energy X-ray absorptiometry (DXA). Biochemical analysis was done using methods well established for clinical and research laboratories. Multiple linear regression analysis was performed to analyse the association between plasma UA and the biochemical and central fat distribution measures. UA was positivly associated with body mass index (BMI) (r (98) = 0.42, P ≤ 0.001), android to gynoid fat ratio (r (98) = 0.62, P ≤ 0.001) and VAT fat mass (r (96) = 0.55, P ≤ 0.001). UA was also positively associated with plasma glucose (r (98) = 0.33, P ≤ 0.001), hemoglobin A1c (r (93) = 0.25, P = 0.014), plasma triglyceride (r s (95) = 0.40, P ≤ 0.001), HDL cholesterol (r (98) = - 0.61, P ≤ 0.001) and CRP (r s (98) = 0.23, P = 0.026). However, these associations were no longer significant after accounting for BMI or/and VAT fat mass. No significant association was observed between UA and SAT fat mass (r (97) = 0.02, P ≥ 0.05), Total cholesterol (r (98) = 0.03, P ≥ 0.05), LDL cholesterol (r (98) = 0.13, P ≥ 0.05), TNF-α (r (97) = 0.12, P ≥ 0.05) and IL-6 (r (96) = -0.02, P ≥ 0

[Utility of atazanavir in special populations].

PubMed

Antela López, Antonio

2008-12-01

ART (antiretroviral therapy) currently continues to indefinitely prolong the survival of patients who live with HIV. Due to this, we are increasingly faced with specific problems that previously did not have time to develop or did not have the importance that they have now, and which are related to the existence of special patient populations. Examples of situations that characterise these special populations are: co-infection with hepatitis virus B and/or C, pregnancy, lipodystrophy, cardiovascular risk, renal failure, treatment of children and adolescents, immigrant health care, and the management of patients receiving methadone replacement therapy, among others. In this article we review the role that Atazanavir (ATV) can play in the ART of patients in the situations mentioned, except those that are already dealt with specifically in other articles, such as co-infection by hepatitis virus B and/or C.

Disruption of the Arabidopsis CGI-58 homologue produces Chanarin-Dorfman-like lipodystrophy in plants

USDA-ARS?s Scientific Manuscript database

CGI-58 is the defective gene in the human neutral lipid storage disease called Chanarin-Dorfman syndrome. This disorder causes intracellular lipid droplets to accumulate in nonadipose tissues, such as skin and blood cells. Here, disruption of the homologous CGI-58 gene in Arabidopsis thaliana result...

Evaluation and Management of Dyslipidemia in Patients with HIV Infection

PubMed Central

Green, Michael L

2002-01-01

OBJECTIVE Persons with HIV infection develop metabolic abnormalities related to their antiretroviral therapy and HIV infection itself. The objective of this study was to summarize the emerging evidence for the incidence, etiology, health risks, and treatment of dyslipidemias in HIV disease. DESIGN Systematic review of original research with quantitative synthesis. MAIN RESULTS Dyslipidemia is common in persons with HIV infection on highly active antiretroviral therapy (HAART), but methodologic differences between studies preclude precise estimates of prevalence and incidence. The typical pattern includes elevated total cholesterol, low-density lipoprotein cholesterol, and triglycerides, which may be markedly elevated. The dyslipidemia may be associated with lipodystrophy, insulin resistance, and, rarely, frank diabetes mellitus. Exposure to protease inhibitors (PIs) is associated with this entire range of metabolic abnormalities. PI-naïve patients on nucleoside reverse transcriptase inhibitors (NRTIs) may develop lipodystrophy, insulin resistance, hypercholesterolemia, and possibly modest elevations in triglycerides but not severe hypertriglyceridemia, which appears to be linked to PIs alone. Most studies have not found an association between CD4 lymphocyte count or HIV viral load and lipid abnormalities. The pathogenesis is incompletely understood and appears to be multifactorial. There are insufficient data to definitively support an increased coronary heart disease risk in patients with HIV-related dyslipidemia. However, some of the same metabolic abnormalities remain firmly established risk factors in other populations. Patients on HAART with severe hypertriglyceridemia may develop pancreatitis or other manifestations of the chylomicronemia syndrome. Some of the metabolic derangements (particularly hypertriglyceridemia) may improve upon replacing a PI with a non-nucleoside reverse transcriptase inhibitor. The limited experience suggests that fibrates

Predicting the short-term risk of diabetes in HIV-positive patients: the Data Collection on Adverse Events of Anti-HIV Drugs (D:A:D) study

PubMed Central

Petoumenos, Kathy; Worm, Signe W; Fontas, Eric; Weber, Rainer; De Wit, Stephane; Bruyand, Mathias; Reiss, Peter; El-Sadr, Wafaa; Monforte, Antonella D'Arminio; Friis-Møller, Nina; Lundgren, Jens D; Law, Matthew G

2012-01-01

Introduction HIV-positive patients receiving combination antiretroviral therapy (cART) frequently experience metabolic complications such as dyslipidemia and insulin resistance, as well as lipodystrophy, increasing the risk of cardiovascular disease (CVD) and diabetes mellitus (DM). Rates of DM and other glucose-associated disorders among HIV-positive patients have been reported to range between 2 and 14%, and in an ageing HIV-positive population, the prevalence of DM is expected to continue to increase. This study aims to develop a model to predict the short-term (six-month) risk of DM in HIV-positive populations and to compare the existing models developed in the general population. Methods All patients recruited to the Data Collection on Adverse events of Anti-HIV Drugs (D:A:D) study with follow-up data, without prior DM, myocardial infarction or other CVD events and with a complete DM risk factor profile were included. Conventional risk factors identified in the general population as well as key HIV-related factors were assessed using Poisson-regression methods. Expected probabilities of DM events were also determined based on the Framingham Offspring Study DM equation. The D:A:D and Framingham equations were then assessed using an internal-external validation process; area under the receiver operating characteristic (AUROC) curve and predicted DM events were determined. Results Of 33,308 patients, 16,632 (50%) patients were included, with 376 cases of new onset DM during 89,469 person-years (PY). Factors predictive of DM included higher glucose, body mass index (BMI) and triglyceride levels, and older age. Among HIV-related factors, recent CD4 counts of<200 cells/µL and lipodystrophy were predictive of new onset DM. The mean performance of the D:A:D and Framingham equations yielded AUROC of 0.894 (95% CI: 0.849, 0.940) and 0.877 (95% CI: 0.823, 0.932), respectively. The Framingham equation over-predicted DM events compared to D:A:D for lower glucose and lower

Cardiovascular risk and dyslipidemia among persons living with HIV: a review.

PubMed

Maggi, Paolo; Di Biagio, Antonio; Rusconi, Stefano; Cicalini, Stefania; D'Abbraccio, Maurizio; d'Ettorre, Gabriella; Martinelli, Canio; Nunnari, Giuseppe; Sighinolfi, Laura; Spagnuolo, Vincenzo; Squillace, Nicola

2017-08-09

may cause dyslipidemia and lipodystrophy, while integrase inhibitors have a minimal impact on lipids profile, and no evidence of lipodystrophy. There is still much to be written with the introduction of new drugs in clinical practice. Cardiovascular risk among HIV infected patients, interventions on behavior and lifestyles, use of drugs to reduce the risk, and switch in antiretroviral therapy, remain nowadays major issues in the management of HIV-infected patients.

A Comparison of Adverse Drug Reaction Profiles in Patients on Antiretroviral and Antitubercular Treatment in Zimbabwe.

PubMed

Masuka, Josiah T; Chipangura, Precious; Nyambayo, Priscilla P; Stergachis, Andy; Khoza, Star

2018-01-01

Few studies describe the adverse drug event profiles in patients simultaneously receiving antiretroviral and anti-tubercular medicines in resource-limited countries. To describe and compare the adverse drug reaction profiles in patients on highly active antiretroviral therapy only (HAART), HAART and isoniazid preventive therapy (HHART), and HAART and antitubercular treatment (ATTHAART). We analysed individual case safety reports (ICSRs) for patients on antiretroviral therapy and antitubercular treatment submitted to the national pharmacovigilance centre during the targeted spontaneous reporting (TSR) programme from 1 September 2012 through 31 August 2016. All reports considered certain, probable or possible were included in the analysis. A total of 1076 ICSRs were included in the analysis. Most of the reports were from the HAART only group (n = 882; 82.0%), followed by patients on HHART (n = 132; 12.3%), and ATTHAART (n = 62; 5.7%). The ATTHAART (35.5%) and HHAART (34.1%) had a higher frequency of hepatic disorders than the HAART group (5.0%) (p < 0.0001). A higher frequency of rash was reported in the HHAART (35.6%) and HAART groups (29.4%) than the ATTHAART group (14.5%) (p = 0.011). Peripheral neuropathy occurred more frequently in the ATTHAART group (19.3%) than other groups (p = 0.001) while Stevens-Johnson syndrome (14.7%; p < 0.001), gynaecomastia (18.2%; p < 0.001), and lipodystrophy (4.5%; p = 0.012) occurred more frequently in the HAART group. The HHAART group was associated with a higher frequency of psychosis (4.5%; p = 0.002). Antiretroviral therapy was associated with a higher frequency of Stevens-Johnson syndrome, gynaecomastia, and lipodystrophy. Co-administration of antiretroviral and antitubercular medicines was associated with a higher frequency of drug-induced liver injury and peripheral neuropathy. Similarly, co-administration of isoniazid preventive therapy and antiretroviral drugs was associated with a higher risk for

Non-invasive therapy of wrinkles and lax skin using a novel multisource phase-controlled radio frequency system.

PubMed

Elman, Monica; Vider, Itzhak; Harth, Yoram; Gottfried, Varda; Shemer, Avner

2010-04-01

Abstract The last few years have shown an increased demand for non-invasive skin tightening to improve body contour. Since light (lasers or intense pulsed light sources) has a limited ability to penetrate deep into the tissue, radio frequency (RF) modalities were introduced for the reduction of lax skin to achieve skin tightening and body circumference reduction. This study presents the use of the novel 3DEEP technology for body contouring. 3DEEP is a next generation RF technology that provides targeted heating to deeper skin layers without pain or other local or systemic side effects associated with the use of the earlier generation RF systems available today. The study included 30 treatment areas on 23 healthy volunteers at two sites. The treatment protocol included four weekly and two bi-weekly (n= 6) treatments on different body areas. Results were evaluated by standardized photography and by circumference measurements at the treatment area, and were compared to changes in body weight. Significant improvement could be observed in wrinkles and skin laxity, and in the appearance of stretch marks and cellulite. Some changes appeared as early as after a single treatment. Circumference changes of up to 4.3 cm were measured.

A randomized, controlled clinical study to investigate the safety and efficacy of acoustic wave therapy in body contouring.

PubMed

Nassar, Amer H; Dorizas, Andrew S; Shafai, Aria; Sadick, Neil S

2015-03-01

There is an increased demand for the reduction of localized adipose tissue by noninvasive methods. The objective of this study was to determine the safety and efficacy of noninvasive lipolysis of excess adiposities overlying the lateral thigh region using acoustic wave therapy (AWT). This study incorporates 2 mechanical waves with varying properties in the same session: radial and planar AWT. The treatment was performed using AWT on the lateral thigh areas of 15 female patients. The study was performed using the planar and radial pulse handpieces, with 8 sessions performed within 4 weeks. Follow-up visits were performed 1, 4, and 12 weeks after the last treatment. Reduction in both thigh circumference and subcutaneous fat layer thickness, measured through ultrasound, was observed. This study demonstrates that AWT is safe and efficacious for the treatment of localized adiposities in the saddlebag area. However, the results obtained were not statistically significant. Larger studies will be needed to further access the effects of AWT on thigh circumference reduction. Furthermore, the authors also found an improvement in the appearance of both cellulite and skin firmness after the treatments.

Coinfection by Aspergillus and zygomycetes species in a case of acute rhinosinusitis.

PubMed

Vaidya, Dhara; Shah, Parul

2011-01-01

Invasive mycotic infections can be effectively treated if rapid identification of fungus is obtained. We reported a case of coinfection by Aspergillus and Rhizopus sp. involving nose, paranasal sinuses, orbit, and brain in a 68-year-old known hypertensive male. He was presented to ENT OPD with history of fever and intermittent headache since fifteen days along with history of right-sided nasal obstruction and proptosis since seven days. CT scan of brain and paranasal sinuses showed findings of pansinusitis with cellulitic changes in right orbit. MRI confirmed the same along with features of intracranial extension with focal meningitis in right frontotemporal region. Laboratory parameters did not conclude much except for leucocytosis and hyponatremia. Patient was taken for endoscopic debridement from nose and paranasal sinuses, and tissue was sent for microbiological and histopathological examination. Minced tissue was processed, and after 48 hrs of incubation two types of growth were identified, one was yellowish, granular, and powdery consistent with Aspergillus sp., and another was cottony and woolly consistent with Rhizopus sp. LCB mount confirmed presence of Aspergillus flavus and Rhizopus arrhizus. Patient responded to therapy with IV amphotericin B and surgical debridement. On discharge patient's condition was good.

Elevated Adiponectin Serum Levels in Women with Systemic Autoimmune Diseases

PubMed Central

Toussirot, Éric; Gaugler, Béatrice; Bouhaddi, Malika; Nguyen, Nhu Uyen; Saas, Philippe; Dumoulin, Gilles

2010-01-01

Adipose tissue produces a wide range of proteins that may influence the immune system. In this study, we assessed the serum levels of leptin, adiponectin, and ghrelin, in association with the measurements of body composition, in 15 female patients with various autoimmune diseases (systemic lupus erythematosus, primary Sjögren's syndrome, sarcoidosis, mixed connective tissue disease, vasculitis, CREST syndrome, and polymyositis) and in 15 healthy female controls. There were no statistically significant differences between the patients and controls with regard to serum leptin, serum ghrelin, global fat mass, adiposity, and fat mass in the android or gynoid regions, whereas serum adiponectin levels were higher in patients than controls (16.3 ± 1.6 μg/mL versus 9.7 ± 0.6 μg/mL; P = .01). As adiponectin is known to exhibit potent anti-inflammatory properties, a high adiponectinemia in patients with systemic autoimmune disease may mitigate the inflammatory response. However, the precise consequences of these elevated serum adiponectin levels on the metabolic syndrome development and atherosclerotic cardiovascular risk in this patient population still needs to be determined. PMID:21234350

Pancreatic Islet Responses to Metabolic Trauma

PubMed Central

Burke, Susan J.; Karlstad, Michael D.; Collier, J. Jason

2016-01-01

Carbohydrate, lipid, and protein metabolism are largely controlled by the interplay of various hormones, which includes those secreted by the pancreatic islets of Langerhans. While typically representing only 1–2% of the total pancreatic mass, the islets have a remarkable ability to adapt to disparate situations demanding a change in hormone release, such as peripheral insulin resistance. There are many different routes to the onset of insulin resistance, including obesity, lipodystrophy, glucocorticoid excess, and the chronic usage of atypical anti-psychotic drugs. All of these situations are coupled to an increase in pancreatic islet size, often with a corresponding increase in insulin production. These adaptive responses within the islets are ultimately intended to maintain glycemic control and to promote macronutrient homeostasis during times of stress. Herein, we review the consequences of specific metabolic trauma that lead to insulin resistance and the corresponding adaptive alterations within the pancreatic islets. PMID:26974425

Juvenile Dermatomyositis: Key Roles of Muscle Magnetic Resonance Imaging and Early Aggressive Treatment.

PubMed

Corral-Magaña, O; Bauzá-Alonso, A F; Escudero-Góngora, M M; Lacruz, L; Martín-Santiago, A

2017-09-12

Juvenile dermatomyositis is a rare systemic connective tissue disease with onset during childhood. It presents clinically with proximal muscle weakness and characteristic skin involvement. Diagnosis is based on the Bohan and Peter criteria, though many authors are now substituting biopsy with muscle magnetic resonance imaging (MRI) for both diagnosis and follow-up. Without intensive early treatment, complications such as calcinosis cutis and lipodystrophy can develop in the chronic phases of the disease. Early recognition is therefore key to management. We present a series of 5 patients who were diagnosed with Juvenile dermatomyositis on muscle MRI without undergoing muscle biopsy and who received early treatment. We draw attention to the usefulness of muscle MRI for the diagnosis of muscle involvement and to the importance of early initiation of intensive treatment to prevent complications. Copyright © 2017 AEDV. Publicado por Elsevier España, S.L.U. All rights reserved.

[HIV infection in France in 2012: reality, risks and challenges for a chronic multisystem disease].

PubMed

Blot, M; Piroth, L

2012-06-01

Thirty years after the discovery of HIV and 15 years since the advent of Highly Active Antiretroviral Therapy (HAART), the features of HIV infection have evolved and need a new approach, which is both more comprehensive and specialized. Indeed, the burden of a chronic disease with multiple determining features has replaced the rapidly fatal infection of the past, which was almost exclusively related to the effects of immunosuppression. Physicians have to be concerned with "new risks" associated with treatment side effects; the consequences of ongoing inflammation and ageing of the HIV-infected population. These include metabolic, cardiovascular, neurocognitive and renal disease as well as lipodystrophy and malignancy. Antiretroviral treatment has been a major step forward, subject to accessibility, tolerance and adherence, but it has not solved all the problems associated with this infection, as it becomes a chronic illness. Copyright © 2012 SPLF. Published by Elsevier Masson SAS. All rights reserved.

Metabolic effects of the HIV protease inhibitor--saquinavir in differentiating human preadipocytes.

PubMed

Bociąga-Jasik, Monika; Polus, Anna; Góralska, Joanna; Czech, Urszula; Gruca, Anna; Śliwa, Agnieszka; Garlicki, Aleksander; Mach, Tomasz; Dembińska-Kieć, Aldona

2013-01-01

The iatrogenic, HIV-related lipodystrophy is associated with development of the significant metabolic and cardiovascular complications. The underlying mechanisms of antiretroviral (ARV) drugs are not completely explored. The aim of the study was to characterize effects of the protease inhibitor (PI)--saquinavir (SQV) on metabolic functions, and gene expression during differentiation in cells (Chub-S7) culture. SQV in concentrations observed during antiretroviral therapy (ART) significantly decreased mitochondrial membrane potential (MMP), oxygen consumption and ATP generation. The effects were greater in already differentiated cells. This was accompanied by characteristic changes in the expression of the genes involved in endoplasmic reticulum (ER) stress, and differentiation (lipid droplet formation) process such as: WNT10a, C/EBPa, AFT4, CIDEC, ADIPOQ, LPIN1. The results indicate that SQV affects not only metabolic (mitochondrial) activity of adipocytes, but affects the expression of genes related to differentiation and to a lesser extent to cell apoptosis.

Bone disorders associated with the human immunodeficiency virus: pathogenesis and management.

PubMed

Qaqish, Roula B; Sims, Keri A

2004-10-01

Bone disorders such as osteopenia, osteoporosis, and osteonecrosis have been reported in patients infected with the human immunodeficiency virus (HIV), but the etiology and mechanism of these disorders are unknown. The prevalence estimates vary widely among studies and may be influenced by the presence or absence of antiretroviral therapy and lipodystrophy, severity of HIV disease, and overlapping bone loss risk factors. Addressing potential underlying bone disease risk factors (e.g., smoking and alcohol intake), evaluating calcium and vitamin D intake, and performing dual x-ray absorptiometry in patients with HIV who have risks for bone disease are important strategies in preventing osteopenia and osteoporosis in HIV-infected patients. Management of osteopenia and osteoporosis is still being evaluated. Administration of bisphosphonates (e.g., alendronate), with calcium and vitamin D supplementation, may be reasonable in treating osteoporosis; however, surgical intervention is the only method for treating symptomatic osteonecrosis.

Integrative genomic analysis implicates limited peripheral adipose storage capacity in the pathogenesis of human insulin resistance.

PubMed

Lotta, Luca A; Gulati, Pawan; Day, Felix R; Payne, Felicity; Ongen, Halit; van de Bunt, Martijn; Gaulton, Kyle J; Eicher, John D; Sharp, Stephen J; Luan, Jian'an; De Lucia Rolfe, Emanuella; Stewart, Isobel D; Wheeler, Eleanor; Willems, Sara M; Adams, Claire; Yaghootkar, Hanieh; Forouhi, Nita G; Khaw, Kay-Tee; Johnson, Andrew D; Semple, Robert K; Frayling, Timothy; Perry, John R B; Dermitzakis, Emmanouil; McCarthy, Mark I; Barroso, Inês; Wareham, Nicholas J; Savage, David B; Langenberg, Claudia; O'Rahilly, Stephen; Scott, Robert A

2017-01-01

Insulin resistance is a key mediator of obesity-related cardiometabolic disease, yet the mechanisms underlying this link remain obscure. Using an integrative genomic approach, we identify 53 genomic regions associated with insulin resistance phenotypes (higher fasting insulin levels adjusted for BMI, lower HDL cholesterol levels and higher triglyceride levels) and provide evidence that their link with higher cardiometabolic risk is underpinned by an association with lower adipose mass in peripheral compartments. Using these 53 loci, we show a polygenic contribution to familial partial lipodystrophy type 1, a severe form of insulin resistance, and highlight shared molecular mechanisms in common/mild and rare/severe insulin resistance. Population-level genetic analyses combined with experiments in cellular models implicate CCDC92, DNAH10 and L3MBTL3 as previously unrecognized molecules influencing adipocyte differentiation. Our findings support the notion that limited storage capacity of peripheral adipose tissue is an important etiological component in insulin-resistant cardiometabolic disease and highlight genes and mechanisms underpinning this link.

Berardinelli–Seip syndrome: highlight of treatment challenge

PubMed Central

Ferraria, Nélia; Pedrosa, Cristina; Amaral, Daniela; Lopes, Lurdes

2013-01-01

Berardinelli–Seip congenital lipodystrophy (BSCL) syndrome is a rare autosomal-recessive disease characterised by lipoatrophy and associated with deregulations of glycidic and lipid metabolism. We report three BSCL cases with its typical clinical picture and complications. Clinically, they all show marked atrophy of adipose tissue, acromegaly, acanthosis nigricans and tall stature. Two cases present attention deficit hyperactivity and developmental learning disorders; another patient has hypertrophic myocardiopathy and polycystic ovary syndrome. In all the cases AGPAT2 was the identified mutation. All the cases present hypertriglyceridemia. One case has developed hyperinsulinism controlled with metformin and another case already has type 2 diabetes with a difficult clinical control. There is no curative treatment and the current treatment options are based only on symptomatic control of the complications. Recently, published studies showed that leptin-replacement therapy appears a promising tool in the metabolic correction of BSCL complications, highlighting the importance of further investigations in BSCL treatment. PMID:23362058

Human biallelic MFN2 mutations induce mitochondrial dysfunction, upper body adipose hyperplasia, and suppression of leptin expression.

PubMed

Rocha, Nuno; Bulger, David A; Frontini, Andrea; Titheradge, Hannah; Gribsholt, Sigrid Bjerge; Knox, Rachel; Page, Matthew; Harris, Julie; Payne, Felicity; Adams, Claire; Sleigh, Alison; Crawford, John; Gjesing, Anette Prior; Bork-Jensen, Jette; Pedersen, Oluf; Barroso, Inês; Hansen, Torben; Cox, Helen; Reilly, Mary; Rossor, Alex; Brown, Rebecca J; Taylor, Simeon I; McHale, Duncan; Armstrong, Martin; Oral, Elif A; Saudek, Vladimir; O'Rahilly, Stephen; Maher, Eamonn R; Richelsen, Bjørn; Savage, David B; Semple, Robert K

2017-04-19

MFN2 encodes mitofusin 2, a membrane-bound mediator of mitochondrial membrane fusion and inter-organelle communication. MFN2 mutations cause axonal neuropathy, with associated lipodystrophy only occasionally noted, however homozygosity for the p.Arg707Trp mutation was recently associated with upper body adipose overgrowth. We describe similar massive adipose overgrowth with suppressed leptin expression in four further patients with biallelic MFN2 mutations and at least one p.Arg707Trp allele. Overgrown tissue was composed of normal-sized, UCP1-negative unilocular adipocytes, with mitochondrial network fragmentation, disorganised cristae, and increased autophagosomes. There was strong transcriptional evidence of mitochondrial stress signalling, increased protein synthesis, and suppression of signatures of cell death in affected tissue, whereas mitochondrial morphology and gene expression were normal in skin fibroblasts. These findings suggest that specific MFN2 mutations cause tissue-selective mitochondrial dysfunction with increased adipocyte proliferation and survival, confirm a novel form of excess adiposity with paradoxical suppression of leptin expression, and suggest potential targeted therapies.

Lipotoxicity, fatty acid uncoupling and mitochondrial carrier function.

PubMed

Rial, Eduardo; Rodríguez-Sánchez, Leonor; Gallardo-Vara, Eunate; Zaragoza, Pilar; Moyano, Eva; González-Barroso, M Mar

2010-01-01

Diseases like obesity, diabetes or generalized lipodystrophy cause a chronic elevation of circulating fatty acids that can become cytotoxic, a condition known as lipotoxicity. Fatty acids cause oxidative stress and alterations in mitochondrial structure and function. The uncoupling of the oxidative phosphorylation is one of the most recognized deleterious fatty acid effects and several metabolite transporters are known to mediate in their action. The fatty acid interaction with the carriers leads to membrane depolarization and/or the conversion of the carrier into a pore. The result is the opening of the permeability transition pore and the initiation of apoptosis. Unlike the other members of the mitochondrial carrier superfamily, the eutherian uncoupling protein UCP1 has evolved to achieve its heat-generating capacity in the physiological context provided by the brown adipocyte and therefore it is activated by the low fatty acid concentrations generated by the noradrenaline-stimulated lipolysis. Copyright © 2010 Elsevier B.V. All rights reserved.

A TALEN genome editing system to generate human stem cell-based disease models

PubMed Central

Ding, Qiurong; Lee, Youn-Kyoung; Schaefer, Esperance A. K.; Peters, Derek T.; Veres, Adrian; Kim, Kevin; Kuperwasser, Nicolas; Motola, Daniel L.; Meissner, Torsten B.; Hendriks, William T.; Trevisan, Marta; Gupta, Rajat M.; Moisan, Annie; Banks, Eric; Friesen, Max; Schinzel, Robert T.; Xia, Fang; Tang, Alexander; Xia, Yulei; Figueroa, Emmanuel; Wann, Amy; Ahfeldt, Tim; Daheron, Laurence; Zhang, Feng; Rubin, Lee L.; Peng, Lee F.; Chung, Raymond T.; Musunuru, Kiran; Cowan, Chad A.

2012-01-01

SUMMARY Transcription activator-like effector nucleases (TALENs) are a new class of engineered nucleases that are easier to design to cleave at desired sites in a genome than previous types of nucleases. We report the use of TALENs to rapidly and efficiently generate mutant alleles of 15 genes in cultured somatic cells or human pluripotent stem cells, the latter of which we differentiated both the targeted lines and isogenic control lines into various metabolic cell types. We demonstrate cell-autonomous phenotypes directly linked to disease—dyslipidemia, insulin resistance, hypoglycemia, lipodystrophy, motor neuron death, and hepatitis C infection. We find little evidence of TALEN off-target effects, but each clonal line nevertheless harbors a significant number of unique mutations. Given the speed and ease with which we were able to derive and characterize these cell lines, we anticipate TALEN-mediated genome editing of human cells becoming a mainstay for the investigation of human biology and disease. PMID:23246482

The nuclear lamina in health and disease

PubMed Central

Dobrzynska, Agnieszka; Gonzalo, Susana; Shanahan, Catherine; Askjaer, Peter

2016-01-01

ABSTRACT The nuclear lamina (NL) is a structural component of the nuclear envelope and makes extensive contacts with integral nuclear membrane proteins and chromatin. These interactions are critical for many cellular processes, such as nuclear positioning, perception of mechanical stimuli from the cell surface, nuclear stability, 3-dimensional organization of chromatin and regulation of chromatin-binding proteins, including transcription factors. The NL is present in all nucleated metazoan cells but its composition and interactome differ between tissues. Most likely, this contributes to the broad spectrum of disease manifestations in humans with mutations in NL-related genes, ranging from muscle dystrophies to neurological disorders, lipodystrophies and progeria syndromes. We review here exciting novel insight into NL function at the cellular level, in particular in chromatin organization and mechanosensation. We also present recent observations on the relation between the NL and metabolism and the special relevance of the NL in muscle tissues. Finally, we discuss new therapeutic approaches to treat NL-related diseases. PMID:27158763

The nuclear lamina in health and disease.

PubMed

Dobrzynska, Agnieszka; Gonzalo, Susana; Shanahan, Catherine; Askjaer, Peter

2016-05-03

The nuclear lamina (NL) is a structural component of the nuclear envelope and makes extensive contacts with integral nuclear membrane proteins and chromatin. These interactions are critical for many cellular processes, such as nuclear positioning, perception of mechanical stimuli from the cell surface, nuclear stability, 3-dimensional organization of chromatin and regulation of chromatin-binding proteins, including transcription factors. The NL is present in all nucleated metazoan cells but its composition and interactome differ between tissues. Most likely, this contributes to the broad spectrum of disease manifestations in humans with mutations in NL-related genes, ranging from muscle dystrophies to neurological disorders, lipodystrophies and progeria syndromes. We review here exciting novel insight into NL function at the cellular level, in particular in chromatin organization and mechanosensation. We also present recent observations on the relation between the NL and metabolism and the special relevance of the NL in muscle tissues. Finally, we discuss new therapeutic approaches to treat NL-related diseases.

New Described Dermatological Disorders

PubMed Central

Cevirgen Cemil, Bengu; Keseroglu, Havva Ozge; Kaya Akis, Havva

2014-01-01

Many advances in dermatology have been made in recent years. In the present review article, newly described disorders from the last six years are presented in detail. We divided these reports into different sections, including syndromes, autoinflammatory diseases, tumors, and unclassified disease. Syndromes included are “circumferential skin creases Kunze type” and “unusual type of pachyonychia congenita or a new syndrome”; autoinflammatory diseases include “chronic atypical neutrophilic dermatosis with lipodystrophy and elevated temperature (CANDLE) syndrome,” “pyoderma gangrenosum, acne, and hidradenitis suppurativa (PASH) syndrome,” and “pyogenic arthritis, pyoderma gangrenosum, acne, and hidradenitis suppurativa (PAPASH) syndrome”; tumors include “acquired reactive digital fibroma,” “onychocytic matricoma and onychocytic carcinoma,” “infundibulocystic nail bed squamous cell carcinoma,” and “acral histiocytic nodules”; unclassified disorders include “saurian papulosis,” “symmetrical acrokeratoderma,” “confetti-like macular atrophy,” and “skin spicules,” “erythema papulosa semicircularis recidivans.” PMID:25243162

Impact of antiretroviral therapy on lipid metabolism of human immunodeficiency virus-infected patients: Old and new drugs

PubMed Central

da Cunha, Joel; Maselli, Luciana Morganti Ferreira; Stern, Ana Carolina Bassi; Spada, Celso; Bydlowski, Sérgio Paulo

2015-01-01

For human immunodeficiency virus (HIV)-infected patients, the 1990s were marked by the introduction of highly active antiretroviral therapy (HAART) representing a new perspective of life for these patients. The use of HAART was shown to effectively suppress the replication of HIV-1 and dramatically reduce mortality and morbidity, which led to a better and longer quality of life for HIV-1-infected patients. Apart from the substantial benefits that result from the use of various HAART regimens, laboratory and clinical experience has shown that HAART can induce severe and considerable adverse effects related to metabolic complications of lipid metabolism, characterized by signs of lipodystrophy, insulin resistance, central adiposity, dyslipidemia, increased risk of cardiovascular disease and even an increased risk of atherosclerosis. New drugs are being studied, new therapeutic strategies are being implemented, and the use of statins, fibrates, and inhibitors of intestinal cholesterol absorption have been effective alternatives. Changes in diet and lifestyle have also shown satisfactory results. PMID:25964872

Sexual difficulties in people living with HIV in France--results from a large representative sample of outpatients attending French hospitals (ANRS-EN12-VESPA).

PubMed

Bouhnik, Anne-Déborah; Préau, Marie; Schiltz, Marie-Ange; Obadia, Yolande; Spire, Bruno

2008-07-01

We analysed sexual difficulties in a nationally representative sample of HIV-infected outpatients in France. Analyses were restricted to the 1,812 HIV-treated participants who reported at least one sexual partner during the 12 months prior to the study. The sample included 40.6% homosexual men and 24.4% women; 68.1% had a steady partner and 48.2% reported casual partners. Sexual difficulties were reported by 33.3% of the selected individuals and were more frequent in those with low sexual activity. Immuno-virological outcomes were not associated with sexual difficulties. After multiple adjustment for sexual frequency and antidepressant consumption, it was found that a larger HIV-network, reporting HIV-discrimination from friends and/or sexual partners, suffering from lipodystrophy and reporting very disturbing HIV-related symptoms were all significantly associated with sexual difficulties. HIV and HIV-treatment experience are associated with sexual difficulties. Psychological support focused on HIV-experience should be tested as a possible tool for improving sexual quality of life.

The Inner Nuclear Membrane Is a Metabolically Active Territory that Generates Nuclear Lipid Droplets.

PubMed

Romanauska, Anete; Köhler, Alwin

2018-06-13

The inner nuclear membrane (INM) encases the genome and is fused with the outer nuclear membrane (ONM) to form the nuclear envelope. The ONM is contiguous with the endoplasmic reticulum (ER), the main site of phospholipid synthesis. In contrast to the ER and ONM, evidence for a metabolic activity of the INM has been lacking. Here, we show that the INM is an adaptable membrane territory capable of lipid metabolism. S. cerevisiae cells target enzymes to the INM that can promote lipid storage. Lipid storage involves the synthesis of nuclear lipid droplets from the INM and is characterized by lipid exchange through Seipin-dependent membrane bridges. We identify the genetic circuit for nuclear lipid droplet synthesis and a role of these organelles in regulating this circuit by sequestration of a transcription factor. Our findings suggest a link between INM metabolism and genome regulation and have potential relevance for human lipodystrophy. Copyright © 2018 Elsevier Inc. All rights reserved.

The Potential of Leptin for Treating Diabetes and Its Mechanism of Action

PubMed Central

Coppari, Roberto; Bjørbæk, Christian

2014-01-01

Following the discovery of leptin in 1994, major research efforts have brought us much closer to a fuller understanding of the cellular and molecular mechanisms underlying the biological effects of the hormone. Interestingly, leptin exerts potent anti-diabetic actions that are independent of its effects on body weight and food intake. In particular, leptin can correct diabetes in animal models of either diabetes mellitus type 1 (T1DM) or type 2 (T2DM). In addition, long-term leptin-replacement therapy is well tolerated and dramatically improves glycemic control, insulin sensitivity, and plasma triglycerides in patients with severe insulin resistance due to lipodystrophy. Together, these results have spurred enthusiasm for the use of leptin therapy to treat humans suffering from diabetes mellitus. Here, we review current understandings of these glucoregulatory functions of leptin, with particular emphasis on its central mechanisms of action, lessons from clinical studies and discuss possible therapeutic applications of leptin in the treatment of T1DM and T2DM. PMID:22935803

Body shaping with acoustic wave therapy AWT(®)/EPAT(®): randomized, controlled study on 14 subjects.

PubMed

Adatto, Maurice A; Adatto-Neilson, Robin; Novak, Pavel; Krotz, Alexander; Haller, Gerd

2011-12-01

Reduction of localised adiposities by non invasive means is a very frequent request among the female and male population. The objective of this study is to demonstrate the efficacy and safety of AWT(®), combining two different mechanical waves, planar AWT and radial AWT during the same session, in volume reduction of saddle bags in women. Treatment was performed on the saddle bag areas of 14 female patients, with the CELLACTOR(®) SC1 (Storz Medical AG, Tägerwilen, Switzerland) using extracorporeal pulse activation technology, EPAT(®). This device includes two handpieces, the C-ACTOR(®) and the D-ACTOR(®). Within 4 weeks, eight AWT(®) treatment sessions have been performed with both applicators. Follow-up visits were performed 1, 4 and 12 weeks after the last treatment. Measurements with the ultrasound system clearly demonstrate a significant diminution in the subcutaneous fat layer thickness and a reduction of the averaged circumference of thighs. This study, although performed on a small number of patients, tends to show the safety and efficacy of AWT(®) in treating localized fat areas in a non-invasive way. There is also an additional benefit for patients in reducing the cellulite appearance and improving the skin firmness at the same time by using AWT(®).

Current concepts in aesthetic endocrinology.

PubMed

Gruber, C J; Wieser, F; Gruber, I M L; Ferlitsch, K; Gruber, D M; Huber, J C

2002-12-01

The extragenital effects of ovarian steroids are relevant to the metabolism of skin and hair, the changes in body composition and the alterations of the subcutaneous fat distribution throughout life. When ovarian steroids become deficient or are produced in excess, different problems may arise in these tissues and some of these problems, i.e., obesity and cellulite, display gender-specific components. Therefore, a new field in endocrine research known as aesthetic endocrinology is gaining more interest. Because sex steroids are small molecules they can be transported into the skin by topical application when properly formulated. This possibility is used in aesthetic endocrinology in order to achieve local effects but to avoid systemic reactions. After reviewing the current data it collectively seems legitimate to recommend estrogens, either orally or topically, in order to counteract the aging of the skin after menopause. Although a reconstitution of juvenile skin cannot be achieved through this method, a slowing in the skin aging process seems a reasonable expectation. In contrast, the successful treatment of hair loss in women is only confirmed for the application of the non-hormonal compound minoxidil. Apart from the difficult problem of hirsutism, acne and changes in body composition offer promising therapeutical options for endocrinological methods.

A case of meningitis caused by Streptococcus pyogenes in a previously healthy woman.

PubMed

Ulug, Mehmet; Ulug, Nuray Can; Celen, Mustafa Kemal; Geyik, Mehmet Faruk; Ayaz, Celal

2009-04-01

Streptococcus pyogenes is a well-known cause of a variety of clinical infections including local symptoms such as tonsillopharyngitis, cervical lymphadenitis, otitis media, cellulites, erysipelas, as well as more severe diseases such as scarlet fever, osteomyelitis, necrotizing fasciitis, sepsis, and toxic shock syndrome. However, acute bacterial meningitis caused by this pathogen is unusual. We report a case of group A streptococcus (GAS) meningitis in a previously healthy woman with a dramatically rapid course and fatal outcome. A 41-year-old previously healthy woman presented a history of fever, headache, vomiting, and sore throat of three days' duration. Neurological examination revealed diminished consciousness and neck rigidity. The cerebrospinal fluid (CSF) was turbid with 10,000 leukocytes/mm(3). Direct examination of CSF showed Gram-positive cocci in chains, and cultures yielded S. pyogenes. Blood cultures yielded growth of S. pyogenes. The patient was treated initially with ceftriaxone (4 g/day) and the control CSF examination was not changed on the third day, so vancomycin (2 g/day) was added to the treatment; however, she died on the fourth day of the treatment. S. pyogenes meningitis is uncommon and the incidence seems to be persistently low; nevertheless, clinicians should be aware that sporadic cases may occur and may have a fulminant course with a relevant neurological sequel.

Clinical and histopathological results following TriPollar radiofrequency skin treatments.

PubMed

Kaplan, Haim; Gat, Andrea

2009-06-01

Skin laxity, wrinkles and cellulite are common aesthetic problems associated with the aging process. These symptoms are due to the weakening and thinning of dermal connective tissue and the enlargement of hypodermal fat cells. The aim of this study was to evaluate the safety and efficacy of the TriPollar RF technology in reducing fat and collagen regeneration. Twelve healthy patients underwent weekly treatments on different body sites using the TriPollar technology. Treatment areas were photographed and measured and patient satisfaction was monitored. One abdominal patient consented to a series of TriPollar treatments prior to her scheduled abdominoplasty. A controlled histopathology analysis was performed on skin samples taken during the abdominoplasty procedure. Histopathological examination revealed marked differences between treated and non-treated abdominal skin areas. An increase of 49% in dermal thickness, focal thickening of collagen fibers and focal shrinkage of fat cells was shown following TriPollar treatments. Average patient satisfaction indicated clear satisfaction with the clinical results achieved. The TriPollar is a safe and effective non-invasive technology leading to skin tightening and body shaping. Histology results indicate changes at the dermal and fat layers following TriPollar treatments resulting in increased collagen regeneration and stimulated fat metabolism.

Coinfection by Aspergillus and Zygomycetes Species in a Case of Acute Rhinosinusitis

PubMed Central

Vaidya, Dhara; Shah, Parul

2011-01-01

Invasive mycotic infections can be effectively treated if rapid identification of fungus is obtained. We reported a case of coinfection by Aspergillus and Rhizopus sp. involving nose, paranasal sinuses, orbit, and brain in a 68-year-old known hypertensive male. He was presented to ENT OPD with history of fever and intermittent headache since fifteen days along with history of right-sided nasal obstruction and proptosis since seven days. CT scan of brain and paranasal sinuses showed findings of pansinusitis with cellulitic changes in right orbit. MRI confirmed the same along with features of intracranial extension with focal meningitis in right frontotemporal region. Laboratory parameters did not conclude much except for leucocytosis and hyponatremia. Patient was taken for endoscopic debridement from nose and paranasal sinuses, and tissue was sent for microbiological and histopathological examination. Minced tissue was processed, and after 48 hrs of incubation two types of growth were identified, one was yellowish, granular, and powdery consistent with Aspergillus sp., and another was cottony and woolly consistent with Rhizopus sp. LCB mount confirmed presence of Aspergillus flavus and Rhizopus arrhizus. Patient responded to therapy with IV amphotericin B and surgical debridement. On discharge patient's condition was good. PMID:22937365

The influence of body fat distribution patterns and body mass index on MENQOL in women living in an urban area.

PubMed

Kutheerawong, L; Vichinsartvichai, P

2016-01-01

To investigate the influence of patterns of body fat distribution and body mass index (BMI) on menopause-specific quality of life in peri- and postmenopausal women living in an urban area. A total of 214 peri- and postmenopausal women, mean age 55 years, with intact uterus and no history of hormonal treatment were recruited. Anthropometric measurements were conducted as standard techniques. The Menopause-specific Quality of Life (MENQOL) questionnaire was used to evaluate menopause-specific quality of life. The Mann-Whitney U test and Kruskal-Wallis test were used to compare MENQOL between body fat patterns or BMI. According to the body fat distribution patterns, 53.3% were women of the android type and 46.7% were of the gynoid type. The android body pattern was associated with worsening of vasomotor and psychosocial domains (p < 0.05). However, overweight and obese women had slightly better scores in the sexual domain of the MENQOL. Peri- and postmenopausal women with the android body pattern have lower quality of life in the vasomotor and psychosocial domains while women with normal BMI have the slightly lower quality of life in the sexual domain. The maintenance of premenopausal body proportion might mitigate the menopause-specific quality of life.

Maternal caffeine intake during pregnancy, early growth, and body fat distribution at school age.

PubMed

Voerman, Ellis; Jaddoe, Vincent W V; Gishti, Olta; Hofman, Albert; Franco, Oscar H; Gaillard, Romy

2016-05-01

The associations of maternal caffeine intake during pregnancy with offspring growth patterns and body fat and insulin levels at school age were examined. In a population-based birth cohort among 7,857 mothers and their children, maternal caffeine intake during pregnancy was assessed by questionnaires. Growth characteristics were measured from birth onward. At 6 years, body fat and insulin levels were measured. Compared to children whose mothers consumed <2 units of caffeine per day during pregnancy (1 unit of caffeine is equivalent to 1 cup of coffee (90 mg caffeine)), those whose mothers consumed ≥6 units of caffeine per day tended to have a lower weight at birth, higher weight gain from birth to 6 years, and higher body mass index from 6 months to 6 years. Both children whose mothers consumed 4-5.9 and ≥6 units of caffeine per day during pregnancy tended to have a higher childhood body mass index and total body fat mass. Only children whose mothers consumed ≥6 units of caffeine per day had a higher android/gynoid fat mass ratio. These results suggest that high levels of maternal caffeine intake during pregnancy are associated with adverse offspring growth patterns and childhood body fat distribution. © 2016 The Obesity Society.

Predictors of parental perceptions and concerns about child weight

PubMed Central

Keller, Kathleen L.; Olsen, Annemarie; Kuilema, Laura; Meyermann, Karol; van Belle, Christopher

2012-01-01

Appropriate levels of parental perception and concern about child weight are important components of successful obesity treatment, but the factors that contribute to these attitudes need clarification. The aim of this study was to identify child and parent characteristics that best predict parental perceptions and concerns about child weight. A cross-sectional design was used to assess characteristics of parents (e.g. age, income, and feeding attitudes) and children (e.g. body composition, ad libitum intake, and reported physical activity). Results are reported for 75, 4–6 year-olds from diverse ethnicities. Perceived child weight and concern were measured with the Child Feeding Questionnaire (CFQ). Multiple linear regression was used to identify the best models for perceived child weight and concern. For perceived child weight, the best model included parent age, children’s laboratory intake of sugar-sweetened beverages (SSB) and palatable buffet items, and two measures of child body composition (ratio of trunk fat-to-total fat and ratio of leg fat-to-total fat). For concern, child android/gynoid fat ratio explained the largest amount of variance, followed by restrictive feeding and SSB intake. Parental perceptions and concerns about child weight are best explained by models that account for children’s eating behavior and body fat distribution. PMID:23207190

Maternal caffeine intake during pregnancy, early growth and body fat distribution at school-age. The Generation R Study

PubMed Central

Voerman, Ellis; Jaddoe, Vincent WV; Gishti, Olta; Hofman, Albert; Franco, Oscar H.; Gaillard, Romy

2017-01-01

Objective We examined the associations of maternal caffeine intake during pregnancy with offspring growth patterns, and body fat and insulin levels at school-age. Methods In a population-based birth cohort among 7,857 mothers and their children, we assessed maternal caffeine intake during pregnancy by questionnaires. Growth characteristics were measured from birth onwards. At 6 years, body fat and insulin levels were measured. Results Compared to children whose mothers consumed <2 units of caffeine per day during pregnancy (1 unit of caffeine is equivalent to 1 cup of coffee (90 mg caffeine)), those whose mothers consumed ≥6 units of caffeine per day tended to have a lower weight at birth, higher weight gain from birth to 6 years and higher body mass index from 6 months to 6 years. Both children whose mothers consumed 4-5.9 and ≥6 units of caffeine per day during pregnancy tended to have a higher childhood body mass index and total body fat mass. Only children whose mothers consumed ≥6 units of caffeine per day had a higher android/gynoid fat mass ratio. Conclusions Our results suggest that high levels of maternal caffeine intake during pregnancy are associated with adverse offspring growth patterns and childhood body fat distribution. PMID:27015969

Activation of PPARγ Ameliorates Spatial Cognitive Deficits through Restoring Expression of AMPA Receptors in Seipin Knock-Out Mice.

PubMed

Zhou, Libin; Chen, Tingting; Li, Guoxi; Wu, Chaoming; Wang, Conghui; Li, Lin; Sha, Sha; Chen, Lei; Liu, George; Chen, Ling

2016-01-27

A characteristic phenotype of congenital generalized lipodystrophy 2 (CGL2) that is caused by loss-of-function of seipin gene is mental retardation. Here, we show that seipin deficiency in hippocampal CA1 pyramidal cells caused the reduction of peroxisome proliferator-activated receptor gamma (PPARγ). Twelve-week-old systemic seipin knock-out mice and neuronal seipin knock-out (seipin-nKO) mice, but not adipose seipin knock-out mice, exhibited spatial cognitive deficits as assessed by the Morris water maze and Y-maze, which were ameliorated by the treatment with the PPARγ agonist rosiglitazone (rosi). In addition, seipin-nKO mice showed the synaptic dysfunction and the impairment of NMDA receptor-dependent LTP in hippocampal CA1 regions. The density of AMPA-induced current (IAMPA) in CA1 pyramidal cells and GluR1/GluR2 expression were significantly reduced in seipin-nKO mice, whereas the NMDA-induced current (INMDA) and NR1/NR2 expression were not altered. Rosi treatment in seipin-nKO mice could correct the decrease in expression and activity of AMPA receptor (AMPAR) and was accompanied by recovered synaptic function and LTP induction. Furthermore, hippocampal ERK2 and CREB phosphorylation in seipin-nKO mice were reduced and this could be rescued by rosi treatment. Rosi treatment in seipin-nKO mice elevated BDNF concentration. The MEK inhibitor U0126 blocked rosi-restored AMPAR expression and LTP induction in seipin-nKO mice, but the Trk family inhibitor K252a did not. These findings indicate that the neuronal seipin deficiency selectively suppresses AMPAR expression through reducing ERK-CREB activities, leading to the impairment of LTP and spatial memory, which can be rescued by PPARγ activation. Congenital generalized lipodystrophy 2 (CGL2), caused by loss-of-function mutation of seipin gene, is characterized by mental retardation. By the generation of systemic or neuronal seipin knock-out mice, the present study provides in vivo evidence that neuronal seipin

Nuclear lamina remodelling and its implications for human disease.

PubMed

Chojnowski, Alexandre; Ong, Peh Fern; Dreesen, Oliver

2015-06-01

The intermediate filament A- and B-type lamins are key architectural components of the nuclear lamina, a proteinaceous meshwork that lies underneath the inner nuclear membrane. In the past decade, many different monogenic human diseases have been linked to mutations in various components of the nuclear lamina. Mutations in LMNA (encoding lamin A and C) cause a variety of human diseases, collectively called laminopathies. These include cardiomyopathies, muscular dystrophies, lipodystrophies and progeroid syndromes. In addition, elevated levels of lamin B1, attributable to genomic duplications of the LMNB1 locus, cause adult-onset autosomal dominant leukodystrophy. The molecular mechanism(s) enabling the mutations and perturbations of the nuclear lamina to give rise to such a wide variety of diseases that affect various tissues remains unclear. The composition of the nuclear lamina changes dynamically during development, between cell types and even within the same cell during differentiation and ageing. Here, we discuss the functional and cellular aspects of lamina remodelling and their implications for the tissue-specific nature of laminopathies.

Leptin, An Adipokine With Central Importance in the Global Obesity Problem.

PubMed

Mechanick, Jeffrey I; Zhao, Shan; Garvey, W Timothy

2017-12-13

Leptin has central importance in the global obesity and cardiovascular disease problem. Leptin is principally secreted by adipocytes and acts in the hypothalamus to suppress appetite and food intake, increase energy expenditure, and regulate body weight. Based on clinical translation of specific and networked actions, leptin affects the cardiovascular system and may be a marker and driver of cardiometabolic risk factors with interventions that are actionable by cardiologists. Leptin subnetwork analysis demonstrates a statistically significant role for ethnoculturally and socioeconomically appropriate lifestyle intervention in cardiovascular disease. Emergent mechanistic components and potential diagnostic or therapeutic targets include hexokinase 3, urocortins, clusterin, sialic acid-binding immunoglobulin-like lectin 6, C-reactive protein, platelet glycoprotein VI, albumin, pentraxin 3, ghrelin, obestatin prepropeptide, leptin receptor, neuropeptide Y, and corticotropin-releasing factor receptor 1. Emergent associated symptoms include weight change, eating disorders, vascular necrosis, chronic fatigue, and chest pain. Leptin-targeted therapies are reported for lipodystrophy and leptin deficiency, but they are investigational for leptin resistance, obesity, and other chronic diseases. Copyright © 2017 World Heart Federation (Geneva). Published by Elsevier B.V. All rights reserved.

[Features of Acquired Immunodeficiency Syndrome-related Lymphoma on (18)F-fluorodeoxyglucose Positron Emission Tomography/Computed Tomography].

PubMed

Niu, Na; Zhu, Zhao-hui; Ma, Yan-ru; Xing, Hai-qun; Li, Fang

2015-10-01

To analyze the imaging features of (18)F-fluorodeoxyglucose (¹⁸F-FDG) positron emission tomography(PET)/computed tomography (CT) in acquired immune deficiency syndrome-related lymphoma (ARL) patients correlated with their clinical signs, symptoms, and treatments. Five ARL patients underwent ¹⁸F-FDG PET/CT at Peking Union Medical College Hospital from October 2008 to January 2013. Two patients received two additional follow-up studies 6 months later. Among these 5 patients, ¹⁸FDG-PET/CT helped in diagnosis of two patient and changed therapeutic strategy in other two patients. In two patients underwent ¹⁸F-FDG PET/CT brain scans, low-metabolism lesion was newly found in cerebral cortex. Of 4 patients receiving highly active antiretroviral therapy, PET/CT also demonstrated diffusely elevated ¹⁸F-FDG uptake in subcutaneous adipose tissue in two patients. ¹⁸F-FDG PET/CT is a highly useful tool in the diagnosis and treatment of ARL patients, in particular in the identification of associated encephalopathy and lipodystrophy.

[Severe type A insulin resistance syndrome due to a mutation in the insulin receptor gene].

PubMed

Ros, P; Colino-Alcol, E; Grasso, V; Barbetti, F; Argente, J

2015-01-01

Insulin resistance syndromes without lipodystrophy are an infrequent and heterogeneous group of disorders with variable clinical phenotypes, associated with hyperglycemia and hyperinsulinemia. The three conditions related to mutations in the insulin receptor gene are leprechaunism or Donohue syndrome, Rabson-Mendenhall syndrome, and Type A syndrome. A case is presented on a patient diagnosed with type A insulin resistance, defined by the triad of extreme insulin resistance, acanthosis nigricans, and hyperandrogenism, carrying a heterozygous mutation in exon 19 of the insulin receptor gene coding for its tyrosine kinase domain that is crucial for the catalytic activity of the receptor. The molecular basis of the syndrome is reviewed, focusing on the structure-function relationships of the insulin receptor, knowing that the criteria for survival are linked to residual insulin receptor function. It is also pointed out that, although type A insulin resistance appears to represent a somewhat less severe condition, these patients have a high morbidity and their treatment is still unsatisfactory. Copyright © 2014 Asociación Española de Pediatría. Published by Elsevier Espana. All rights reserved.

Genetic Determination of Serum Levels of Diabetes-Associated Adipokines

PubMed Central

Schleinitz, Dorit

2015-01-01

Adipose tissue secretes an abundance of proteins. Some of these proteins are known as adipokines and adipose-derived hormones which have been linked with metabolic disorders, including type 2 diabetes, and even with cancer. Variance in serum adipokine concentration is often closely associated with an increase (obesity) or decrease (lipodystrophy) in fat tissue mass, and it is affected by age, gender, and localization of the adipose tissue. However, there may be genetic variants which, in consequence, influence the serum concentration of a certain adipokine, and thereby promote metabolic disturbances or, with regard to the “protective” allele, exert beneficial effects. This review focuses on the genetic determination of serum levels of the following adipokines: adiponectin, chemerin, leptin, progranulin, resistin, retinol binding protein 4, vaspin, adipsin, apelin, and omentin. The article reports on the latest findings from genome-wide association studies (GWAS) and candidate gene studies, showing variants located in/nearby the adipokine genes and other (non-receptor) genes. An extra chapter highlights adipokine-receptor variants. Epigenetic studies on adipokines are also addressed. PMID:26859657

Leptin in pediatrics: A hormone from adipocyte that wheels several functions in children

PubMed Central

Soliman, Ashraf T.; Yasin, Mohamed; Kassem, Ahmed

2012-01-01

The protein leptin, a pleiotropic hormone regulates appetite and energy balance of the body and plays important roles in controlling linear growth, pubertal development, cardiovascular function, and immunity. Recent findings in the understanding of the structure, functional roles, and clinical significance of conditions with increased and decreased leptin secretion are summarized. Balance between leptin and other hormones is significantly regulated by nutritional status. This balance influences many organ systems, including the brain, liver, and skeletal muscle, to mediate the essential adaptation process. The aim of this review is to summarize the possible physiological functions of leptin and its signaling pathways during childhood and adolescence including control of food intake, energy regulation, growth and puberty, and immunity. Moreover, its secretion and possible roles in the adaptation process during different disease states (obesity, malnutrition, eating disorders, delayed puberty, congenital heart diseases and hepatic disorders) are discussed. The clinical manifestations and the successful management of patients with genetic leptin deficiency and the application of leptin therapy in other diseases including lipodystrophy, states with severe insulin resistance, and diabetes mellitus are discussed. PMID:23565493

The Effects of Leptin Replacement on Neural Plasticity

PubMed Central

Paz-Filho, Gilberto J.

2016-01-01

Leptin, an adipokine synthesized and secreted mainly by the adipose tissue, has multiple effects on the regulation of food intake, energy expenditure, and metabolism. Its recently-approved analogue, metreleptin, has been evaluated in clinical trials for the treatment of patients with leptin deficiency due to mutations in the leptin gene, lipodystrophy syndromes, and hypothalamic amenorrhea. In such patients, leptin replacement therapy has led to changes in brain structure and function in intra- and extrahypothalamic areas, including the hippocampus. Furthermore, in one of those patients, improvements in neurocognitive development have been observed. In addition to this evidence linking leptin to neural plasticity and function, observational studies evaluating leptin-sufficient humans have also demonstrated direct correlation between blood leptin levels and brain volume and inverse associations between circulating leptin and risk for the development of dementia. This review summarizes the evidence in the literature on the role of leptin in neural plasticity (in leptin-deficient and in leptin-sufficient individuals) and its effects on synaptic activity, glutamate receptor trafficking, neuronal morphology, neuronal development and survival, and microglial function. PMID:26881138

The Effects of Leptin Replacement on Neural Plasticity.

PubMed

Paz-Filho, Gilberto J

2016-01-01

Leptin, an adipokine synthesized and secreted mainly by the adipose tissue, has multiple effects on the regulation of food intake, energy expenditure, and metabolism. Its recently-approved analogue, metreleptin, has been evaluated in clinical trials for the treatment of patients with leptin deficiency due to mutations in the leptin gene, lipodystrophy syndromes, and hypothalamic amenorrhea. In such patients, leptin replacement therapy has led to changes in brain structure and function in intra- and extrahypothalamic areas, including the hippocampus. Furthermore, in one of those patients, improvements in neurocognitive development have been observed. In addition to this evidence linking leptin to neural plasticity and function, observational studies evaluating leptin-sufficient humans have also demonstrated direct correlation between blood leptin levels and brain volume and inverse associations between circulating leptin and risk for the development of dementia. This review summarizes the evidence in the literature on the role of leptin in neural plasticity (in leptin-deficient and in leptin-sufficient individuals) and its effects on synaptic activity, glutamate receptor trafficking, neuronal morphology, neuronal development and survival, and microglial function.

Lamina-independent lamins in the nuclear interior serve important functions.

PubMed

Dechat, T; Gesson, K; Foisner, R

2010-01-01

Nuclear lamins were originally described as the main constituents of the nuclear lamina, a filamentous meshwork closely associated with the inner nuclear membrane. However, within recent years, it has become increasingly evident that a fraction of lamins also resides throughout the nuclear interior. As intermediate-filament-type proteins, lamins have been suggested to fulfill mainly structural functions such as providing shape and mechanical stability to the nucleus. But recent findings show that both peripheral and nucleoplasmic lamins also have important roles in essential cellular processes such as transcription, DNA replication, cell cycle progression, and chromatin organization. Furthermore, more than 300 mutations in the gene encoding A-type lamins have been associated with several human diseases now generally termed laminopathies and comprising muscular dystrophies, lipodystrophies, cardiomyopathies, and premature aging diseases. This review focuses on the lamina-independent pool of lamins in the nuclear interior, which surprisingly has not been studied in much detail so far. We discuss the properties and regulation of nucleoplasmic lamins during the cell cycle, their interaction partners, and their potential involvement in cellular processes and the development of laminopathies.

[A complex case of diabetes due to LMNA mutation].

PubMed

Ambonville, C; Bouldouyre, M-A; Laforêt, P; Richard, P; Benveniste, O; Vigouroux, C

2017-10-01

Laminopathies (diseases related to A/C mutations of lamines) are rare genetic diseases with an extensive phenotypic spectrum, including lipodystrophic syndromes-characterized by a selective loss of adipose tissue-of which the partial Dunnigan family type is the most frequent. We report on a 55-year-old woman with diabetes and long-term disabling myalgia. Her cushingoid morphotype, associated with cutaneous lipo-atrophy and muscle hypertrophy in addition to a genetic heritage, led us to the diagnosis of complex partial familial lipodystrophy heterozygous LMNA_c.82C>T, p.Arg28Trp mutation. Familial partial lipodystrophic syndromes may have varied phenotypes, mainly cardio-metabolic, which could mimic a particularly severe type 2 diabetes. The diagnostic work-up of this disease has to include a careful investigation of gait troubles and paroxysmal conduction that could lead to sudden death, as well as a genetic examination. In some cases, recombinant leptin can be proposed. Copyright © 2017 Société Nationale Française de Médecine Interne (SNFMI). Published by Elsevier SAS. All rights reserved.

Metabolic recovery of lipodystrophy, liver steatosis, and pancreatic β cell proliferation after the withdrawal of OSI-906.

PubMed

Tajima, Kazuki; Shirakawa, Jun; Togashi, Yu; Yamazaki, Shunsuke; Okuyama, Tomoko; Kyohara, Mayu; Konishi, Hiromi; Terauchi, Yasuo

2017-06-23

Growth factor signaling via insulin receptor (IR) and IGF-1 receptor (IGF1R) plays several important roles in the pathogenesis of metabolic syndrome and diabetes. OSI-906 (linsitinib), an anti-tumor drug, is an orally bioavailable dual inhibitor of IR and IGF1R. To investigate the recovery from metabolic changes induced by the acute inhibition of IR and IGF1R in adult mice, mice were treated with OSI-906 or a vehicle for 7 days and the results were analyzed on the last day of injection (Day 7) or after 7 or 21 days of withdrawal (Day 14 or Day 28). On day 7, the visceral white fat mass was significantly reduced in mice treated with OSI-906 accompanied by a reduced expression of leptin and an increased expression of the lipolysis-related genes Lpl and Atgl. Interestingly, the lipoatrophy and the observed changes in gene expression were completely reversed on day 14. Similarly, liver steatosis and β cell proliferation were transiently observed on day 7 but had disappeared by day 14. Taken together, these results suggest that this model for the acute inhibition of systemic IR/IGF1R signaling may be useful for investigating the recovery from metabolic disorders induced by impaired growth factor signaling.

Skin and soft tissue infections caused by community-associated methicillin-resistant staphylococcus aureus among children in China.

PubMed

Geng, W; Yang, Y; Wang, C; Deng, L; Zheng, Y; Shen, X

2010-04-01

To investigate the characteristic of community-associated methicillin-resistant staphylococcus aureus (CA-MRSA) skin and soft tissue infections (SSTIs) among children in China. Forty-seven children with CA-MRSA SSTIs were enrolled in this study. Clinical information was collected and analysed. The strains from the children were analysed by multilocus sequence typing (MLST), staphylococcus cassette chromosome mec (SCCmec) typing and spa typing. The Panton-Valentine leukocidin (PVL) gene was also detected. The majority of the 47 cases were impetigo (20; 42.6%) and abscesses (14; 29.8%). The rest was cellulites, infected wounds, omphalitis, paronychia and conjunctivitis combined folliculitis. Thirty-two of the isolates (68.1%) were PVL-positive, and the abscesses infected with PVL-positive strains usually required incision and drainage (87.5% vs. 16.7%, p = 0.026). Most of the isolates belonged to ST type 59, which accounted for 46.8%, followed by ST1 (7/47, 14.9%) and ST910 (5/47, 10.6%). The clone of ST59-MRSA-IV with t437 was the most prevalent one. The multiresistant rate of these strains was 93.6%. The most common disease of CA-MRSA SSTIs was impetigo, and PVL-positive abscess was associated with incision and drainage. ST59-MRSA-IV with t437 was the most prevalent clone, and the multiresistant rate was high in Chinese children.

Longitudinal analysis of inpatient care utilization among people with intellectual disabilities: 1999-2002.

PubMed

Loh, C-H; Lin, J-D; Choi, I-C; Yen, C-F; Hsu, S-W; Wu, J-L; Tang, C C

2007-02-01

There has been no longitudinal study in Taiwan to identify the nature and the scale of medical care utilization of people with intellectual disabilities (IDs) up to the present. The aim of this study is to describe inpatient utilization among people under ID care in institutions in order to identify the pattern of medical care needs and the factors affecting utilization in Taiwan. The subject cohort was 168 individuals with ID who were cared for by a large public disability institution from 1999 to 2002 in Taipei, Taiwan. On the examination of the inpatient care that these persons underwent, it was found that these individuals had a heightened need (inpatient rate: 10.1-14.9%) for inpatient care compared with the general population with disabilities (9.37%) in Taiwan. The main reasons for hospitalization were pneumonia, gastrointestinal disorders, cellulites, orthopaedic problems, epilepsy and bronchitis. Using the full model of Generalized Estimating Equations for inpatient care utilization, the factors including low income family, living in an institution, being a subject with cerebral palsy and being a high outpatient user all influenced the use of inpatient care. This study highlights that health authorities need to promote health planning more in order to ensure an excellent quality of health monitoring and health promotion among people with ID cared for by institutions.

Clinical and histopathological study of the TriPollar home-use device for body treatments.

PubMed

Boisnic, Sylvie; Branchet, Marie-Christine; Birnstiel, Oliver; Beilin, Ghislaine

2010-01-01

Professional non invasive treatments for body contouring based on radiofrequency (RF) became popular in aesthetic clinics due to proven efficacy and safety. A new home-use RF device for body treatments has been developed based on TriPollar technology. Our objective was to evaluate the TriPollar home-use device for circumference reduction, cellulite improvement and skin tightening using objective and subjective methods. An ex-vivo human skin model was used for histological and biochemical evaluations of the TriPollar clinical effect. Additionally, twenty four subjects used the new device on the abdomen and thigh areas and the circumference reduction was measured. Ex-vivo models indicated a significant increase of 82% in hypodermal glycerol release. Histology revealed a 34% alteration in adipocyte appearance. Collagen synthesis increased by 31% following TriPollar treatment. A significant average reduction of 2.4 cm was measured on the treated thighs. On the control thighs a lesser, non-significant reduction was found. Average abdominal laxity was reduced from 1.4 at baseline to 0.8 following treatments. A certain reduction was measured in the abdomen circumferences, although it was not significant. The reported results demonstrate the safety and efficacy of the new TriPollar home-use device for body contouring and skin tightening. Treatment may lead to discrete circumference reduction and moderate laxity improvement.

Modulation of plasma N-acylethanolamine levels and physiological parameters by dietary fatty acid composition in humans

PubMed Central

Jones, Peter J. H.; Lin, Lin; Gillingham, Leah G.; Yang, Haifeng; Omar, Jaclyn M.

2014-01-01

N-acylethanolamines (NAEs) are endogenous lipid-signaling molecules involved in satiety and energetics; however, how diet impacts circulating NAE concentrations and their downstream metabolic actions in humans remains unknown. Objectives were to examine effects of diets enriched with high-oleic canola oil (HOCO) or HOCO blended with flaxseed oil (FXCO), compared with a Western diet (WD), on plasma NAE levels and the association with energy expenditure and substrate oxidation. Using a randomized controlled crossover design, 36 hypercholesterolemic participants consumed three isoenergetic diets for 28 days, each containing 36% energy from fat, of which 70% was HOCO, FXCO, or WD. Ultra-performance liquid chromatography-MS/MS was used to measure plasma NAE levels and indirect calorimetry to assess energy expenditure and substrate oxidation. After 28 days, compared with WD, plasma oleoylethanolamide (OEA) and alpha-linolenoyl ethanolamide (ALEA) levels were significantly increased in response to HOCO and FXCO (P = 0.002, P < 0.001), respectively. Correlation analysis demonstrated an inverse association between plasma OEA levels and percent body fat (r = −0.21, P = 0.04), and a positive association was observed between the plasma arachidonoyl ethanolamide (AEA)/OEA ratio and android:gynoid fat (r = 0.23, P = 0.02), respectively. Results suggest that plasma NAE levels are upregulated via their dietary lipid substrates and may modulate regional and total fat mass through lipid-signaling mechanisms. PMID:25262934

Endocrinopathies, Bone Health, and Insulin Resistance in Patients with Fanconi Anemia after Hematopoietic Cell Transplantation

PubMed Central

Barnum, Jessie L.; Petryk, Anna; Zhang, Lei; DeFor, Todd E.; Baker, K. Scott; Steinberger, Julia; Nathan, Brandon; Wagner, John E.; MacMillan, Margaret L.

2017-01-01

A number of endocrinopathies have been described after hematopoietic cell transplantation (HCT), but data are limited in patients with Fanconi anemia (FA). We report several endocrine-based disorders in a cohort of 44 patients with FA after HCT compared with both 74 patients who received HCT for hematologic malignancies and with 275 healthy controls. Endocrinopathies assessed included hypothyroidism, hypogonadism, short stature, dyslipidemia, insulin resistance, abnormalities in body composition, and bone health. Most (86%) patients with FA had at least 1 endocrinopathy, with 11% having 3 or more. Hypothyroidism was seen in 57%, hypogonadism in 27%, short stature in 50%, and reduced total body and lumbar spine bone mineral density (BMD) (height adjusted Z-score < −1) in 57% and 21%, respectively. Vitamin D deficiency was seen in 71%. Short stature was associated with younger age at HCT and gonadal failure was associated with older age at HCT. Insulin resistance was associated with increased percent fat mass and increased android/gynoid ratio by dual energy X-ray absorptiometry. Hypothyroidism, short stature, and reduced total body BMD were more prevalent in patients with FA compared with patients with hematologic malignancies. We recommend an assessment before transplantation and close follow-up afterwards to ensure proper clinical management. Future studies should continue to explore the impact of HCT on endocrinopathies in FA patients. PMID:27180116

Association of serum glypican-4 levels with cardiovascular risk predictors in women with polycystic ovary syndrome - a pilot study.

PubMed

Jędrzejuk, Diana; Lwow, Felicja; Kuliczkowska-Płaksej, Justyna; Hirnle, Lidia; Trzmiel-Bira, Anna; Lenarcik-Kabza, Agnieszka; Kolackov, Katarzyna; Łaczmański, Łukasz; Milewicz, Andrzej

2016-01-01

Glypican-4 (Gpc4) is an adipokine which interacts with the insulin receptor and affects insulin sensitivity in proteoglycans. Insulin resistance plays a crucial role in the etiology of polycystic ovary syndrome (PCOS). PCOS is associated with metabolic disturbances such as abdominal obesity, dyslipidemia and type 2 diabetes. Thus, higher levels of Gpc4 released from visceral adipose tissue in women with PCOS may suggest an increased risk of cardiovascular disease (CVD). The aim of this pilot study was to determine whether the serum Gpc4 level is associated with cardiovascular risk predictors in women with PCOS. Sixty-two women with PCOS according to the Rotterdam criteria (20-35 years old) and 43 healthy controls were studied. Cardiovascular risk predictors such as obesity indices, fat deposits according to dual-energy X-ray absorptiometry, biochemical lipid profile parameters and Homeostasis Model Assessment were estimated. The serum Gpc4 level in PCOS women was significantly higher (2.61 ± 1.17 ng/ml) than in the control group (1.55 ± 0.47 ng/ml) and correlated with waist circumference, waist-to-hip ratio, total fat and android fat deposit to gynoid fat deposit ratio only in the PCOS group. The Gpc4 level was higher in the PCOS group and correlated with CVD risk predictors, especially fat distribution.

Youth and young adult physical activity and body composition of young adult women: findings from the dietary intervention study in children.

PubMed

Hodge, Melissa G; Hovinga, Mary; Shepherd, John A; Egleston, Brian; Gabriel, Kelley; Van Horn, Linda; Robson, Alan; Snetselaar, Linda; Stevens, Victor K; Jung, Seungyoun; Dorgan, Joanne

2015-02-01

This study prospectively investigates associations between youth moderate-to-vigorous-intensity physical activity (MVPA) and body composition in young adult women using data from the Dietary Intervention Study in Children (DISC) and the DISC06 Follow-Up Study. MVPA was assessed by questionnaire on 5 occasions between the ages 8 and 18 years and at age 25-29 years in 215 DISC female participants. Using whole body dual-energy x-ray absorptiometry (DXA), overall adiposity and body fat distribution were assessed at age 25-29 years by percent body fat (%fat) and android-to-gynoid (A:G) fat ratio, respectively. Linear mixed effects models and generalized linear latent and mixed models were used to assess associations of youth MVPA with both outcomes. Young adult MVPA, adjusted for other young adult characteristics, was significantly inversely associated with young adult %fat (%fat decreased from 37.4% in the lowest MVPA quartile to 32.8% in the highest (p-trend = 0.02)). Adjusted for youth and young adult characteristics including young adult MVPA, youth MVPA also was significantly inversely associated with young adult %fat (β=-0.40 per 10 MET-hrs/wk, p = .02) . No significant associations between MVPA and A:G fat ratio were observed. Results suggest that youth and young adult MVPA are important independent predictors of adiposity in young women.

Lipid phosphate phosphatase 3 regulates adipocyte sphingolipid synthesis, but not developmental adipogenesis or diet-induced obesity in mice.

PubMed

Federico, Lorenzo; Yang, Liping; Brandon, Jason; Panchatcharam, Manikandan; Ren, Hongmei; Mueller, Paul; Sunkara, Manjula; Escalante-Alcalde, Diana; Morris, Andrew J; Smyth, Susan S

2018-01-01

Dephosphorylation of phosphatidic acid (PA) is the penultimate step in triglyceride synthesis. Adipocytes express soluble intracellular PA-specific phosphatases (Lipins) and broader specificity membrane-associated lipid phosphate phosphatases (LPPs) that can also dephosphorylate PA. Inactivation of lipin1 causes lipodystrophy in mice due to defective developmental adipogenesis. Triglyceride synthesis is diminished but not ablated by inactivation of lipin1 in differentiated adipocytes implicating other PA phosphatases in this process. To investigate the possible role of LPPs in adipocyte lipid metabolism and signaling we made mice with adipocyte-targeted inactivation of LPP3 encoded by the Plpp3(Ppap2b) gene. Adipocyte LPP3 deficiency resulted in blunted ceramide and sphingomyelin accumulation during diet-induced adipose tissue expansion, accumulation of the LPP3 substrate sphingosine 1- phosphate, and reduced expression of serine palmitoyl transferase. However, adiposity was unaffected by LPP3 deficiency on standard, high fat diet or Western diets, although Western diet-fed mice with adipocyte LPP3 deficiency exhibited improved glucose tolerance. Our results demonstrate functional compartmentalization of lipid phosphatase activity in adipocytes and identify an unexpected role for LPP3 in the regulation of diet-dependent sphingolipid synthesis that may impact on insulin signaling.

A homozygous FITM2 mutation causes a deafness-dystonia syndrome with motor regression and signs of ichthyosis and sensory neuropathy.

PubMed

Zazo Seco, Celia; Castells-Nobau, Anna; Joo, Seol-Hee; Schraders, Margit; Foo, Jia Nee; van der Voet, Monique; Velan, S Sendhil; Nijhof, Bonnie; Oostrik, Jaap; de Vrieze, Erik; Katana, Radoslaw; Mansoor, Atika; Huynen, Martijn; Szklarczyk, Radek; Oti, Martin; Tranebjærg, Lisbeth; van Wijk, Erwin; Scheffer-de Gooyert, Jolanda M; Siddique, Saadat; Baets, Jonathan; de Jonghe, Peter; Kazmi, Syed Ali Raza; Sadananthan, Suresh Anand; van de Warrenburg, Bart P; Khor, Chiea Chuen; Göpfert, Martin C; Qamar, Raheel; Schenck, Annette; Kremer, Hannie; Siddiqi, Saima

2017-02-01

A consanguineous family from Pakistan was ascertained to have a novel deafness-dystonia syndrome with motor regression, ichthyosis-like features and signs of sensory neuropathy. By applying a combined strategy of linkage analysis and whole-exome sequencing in the presented family, a homozygous nonsense mutation, c.4G>T (p.Glu2*), in FITM2 was identified. FITM2 and its paralog FITM1 constitute an evolutionary conserved protein family involved in partitioning of triglycerides into cellular lipid droplets. Despite the role of FITM2 in neutral lipid storage and metabolism, no indications for lipodystrophy were observed in the affected individuals. In order to obtain independent evidence for the involvement of FITM2 in the human pathology, downregulation of the single Fitm ortholog, CG10671, in Drosophila melanogaster was pursued using RNA interference. Characteristics of the syndrome, including progressive locomotor impairment, hearing loss and disturbed sensory functions, were recapitulated in Drosophila, which supports the causative nature of the FITM2 mutation. Mutation-based genetic counseling can now be provided to the family and insight is obtained into the potential impact of genetic variation in FITM2. © 2017. Published by The Company of Biologists Ltd.

Improvements in Vertebral-Column Angles and Psychological Metrics After Abdominoplasty With Rectus Plication.

PubMed

Temel, Metin; Türkmen, Arif; Berberoğlu, Ömer

2016-05-01

Substantial fluctuations in body weight can result in diastasis recti and weakening of the connections between the lateral abdominal muscles and the rectus sheath. The authors sought to determine the postural and psychological effects of abdominoplasty with vertical rectus plication. Forty women with substantial back and lumbar pain owing to abdominal lipodystrophy were evaluated in a prospective study. Preoperatively and 6 months postoperatively, patients underwent bidirectional radiography of the thoracic and lumbar regions. A visual analog scale (VAS), the Beck Depression Inventory (BDI), and the Nottingham Health Profile (NHP) were applied to assess physical, psychological, and quality-of-life changes following surgery. Significant improvements in posture, assessed in terms of lumbar lordosis, thoracic kyphosis, and the lumbosacral angle, were observed 6 months after abdominoplasty with rectus plication. Results of the VAS and BDI indicated significant improvements in pain and quality of life, respectively. Results of the NHP indicated significant postoperative improvements in fatigue, pain, and sleep. Abdominoplasty with rectus plication improves posture by tightening the thoracolumbar fascia. In selected patients, abdominoplasty can reduce back and lumbar pain, thereby improving quality of life. © 2016 The American Society for Aesthetic Plastic Surgery, Inc. Reprints and permission: journals.permissions@oup.com.

Objective evidence for the use of polylactic acid implants in HIV-associated facial lipoatrophy using three-dimensional surface laser scanning and psychological assessment.

PubMed

Ong, J; Clarke, A; White, P; Johnson, M A; Withey, S; Butler, P E M

2009-12-01

The advent of highly active antiretroviral therapy (HAART) has dramatically improved the life expectancy of people infected with human immunodeficiency virus (HIV). Although patients often have excellent disease control with these combinations of antiretrovirals, they are at risk for the multiple toxicities associated with these drugs. Facial lipoatrophy is a particularly distressing complication of some HAART regimes. This disfigurement can lead to significant psychosocial stress, resulting in decreased treatment compliance. Polylactic acid (PLA) facial implants provide a potential method of restoring a normal appearance. One hundred consecutive patients had a course of PLA facial implants. All patients were assessed clinically and had photographs, facial surface laser scans and completed psychological questionnaires throughout the course of treatment. After a mean of 4.85 treatments per patient, there were improvements in all measures. The mean clinical scores improved from a moderate-severe grade to none-mild grade after treatment. Three-dimensional (3D) laser surface scans showed a volume increase of 2.81 cc over the treated area of the cheek. There were significant improvements in all of the psychological measures. This study shows clear objective evidence of the psychological and physical benefit of PLA implants in HIV-associated facial lipodystrophy.

Evaluation of the enzymatic activity and stability of commercial bromelain incorporated in topical formulations.

PubMed

Lourenço, C B; Ataide, J A; Cefali, L C; Novaes, L C D L; Moriel, P; Silveira, E; Tambourgi, E B; Mazzola, P G

2016-10-01

Bromelain is a mixture of proteolytic enzymes found in various tissues of the pineapple plant (Ananas comosus) and other species of Bromeliaceae. Owing to its proteolytic activity, bromelain has been used in the food, medical, pharmaceutical and cosmetic industries, for its cell renewal, anti-ageing, whitening and anti-cellulite properties. This study evaluated the stability of bromelain (commercial powder) incorporated in topical formulations. Bromelain was incorporated at three concentrations, 0.5%, 1.0% and 2.0%, in oil-in-water emulsion and gel, and stored for six months at varying stress conditions. Stability was accessed by measuring the changes in the protein content, enzymatic activity, viscosity, rheology, pH and colour of the selected formulations. The colour of all the samples changed after 180 days of incubation, indicating the concentration-dependence and temperature-sensitive nature of these formulations. No relationship was observed between the changes in the pH, temperature and luminosity exposure in all the samples. Gels proved to be the least preferred base for incorporation of bromelain for use as a topical formulation, owing to its inability to maintain the integrity of bromelain, thereby affecting the formulation characteristics. The emulsion-based formulations at all the concentrations of bromelain were more stable than the gel-based formulation over 180 days of evaluation, at a temperature of 5°C, protected from light. © 2016 Society of Cosmetic Scientists and the Société Française de Cosmétologie.

Complementary clinical effects of topical tightening treatment in conjunction with a radiofrequency procedure.

PubMed

Goldberg, David J; Yatskayer, Margarita; Raab, Susana; Chen, Nannan; Krol, Yevgeniy; Oresajo, Christian

2014-10-01

Abstract Background: Skin laxity and cellulite on the buttocks and thighs are two common cosmetic concerns. Skin tightening with radiofrequency (RF) devices has become increasingly popular. The purpose of this study is to evaluate the efficacy and safety of a topical skin laxity tightening agent when used in combination with an RF device. A double-blinded, randomized clinical trial enrolled twenty females with mild-to-moderate skin laxity on the posterior thighs/buttocks. Each subject underwent two monthly treatments with an RF source (Alma Accent) to both legs. Subjects were then randomized to apply a topical agent (Skinceuticals Body Tightening Concentrate) twice daily to only one designated thigh/buttock throughout the eight-week duration of the study. All subjects were evaluated for improvement in lifting, skin tone, radiance, firmness/tightness, skin texture, and overall appearance based on photographic evaluation by blinded investigators at 12 weeks following the final RF treatment. A statistically significant improvement was found in the overall appearance on both sides treated with the RF device when compared to baseline. However, the area treated with the topical agent showed a statistically significantly greater degree of improvement than the side where no topical agent was applied. No adverse effects were reported. The use of a novel skin tightening agent used after RF procedures is both safe and effective for treatment of skin laxity on the buttocks and thighs. Combined therapy leads to a better result.

Modulation of plasma N-acylethanolamine levels and physiological parameters by dietary fatty acid composition in humans.

PubMed

Jones, Peter J H; Lin, Lin; Gillingham, Leah G; Yang, Haifeng; Omar, Jaclyn M

2014-12-01

N-Acylethanolamines (NAEs) are endogenous lipid-signaling molecules involved in satiety and energetics; however, how diet impacts circulating NAE concentrations and their downstream metabolic actions in humans remains unknown. Objectives were to examine effects of diets enriched with high-oleic canola oil (HOCO) or HOCO blended with flaxseed oil (FXCO), compared with a Western diet (WD), on plasma NAE levels and the association with energy expenditure and substrate oxidation. Using a randomized controlled crossover design, 36 hypercholesterolemic participants consumed three isoenergetic diets for 28 days, each containing 36% energy from fat, of which 70% was HOCO, FXCO, or WD. Ultra-performance liquid chromatography-MS/MS was used to measure plasma NAE levels and indirect calorimetry to assess energy expenditure and substrate oxidation. After 28 days, compared with WD, plasma oleoylethanolamide (OEA) and alpha-linolenoyl ethanolamide (ALEA) levels were significantly increased in response to HOCO and FXCO (P = 0.002, P < 0.001), respectively. Correlation analysis demonstrated an inverse association between plasma OEA levels and percent body fat (r = -0.21, P = 0.04), and a positive association was observed between the plasma arachidonoyl ethanolamide (AEA)/OEA ratio and android:gynoid fat (r = 0.23, P = 0.02), respectively. Results suggest that plasma NAE levels are upregulated via their dietary lipid substrates and may modulate regional and total fat mass through lipid-signaling mechanisms. Copyright © 2014 by the American Society for Biochemistry and Molecular Biology, Inc.

Psyllium supplementation in adolescents improves fat distribution & lipid profile: a randomized, participant-blinded, placebo-controlled, crossover trial.

PubMed

de Bock, Martin; Derraik, José G B; Brennan, Christine M; Biggs, Janene B; Smith, Greg C; Cameron-Smith, David; Wall, Clare R; Cutfield, Wayne S

2012-01-01

We aimed to assess the effects of psyllium supplementation on insulin sensitivity and other parameters of the metabolic syndrome in an at risk adolescent population. This study encompassed a participant-blinded, randomized, placebo-controlled, crossover trial. Subjects were 47 healthy adolescent males aged 15-16 years, recruited from secondary schools in lower socio-economic areas with high rates of obesity. Participants received 6 g/day of psyllium or placebo for 6 weeks, with a two-week washout before crossing over. Fasting lipid profiles, ambulatory blood pressure, auxological data, body composition, activity levels, and three-day food records were collected at baseline and after each 6-week intervention. Insulin sensitivity was measured by the Matsuda method using glucose and insulin values from an oral glucose tolerance test. 45 subjects completed the study, and compliance was very high: 87% of participants took >80% of prescribed capsules. At baseline, 44% of subjects were overweight or obese. 28% had decreased insulin sensitivity, but none had impaired glucose tolerance. Fibre supplementation led to a 4% reduction in android fat to gynoid fat ratio (p = 0.019), as well as a 0.12 mmol/l (6%) reduction in LDL cholesterol (p = 0.042). No associated adverse events were recorded. Dietary supplementation with 6 g/day of psyllium over 6 weeks improves fat distribution and lipid profile (parameters of the metabolic syndrome) in an at risk population of adolescent males. Australian New Zealand Clinical Trials Registry ACTRN12609000888268.

Body fat distribution, metabolic and inflammatory markers and retinal microvasculature in school-age children. The Generation R Study.

PubMed

Gishti, O; Jaddoe, V W V; Hofman, A; Wong, T Y; Ikram, M K; Gaillard, R

2015-10-01

To examine the associations of body fatness, metabolic and inflammatory markers with retinal vessel calibers among children. We performed a population-based cohort study among 4145 school-age children. At the median age of 6.0 years (95% range 5.8, 8.0 years), we measured body mass index, total and abdominal fat mass, metabolic and inflammatory markers (blood levels of lipids, insulin and C-peptide and C-reactive protein) and retinal vascular calibers from retinal photographs. We observed that compared with normal weight children, obese children had narrower retinal arteriolar caliber (difference -0.21 s.d. score (SDS; 95% confidence interval (CI) -0.35, -0.06)), but not venular caliber. Continuous analyses showed that higher body mass index and total body fat mass, but not android/gynoid fat mass ratio and pre-peritoneal fat mass, were associated with narrower retinal arteriolar caliber (P<0.05 for body mass index and total body fat mass), but not with retinal venular caliber. Lipid and insulin levels were not associated with retinal vessel calibers. Higher C-reactive protein was associated with only wider retinal venular caliber (difference 0.10 SDS (95% CI 0.06, 0.14) per SDS increase in C-reactive protein). This latter association was not influenced by body mass index. Higher body fatness is associated with narrower retinal arteriolar caliber, whereas increased C-reactive protein levels are associated with wider retinal venular caliber. Increased fat mass and inflammation correlate with microvascular development from school-age onwards.

Cardiovascular function is better in veteran football players than age-matched untrained elderly healthy men.

PubMed

Schmidt, J F; Andersen, T R; Andersen, L J; Randers, M B; Hornstrup, T; Hansen, P R; Bangsbo, J; Krustrup, P

2015-02-01

The aim of the study was to determine whether lifelong football training may improve cardiovascular function, physical fitness, and body composition. Our subjects were 17 male veteran football players (VPG; 68.1 ± 2.1 years) and 26 healthy age-matched untrained men who served as a control group (CG; 68.2 ± 3.2 years). Examinations included measurements of cardiac function, microvascular endothelial function [reactive hyperemic index (RHI)], maximum oxygen uptake (VO2max), and body composition. In VPG, left ventricular (LV) end-diastolic volume was 20% larger (P < 0.01) and LV ejection fraction was higher (P < 0.001). Tissue Doppler imaging revealed an augmented LV longitudinal displacement, i.e., LV shortening of 21% (P < 0.001) and longitudinal 2D strain was 12% higher (P < 0.05), in VPG. In VPG, resting heart rate was lower (6 bpm, P < 0.05), and VO2max was higher (18%, P < 0.05). In addition, RHI was 21% higher (P < 0.05) in VPG. VPG also had lower body mass index (P < 0.05), body fat percentage, total body fat mass, android fat percentage, and gynoid fat percentage (all P < 0.01). Lifelong participation in football training is associated with better LV systolic function, physical fitness, microvascular function, and a healthier body composition. Overall, VPG have better cardiovascular function compared with CG, which may reduce their cardiovascular morbidity and mortality. © 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Comparison of Different Physical Activity Measurement Methods in Adults Aged 45 to 64 Years Under Free-Living Conditions.

PubMed

Lipert, Anna; Jegier, Anna

2017-07-01

To compare physical activity (PA) measured by 4 methods in adults under free-living conditions in relation to selected demographic and anthropometric variables. Cohort study. Department of Sports Medicine. Clinically healthy men (81) and women (69) aged 45 to 64 years. Physical activity monitoring for 7 consecutive days under free-living conditions by pedometer (P) and accelerometer (A) simultaneously and PA questionnaires: International Physical Activity Questionnaire (IPAQ) and Seven-Day Physical Activity Questionnaire Recall (SDPAR) completed after the 7-day PA. Comparison of PA measured by pedometer, IPAQ, and SDPAR with accelerometer with regard to age, body mass, gender, and obesity type. Total energy expenditure (EE) by IPAQ was higher than A (P < 0.001) in both groups regardless of age, body mass, or obesity type. Mean EE value by P was greater than A (P < 0.001) in central-obesity males and lower than A (P < 0.001) in central-obesity females. There were differences in step counts in women, unnoticed in men. SDPAR overestimated total EE in gynoid-obesity males and in central-obesity females compared with A. Ninety-five percent CI was the largest around IPAQ compared with P and SDPAR, with SDPAR showing the best agreement with A. Body mass and obesity type influenced PA measurements. To monitor PA, it is recommended to use pedometer in normal bodyweight and overweight groups while accelerometer is advisable in obese subjects. A combined approach of objective and subjective PA monitoring tools is preferable.

Effect of high-oleic canola and flaxseed oils on energy expenditure and body composition in hypercholesterolemic subjects.

PubMed

Gillingham, Leah G; Robinson, Kimberley S; Jones, Peter J H

2012-11-01

The fatty acid profile of dietary fats may contribute to its channelling toward oxidation versus storage, influencing energy and weight balance. Our objective was to compare the effects of diets enriched with high-oleic canola oil (HOCO), alone or blended with flaxseed oil (FXCO), on energy expenditure, substrate utilization, and body composition versus a typical Western diet (WD). Using a randomized crossover design, 34 hypercholesterolemic subjects (n=22 females) consumed 3 controlled diets for 28 days containing ~49% energy from carbohydrate, 14% energy from protein, and 37% energy from fat, of which 70% of fat was provided by HOCO rich in oleic acid, FXCO rich in alpha-linolenic acid, or WD rich in saturated fat. Indirect calorimetry measured energy expenditure and substrate oxidation. Body composition was analyzed by dual-energy x-ray absorptiometry. After 28 days, resting and postprandial energy expenditure and substrate oxidation were not different after consumption of the HOCO or FXCO diets compared with a typical Western diet. No significant changes in body composition measures were observed between diets. However, the android-to-gynoid ratio tended to increase (P=.055) after the FXCO diet compared with the HOCO diet. The data suggest that substituting a typical Western dietary fatty acid profile with HOCO or FXCO does not significantly modulate energy expenditure, substrate oxidation or body composition in hypercholesterolemic males and females. Copyright © 2012 Elsevier Inc. All rights reserved.

Significant Beneficial Association of High Dietary Selenium Intake with Reduced Body Fat in the CODING Study

PubMed Central

Wang, Yongbo; Gao, Xiang; Pedram, Pardis; Shahidi, Mariam; Du, Jianling; Yi, Yanqing; Gulliver, Wayne; Zhang, Hongwei; Sun, Guang

2016-01-01

Selenium (Se) is a trace element which plays an important role in adipocyte hypertrophy and adipogenesis. Some studies suggest that variations in serum Se may be associated with obesity. However, there are few studies examining the relationship between dietary Se and obesity, and findings are inconsistent. We aimed to investigate the association between dietary Se intake and a panel of obesity measurements with systematic control of major confounding factors. A total of 3214 subjects participated in the study. Dietary Se intake was determined from the Willett food frequency questionnaire. Body composition was measured using dual-energy X-ray absorptiometry. Obese men and women had the lowest dietary Se intake, being 24% to 31% lower than corresponding normal weight men and women, classified by both BMI and body fat percentage. Moreover, subjects with the highest dietary Se intake had the lowest BMI, waist circumference, and trunk, android, gynoid and total body fat percentages, with a clear dose-dependent inverse relationship observed in both gender groups. Furthermore, significant negative associations discovered between dietary Se intake and obesity measurements were independent of age, total dietary calorie intake, physical activity, smoking, alcohol, medication, and menopausal status. Dietary Se intake alone may account for 9%–27% of the observed variations in body fat percentage. The findings from this study strongly suggest that high dietary Se intake is associated with a beneficial body composition profile. PMID:26742059

Treatment-limiting toxicities associated withnucleoside analogue reverse transcriptase inhibitor therapy: A prospective, observational study**

PubMed Central

Palacios, Rosario; Santos, Jesús; Camino, Xavier; Arazo, Piedad; Torres Perea, Rafael; Echevarrfa, Santiago; Ribera, Esteban; Sánchez de la Rosa, Rainel; Moreno Guillen, Santiago

2005-01-01

regimens. The NRTIs with the highest discontinuation rates were stavudine (914 patients [65.7%]) and zidovudine (177 [12.7%]). The most frequent NRTI-related AEs were lipoatrophy (550 patients [39.5%]) and peripheral neuropathy (170 [12.2%]). Lipoatrophy was most commonly associated with stavudine (480/550 cases [87.3%]); periph eral neuropathy, with stavudine and didanosine (107/170 [62.9%] and 48/170 [28.2%] cases, respectively); and anemia, with zidovudine (70/77 cases [90.9%]). Conclusions: The results of this study in patients with HIV-1 recruited in the10 Recover Study and undergoing HAART suggest that long-term treatment with NRTIs is associated with AEs (lipoatrophy, peripheral neuropathy, and lipodystrophy), with morphologic disorders (lipoatrophy, lipodystrophy) being the most common AEs leading to discontinuation. Minimizing these AEs by switching to an NRTI not associated with these AEs (eg, tenofovir) would contribute to adherence and hence efficacy of long-term HAART. PMID:24672118

Vitamin D status, body composition and hypertensive target organ damage in primary hypertension.

PubMed

Pludowski, Pawel; Jaworski, Maciej; Niemirska, Anna; Litwin, Mieczyslaw; Szalecki, Mieczyslaw; Karczmarewicz, Elżbieta; Michalkiewicz, Jacek

2014-10-01

Overweight/obesity and high blood pressure during growth period are important risk factors of cardiovascular disease later in life. Cardiovascular system, fat and muscles are among target tissues for vitamin D and low 25(OH)D levels are likely to attenuate potential benefits of its action. The study was aimed to evaluate vitamin D status and body composition in children and adolescents with primary hypertension (PH). The study population comprised 78 patients aged 15.4±2.3yrs (9-18yrs; 15 girls) with diagnosed PH. Total 25(OH)D and parathyroid hormone (PTH) were assayed by Cobas e411 machine (Roche Diagnostics). DXA (Prodigy, GE Lunar) was used to assess total body bone mineral content (TBBMC; g), total body bone mineral density (TBBMD; g/cm(2)), lean body mass (LBM; g), % lean body mass (%LBM), fat mass (FM; g), % fat mass (% FM), Android %Fat, Gynoid %Fat and Trunk fat mass (Trunk FM; g). Hypertensive cases (BMI=25.6±4.2kg/m(2)), compared to reference, had slightly increased TBBMD and TBBMC Z-scores (+0.40±0.91 and +0.59±0.96; both p<0.001), and had markedly increased FM and FM/body weight ratio Z-scores of ±1.83±1.63 (p<0.0001) and +1.43±1.05 (p<0.0001). LBM Z-scores were slightly increased as well (+0.34±1.08, p<0.001). In contrast, markedly reduced LBM/body weight ratio Z-scores of -1.47±0.90 (p<0.0001) and disturbed relationship between FM and LBM as assessed by FM/LBM ratio Z-score of +1.53±1.29 (p<0.0001) were noted. The average serum levels of 25(OH)D of 17.8±6.9ng/mL and PTH of 34.8±16.8pg/mL were noted in PH group. 91% PH cases showed 25(OH)D levels lower than 30ng/mL. 71% of PH subjects revealed vitamin D deficiency (25(OH)D<20ng/ml). 10% of PH cases showed 25(OH)D levels lower than 10ng/mL. 25(OH)D levels negatively correlated with PTH showing r=-0.24 (p=0.03). Absolute LBM/body weight ratio values positively correlated with 25(OH)D levels (r=0.31; p=0.01). In contrast, absolute FM/body weight ratio values correlated negatively with 25(OH

Changes in visceral adipose tissue plasma membrane lipid composition in old rats are associated with adipocyte hypertrophy with aging.

PubMed

Bonzón-Kulichenko, Elena; Moltó, Eduardo; Pintado, Cristina; Fernández, Alejandro; Arribas, Carmen; Schwudke, Dominik; Gallardo, Nilda; Shevchenko, Andrej; Andrés, Antonio

2018-04-16

Increased adiposity, through adipocyte hypertrophy and/or hyperplasia, characterizes aging and obesity. Both are leptin-resistant states, associated to disturbed lipid metabolism, reduced insulin sensitivity and inflammation. Nevertheless, fat tissue dysfunction appears earlier in obesity than in normal aging. In contrast, lipodystrophy is accompanied by diabetes, and improving the fat cell capacity to expand rescues the diabetic phenotype. Fat tissue dysfunction is extensively studied in the diet-induced obesity, but remains relatively neglected in the aging-associated obesity. In the Wistar rat, as occurs in humans, early or middle aging is accompanied by an increase in adiposity. Using this experimental model, we describe the molecular mechanisms contributing to the white adipose tissue (WAT) hypertrophy. WAT from middle-old age rats is characterized by decreased basal lipogenesis and lipolysis, increased esterification, as demonstrated by the higher TAG and cholesterol content in visceral WAT, and the maintenance of total ceramide levels within normal values. In addition, we describe alterations in the adipose tissue plasma membrane lipid composition, as increased total ether-phosphatidylcholine, sphingomyelin and free cholesterol levels that favor an enlarged fat cell size with aging. All these metabolic changes may be regarded as a survival advantage that prevents the aged rats from becoming overtly diabetic.

Treatment of facial lipoatrophy with polymethylmethacrylate among patients with human immunodeficiency virus/acquired immunodeficiency syndrome (HIV/AIDS): impact on the quality of life.

PubMed

Quintas, Rodrigo C S; de França, Emmanuel R; de Petribú, Kátia C L; Ximenes, Ricardo A A; Quintas, Lóren F F M; Cavalcanti, Ernando L F; Kitamura, Marco A P; Magalhães, Kássia A A; Paiva, Késsia C F; Filho, Demócrito B Miranda

2014-04-01

The lipodystrophy syndrome is characterized by selective loss of subcutaneous fat on the face and extremities (lipoatrophy) and/or accumulation of fat around the neck, abdomen, and thorax (lipohypertrophy). The aim of this study has been to assess the impact of polymethylmethacrylate facial treatment on quality of life, self-perceived facial image, and the severity of depressive symptoms in patients living with HIV/AIDS. A non-randomized before and after interventional study was developed. Fifty-one patients underwent facial filling. The self-perceived quality of life, facial image, and degree of depressive symptoms were measured by the Short-Form 36 and HIV/AIDS--Targeted quality of life questionnaires, by a visual analogue scale and by the Beck depression inventory, respectively, before and three months after treatment. Six of the eight domains of Short-Form 36 and eight of the nine dimensions of the HIV/AIDS--Targeted quality of life questionnaires, together with the visual analogue scale and by the Beck depression inventory scores, revealed a statistically significant improvement. The only adverse effects registered were edema and ecchymosis. The treatment of facial lipoatrophy improved the self-perceived quality of life and facial image as well as any depressive symptoms among patients with HIV/AIDS. © 2014 The International Society of Dermatology.

Rapamycin Reverses Elevated mTORC1 Signaling in Lamin A/C–Deficient Mice, Rescues Cardiac and Skeletal Muscle Function, and Extends Survival

PubMed Central

Ramos, Fresnida J.; Chen, Steven C.; Garelick, Michael G.; Dai, Dao-Fu; Liao, Chen-Yu; Schreiber, Katherine H.; MacKay, Vivian L.; An, Elroy H.; Strong, Randy; Ladiges, Warren C.; Rabinovitch, Peter S.; Kaeberlein, Matt; Kennedy, Brian K.

2013-01-01

Mutations in LMNA, the gene that encodes A-type lamins, cause multiple diseases including dystrophies of the skeletal muscle and fat, dilated cardiomyopathy, and progeria-like syndromes (collectively termed laminopathies). Reduced A-type lamin function, however, is most commonly associated with skeletal muscle dystrophy and dilated cardiomyopathy rather than lipodystrophy or progeria. The mechanisms underlying these diseases are only beginning to be unraveled. We report that mice deficient in Lmna, which corresponds to the human gene LMNA, have enhanced mTORC1 (mammalian target of rapamycin complex 1) signaling specifically in tissues linked to pathology, namely, cardiac and skeletal muscle. Pharmacologic reversal of elevated mTORC1 signaling by rapamycin improves cardiac and skeletal muscle function and enhances survival in mice lacking A-type lamins. At the cellular level, rapamycin decreases the number of myocytes with abnormal desmin accumulation and decreases the amount of desmin in both muscle and cardiac tissue of Lmna–/– mice. In addition, inhibition of mTORC1 signaling with rapamycin improves defective autophagic-mediated degradation in Lmna–/– mice. Together, these findings point to aberrant mTORC1 signaling as a mechanistic component of laminopathies associated with reduced A-type lamin function and offer a potential therapeutic approach, namely, the use of rapamycin-related mTORC1 inhibitors. PMID:22837538

Accelerated telomere shortening and replicative senescence in human fibroblasts overexpressing mutant and wild-type lamin A

DOE Office of Scientific and Technical Information (OSTI.GOV)

Huang Shurong; Risques, Rosa Ana; Martin, George M.

2008-01-01

LMNA mutations are responsible for a variety of genetic disorders, including muscular dystrophy, lipodystrophy, and certain progeroid syndromes, notably Hutchinson-Gilford Progeria. Although a number of clinical features of these disorders are suggestive of accelerated aging, it is not known whether cells derived from these patients exhibit cellular phenotypes associated with accelerated aging. We examined a series of isogenic skin fibroblast lines transfected with LMNA constructs bearing known pathogenic point mutations or deletion mutations found in progeroid syndromes. Fibroblasts overexpressing mutant lamin A exhibited accelerated rates of loss of telomeres and shortened replicative lifespans, in addition to abnormal nuclear morphology. Tomore » our surprise, these abnormalities were also observed in lines overexpressing wild-type lamin A. Copy number variants are common in human populations; those involving LMNA, whether arising meiotically or mitotically, might lead to progeroid phenotypes. In an initial pilot study of 23 progeroid cases without detectable WRN or LMNA mutations, however, no cases of altered LMNA copy number were detected. Nevertheless, our findings raise a hypothesis that changes in lamina organization may cause accelerated telomere attrition, with different kinetics for overexpession of wild-type and mutant lamin A, which leads to rapid replicative senescence and progroid phenotypes.« less

Inhibition of cisplatin-induced lipid catabolism and weight loss by ghrelin in male mice.

PubMed

Garcia, Jose M; Scherer, Thomas; Chen, Ji-an; Guillory, Bobby; Nassif, Anriada; Papusha, Victor; Smiechowska, Joanna; Asnicar, Mark; Buettner, Christoph; Smith, Roy G

2013-09-01

Cachexia, defined as an involuntary weight loss ≥ 5%, is a serious and dose-limiting side effect of chemotherapy that decreases survival in cancer patients. Alterations in lipid metabolism are thought to cause the lipodystrophy commonly associated with cachexia. Ghrelin has been proposed to ameliorate the alterations in lipid metabolism due to its orexigenic and anabolic properties. However, the mechanisms of action through which ghrelin could potentially ameliorate chemotherapy-associated cachexia have not been elucidated. The objectives of this study were to identify mechanisms by which the chemotherapeutic agent cisplatin alters lipid metabolism and to establish the role of ghrelin in reversing cachexia. Cisplatin-induced weight and fat loss were prevented by ghrelin. Cisplatin increased markers of lipolysis in white adipose tissue (WAT) and of β-oxidation in liver and WAT and suppressed lipogenesis in liver, WAT, and muscle. Ghrelin prevented the imbalance between lipolysis, β-oxidation, and lipogenesis in WAT and muscle. Pair-feeding experiments demonstrated that the effects of cisplatin and ghrelin on lipogenesis, but not on lipolysis and β-oxidation, were due to a reduction in food intake. Thus, ghrelin prevents cisplatin-induced weight and fat loss by restoring adipose tissue functionality. An increase in caloric intake further enhances the anabolic effects of ghrelin.

Oligosaccharide composition is similar in drusen and dense deposits in membranoproliferative glomerulonephritis type II.

PubMed

D'souza, Yvonne B; Jones, Carolyn J P; Short, Colin D; Roberts, Ian S D; Bonshek, Richard E

2009-04-01

Drusen are a feature of age-related macular degeneration (AMD). Lesions similar in appearance to drusen are also found in the fundi of patients with membranoproliferative glomerulonephritis type II (dense deposit disease, DDD). The lamina densa of the glomerular basement membrane, in DDD, is transformed into an electron-dense structure by deposition of microscopically homogeneous material. Our study sought to compare the saccharide composition of drusen and dense deposits in the formalin-fixed, paraffin-embedded tissue from the eye and kidney. Six eye specimens were obtained from patients diagnosed with AMD but another eye was obtained from a patient with partial lipodystrophy, who died after renal failure presumably because of DDD. The kidney specimens were from three biopsy-proven cases of DDD. Glycosylation patterns were measured by the binding of 19 biotinylated lectins before and after neuraminidase pre-treatment. High mannose, bi/tri-antennary non-bisected and bisected complex N-glycan, N-acetyl glucosamine, galactose, and sialic acid residues were found in both drusen and dense deposits. Treatment with neuraminidase exposed subterminal galactose in both sites and sparse N-acetyl galactosamine residues in drusen alone. Our study found similar pathologic oligosaccharide structures in the eye and kidney, suggesting that drusen may be a common end result of retinal and glomerular disease.

Secondary hypertriglyceridemia in children and adolescents.

PubMed

Blackett, Piers R; Wilson, Don P; McNeal, Catherine J

2015-01-01

Secondary dyslipidemia with predominant hypertriglyceridemia may occur as a consequence of both common and rare causes. After accounting for obesity and associated insulin resistance, clinicians should carefully consider other contributing factors and conditions. Genetic background and causative factors prevail during gestation, infancy, and childhood and continue in adults. Elevations in triglyceride (TG) are associated with transfer of TG to high-density lipoprotein (HDL) and low-density lipoprotein (LDL) resulting in lipolysis, HDL degradation, and formation of atherogenic LDL particles. Defining and treating the underlying cause is the first step toward restoring the lipids and lipoproteins to normal, especially in cases with severe hypertriglyceridemia, who are at risk for acute pancreatitis. Disorders involving the liver, kidney, endocrine, and immune systems and medications need to be considered. Rare diseases such as lipodystrophy and glycogen storage disease are particularly challenging, and there have been promising new developments. Treatment depends on the severity; prevention of acute pancreatitis being a priority in severe cases and lifestyle modification being a foundation for general management followed by targeting TG and predictors of coronary artery disease such as LDL cholesterol and non-HDL cholesterol, when they exceed cutpoints. Copyright © 2015 National Lipid Association. Published by Elsevier Inc. All rights reserved.

Human immunodeficiency virus atropy induces modification of subcutaneous adipose tissue architecture: in vivo visualization by high-resolution magnetic resonance imaging.

PubMed

Josse, G; Gensanne, D; Aquilina, C; Bernard, J; Saint-Martory, C; Lagarde, J M; Schmitt, A M

2009-04-01

Human immunodeficiency virus (HIV) infection generally induces lipodystrophy. For targeted treatment a better understanding of its development is necessary. The utility of high-resolution magnetic resonance imaging (MRI) is explored. The present study presents a way to visualize the adipose tissue architecture in vivo and to inspect modifications associated with the atrophy. High-resolution MRI scans with surface coils were performed on the calf and at the lumbar region of three groups of patients: HIV patients with lipoatrophy, HIV patients without lipoatrophy and healthy volunteers. All patients underwent a clinical examination. In addition, dual energy X-ray absorptiometry (DEXA) measurements were taken. On the MRI scans adipose tissue thickness and adipose nodule size were measured. Results High-resolution MRI enabled identification of a clear disorganization of adipose tissue in patients with lipoatrophy. In addition, these patients presented a very small adipose tissue thickness on the calf and a very small nodule size. led to the hypothesis that adipose tissue disorganization appears before changes in DEXA measurements or clinically visible modifications. High-resolution MRI enabled visualization in vivo of precise changes in tissue organization due to HIV lipoatrophy. This imaging technique should be very informative for better monitoring of the atrophy.

Low-level laser therapy (LLLT) associated with aerobic plus resistance training to improve inflammatory biomarkers in obese adults.

PubMed

da Silveira Campos, Raquel Munhoz; Dâmaso, Ana Raimunda; Masquio, Deborah Cristina Landi; Aquino, Antonio Eduardo; Sene-Fiorese, Marcela; Duarte, Fernanda Oliveira; Tock, Lian; Parizotto, Nivaldo Antonio; Bagnato, Vanderlei Salvador

2015-07-01

Recently, investigations suggest the benefits of low-level laser (light) therapy (LLLT) in noninvasive treatment of cellulite, improvement of body countering, and control of lipid profile. However, the underlying key mechanism for such potential effects associated to aerobic plus resistance training to reduce body fat and inflammatory process, related to obesity in women still unclear. The purpose of the present investigation was to evaluate the effects of combined therapy of LLLT and aerobic plus resistance training in inflammatory profile and body composition of obese women. For this study, it involved 40 obese women with age of 20-40 years. Inclusion criteria were primary obesity and body mass index (BMI) greater than 30 kg/m(2) and less than 40 kg/m(2). The voluntaries were allocated in two different groups: phototherapy group and SHAM group. The interventions consisted on physical exercise training and application of phototherapy (808 nm), immediately after the physical exercise, with special designed device. Proinflammatory/anti-inflammatory adipokines were measured. It was showed that LLLT associated to physical exercise is more effective than physical exercise alone to increase adiponectin concentration, an anti-inflammatory adipokine. Also, it showed reduced values of neck circumference (cm), insulin concentration (μU/ml), and interleukin-6 (pg/ml) in LLLT group. In conclusion, phototherapy can be an important tool in the obesity, mostly considering its potential effects associated to exercise training in attenuating inflammation in women, being these results applicable in the clinical practices to control related risk associated to obesity.

Relationship between sleep characteristics and measures of body size and composition in a nationally-representative sample.

PubMed

Xiao, Qian; Gu, Fangyi; Caporaso, Neil; Matthews, Charles E

2016-01-01

Short sleep has been linked to obesity. However, sleep is a multidimensional behavior that cannot be characterized solely by sleep duration. There is limited study that comprehensively examined different sleep characteristics in relation to obesity. We examined various aspects of sleep in relation to adiposity in 2005-2006 NHANES participants who were 18 or older and free of cardiovascular disease, cancer, emphysema, chronic bronchitis and depression ( N  = 3995). Sleep characteristics were self-reported, and included duration, overall quality, onset latency, fragmentation, daytime sleepiness, snoring, and sleep disorders. Body measurements included weight, height, waist circumference, and dual-energy X-ray absorptiometry measured fat mass. Snoring was associated with higher BMI (adjusted difference in kg/m 2 comparing snoring for 5+ nights/week with no snoring (95 % confidence interval), 1.85 (0.88, 2.83)), larger waist circumference (cm, 4.52 (2.29, 6.75)), higher percentage of body fat (%, 1.61 (0.84, 2.38)), and higher android/gynoid ratio (0.03 (0.01, 0.06)). The associations were independent of sleep duration and sleep quality, and cannot be explained by the existence of sleep disorders such as sleep apnea. Poor sleep quality (two or more problematic sleep conditions) and short sleep duration (<6 h) were also associated with higher measures of body size and fat composition, although the effects were attenuated after snoring was adjusted. In a nationally representative sample of healthy US adults, snoring, short sleep, and poor sleep quality were associated with higher adiposity.

Depression-related differences in lean body mass distribution from National Health and Nutrition Examination Survey 2005-2006.

PubMed

Li, Ying; Meng, Lu; Li, Yue; Sato, Yasuto

2014-03-01

Although the association between depression and body composition has been widely discussed, the effects of depression on lean body mass (LBM) are unclear. The present study aimed to investigate the association of depression with LBM. The study included 2406 participants aged 18-69 years. The sex and body mass index (BMI) stratified analysis of covariance was performed to compare total LBM and percentage LBM (%LBM) in subjects with different depression score levels. Multiple linear regression analysis was conducted to estimate the association between depression score and serum albumin level. An analysis of covariance stratified by sex showed that participants with moderate-to-severe depression had significantly decreased total LBM and total and regional %LBM in men, except for total LBM and percentage gynoid LBM, which was observed in women. In the BMI stratified analysis of covariance, depression was significantly associated with decreased total and regional %LBM and with increased total and regional percentage fat body mass. In people with BMI≥25kg/m(2), the associations between depression or depressive syndrome and LBM, and total and regional %LBM are stronger compared to those with BMI<25kg/m(2). Multiple linear regression analysis showed that depression score was significantly negatively associated with serum albumin level. This is a cross-sectional study based on a general population, some information about clinical diagnosis and medication use is not available. Depression had a significant negative association with LBM and serum albumin level. Copyright © 2014 Elsevier B.V. All rights reserved.

Interval training in the fed or fasted state improves body composition and muscle oxidative capacity in overweight women.

PubMed

Gillen, Jenna B; Percival, Michael E; Ludzki, Alison; Tarnopolsky, Mark A; Gibala, Martin J

2013-11-01

To investigate the effects of low-volume high-intensity interval training (HIT) performed in the fasted (FAST) versus fed (FED) state on body composition, muscle oxidative capacity, and glycemic control in overweight/obese women. Sixteen women (27 ± 8 years, BMI: 29 ± 6 kg/m(2) , VO2peak : 28 ± 3 ml/kg/min) were assigned to either FAST or FED (n = 8 each) and performed 18 sessions of HIT (10× 60-s cycling efforts at ∼90% maximal heart rate, 60-s recovery) over 6 weeks. There was no significant difference between FAST and FED for any measured variable. Body mass was unchanged following training; however, dual energy X-ray absorptiometry revealed lower percent fat in abdominal and leg regions as well as the whole body level (main effects for time, P ≤ 0.05). Fat-free mass increased in leg and gynoid regions (P ≤ 0.05). Resting muscle biopsies revealed a training-induced increase in mitochondrial capacity as evidenced by increased maximal activities of citrate synthase and β-hydroxyacyl-CoA dehydrogenase (P ≤ 0.05). There was no change in insulin sensitivity, although change in insulin area under the curve was correlated with change in abdominal percent fat (r = 0.54, P ≤ 0.05). Short-term low-volume HIT is a time-efficient strategy to improve body composition and muscle oxidative capacity in overweight/obese women, but fed- versus fasted-state training does not alter this response. Copyright © 2013 The Obesity Society.

Placental vascular dysfunction, fetal and childhood growth, and cardiovascular development: the generation R study.

PubMed

Gaillard, Romy; Steegers, Eric A P; Tiemeier, Henning; Hofman, Albert; Jaddoe, Vincent W V

2013-11-12

Suboptimal fetal nutrition may influence early growth and cardiovascular development. We examined whether umbilical and uterine artery resistance indices, as measures of feto-placental and utero-placental vascular function, respectively, are associated with fetal and childhood growth and cardiovascular development. This study was embedded in a population-based prospective cohort study among 6716 mothers and their children. Umbilical artery pulsatility index and uterine artery resistance index and fetal growth were measured in third trimester. Childhood growth was repeatedly assessed from birth to the age of 6 years. We measured body fat distribution, left ventricular mass, and blood pressure at the age of 6 years. Higher third trimester umbilical and uterine artery vascular resistance were associated with lower fetal length and weight growth in third trimester resulting in a smaller size at birth among boys and girls (P values < 0.05). These differences in length and weight growth became smaller from the age of 6 months onwards, but were still present at the age of 6 years. Higher third trimester umbilical artery vascular resistance, but not uterine artery vascular resistance, was associated with higher childhood body mass index, total fat mass, android/gynoid fat mass ratio, and systolic blood pressure, and with a lower left ventricular mass (P values<0.05). These associations were not explained by birth weight. Stronger associations tended to be present among girls as compared with boys. Higher third trimester feto-placental vascular resistance, but not utero-placental vascular resistance, was associated with slower fetal growth rates and cardiovascular adaptations in childhood.

Interactions between dietary oil treatments and genetic variants modulate fatty acid ethanolamides in plasma and body weight composition.

PubMed

Pu, Shuaihua; Eck, Peter; Jenkins, David J A; Connelly, Philip W; Lamarche, Benoît; Kris-Etherton, Penny M; West, Sheila G; Liu, Xiaoran; Jones, Peter J H

2016-03-28

Fatty acid ethanolamides (FAE), a group of lipid mediators derived from long-chain fatty acids (FA), mediate biological activities including activation of cannabinoid receptors, stimulation of fat oxidation and regulation of satiety. However, how circulating FAE levels are influenced by FA intake in humans remains unclear. The objective of the present study was to investigate the response of six major circulating FAE to various dietary oil treatments in a five-period, cross-over, randomised, double-blind, clinical study in volunteers with abdominal obesity. The treatment oils (60 g/12 552 kJ per d (60 g/3000 kcal per d)) provided for 30 d were as follows: conventional canola oil, high oleic canola oil, high oleic canola oil enriched with DHA, flax/safflower oil blend and corn/safflower oil blend. Two SNP associated with FAE degradation and synthesis were studied. Post-treatment results showed overall that plasma FAE levels were modulated by dietary FA and were positively correlated with corresponding plasma FA levels; minor allele (A) carriers of SNP rs324420 in gene fatty acid amide hydrolase produced higher circulating oleoylethanolamide (OEA) (P=0·0209) and docosahexaenoylethanolamide (DHEA) levels (P=0·0002). In addition, elevated plasma DHEA levels in response to DHA intake tended to be associated with lower plasma OEA levels and an increased gynoid fat mass. In summary, data suggest that the metabolic and physiological responses to dietary FA may be influenced via circulating FAE. Genetic analysis of rs324420 might help identify a sub-population that appears to benefit from increased consumption of DHA and oleic acid.

Long-term interdisciplinary therapy decreases symptoms of binge eating disorder and prevalence of metabolic syndrome in adults with obesity.

PubMed

Leite, Paula Bresciani; Dâmaso, Ana Raimunda; Poli, Vanessa Schoenardie; Sanches, Ricardo Badan; Silva, Stephan Garcia Andrade; Fidalgo, João Pedro Novo; Nascimento, Maythe Amaral; de Oliveira, Camila Aparecida Machado; Caranti, Danielle Arisa

2017-04-01

Obesity-associated comorbidities greatly impact the quality and expectancy of life. Binge eating disorder (BED) is the most prevalent eating disorder and it is an important risk factor for obesity and metabolic syndrome (MetS). For these reasons, we aimed to assess the effect of an interdisciplinary therapy on the symptoms of BED and the prevalence of MetS in obese adults. It was hypothesized that the interdisciplinary therapy would decrease symptoms of BED and markers of MetS. Twenty-four volunteers (BMI 34.80±3.17 kg/m 2 ; 41.21±6.28 years old) completed a 32-week intervention. Biochemical characteristics, body composition, the degree of symptoms of binge eating, and macronutrients, and sodium consumption pre- and post-treatment were determined. The prevalence of MetS dropped from 75% to 45.8%, post-therapy. Among the markers of MetS, waist circumference and systolic blood pressure decreased significantly, whereas high-density lipoprotein levels increased. Fasting plasma glucose, diastolic blood pressure, and triglycerides did not change. Based on binge-eating scale (BES) scores, before therapy, 33.3% of volunteers were classified as moderate bingers, and after therapy all volunteers were classified as having no BED symptoms. No difference in the prevalence of MetS between individuals classified as normal or moderate bingers was observed, but we found a positive post-therapy correlation between the BES score and body fat, gynoid fat and trunk fat. Sodium, fat, and carbohydrate consumption decreased. Protein intake did not change. In conclusion, the interdisciplinary approach was efficient in reducing symptoms of BED and MetS prevalence in this population. Copyright © 2017 Elsevier Inc. All rights reserved.

Changes in HDL-c concentrations after 16 weeks of combined training in postmenopausal women: characteristics of positive and negative responders.

PubMed

Diniz, Tiego A; Rossi, Fabricio E; Fortaleza, Ana Claudia Souza; Neves, Lucas Melo; Christofaro, Diego Giulliano Destro; Buonani, Camila; Lira, Fabio S; Campos, Eduardo Zapaterra; Prado, Wagner Luiz do; Freitas, Ismael Forte

2018-01-01

This study aimed to investigate the individual characteristics of body composition and metabolic profile that could explain interindividual variation in high-density lipoprotein cholesterol (HDL-c) concentrations in response to 16 weeks of combined strength plus aerobic (combined) training in postmenopausal women. The participants were divided into tertiles based on percentage of changes in HDL-c concentrations after combined training. Only women in the upper tertile (positive responders: Δ > 10.4%; n = 19) and lower tertile (negative responders: Δ < -1.4%; n = 19) were considered for analyses. The total body fat (BF), trunk fat (TF), android fat (AF), gynoid fat, and lean body mass were estimated by dual-energy X-ray absorptiometry. The metabolic profile - glucose, triacylglycerol, total cholesterol, HDL-c, low-density lipoprotein cholesterol, and very-low-density lipoprotein (VLDL) - were assessed. After 16 weeks, both positive and negative responders presented similar improvement in body composition, such as a decrease in percentage and kilograms of BF, TF, and AF, and increase in lean body mass (p value for time < 0.05). As expected, there was an effect of time and also a significant interaction (time vs. group) (p value < 0.001) in the improvement of HDL-c, with higher values for positive responders. Regarding metabolic profile, there were significant interactions (time vs. group) for triacylglycerol (p value = 0.032) and VLDL (p value = 0.027) concentrations, with lower values for positive responders. Our results suggests there is heterogeneity in combined training-induced HDL-c changes in postmenopausal women, and the positive responders were those who presented more pronounced decreases in triacylglycerol and VLDL concentrations.

Body mass index and waist circumference in early adulthood are associated with thoracolumbar spine shape at age 60-64: The Medical Research Council National Survey of Health and Development.

PubMed

Pavlova, Anastasia V; Muthuri, Stella G; Cooper, Rachel; Saunders, Fiona R; Gregory, Jennifer S; Barr, Rebecca J; Martin, Kathryn R; Adams, Judith E; Kuh, Diana; Hardy, Rebecca J; Aspden, Richard M

2018-01-01

This study investigated associations between measures of adiposity from age 36 and spine shape at 60-64 years. Thoracolumbar spine shape was characterised using statistical shape modelling on lateral dual-energy x-ray absorptiometry images of the spine from 1529 participants of the MRC National Survey of Health and Development, acquired at age 60-64. Associations of spine shape modes with: 1) contemporaneous measures of total and central adiposity (body mass index (BMI), waist circumference (WC)) and body composition (android:gynoid fat mass ratio and lean and fat mass indices, calculated as whole body (excluding the head) lean or fat mass (kg) divided by height2 (m)2); 2) changes in total and central adiposity between age 36 and 60-64 and 3) age at onset of overweight, were tested using linear regression models. Four modes described 79% of the total variance in spine shape. In men, greater lean mass index was associated with a larger lordosis whereas greater fat mass index was associated with straighter spines. Greater current BMI was associated with a more uneven curvature in men and with larger anterior-posterior (a-p) vertebral diameters in both sexes. Greater WC and fat mass index were also associated with a-p diameter in both sexes. There was no clear evidence that gains in BMI and WC during earlier stages of adulthood were associated with spine shape but younger onset of overweight was associated with a more uneven spine and greater a-p diameter. In conclusion, sagittal spine shapes had different associations with total and central adiposity; earlier onset of overweight and prior measures of WC were particularly important.

Serum adipokines, adipose tissue measurements and metabolic parameters in patients with advanced radiographic knee osteoarthritis.

PubMed

Toussirot, Eric; Michel, Fabrice; Béreau, Matthieu; Dehecq, Barbara; Gaugler, Béatrice; Wendling, Daniel; Grandclément, Emilie; Saas, Philippe; Dumoulin, Gilles

2017-11-01

We conducted the present study to evaluate the serum levels of adipokines (leptin, total and high molecular adiponectin, resistin), a marker of cartilage breakdown (C2C), and ghrelin together with body composition in patients with knee osteoarthritis (OA). Fifty patients and 50 sex-matched healthy subjects (HS) were evaluated. Knee OA was scored according to the Kellgren-Lawrence (KL) grade. Body composition parameters including lean mass and measurements of fat mass (total fat, adiposity, fat in the android and gynoid regions, visceral fat and trunk/legs fat ratio) were obtained using dual energy X-ray absorptiometry. Most of the recruited patients (88%) had advanced knee OA with KL grade 3 or 4. The patients had higher body mass index than HS (p < 0.0001). Serum leptin, high molecular adiponectin, resistin and ghrelin levels did not differ between patients and HS. Total adiponectin was higher in women with OA compared to women from the HS group (p = 0.004). Total fat mass, adiposity and measurements of central adiposity (fat in the android region, trunk/lower limbs fat ratio and visceral fat) were increased in patients with knee OA (all p < 0.05). Total adiponectin was borderline associated with the severity of OA. Our results show that total adiponectin is significantly increased in women with advanced knee OA. Independently of gender, patients with severe knee OA were characterized by a significant excess of fat with a distribution toward the visceral region. This abnormal body composition may contribute to the cardiometabolic profile that is described in patients with knee OA.

Visual Representation of Body Shape in African-American and European American Women: Clinical Considerations

PubMed Central

Capers, Patrice L.; Kinsey, Amber W.; Miskell, Edrika L.; Affuso, Olivia

2016-01-01

BACKGROUND Body mass index (BMI) has been used widely among clinicians to assess obesity in their patients due to its ease and availability. However, BMI has some diagnostic limitations and other measures related to health risks; in particular, body shape may be of greater relevance to health outcomes. OBJECTIVE The objective of this study was to illustrate the importance of body shape assessments above and beyond BMI and its relationship to health risk among a sample of African-American and European American women. METHODS African-American and European American women aged 19–78 years (n = 552) in Birmingham, Alabama, were recruited and stratified by menopausal status (ie, pre- or postmenopausal). Pictorial body shapes were derived from digital photographs, while body fat distribution defined by android–gynoid ratio (AGR) and body composition were obtained from dual-energy X-ray absorptiometry. RESULTS Images of BMI and age-matched women illustrate variability in fat distribution. Among both menopausal status groups, more than 50% of women had a pear body shape (AGR < 1). An apple body shape was associated with higher odds of having diabetes (unadjusted odds ratio [OR]: 4.1, 95% confidence interval [CI]: 1.9–9.3), hypertension (unadjusted OR: 3.1, 95% CI: 2.0–4.7), and high cholesterol (unadjusted OR: 3.0, 95% CI: 1.8–5.1). CONCLUSION Use of visual cues alongside traditional methods of weight status assessment may help to facilitate weight management conversations between physicians and female patients. However, next steps should include the validation of visual assessments of body shape in women for use by physicians. PMID:27478392

Vanishing testes syndrome-related osteoporosis and high cardio-metabolic risk in an adult male with long term untreated hypergonadotropic hypogonadism.

PubMed

Carsote, Mara; Capatina, Cristina; Valea, Ana; Dumitrascu, Anda

2016-02-01

The male hypogonadism-related bone mass loss is often under diagnosed. Peak bone mass is severely affected if the hypogonadism occurs during puberty and is left untreated. We present an interesting; almost bizarre case of a male with non-functional testes early during childhood and undiagnosed and untreated hypogonadism until his fifth decade of life. Forty six year male is referred for goitre, complaining of back pain. Phenotype suggested intersexuality: gynoid proportions, micropenis, no palpable testes into the scrotum, no facial or truncal hair. His medical history had been unremarkable until the previous year when primary hypothyroidism was diagnosed and levothyroxine replacement was initiated. Later, he was diagnosed with ischemic heart disease, with inaugural unstable angina. On admission, the testosterone was 0.2 ng/mL (normal: 1.7-7.8 ng/mL), FSH markedly increased (56 mUI/mL), with normal adrenal axis, and TSH (under thyroxine replacement). High bone turnover markers, and blood cholesterol, and impaired glucose tolerance were diagnosed. The testes were not present in the scrotum. Abdominal computed tomography suggested bilateral masses of 1.6 cm diameter within the abdominal fat that were removed but no gonadal tissue was confirmed histopathologically. Vanishing testes syndrome was confirmed. The central DXA showed lumbar bone mineral density of 0.905 g/cm2, Z-score of -2.9SD. The spine profile X-Ray revealed multiple thoracic vertebral fractures. Alendronate therapy together with vitamin D and calcium supplements and trans-dermal testosterone were started. Four decades of hypogonadism associate increased cardiac risk, as well as decreased bone mass and high fracture risk.

Association of the FTO and ADRB2 genes with body composition and fat distribution in obese women.

PubMed

Rauhio, Anne; Uusi-Rasi, Kirsti; Nikkari, Seppo T; Kannus, Pekka; Sievänen, Harri; Kunnas, Tarja

2013-10-01

The aim of this study was to investigate whether the polymorphisms of the fat mass and obesity-associated gene (FTO, rs9939609:T>A) and the β2-adrenergic receptor gene (ADRB2, rs1042714:Gln>Glu) are associated with weight loss in dieting obese premenopausal women and the association of these SNPs with body weight, body composition and distribution of fat mass. 75 obese (BMI>30) premenopausal women participated in the intervention including a 3-month weight reduction period and a subsequent 9-month weight maintenance period. Weight and height were measured and BMI calculated. Body composition and fat mass distribution were assessed by dual energy X-ray absorptiometry. At baseline, the AA homozygotes of the FTO gene were 10.1 kg heavier (p=0.031), they had higher BMI (p=0.038), and greater waist and greater hip circumference (p=0.08 and p=0.067, respectively) compared to the TT homozygotes. Gln/Gln carriers of the ADRB2 gene had smaller gynoid fat-% compared with both the Gln/Glu and Glu/Glu carriers (p=0.050 and p=0.009, respectively). The Gln homozygotes had also smaller total body fat-% and higher total body lean mass-% than that of the Glu homozygotes (p=0.018 and p=0.019, respectively). FTO genotype was associated with body weight in general, whereas ADRB2 genotype was associated with fat distribution. However, all women in the study group lost weight similarly independently of their genotypes. Neither the FTO nor ADRB2 genotype had statistically significant effect on weight reduction or weight maintenance. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

Validation by simulation of a clinical trial model using the standardized mean and variance criteria.

PubMed

Abbas, Ismail; Rovira, Joan; Casanovas, Josep

2006-12-01

To develop and validate a model of a clinical trial that evaluates the changes in cholesterol level as a surrogate marker for lipodystrophy in HIV subjects under alternative antiretroviral regimes, i.e., treatment with Protease Inhibitors vs. a combination of nevirapine and other antiretroviral drugs. Five simulation models were developed based on different assumptions, on treatment variability and pattern of cholesterol reduction over time. The last recorded cholesterol level, the difference from the baseline, the average difference from the baseline and level evolution, are the considered endpoints. Specific validation criteria based on a 10% minus or plus standardized distance in means and variances were used to compare the real and the simulated data. The validity criterion was met by all models for considered endpoints. However, only two models met the validity criterion when all endpoints were considered. The model based on the assumption that within-subjects variability of cholesterol levels changes over time is the one that minimizes the validity criterion, standardized distance equal to or less than 1% minus or plus. Simulation is a useful technique for calibration, estimation, and evaluation of models, which allows us to relax the often overly restrictive assumptions regarding parameters required by analytical approaches. The validity criterion can also be used to select the preferred model for design optimization, until additional data are obtained allowing an external validation of the model.

CD36/Sirtuin 1 Axis Impairment Contributes to Hepatic Steatosis in ACE2-Deficient Mice

PubMed Central

Qadri, Fatimunnisa; Penninger, Josef M.; Santos, Robson Augusto S.; Bader, Michael

2016-01-01

Background and Aims. Angiotensin converting enzyme 2 (ACE2) is an important component of the renin-angiotensin system. Since angiotensin peptides have been shown to be involved in hepatic steatosis, we aimed to evaluate the hepatic lipid profile in ACE2-deficient (ACE2−/y) mice. Methods. Male C57BL/6 and ACE2−/y mice were analyzed at the age of 3 and 6 months for alterations in the lipid profiles of plasma, faeces, and liver and for hepatic steatosis. Results. ACE2−/y mice showed lower body weight and white adipose tissue at all ages investigated. Moreover, these mice had lower levels of cholesterol, triglycerides, and nonesterified fatty acids in plasma. Strikingly, ACE2−/y mice showed high deposition of lipids in the liver. Expression of CD36, a protein involved in the uptake of triglycerides in liver, was increased in ACE2−/y mice. Concurrently, these mice exhibited an increase in hepatic oxidative stress, evidenced by increased lipid peroxidation and expression of uncoupling protein 2, and downregulation of sirtuin 1. ACE2−/y mice also showed impairments in glucose metabolism and insulin signaling in the liver. Conclusions. Deletion of ACE2 causes CD36/sirtuin 1 axis impairment and thereby interferes with lipid homeostasis, leading to lipodystrophy and steatosis. PMID:28101297

The Role of Therapeutic Drugs on Acquired Mitochondrial Toxicity.

PubMed

Morén, Constanza; Juárez-Flores, Diana Luz; Cardellach, Francesc; Garrabou, Glòria

2016-01-01

Certain therapeutic drugs used in medical practice may trigger mitochondrial toxicity leading to a wide range of clinical symptoms including deafness, neuropathy, myopathy, hyperlactatemia, lactic acidosis, pancreatitis and lipodystrophy, among others, which could even compromise the life of the patient. The aim of this work is to review the potential mitochondrial toxicity derived from drugs used in health care, including anesthetics, antiepileptics, neuroleptics, antidepressants, antivirals, antibiotics, antifungals, antimalarics, antineoplastics, antidiabetics, hypolipemiants, antiarrhythmics, anti-inflammatories and nitric oxide. We herein have reviewed data from experimental and clinical studies to document the molecular mitochondrial basis, potential biomarkers and putative clinical symptoms associated to secondary effects of drugs. One hundred and forty-five articles were selected and the information was organized by means of the primary target to which pharmacologic drugs were directed. Adverse toxic events were classified depending on the mitochondrial offtarget effect and whether they had been demonstrated in the experimental or clinical setting. Since treatment of acquired mitochondriopathies remains supportive and therapeutic interventions cannot be avoided, information of molecular and clinical consequences of toxic exposure becomes fundamental to assess riskbenefit imbalance of treatment prescription. Additionally, there is a crucial need to develop less mitochondrial toxic compounds, novel biomarkers to follow up mitochondrial toxicity (or implement those already proposed) and new approaches to prevent or revert unintended mitochondrial damage.

The Histological and Immunohistochemical Features of the Skin Lesions in CANDLE Syndrome

PubMed Central

Torrelo, Antonio; Colmenero, Isabel; Requena, Luis; Paller, Amy S.; Ramot, Yuval; Lee, Chyi-Chia Richard; Vera, Angel; Zlotogorski, Abraham; Goldbach-Mansky, Raphaela; Kutzner, Heinz

2015-01-01

Chronic atypical neutrophilic dermatosis with lipodystrophy and elevated temperature (CANDLE) syndrome is a newly characterized autoinflammatory disorder, caused by mutations in PSMB8. It is characterized by early-onset fevers, accompanied by a widespread, violaceous and often annular, cutaneous eruption. While the exact pathogenesis of this syndrome is still obscure, it is postulated that the inflammatory disease manifestations stem from excess secretion of interferons. Based on preliminary blood cytokine and gene expression studies, the signature seems to come mostly from type I interferons, which are proposed to lead to the recruitment of immature myeloid cells into the dermis and subcutis. In this study, we systematically analyzed skin biopsies from 6 CANDLE syndrome patients by routine histopathology and immunohistochemistry methods. Skin lesions showed the presence of extensive mixed dermal and subcutaneous inflammatory infiltrate, composed of mononuclear cells, atypical myeloid cells, neutrophils, eosinophils and some mature lymphocytes. Positive LEDER and myeloperoxidase staining supported the presence of myeloid cells. Positive CD68/PMG1 and CD163 staining confirmed the existence of histiocytes and monocytic macrophages in the inflammatory infiltrate. CD123 staining was positive, demonstrating the presence of plasmacytoid dendritic cells. Uncovering the unique histopathologic and immunohistochemical features of CANDLE syndrome provides tools for rapid and specific diagnosis of this disorder as well as further insight into the pathogenesis of this severe, life-threatening condition. PMID:26091509

Copy number variation in metabolic phenotypes.

PubMed

Lanktree, M; Hegele, R A

2008-01-01

Despite successes in identifying genetic contributors to common metabolic phenotypes, only part of the heritable component of these traits has thus far been explained. Copy number variation (CNV) is likely to be responsible for some of the unexplained variation. As observed with single nucleotide changes, it is probable that both rare and common CNVs will contribute to susceptibility to metabolic disease. For instance, CNVs in the LDLR gene underlie a substantial portion of disease in patients with heterozygous familial hypercholesterolemia. As well, a common CNV in LPA encoding apolipoprotein(a) is the primary determinant of plasma lipoprotein(a) concentrations, a risk factor for atherosclerosis. Recent efforts to map CNVs in control populations have defined their size, frequency and distribution. Many of the identified CNVs overlap genes with important functions in metabolic pathways. The overlap of CNVs that were found in control datasets with functional candidate genes or genes with previous evidence of association with metabolic syndrome presents an important subset for future CNV association studies. Finally, we describe an approach to search for CNVs in a rare high-penetrance metabolic disorder, namely lipodystrophy. As methods to identify CNVs increase in precision and accuracy, the prospect of identifying their role in both rare Mendelian and common complex metabolic phenotypes will become a reality. Copyright 2009 S. Karger AG, Basel.

Human Monocytes Accelerate Proliferation and Blunt Differentiation of Preadipocytes in Association With Suppression of C/Ebpα mRNA

PubMed Central

Couturier, Jacob; Patel, Sanjeet G.; Iyer, Dinakar; Balasubramanyam, Ashok; Lewis, Dorothy E.

2015-01-01

Obesity, type 2 diabetes, and HIV-associated lipodystrophy are associated with abnormalities in adipocyte growth and differentiation. In persons with these conditions, adipose depots contain increased numbers of macrophages, but the origins of these cells and their specific effects are uncertain. Peripheral blood mononuclear cells (PBMC)-derived monocytes, but not T cells, cocultured via transwells with primary subcutaneous preadipocytes, increased proliferation (approximately twofold) and reduced differentiation (~50%) of preadipocytes. Gene expression analyses in proliferating preadipocytes (i.e., prior to hormonal induction of terminal differentiation) revealed that monocytes down-regulated mRNA levels of CCAAT/enhancer binding protein, alpha (C/EBPα) and up-regulated mRNA levels of G0/G1 switch 2 (G0S2) message, genes important for the regulation of adipogenesis and the cell cycle. These data indicate that circulating peripheral blood monocytes can disrupt adipogenesis by interfering with a critical step in C/EBPα and G0S2 transcription required for preadipocytes to make the transition from proliferation to differentiation. Interactions between preadipocytes and monocytes also increased the inflammatory cytokines IL-6 and IL-8, as well as a novel chemotactic cytokine, CXCL1. Additionally, the levels of both IL-6 and CXCL1 were highest when preadipocytes and monocytes were cultured together, compared to each cell in culture alone. Such cross-talk amplifies the production of mediators of tissue inflammation. PMID:21869759

Evaluation of the combination of radio frequency, infrared energy and mechanical rollers with suction to improve skin surface irregularities (cellulite) in a limited treatment area.

PubMed

Kulick, Michael

2006-12-01

This IRB-approved (Institutional Review Board) study evaluated the efficacy of a device that combines radio frequency, infrared energy and mechanical rollers/suction (ELOS technology) to reduce skin surface irregularities in a limited treatment zone. Sixteen patients were enrolled and received two treatments per week for 4 consecutive weeks. Treatments were limited to a 20.53 cm x 33.02 cm area of the posterior or lateral thigh and lasted for 15 minutes. Maximum machine settings were used for all but one individual at every treatment. Evaluations consisted of a patient questionnaire and photographic assessment of skin contour by three physicians at 3 and 6 months after the last session who were blind to the treatment each patient received. Physician evaluators determined that all patients were improved at both post-treatment periods. The average improvement at 3 and 6 months was 62% and 50%, respectively. All patients felt they were improved. One patient described the treatment as painful and required reduced treatment parameters after the initial treatment. Bruising within the treatment area was observed in five patients following the initial sessions but this did not alter the treatment protocol and did not occur in subsequent treatments. One patient had a superficial skin burn due to poor electrode contact that did not require corrective treatment.

Snakebite mediated acute kidney injury, prognostic predictors, oxidative and carbonyl stress: A prospective study.

PubMed

Mukhopadhyay, P; Mishra, R; Mukherjee, D; Mishra, R; Kar, M

2016-01-01

Snake bite is an occupational hazard in India and important preventable cause of acute kidney injury (AKI). This study was done to estimate the magnitude of snakebite-induced AKI (SAKI) who required renal replacement therapy, prognostic predictors, and final outcome, and to measure the oxidative and carbonyl stress (CS) level in SAKI patient who underwent hemodialysis (HD). All SAKI patients dialyzed between April 2010 and July 2011 in NRS Medical College were included. Demographical, clinical, and biochemical data were analyzed, and patients are followed to discharge or death. Oxidative and CS markers (advanced oxidation protein product [AOPP], advanced glycation end product, pentosidine, dityrosine, thioberbituric acid reactive substance, and methylglyoxal [MG]) were measured in 48 SAKI patient requiring HD. About 155 SAKI patients (M: F 2.2:1) received HD. Of them. The age was 36.2 (range 4-74) years. The most common site of the bite was lower limb (88.7%). Oliguria and bleeding manifestation were the common presentation. Hypotension was found in 52 (33.5%) cases, cellulitis and inflammation were found in about 63%. Mean creatinine was 4.56 ± 0.24 mg/dl. About 42 (27.1%) had disseminated intravascular coagulation (DIC). 36 (78.2%) had cellulites, 24 (52.2%) had hypotension or shock at initial presentation ( P < 0.05), bleeding manifestation was found in 37 (80.4%), and 22 (47.8%) had DIC ( P < 0.05). Forty-six (29.7%) patient died. DIC and hypotension/shock at initial presentation came out as an independent predictor of death. Among all markers measured for oxidative and CS ( n = 48) AOPP and MG came out as an independent predictor ( P < 0.05) of adverse outcome. Hypotension, DIC, AOPP, and MG were a poor prognostic marker in SAKI patients requiring dialysis.

Nonablative lasers and nonlaser systems in dermatology: current status.

PubMed

Sachdev, Mukta; Hameed, Sunaina; Mysore, Venkataram

2011-01-01

Nonablative lasers and nonlaser systems are newer systems used for skin rejuvenation, tightening, body sculpting, and scar remodeling. Different technologies such as lasers, Intense Pulsed Light (IPL), and radiofrequency have been introduced. Most nonablative laser systems emit light within the infrared portion of the electromagnetic spectrum (1000-1500 nm). At these wavelengths, absorption by superficial water containing tissue is relatively weak, thereby effecting deeper tissue penetration. A detailed understanding of the device being used is recommended. Nonablative technology have been used for several indications such as skin tightening, periorbital tissue tightening, treatment of nasolabial lines and jowl, body sculpting/remodeling, cellulite reduction, scar revision and remodeling and for the treatment of photodamaged skin. Nonablative laser and light modalities can be carried out in a physician treatment room or hospital setting or a nursing home with a small operation theater. The dermatologic consultation should include detailed assessment of the patient's skin condition and skin type. An informed consent is mandatory to protect the rights of the patient as well as the practitioner. All patients must have carefully taken preoperative and postoperative pictures. Depends on the indication, the area to be treated, the acceptable downtime for the desired correction, and to an extent the skin color. These lasers are mostly pain-free and tolerated well by patients but may require topical anesthesia. In most cases, topical cooling and numbing using icepacks is sufficient, even in an apprehensive patient. The nonablative lasers, light sources and radiofrequency systems are safe, even in darker skin types, and postoperative care is minimal. Proper postoperative care is important in avoiding complications. Post-treatment edema and redness settle in a few hours to a few days. Postoperative sun avoidance and use of sunscreen is mandatory.

Higher Dietary Choline and Betaine Intakes Are Associated with Better Body Composition in the Adult Population of Newfoundland, Canada.

PubMed

Gao, Xiang; Wang, Yongbo; Randell, Edward; Pedram, Pardis; Yi, Yanqing; Gulliver, Wayne; Sun, Guang

2016-01-01

Choline is an essential nutrient and betaine is an osmolyte and methyl donor. Both are important to maintain health including adequate lipid metabolism. Supplementation of dietary choline and betaine increase muscle mass and reduce body fat in animals. However, little data is available regarding the role of dietary choline and betaine on body composition in humans. To investigate the association between dietary choline and betaine intakes with body composition in a large population based cross-sectional study. A total of 3214 subjects from the CODING (Complex Disease in Newfoundland population: Environment and Genetics) study were assessed. Dietary choline and betaine intakes were computed from the Willett Food Frequency questionnaire. Body composition was measured using dual-energy X-ray absorptiometry following a 12-hour fast. Major confounding factors including age, sex, total calorie intake and physical activity level were controlled in all analyses. Significantly inverse correlations were found between dietary choline and betaine intakes, with all obesity measurements: total percent body fat (%BF), percent trunk fat (%TF), percent android fat (%AF), percent gynoid fat (%GF) and anthropometrics: weight, body mass index, waist circumference, waist-to-hip ratio in both women and men (r range from -0.13 to -0.47 for choline and -0.09 to -0.26 for betaine, p<0.001 for all). Dietary choline intake had stronger association than betaine. Moreover, obese subjects had the lowest dietary choline and betaine intakes, with overweight subjects in the middle, and normal weight subjects consumed the highest dietary choline and betaine (p<0.001). Vice versa, when subjects were ranked according to dietary choline and betaine intakes, subjects with the highest intake of both had the lowest %TF, %AF, %GF, %BF and highest %LM among the groups in both sexes. Our findings indicate that high dietary choline and betaine intakes are significantly associated with favorable body

Replication and extension of genome-wide association study results for obesity in 4923 adults from northern Sweden

PubMed Central

Renström, Frida; Payne, Felicity; Nordström, Anna; Brito, Ema C.; Rolandsson, Olov; Hallmans, Göran; Barroso, Ines; Nordström, Peter; Franks, Paul W.

2009-01-01

Recent genome-wide association studies (GWAS) have identified multiple risk loci for common obesity (FTO, MC4R, TMEM18, GNPDA2, SH2B1, KCTD15, MTCH2, NEGR1 and PCSK1). Here we extend those studies by examining associations with adiposity and type 2 diabetes in Swedish adults. The nine single nucleotide polymorphisms (SNPs) were genotyped in 3885 non-diabetic and 1038 diabetic individuals with available measures of height, weight and body mass index (BMI). Adipose mass and distribution were objectively assessed using dual-energy X-ray absorptiometry in a sub-group of non-diabetics (n = 2206). In models with adipose mass traits, BMI or obesity as outcomes, the most strongly associated SNP was FTO rs1121980 (P < 0.001). Five other SNPs (SH2B1 rs7498665, MTCH2 rs4752856, MC4R rs17782313, NEGR1 rs2815752 and GNPDA2 rs10938397) were significantly associated with obesity. To summarize the overall genetic burden, a weighted risk score comprising a subset of SNPs was constructed; those in the top quintile of the score were heavier (+2.6 kg) and had more total (+2.4 kg), gynoid (+191 g) and abdominal (+136 g) adipose tissue than those in the lowest quintile (all P < 0.001). The genetic burden score significantly increased diabetes risk, with those in the highest quintile (n = 193/594 cases/controls) being at 1.55-fold (95% CI 1.21–1.99; P < 0.0001) greater risk of type 2 diabetes than those in the lowest quintile (n = 130/655 cases/controls). In summary, we have statistically replicated six of the previously associated obese-risk loci and our results suggest that the weight-inducing effects of these variants are explained largely by increased adipose accumulation. PMID:19164386

Birth order progressively affects childhood height.

PubMed

Savage, Tim; Derraik, José G B; Miles, Harriet L; Mouat, Fran; Cutfield, Wayne S; Hofman, Paul L

2013-09-01

There is evidence suggesting that first-born children and adults are anthropometrically different to later-borns. Thus, we aimed to assess whether birth order was associated with changes in growth and metabolism in childhood. We studied 312 healthy prepubertal children: 157 first-borns and 155 later-borns. Children were aged 3-10 years, born 37-41 weeks gestation, and of birth weight appropriate-for-gestational-age. Clinical assessments included measurement of children's height, weight, fasting lipid and hormonal profiles and DEXA-derived body composition. First-borns were taller than later-borns (P < 0·0001), even when adjusted for parents' heights (0·31 vs 0·03 SDS; P = 0·001). There was an incremental height decrease with increasing birth order, so that first-borns were taller than second-borns (P < 0·001), who were in turn taller than third-borns (P = 0·007). Further, among sibling pairs both height SDS (P = 0·009) and adjusted height SDS (P < 0·0001) were lower in second- vs first-born children. Consistent with differences in stature, first- (P = 0·043) and second-borns (P = 0·003) had higher IGF-I concentrations than third-borns. Both first- (P < 0·001) and second-borns (P = 0·004) also had reduced abdominal adiposity (lower android fat to gynoid fat ratio) when compared with third-borns. Other parameters of adiposity and blood lipids were unaffected by birth order. First-borns were taller than later-born children, with an incremental height reduction from first to third birth order. These differences were present after correction for genetic height, and associated to some extent with alterations in plasma IGF-I. Our findings strengthen the evidence that birth order is associated with phenotypic changes in childhood. © 2013 John Wiley & Sons Ltd.

The relationship between body composition and knee structure in patients with human immunodeficiency virus.

PubMed

Fillipas, S; Tanamas, S K; Davies-Tuck, M L; Wluka, A E; Wang, Y; Holland, A E; Cherry, C L; Cicuttini, F

2015-02-01

Obesity is a risk factor for osteoarthritis. Antiretroviral therapy (ART)-treated HIV-infected patients are frequently affected by overweight and obesity, and may be at increased risk of osteoarthritis. BMI however is a measure which does not discriminate adipose from non-adipose body mass, or fat distribution, which may have different effects. This study aimed to examine relationships between body composition and knee cartilage volume, as assessed by magnetic resonance imaging in HIV infection. 35 ART-treated HIV-infected men aged 51.7 years (mean) 7.9 (SD) and 18 healthy men aged 49.5 years (mean) 6.4 (SD) participated. Cartilage volume was measured on magnetic resonance imaging of the dominant knee using validated methods. Body composition was measured using dual x-ray absorptiometry. HIV-infected participants had less total body and gynoid fat (kg) (p = 0.04 and p = 0.007, respectively) and more percent android fat mass and percent trunk fat mass (p = 0.001 and p < 0.001, respectively) than controls. In HIV-infected participants there was an inverse association between total body fat mass and average tibial cartilage volume (R = -8.01, 95% CI -15.66, -0.36). Also, in HIV-infected participants there was an inverse association between android fat mass and average cartilage volume (R = -90.91, 95% CI -158.66, -23.16). This preliminary study found that both total body and android fat mass were inversely related to average knee cartilage volume in ambulant, ART-treated HIV-infected adults. These findings are features of early knee osteoarthritis and this may be of future significance in HIV. © The Author(s) 2014 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav.

General and abdominal fat outcomes in school-age children associated with infant breastfeeding patterns.

PubMed

Durmuş, Büşra; Heppe, Denise H M; Gishti, Olta; Manniesing, Rashindra; Abrahamse-Berkeveld, Marieke; van der Beek, Eline M; Hofman, Albert; Duijts, Liesbeth; Gaillard, Romy; Jaddoe, Vincent W V

2014-06-01

Breastfeeding may have a protective effect on the development of obesity in later life. Not much is known about the effects of infant feeding on more-specific fat measures. We examined associations of breastfeeding duration and exclusiveness and age at the introduction of solid foods with general and abdominal fat outcomes in children. We performed a population-based, prospective cohort study in 5063 children. Information about infant feeding was obtained by using questionnaires. At the median age of 6.0 y (95% range: 5.7 y, 6.8 y), we measured childhood anthropometric measures, total fat mass and the android:gynoid fat ratio by using dual-energy X-ray absorptiometry, and preperitoneal abdominal fat by using ultrasound. We observed that, in the models adjusted for child age, sex, and height only, a shorter breastfeeding duration, nonexclusive breastfeeding, and younger age at the introduction of solid foods were associated with higher childhood general and abdominal fat measures (P-trend < 0.05) but not with higher childhood body mass index. The introduction of solid foods at a younger age but not breastfeeding duration or exclusivity was associated with higher risk of overweight or obesity (OR: 2.05; 95% CI: 1.41, 2.90). After adjustment for family-based sociodemographic, maternal lifestyle, and childhood factors, the introduction of solid food between 4 and 4.9 mo of age was associated with higher risks of overweight or obesity, but the overall trend was not significant. Associations of infant breastfeeding and age at the introduction of solid foods with general and abdominal fat outcomes are explained by sociodemographic and lifestyle-related factors. Whether infant dietary composition affects specific fat outcomes at older ages should be further studied. © 2014 American Society for Nutrition.

Foot-to-foot bioelectrical impedance accurately tracks direction of adiposity change in overweight and obese 7- to 13-year-old children.

PubMed

Kasvis, Popi; Cohen, Tamara R; Loiselle, Sarah-Ève; Kim, Nicolas; Hazell, Tom J; Vanstone, Catherine A; Rodd, Celia; Plourde, Hugues; Weiler, Hope A

2015-03-01

Body composition measurements are valuable when evaluating pediatric obesity interventions. We hypothesized that foot-to-foot bioelectrical impedance analysis (BIA) will accurately track the direction of adiposity change, but not magnitude, in part due to differences in fat patterning. The purposes of this study were to examine the accuracy of body composition measurements of overweight and obese children over time using dual-energy x-ray absorptiometry (DXA) and BIA and to determine if BIA accuracy was affected by fat patterning. Eighty-nine overweight or obese children (48 girls, 41 boys, age 7-13 years) participating in a randomized controlled trial providing a family-centered, lifestyle intervention, underwent DXA and BIA measurements every 3 months. Bland-Altman plots showed a poor level of agreement between devices for baseline percent body fat (%BF; mean, 0.398%; +2SD, 8.685%; -2SD, -7.889%). There was overall agreement between DXA and BIA in the direction of change over time for %BF (difference between visits 3 and 1: DXA -0.8 ± 0.5%, BIA -0.7 ± 0.5%; P = 1.000) and fat mass (FM; difference between visits 3 and 1: DXA 0.7 ± 0.5 kg, BIA 0.6 ± 0.5 kg; P = 1.000). Bioelectrical impedance analysis measurements of %BF and FM at baseline were significantly different in those with android and gynoid fat (%BF: 35.9% ± 1.4%, 32.2% ± 1.4%, P < .003; FM: 20.1 ± 0.8 kg, 18.4 ± 0.8, P < .013). Bioelectrical impedance analysis accurately reports the direction of change in FM and FFM in overweight and obese children; inaccuracy in the magnitude of BIA measurements may be a result of fat patterning differences. Copyright © 2015 Elsevier Inc. All rights reserved.

Very-low-calorie ketogenic diet with aminoacid supplement versus very low restricted-calorie diet for preserving muscle mass during weight loss: a pilot double-blind study.

PubMed

Merra, G; Miranda, R; Barrucco, S; Gualtieri, P; Mazza, M; Moriconi, E; Marchetti, M; Chang, T F M; De Lorenzo, A; Di Renzo, L

2016-07-01

Obesity plays a relevant pathophysiological role in the development of health problems, arising as result of complex interaction of genetic, nutritional and metabolic factors. We conducted a dietary intervention case-control randomized trial, to compare the effectiveness on body composition of two nutritional protocols: a very-low-carbohydrate ketogenic diet (VLCKD), integrated by an aminoacid supplement with whey protein, and very low restricted-calorie diet (VLCD). The clinical study was conducted with a randomized case-control in which twenty-five healthy subjects gave informed consent to participate in the interventional study and were evaluated for their health and nutritional status, by anthropometric, and body composition evaluation. The results of this pilot study show that a diet low in carbohydrates, associated with a decreased caloric intake, is effective in weight loss. After VLCKD, versus VLCD, no significant differences in body lean of the trunk, body lean distribution (android and gynoid), total body lean were observed (p > 0.05). After VLCKD, no increasing of sarcopenia frequency, according ASSMI, was observed. Many studies have shown the effectiveness of the ketogenic diet on weight loss; even if not know how to work effectively, as some researchers believe that the weight loss is due to reduced calorie intake, satiety could also be induced by the effect of the proteins, rather than the low-carbohydrates. Our pilot study showed that a VLCKD was highly effective in terms of body weight reduction without to induce lean body mass loss, preventing the risk of sarcopenia. Further clinical trials are needed on a larger population and long-term body weight maintenance and risk factors management effects of VLCKD. There is no doubt, however, that a proper dietary approach would impact significantly on the reduction of public expenditure costs, in view of prospective data on increasing the percentage of obese people in our nation.

Foot pain severity is associated with the ratio of visceral to subcutaneous fat mass, fat-mass index and depression in women.

PubMed

Walsh, Tom P; Arnold, John B; Gill, Tiffany K; Evans, Angela M; Yaxley, Alison; Hill, Catherine L; Shanahan, E Michael

2017-07-01

Body composition and poor mental health are risk factors for developing foot pain, but the role of different fat deposits and psychological features related to chronic pain are not well understood. The aim of this study was to investigate the association between body composition, psychological health and foot pain. Eighty-eight women participated in this study: 44 with chronic, disabling foot pain (mean age 55.3 SD 7.0 years, BMI 29.5 SD 6.7 kg/m 2 ), and 44 age and BMI matched controls. Disabling foot pain was determined from the functional limitation domain of the Manchester Foot Pain and Disability Index. Body composition was measured using dual X-ray absorptiometry and psychological health (catastrophisation, central sensitisation and depression) was measured using three validated questionnaires. Between-group analyses found that foot pain was not significantly associated with body composition variables, but was significantly associated with all psychological health measures (P < 0.001-0.047). Within-group analyses found that the severity of foot pain was significantly correlated with body composition measures: fat mass (total, android, gynoid, and visceral), fat-mass ratios [visceral/subcutaneous (VAT/SAT), visceral/android], fat-mass index (FMI), and depression. In multivariable analysis, VAT/SAT (β 1.27, 95% CI 0.28-2.27), FMI (β 0.14, 95% CI 0.02-0.25) and depression (β 0.06, 95% CI 0.00-0.12) were independently associated with foot pain severity. Psychological health, not body composition, was associated with prevalent foot pain. For women with foot pain, VAT/SAT, FMI and depression were associated with severity. Further work is needed to determine if a reduction in fat mass reduces the severity of foot pain.

Physical Activity Producing Low, but Not Medium or Higher, Vertical Impacts Is Inversely Related to BMI in Older Adults: Findings From a Multicohort Study

PubMed Central

Elhakeem, Ahmed; Hannam, Kimberly; Deere, Kevin C; Hartley, April; Clark, Emma M; Moss, Charlotte; Edwards, Mark H; Dennison, Elaine; Gaysin, Tim; Kuh, Diana; Wong, Andrew; Cooper, Cyrus; Cooper, Rachel; Tobias, Jon H

2018-01-01

Abstract Background High impact physical activity (PA) is thought to improve skeletal health, but its relation to other health outcomes are unclear. We investigated associations between PA impact magnitude and body mass index (BMI) in older adults. Methods Data were taken from the Cohort for Skeletal Health in Bristol and Avon (COSHIBA), Hertfordshire Cohort Study, and MRC National Survey of Health and Development. Vertical acceleration peaks from 7-day hip-worn accelerometer recordings were used to classify PA as low (0.5 < g < 1.0g), medium (1 < g < 1.5g), or higher (≥1.5g) impact. Cohort-specific associations of low, medium, and higher impact PA with BMI were examined using linear regressions and estimates combined using random-effects meta-analysis. Results A total of 1182 participants (mean age = 72.7 years, 68% female) were included. Low, medium, and higher impact PA were inversely related to BMI in initial models. After adjustment for confounders and other impacts, low, but not medium or higher, impacts were inversely related to BMI (−0.31, p < .001: overall combined standard deviation change in BMI per doubling in the number of low impacts). In adjusted analyses of body composition measured by dual-energy X-ray absorptiometry in COSHIBA, low, but not medium or higher, impacts were inversely related to total body fat mass (−0.19, p < .001) and android:gynoid fat mass ratio (−0.16, p = .01), whereas high impact PA was weakly and positively associated with lean mass (0.05, p = .06). Conclusions Greater exposure to PA producing low magnitude vertical impacts was associated with lower BMI and fat mass at older age. Low impact PA may help reduce obesity risk in older adults. PMID:29028919

The Impact of Virgin Coconut Oil and High-Oleic Safflower Oil on Body Composition, Lipids, and Inflammatory Markers in Postmenopausal Women.

PubMed

Harris, Margaret; Hutchins, Andrea; Fryda, Lisa

2017-04-01

This randomized crossover study compared the impact of virgin coconut oil (VCO) to safflower oil (SO) on body composition and cardiovascular risk factors. Twelve postmenopausal women (58.8 ± 3.7 year) consumed 30 mL VCO or SO for 28 days, with a 28-day washout. Anthropometrics included body weight and hip and waist circumference. Fat percent for total body, android and gynoid, fat mass, and lean mass were measured using dual-energy X-ray absorptiometry. Women maintained their typical diet recording 28 days of food records during the study. Results were analyzed with SPSS v24 with significance at P ≤ .05. Comparisons are reported as paired t-test since no intervention sequence effect was observed. VCO significantly raised total cholesterol, TC (+18.2 ± 22.8 mg/dL), low-density lipoprotein (+13.5 ± 16.0 mg/dL), and high-density lipoprotein, HDL (+6.6 ± 7.5 mg/dL). SO did not significantly change lipid values. TC and HDL were significantly different between test oils. The TC/HDL ratio change showed a neutral effect of both VCO and SO. One person had adverse reactions to VCO and increased inflammation. VCO decreased IL-1β for each person who had a detected sample. The impact of VCO and SO on other cytokines varied on an individual basis. This was the first study evaluating the impact of VCO on body composition in Caucasian postmenopausal women living in the United States. Results are suggestive that individuals wishing to use coconut oil in their diets can do so safely, but more studies need to be conducted with larger sample sizes, diverse populations, and more specific clinical markers such as particle size.

Socioeconomic position across life and body composition in early old age: findings from a British birth cohort study

PubMed Central

Bann, David; Cooper, Rachel; Wills, Andrew K; Adams, Judith; Kuh, Diana

2014-01-01

Background Previous studies have reported associations between lower lifetime socioeconomic position (SEP) and higher body mass index in adulthood, but few have examined associations with direct measures of fat and lean mass which are likely to have independent roles in health and physical functioning. Methods We examined associations of SEP across life with dual-energy X-ray absorptiometry measures of fat and lean mass at 60–64 years using data from a total of 1558 men and women participating in the Medical Research Council (MRC) National Survey of Health and Development. We also examined whether associations of childhood SEP with fat and lean mass were explained by preadulthood weight gain (birth weight, 0–7 and 7–20 years) and adult SEP. Results Lower SEP across life was associated with higher fat mass and higher android to gynoid fat mass ratio. For example, the mean difference in fat mass index comparing the lowest with the highest paternal occupational class at 4 years (slope index of inequality) was 1.04 kg/m1.2 in men (95% CI 0.09 to 1.99) and 2.61 in women (1.34 to 3.89), equivalent to a 8.6% and 16.1% difference, respectively. After adjustment for fat mass, lower SEP across life was associated with lower lean mass in women, while only contemporaneous household income was associated in men. Associations between childhood SEP and outcomes were partly explained by preadulthood weight gain and adult SEP. Conclusions This study identified lifetime socioeconomic patterning of fat and lean mass in early old age. This is likely to have important implications and may partly explain socioeconomic inequalities in health and physical functioning. PMID:24567442

Sexual dimorphisms in genetic loci linked to body fat distribution

PubMed Central

Pulit, Sara L.; Karaderi, Tugce

2017-01-01

Obesity is a chronic condition associated with increased morbidity and mortality and is a risk factor for a number of other diseases including type 2 diabetes and cardiovascular disease. Obesity confers an enormous, costly burden on both individuals and public health more broadly. Body fat distribution is a heritable trait and a well-established predictor of adverse metabolic outcomes. Body fat distribution is distinct from overall obesity in measurement, but studies of body fat distribution can yield insights into the risk factors for and causes of overall obesity. Sexual dimorphism in body fat distribution is present throughout life. Though sexual dimorphism is subtle in early stages of life, it is attenuated in puberty and during menopause. This phenomenon could be, at least in part, due to the influence of sex hormones on the trait. Findings from recent large genome-wide association studies (GWAS) for various measures of body fat distribution (including waist-to-hip ratio, hip or waist circumference, trunk fat percentage and the ratio of android and gynoid fat percentage) emphasize the strong sexual dimorphism in the genetic regulation of fat distribution traits. Importantly, sexual dimorphism is not observed for overall obesity (as assessed by body mass index or total fat percentage). Notably, the genetic loci associated with body fat distribution, which show sexual dimorphism, are located near genes that are expressed in adipose tissues and/or adipose cells. Considering the epidemiological and genetic evidence, sexual dimorphism is a prominent feature of body fat distribution. Research that specifically focuses on sexual dimorphism in fat distribution can provide novel insights into human physiology and into the development of obesity and its comorbidities, as well as yield biological clues that will aid in the improvement of disease prevention and treatment. PMID:28073971

Sexual dimorphisms in genetic loci linked to body fat distribution.

PubMed

Pulit, Sara L; Karaderi, Tugce; Lindgren, Cecilia M

2017-02-28

Obesity is a chronic condition associated with increased morbidity and mortality and is a risk factor for a number of other diseases including type 2 diabetes and cardiovascular disease. Obesity confers an enormous, costly burden on both individuals and public health more broadly. Body fat distribution is a heritable trait and a well-established predictor of adverse metabolic outcomes. Body fat distribution is distinct from overall obesity in measurement, but studies of body fat distribution can yield insights into the risk factors for and causes of overall obesity. Sexual dimorphism in body fat distribution is present throughout life. Though sexual dimorphism is subtle in early stages of life, it is attenuated in puberty and during menopause. This phenomenon could be, at least in part, due to the influence of sex hormones on the trait. Findings from recent large genome-wide association studies (GWAS) for various measures of body fat distribution (including waist-to-hip ratio, hip or waist circumference, trunk fat percentage and the ratio of android and gynoid fat percentage) emphasize the strong sexual dimorphism in the genetic regulation of fat distribution traits. Importantly, sexual dimorphism is not observed for overall obesity (as assessed by body mass index or total fat percentage). Notably, the genetic loci associated with body fat distribution, which show sexual dimorphism, are located near genes that are expressed in adipose tissues and/or adipose cells. Considering the epidemiological and genetic evidence, sexual dimorphism is a prominent feature of body fat distribution. Research that specifically focuses on sexual dimorphism in fat distribution can provide novel insights into human physiology and into the development of obesity and its comorbidities, as well as yield biological clues that will aid in the improvement of disease prevention and treatment. © 2017 The Author(s).

Liraglutide and obesity in elderly: efficacy in fat loss and safety in order to prevent sarcopenia. A perspective case series study.

PubMed

Perna, Simone; Guido, Davide; Bologna, Chiara; Solerte, Sebastiano Bruno; Guerriero, Fabio; Isu, Antonio; Rondanelli, Mariangela

2016-12-01

For the growing numbers of obese elderly with diabetes, the glucagon-like peptide-1 (GLP-1) receptor analogue (liraglutide) appears a safe way to promote and maintain substantial weight loss. Given this background, the aim of this study was to assess the effect of the liraglutide treatment, at doses up to 3.0 mg per day, on the body composition, focusing on sarcopenia, in overweight and obese elderly with type 2 diabetes mellitus (T2DM). A perspective study was carried out in overweight and obese T2DM patients with HbA1c equal to 7.0 % (53 mmol/mol) ~10.0 % (86), under 3-month treatment (at least) of maximal dose of metformin at stable regime, and additional liraglutide at doses up to 3.0 mg per day. Body composition markers such as skeletal muscle index (SMI), android and gynoid fat mass, and arms and legs fat free mass, was measured by dual-energy X-ray densitometry (DXA) at baseline and after 24 weeks of liraglutide treatment. Glucose control was also carried out by glucose and HbA1c. Nine subjects (male/female 6/3, mean age 68.22 ± 3.86 years, BMI 32.34 ± 4.89 kg/m 2 ) were evaluated. We noted a median decrease in BMI (-0.78 kg/m 2 ), weight (-2000 g), fat mass (-1498 g) and android fat (-0.9 %), and a increase in SMI (+0.03 kg/m 2 ) from baseline. Glycemic control also improved, with a median change HbA1c of -0.80 %. Twenty-four weeks of liraglutide treatment was associated with reductions in fat mass and android fat. In addition, in order to prevent sarcopenia, it preserved the muscular tropism.

Reference standards for body fat measures using GE dual energy x-ray absorptiometry in Caucasian adults.

PubMed

Imboden, Mary T; Welch, Whitney A; Swartz, Ann M; Montoye, Alexander H K; Finch, Holmes W; Harber, Matthew P; Kaminsky, Leonard A

2017-01-01

Dual energy x-ray absorptiometry (DXA) is an established technique for the measurement of body composition. Reference values for these variables, particularly those related to fat mass, are necessary for interpretation and accurate classification of those at risk for obesity-related health complications and in need of lifestyle modifications (diet, physical activity, etc.). Currently, there are no reference values available for GE-Healthcare DXA systems and it is known that whole-body and regional fat mass measures differ by DXA manufacturer. To develop reference values by age and sex for DXA-derived fat mass measurements with GE-Healthcare systems. A de-identified sample of 3,327 participants (2,076 women, 1,251 men) was obtained from Ball State University's Clinical Exercise Physiology Laboratory and University of Wisconsin-Milwaukee's Physical Activity & Health Research Laboratory. All scans were completed using a GE Lunar Prodigy or iDXA and data reported included percent body fat (%BF), fat mass index (FMI), and ratios of android-to-gynoid (A/G), trunk/limb, and trunk/leg fat measurements. Percentiles were calculated and a factorial ANOVA was used to determine differences in the mean values for each variable between age and sex. Normative reference values for fat mass variables from DXA measurements obtained from GE-Healthcare DXA systems are presented as percentiles for both women and men in 10-year age groups. Women had higher (p<0.01) mean %BF and FMI than men, whereas men had higher (p<0.01) mean ratios of A/G, trunk/limb, and trunk/leg fat measurements than women. These reference values provide clinicians and researchers with a resource for interpretation of DXA-derived fat mass measurements specific to use with GE-Healthcare DXA systems.

Complex phenotype linked to a mutation in exon 11 of the lamin A/C gene: Hypertrophic cardiomyopathy, atrioventricular block, severe dyslipidemia and diabetes.

PubMed

Francisco, Ana Rita G; Santos Gonçalves, Inês; Veiga, Fátima; Mendes Pedro, Mónica; Pinto, Fausto J; Brito, Dulce

2017-09-01

The lamin A/C (LMNA) gene encodes lamins A and C, which have an important role in nuclear cohesion and chromatin organization. Mutations in this gene usually lead to the so-called laminopathies, the primary cardiac manifestations of which are dilated cardiomyopathy and intracardiac conduction defects. Some mutations, associated with lipodystrophy but not cardiomyopathy, have been linked to metabolic abnormalities such as diabetes and severe dyslipidemia. Herein we describe a new phenotype associated with a mutation in exon 11 of the LMNA gene: hypertrophic cardiomyopathy, atrioventricular block, severe dyslipidemia and diabetes. A 64-year-old woman with hypertrophic cardiomyopathy and a point mutation in exon 11 of the LMNA gene (c.1718C>T, Ser573Leu) presented with severe symptomatic ventricular hypertrophy and left ventricular outflow tract obstruction. She underwent septal alcohol ablation, followed by Morrow myectomy. The patient was also diagnosed with severe dyslipidemia, diabetes and obesity, and fulfilled diagnostic criteria for metabolic syndrome. No other characteristics of LMNA mutation-related phenotypes were identified. The development of type III atrioventricular block with no apparent cause, and mildly depressed systolic function, prompted referral for cardiac resynchronization therapy. In conclusion, the association between LMNA mutations and different phenotypes is complex and not fully understood, and can present with a broad spectrum of severity. Copyright © 2017 Sociedade Portuguesa de Cardiologia. Publicado por Elsevier España, S.L.U. All rights reserved.

Occurrence of coring in insulin vials and possibility of rubber piece contamination by self-injection.

PubMed

Asakura, T; Seino, H; Nozaki, S; Abe, R

2001-06-01

Coring is reported to occur because rubber pieces are shaved off from a rubber stopper when a needle is inserted into the rubber stopper of transfusion liquid formulation. We verified whether coring really occurs in insulin vials of self-injecting patients. We collected insulin cartridges from 30 hospitalized patients and used the primary injection (trial injection), the secondary injection and the cartridge remaining preparation as samples. We observed the rubber pieces using a microscope and measured the shape, number of pieces. The occurrence rate of coring was 73% for the primary injection, 47% for the secondary injection and 97% for the cartridge remaining preparation. The rubber pieces in the primary injection and the secondary injection which went through the needle are mostly in aggregate shape and the rubber pieces in the cartridge remaining preparation which did not go through the needle are mostly in needle-like shape. A number of small rubber pieces are found in both the primary injection and the secondary injection, indicating a high possibility that rubber pieces may be injected under subcutaneous tissue. The coring is considered to occur because needles are repeatedly inserted and rotated at the same spot. It is required to improve the structure to mount a needle to the pen-type injector in future. Coring is a very serious problem from the medical and pharmaceutical points of view. Further study should be made on the implication to latex allergy and lipodystrophy.

Endocrine and metabolic disorders associated with human immune deficiency virus infection.

PubMed

Unachukwu, C N; Uchenna, D I; Young, E E

2009-01-01

Many reports have described endocrine and metabolic disorders in the human immunodeficiency virus (HIV) infection. This article reviewed various reports in the literature in order to increase the awareness and thus the need for early intervention when necessary. Data were obtained from MEDLINE, Google search and otherjournals on 'HIV, Endocrinopathies/Metabolic Disorders' from 1985 till 2007. Studies related to HIV associated endocrinopathies and metabolic disorders in the last two decades were reviewed. Information on epidemiology, pathogenesis, diagnosis and treatment of the target organ endocrinopathies and metabolic disorders in HIV/AIDS were extracted from relevant literature. Endocrine and metabolic disturbances occur in the course of HIV infection. Pathogenesis includes direct infection of endocrine glands by HIV or opportunistic organisms, infiltration by neoplasms and side effects of drugs. Adrenal insufficiency is the commonest HIV endocrinopathy with cytomegalovirus adrenalitis occurring in 40-88% of cases. Thyroid dysfunction may occur as euthyroid sick syndrome or sub-clinical hypothyroidism. Hypogonadotrophic dysfunction accounts for 75% of HIV-associated hypogonadism, with prolonged amenorrhoea being three times more likely in the women. Pancreatic dysfunction may result in hypoglycaemia or diabetes mellitus (DM). Highly active antiretroviral therapy (HAART) especially protease inhibitors has been noted to result in insulin resistance and lipodystrophy. Virtually every endocrine organ is involved in the course of HIV infection. Detailed endocrinological and metabolic evaluation and appropriate treatment is necessary in the optimal management of patients with HIV infection in our environment.

Role of arsenic exposure in adipose tissue dysfunction and its possible implication in diabetes pathophysiology.

PubMed

Renu, Kaviyarasi; Madhyastha, Harishkumar; Madhyastha, Radha; Maruyama, Masugi; Arunachlam, Sankarganesh; V G, Abilash

2018-03-01

Exposure to arsenic in drinking water can stimulate a diverse number of diseases that originate from impaired lipid metabolism in adipose and glucose metabolism, leading to insulin resistance. Arsenic inhibits differentiation of adipocyte and mediates insulin resistance with diminutive information on arsenicosis on lipid storage and lipolysis. This review focused on different mechanisms and pathways involved in adipogenesis and lipolysis in adipose tissue during arsenic-induced diabetes. Though arsenic is known to cause type2 diabetes through different mechanisms, the role of adipose tissue in causing type2 diabetes is still unclear. With the existing literature, this review exhibits the effect of arsenic on adipose tissue and its signalling events such as SIRT3- FOXO3a signalling pathway, Ras -MAP -AP-1 cascade, PI(3)-K-Akt pathway, endoplasmic reticulum stress protein, C/EBP homologous protein (CHOP10) and GPCR pathway with role of adipokines. There is a need to elucidate the different types of adipokines which are involved in arsenic-induced diabetes. The exhibited information brings to light that arsenic has negative effects on a white adipose tissue (WAT) by decreasing adipogenesis and enhancing lipolysis. Some of the epidemiological studies show that arsenic would causes obesity. Few studies indicate that arsenic might induces lipodystrophy condition. Further research is needed to evaluate the mechanistic link between arsenic and adipose tissue dysfunction which leads to insulin resistance. Copyright © 2017 Elsevier B.V. All rights reserved.

The Effects of Diet Composition on Body Fat and Hepatic Steatosis in an Animal (Peromyscus californicus) Model of the Metabolic Syndrome

PubMed Central

Krugner-Higby, Lisa; Caldwell, Stephen; Coyle, Kathryn; Bush, Eugene; Atkinson, Richard; Joers, Valerie

2011-01-01

The objective of this research was to determine body composition, total fat content, fat distribution, and serum leptin concentration in hyperlipidemic (high responder, HR) and normolipidemic (low responder, LR) California mice (Peromyscus californicus). In our initial experiments, we sought to determine whether differences in regional fat storage were associated with hyperlipidemia in this species. To further characterize the hepatic steatosis in the mice, we performed 2 additional experiments by using a diet containing 45% of energy as fat. The body fat content of mice fed a low fat-diet (12.3% energy as fat) was higher than that of mice fed a moderate-fat diet (25.8% energy as fat). Total body fat did not differ between HR and LR mice. There was no significant difference between intraabdominal, gonadal, or inguinal fat pad weights. Liver weights of HR mice fed the moderate-fat diet were higher than those of LR mice fed the same diet, and the moderate-fat diet was associated with nonalcoholic fatty liver (NAFL). Mice fed the 45% diet had higher histologic score for steatosis but very little inflammatory response. Chemical analysis indicated increased lipid in the livers of mice fed the high-fat diet compared with those fed the low-fat diet. HR and LR mice had similar serum leptin concentrations. California mice develop NAFL without excess fat accumulation elsewhere. NAFL was influenced by genetic and dietary factors. These mice may be a naturally occuring model of partial lipodystrophy. PMID:21819679

Naringin Reverses Hepatocyte Apoptosis and Oxidative Stress Associated with HIV-1 Nucleotide Reverse Transcriptase Inhibitors-Induced Metabolic Complications

PubMed Central

Adebiyi, Oluwafeyisetan O.; Adebiyi, Olubunmi A.; Owira, Peter M. O.

2015-01-01

Nucleoside Reverse Transcriptase Inhibitors (NRTIs) have not only improved therapeutic outcomes in the treatment of HIV infection but have also led to an increase in associated metabolic complications of NRTIs. Naringin’s effects in mitigating NRTI-induced complications were investigated in this study. Wistar rats, randomly allotted into seven groups (n = 7) were orally treated daily for 56 days with 100 mg/kg zidovudine (AZT) (groups I, II III), 50 mg/kg stavudine (d4T) (groups IV, V, VI) and 3 mL/kg of distilled water (group VII). Additionally, rats in groups II and V were similarly treated with 50 mg/kg naringin, while groups III and VI were treated with 45 mg/kg vitamin E. AZT or d4T treatment significantly reduced body weight and plasma high density lipoprotein concentrations but increased liver weights, plasma triglycerides and total cholesterol compared to controls, respectively. Furthermore, AZT or d4T treatment significantly increased oxidative stress, adiposity index and expression of Bax protein, but reduced Bcl-2 protein expression compared to controls, respectively. However, either naringin or vitamin E significantly mitigated AZT- or d4T-induced weight loss, dyslipidemia, oxidative stress and hepatocyte apoptosis compared to AZT- or d4T-only treated rats. Our results suggest that naringin reverses metabolic complications associated with NRTIs by ameliorating oxidative stress and apoptosis. This implies that naringin supplements could mitigate lipodystrophy and dyslipidemia associated with NRTI therapy. PMID:26690471

Classification System for Individualized Treatment of Adult Buried Penis Syndrome.

PubMed

Tausch, Timothy J; Tachibana, Isamu; Siegel, Jordan A; Hoxworth, Ronald; Scott, Jeremy M; Morey, Allen F

2016-09-01

The authors present their experience with reconstructive strategies for men with various manifestations of adult buried penis syndrome, and propose a comprehensive anatomical classification system and treatment algorithm based on pathologic changes in the penile skin and involvement of neighboring abdominal and/or scrotal components. The authors reviewed all patients who underwent reconstruction of adult buried penis syndrome at their referral center between 2007 and 2015. Patients were stratified by location and severity of involved anatomical components. Procedures performed, demographics, comorbidities, and clinical outcomes were reviewed. Fifty-six patients underwent reconstruction of buried penis at the authors' center from 2007 to 2015. All procedures began with a ventral penile release. If the uncovered penile skin was determined to be viable, a phalloplasty was performed by anchoring penoscrotal skin to the proximal shaft, and the ventral shaft skin defect was closed with scrotal flaps. In more complex patients with circumferential nonviable penile skin, the penile skin was completely excised and replaced with a split-thickness skin graft. Complex patients with severe abdominal lipodystrophy required adjacent tissue transfer. For cases of genital lymphedema, the procedure involved complete excision of the lymphedematous tissue, and primary closure with or without a split-thickness skin graft, also often involving the scrotum. The authors' overall success rate was 88 percent (49 of 56), defined as resolution of symptoms without the need for additional procedures. Successful correction of adult buried penis often necessitates an interdisciplinary, multimodal approach. Therapeutic, IV.

Renal injury in Seipin-deficient lipodystrophic mice and its reversal by adipose tissue transplantation or leptin administration alone: adipose tissue-kidney crosstalk.

PubMed

Liu, Xue-Jing; Wu, Xiao-Yue; Wang, Huan; Wang, Su-Xia; Kong, Wei; Zhang, Ling; Liu, George; Huang, Wei

2018-05-08

Seipin deficiency is responsible for type 2 congenital generalized lipodystrophy with severe loss of adipose tissue (AT) and could lead to renal failure in humans. However, the effect of Seipin on renal function is poorly understood. Here we report that Seipin knockout (SKO) mice exhibited impaired renal function, enlarged glomerular and mesangial surface areas, renal depositions of lipid, and advanced glycation end products. Elevated glycosuria and increased electrolyte excretion were also detected. Relative renal gene expression in fatty acid oxidation and reabsorption pathways were impaired in SKO mice. Elevated glycosuria might be associated with reduced renal glucose transporter 2 levels. To improve renal function, AT transplantation or leptin administration alone was performed. Both treatments effectively ameliorated renal injury by improving all of the parameters that were measured in the kidney. The treatments also rescued insulin resistance and low plasma leptin levels in SKO mice. Our findings demonstrate for the first time that Seipin deficiency induces renal injury, which is closely related to glucolipotoxicity and impaired renal reabsorption in SKO mice, and is primarily caused by the loss of AT and especially the lack of leptin. AT transplantation and leptin administration are two effective treatments for renal injury in Seipin-deficient mice.-Liu, X.-J., Wu, X.-Y., Wang, H., Wang, S.-X., Kong, W., Zhang, L., Liu, G., Huang, W. Renal injury in Seipin-deficient lipodystrophic mice and its reversal by adipose tissue transplantation or leptin administration alone: adipose tissue-kidney crosstalk.

Radiesse: Advanced Techniques and Applications for a Unique and Versatile Implant.

PubMed

Eviatar, Joseph; Lo, Christopher; Kirszrot, James

2015-11-01

Radiesse is a well-tolerated facial injectable with unique filling and lifting capabilities. Although initially approved for facial volumizing in HIV-related lipodystrophy patients, it quickly gained wide acceptance for aesthetic facial rejuvenation. In the USA, the Food and Drug Administration has approved several new indications for its use. This synopsis presents the experience and injection techniques currently favored by the primary author after many years of use in thousands of patients. The anecdotal practice of an experienced injector is presented along with the current Food and Drug Administration-approved standards of Radiesse injection. Radiesse has many on- and off-label applications that can be thoughtfully incorporated into clinical practice. Its unique chemical composition allows for immediate lifting and filling with long-term collagen stimulation. The product can be reconstituted to increase its versatility and minimize adverse events. Injections can be performed in the supraperiosteal space and the subcutaneous layer and are best administered in small, calculated doses to prevent nodules or vascular occlusion. Various techniques for Radiesse injection in specific areas are discussed in detail. Radiesse is a versatile injectable implant and a valuable tool for short- and long-term cosmetic and reconstructive treatments. In addition to various off-label uses, this injectable is often used in conjunction with botox, other injectables, collagen stimulators and tightening devices. A customized reconstitution of product increases its versatility for natural appearing and long lasting results that are both economical and effective for full facial rejuvenation.

Gluteal Augmentation With Intramuscular Implants in Patients With Human Immunodeficiency Virus With Lipoatrophy Related to the Use of Antiretroviral Therapy.

PubMed

Andrade, Guilherme Augusto; Coltro, Pedro Soler; Barros, Mário Eduardo; Müller Neto, Bruno Francisco; Lima, Renan Victor; Farina, Jayme Adriano

2017-11-01

Lipodystrophy syndrome associated with highly active antiretroviral therapy (HAART) may lead to low self-esteem and poor compliance with the drug treatment on patients infected with human immunodeficiency virus (HIV), which is a matter of concern for the health system. The aim of this study was to evaluate patients with HIV submitted to gluteal augmentation with intramuscular silicone implants to correct gluteal lipoatrophy related to the use of HAART. This is a retrospective evaluation of 10 patients submitted to gluteal augmentation with intramuscular silicone implant for correction of gluteal lipoatrophy related to the use of HAART, operated between 2012 and 2015. Postoperative complications and the degree of patient's satisfaction were analyzed. There were 3 postoperative complications including 1 case of surgical wound dehiscence and 2 cases of seroma. Six months after surgery, 8 patients had an excellent degree of satisfaction, and 2 patients had a good degree of satisfaction related to the procedure. Although this intervention does not offer functional advantages, it improves the body contour, increases patients' self-esteem, and helps them to accept their body image. These advantages can lead to higher compliance with prolonged HAART. Gluteal augmentation with intramuscular silicone implant can be a viable option to treat patients with HIV with gluteal lipoatrophy related to the use of HAART. The patients were satisfied with the outcomes of the procedure, and there were only minor self-limited postoperative complications.

Quantitative Assessment of Liver Fat with Magnetic Resonance Imaging and Spectroscopy

PubMed Central

Reeder, Scott B.; Cruite, Irene; Hamilton, Gavin; Sirlin, Claude B.

2011-01-01

Hepatic steatosis is characterized by abnormal and excessive accumulation of lipids within hepatocytes. It is an important feature of diffuse liver disease, and the histological hallmark of non-alcoholic fatty liver disease (NAFLD). Other conditions associated with steatosis include alcoholic liver disease, viral hepatitis, HIV and genetic lipodystrophies, cystic fibrosis liver disease, and hepatotoxicity from various therapeutic agents. Liver biopsy, the current clinical gold standard for assessment of liver fat, is invasive and has sampling errors, and is not optimal for screening, monitoring, clinical decision making, or well-suited for many types of research studies. Non-invasive methods that accurately and objectively quantify liver fat are needed. Ultrasound (US) and computed tomography (CT) can be used to assess liver fat but have limited accuracy as well as other limitations. Magnetic resonance (MR) techniques can decompose the liver signal into its fat and water signal components and therefore assess liver fat more directly than CT or US. Most magnetic resonance (MR) techniques measure the signal fat-fraction (the fraction of the liver MR signal attributable to liver fat), which may be confounded by numerous technical and biological factors and may not reliably reflect fat content. By addressing the factors that confound the signal fat-fraction, advanced MR techniques measure the proton density fat-fraction (the fraction of the liver proton density attributable to liver fat), which is a fundamental tissue property and a direct measure of liver fat content. These advanced techniques show promise for accurate fat quantification and are likely to be commercially available soon. PMID:22025886

Leptin as a Modulator of Neuroendocrine Function in Humans

PubMed Central

Khan, Sami M.; Hamnvik, Ole-Petter R.; Brinkoetter, Mary

2012-01-01

Leptin, a peptide hormone secreted by adipocytes in proportion of the amount of energy stored in fat, plays a central role in regulating human energy homeostasis. In addition, leptin plays a significant permissive role in the physiological regulation of several neuroendocrine axes, including the hypothalamic-pituitary-gonadal, -thyroid, -growth hormone, and -adrenal axes. Decreased levels of leptin, also known as hypoleptinemia, signal to the brain a state of energy deprivation. Hypoleptinemia can be a congenital or acquired condition, and is associated with alterations of the aforementioned axes aimed at promoting survival. More specifically, gonadotropin levels decrease and become less pulsatile under conditions of energy deprivation, and these changes can be at least partially reversed through leptin administration in physiological replacement doses. Similarly, leptin deficiency is associated with thyroid axis abnormalities including abnormal levels of thyrotropin-releasing hormone, and leptin administration may at least partially attenuate this effect. Leptin deficiency results in decreased insulin-like growth factor 1 levels which can be partially ameliorated through leptin administration, and leptin appears to have a much more pronounced effect on the growth of rodents than that of humans. Similarly, adrenal axis function is regulated more tightly by low leptin in rodents than in humans. In addition to congenital leptin deficiency, conditions that may be associated with decreased leptin levels include hypothalamic amenorrhea, anorexia nervosa, and congenital or acquired lipodystrophy syndromes. Accumulating evidence from proof of concept studies suggests that leptin administration, in replacement doses, may ameliorate neuroendocrine abnormalities in individuals who suffer from these conditions. PMID:22665330

Leptin in humans: lessons from translational research.

PubMed

Blüher, Susann; Mantzoros, Christos S

2009-03-01

Leptin has emerged over the past decade as a key hormone in not only the regulation of food intake and energy expenditure but also in the regulation of neuroendocrine and immune function as well as the modulation of glucose and fat metabolism as shown by numerous observational and interventional studies in humans with (complete) congenital or relative leptin deficiency. These results have led to proof-of-concept studies that have investigated the effect of leptin administration in subjects with complete (congenital) leptin deficiency caused by mutations in the leptin gene as well as in humans with relative leptin deficiency, including states of lipoatrophy or negative energy balance and neuroendocrine dysfunction, as for instance seen with hypothalamic amenorrhea in states of exercise-induced weight loss. In those conditions, most neuroendocrine, metabolic, or immune disturbances can be restored by leptin administration. Leptin replacement therapy is thus a promising approach in several disease states, including congenital complete leptin deficiency, states of energy deprivation, including anorexia nervosa or milder forms of hypothalamic amenorrhea, as well as syndromes of insulin resistance seen in conditions such as congenital or acquired lipodystrophy. In contrast, states of energy excess such as garden-variety obesity are associated with hyperleptinemia that reflects either leptin tolerance or leptin resistance. For those conditions, development of leptin sensitizers is currently a focus of pharmaceutical research. This article summarizes our current understanding of leptin's role in human physiology and its potential role as a novel therapeutic option in human disease states associated with a new hormone deficiency, ie, leptin deficiency.

The genetics of fat distribution.

PubMed

Schleinitz, Dorit; Böttcher, Yvonne; Blüher, Matthias; Kovacs, Peter

2014-07-01

Fat stored in visceral depots makes obese individuals more prone to complications than subcutaneous fat. There is good evidence that body fat distribution (FD) is controlled by genetic factors. WHR, a surrogate measure of FD, shows significant heritability of up to ∼60%, even after adjusting for BMI. Genetic variants have been linked to various forms of altered FD such as lipodystrophies; however, the polygenic background of visceral obesity has only been sparsely investigated in the past. Recent genome-wide association studies (GWAS) for measures of FD revealed numerous loci harbouring genes potentially regulating FD. In addition, genes with fat depot-specific expression patterns (in particular subcutaneous vs visceral adipose tissue) provide plausible candidate genes involved in the regulation of FD. Many of these genes are differentially expressed in various fat compartments and correlate with obesity-related traits, thus further supporting their role as potential mediators of metabolic alterations associated with a distinct FD. Finally, developmental genes may at a very early stage determine specific FD in later life. Indeed, genes such as TBX15 not only manifest differential expression in various fat depots, but also correlate with obesity and related traits. Moreover, recent GWAS identified several polymorphisms in developmental genes (including TBX15, HOXC13, RSPO3 and CPEB4) strongly associated with FD. More accurate methods, including cardiometabolic imaging, for assessment of FD are needed to promote our understanding in this field, where the main focus is now to unravel the yet unknown biological function of these novel 'fat distribution genes'.

Neuropsychiatric adverse events after switching from an antiretroviral regimen containing efavirenz without tenofovir to an efavirenz regimen containing tenofovir: a report of nine cases.

PubMed

Allavena, Clotilde; Le Moal, Gwenael; Michau, Christophe; Chiffoleau, Anne; Raffi, François

2006-01-01

The combination of tenofovir (TDF) and efavirenz (EFV) has not been associated with any pharmakokinetic interaction or with enhancement of neuropsychiatric disturbances. We report nine cases of neuropsychiatric intolerance occurring early after a switch from an antiretroviral regimen without TDF to an EFV and TDF-containing regimen. Nine HIV-1-infected patients were treated with an EFV-containing regimen for a median duration of 31 months without any EFV-related central nervous system (CNS) effects. They were switched to an EFV-TDF-containing regimen because of lipodystrophy (n=2) and/or the wish to simplify to a once-daily regimen (n=9). Moderate to severe neuropsychiatric events occurred immediately (<48 hours) after TDF initiation in five patients and 2 weeks to 24 months after the switch in the remaining four patients. Treatment modifications occurred in six patients (switch to EFV-nevirapine [n=3], TDF-zidovudine [n=2] or treatment discontinuation [n=1]), leading to a marked improvement of CNS intolerance. Treatment remained unchanged in three patients; two patients experienced chronic persistent sleeping disorders and one patient underwent a spontaneous improvement of symptoms within 2 weeks. EFV plasma concentrations, which were available in two patients before the switch and in four patients after the switch, remained in the therapeutic range. Although the exact mechanism of these symptoms remains hypothetical, neuropsychiatric disorders could be either a consequence of an unexplained interaction between EFV and TDF or an infrequent TDF-related side effect. The incidence of these side effects needs to be evaluated in large databases or pharmacokinetic studies.

Reorganization of the nuclear lamina and cytoskeleton in adipogenesis.

PubMed

Verstraeten, Valerie L R M; Renes, Johan; Ramaekers, Frans C S; Kamps, Miriam; Kuijpers, Helma J; Verheyen, Fons; Wabitsch, Martin; Steijlen, Peter M; van Steensel, Maurice A M; Broers, Jos L V

2011-03-01

A thorough understanding of fat cell biology is necessary to counter the epidemic of obesity. Although molecular pathways governing adipogenesis are well delineated, the structure of the nuclear lamina and nuclear-cytoskeleton junction in this process are not. The identification of the 'linker of nucleus and cytoskeleton' (LINC) complex made us consider a role for the nuclear lamina in adipose conversion. We herein focused on the structure of the nuclear lamina and its coupling to the vimentin network, which forms a cage-like structure surrounding individual lipid droplets in mature adipocytes. Analysis of a mouse and human model system for fat cell differentiation showed fragmentation of the nuclear lamina and subsequent loss of lamins A, C, B1 and emerin at the nuclear rim, which coincides with reorganization of the nesprin-3/plectin/vimentin complex into a network lining lipid droplets. Upon 18 days of fat cell differentiation, the fraction of adipocytes expressing lamins A, C and B1 at the nuclear rim increased, though overall lamin A/C protein levels were low. Lamin B2 remained at the nuclear rim throughout fat cell differentiation. Light and electron microscopy of a subcutaneous adipose tissue specimen showed striking indentations of the nucleus by lipid droplets, suggestive for an increased plasticity of the nucleus due to profound reorganization of the cellular infrastructure. This dynamic reorganization of the nuclear lamina in adipogenesis is an important finding that may open up new venues for research in and treatment of obesity and nuclear lamina-associated lipodystrophy.

A journey through liposuction and liposculture: Review.

PubMed

Bellini, Elisa; Grieco, Michele P; Raposio, Edoardo

2017-12-01

Nowadays, liposuction is the most frequently performed aesthetic surgery procedure in Western Countries. This technique has had rapid development since the 1970s, when it was experimented for the first time by A. and G. Fischer. It is currently widely used in clinical practice for many different situations in aesthetic, reconstructive and functional fields. This review aims to describe the historical evolution of liposuction by analyzing the transformation of the method in function of the introduction of innovative ideas or instruments. We have also focused on reporting the major clinical applications of this surgical technique, applicable to almost the entire body surface. We finally analyzed the complications, both major and minor, associated with this surgical technique. Liposuction is mainly used to correct deep and superficial fat accumulations and remodel the body contour. It has become an essential complementary technique to enhance the aesthetic result of many other aesthetic procedures such as reduction mammoplasty, abdominoplasty, brachioplasty, thigh lift and post bariatric body contouring. However, it can be largely used for the treatment of innumerable pathologies in reconstructive surgery such as lipomas, lipedema, lipodystrophies, pneudogynecomastia and gynecomastia, macromastia e gigantomastia, lymphedema and many others. The complication rate is very low, especially when compared with conventional excisional surgery and the major, complications are generally associated with improper performance of the technique and poor patient management before and after surgery. Liposuction is a safe, simple and effective method of body contouring. It has enormous potential for its application in ablative and reconstructive surgery, far from the most common aesthetic processes with a very low complication rate.

Additive loss-of-function proteasome subunit mutations in CANDLE/PRAAS patients promote type I IFN production

PubMed Central

Brehm, Anja; Liu, Yin; Sheikh, Afzal; Marrero, Bernadette; Omoyinmi, Ebun; Zhou, Qing; Montealegre, Gina; Biancotto, Angelique; Reinhardt, Adam; Almeida de Jesus, Adriana; Pelletier, Martin; Tsai, Wanxia L.; Remmers, Elaine F.; Kardava, Lela; Hill, Suvimol; Kim, Hanna; Lachmann, Helen J.; Megarbane, Andre; Chae, Jae Jin; Brady, Jilian; Castillo, Rhina D.; Brown, Diane; Casano, Angel Vera; Gao, Ling; Chapelle, Dawn; Huang, Yan; Stone, Deborah; Chen, Yongqing; Sotzny, Franziska; Lee, Chyi-Chia Richard; Kastner, Daniel L.; Torrelo, Antonio; Zlotogorski, Abraham; Moir, Susan; Gadina, Massimo; McCoy, Phil; Wesley, Robert; Rother, Kristina; Hildebrand, Peter W.; Brogan, Paul; Krüger, Elke; Aksentijevich, Ivona; Goldbach-Mansky, Raphaela

2015-01-01

Autosomal recessive mutations in proteasome subunit β 8 (PSMB8), which encodes the inducible proteasome subunit β5i, cause the immune-dysregulatory disease chronic atypical neutrophilic dermatosis with lipodystrophy and elevated temperature (CANDLE), which is classified as a proteasome-associated autoinflammatory syndrome (PRAAS). Here, we identified 8 mutations in 4 proteasome genes, PSMA3 (encodes α7), PSMB4 (encodes β7), PSMB9 (encodes β1i), and proteasome maturation protein (POMP), that have not been previously associated with disease and 1 mutation in PSMB8 that has not been previously reported. One patient was compound heterozygous for PSMB4 mutations, 6 patients from 4 families were heterozygous for a missense mutation in 1 inducible proteasome subunit and a mutation in a constitutive proteasome subunit, and 1 patient was heterozygous for a POMP mutation, thus establishing a digenic and autosomal dominant inheritance pattern of PRAAS. Function evaluation revealed that these mutations variably affect transcription, protein expression, protein folding, proteasome assembly, and, ultimately, proteasome activity. Moreover, defects in proteasome formation and function were recapitulated by siRNA-mediated knockdown of the respective subunits in primary fibroblasts from healthy individuals. Patient-isolated hematopoietic and nonhematopoietic cells exhibited a strong IFN gene-expression signature, irrespective of genotype. Additionally, chemical proteasome inhibition or progressive depletion of proteasome subunit gene transcription with siRNA induced transcription of type I IFN genes in healthy control cells. Our results provide further insight into CANDLE genetics and link global proteasome dysfunction to increased type I IFN production. PMID:26524591

Selection of molecular descriptors with artificial intelligence for the understanding of HIV-1 protease peptidomimetic inhibitors-activity.

PubMed

Sirois, S; Tsoukas, C M; Chou, Kuo-Chen; Wei, Dongqing; Boucher, C; Hatzakis, G E

2005-03-01

Quantitative Structure Activity Relationship (QSAR) techniques are used routinely by computational chemists in drug discovery and development to analyze datasets of compounds. Quantitative numerical methods like Partial Least Squares (PLS) and Artificial Neural Networks (ANN) have been used on QSAR to establish correlations between molecular properties and bioactivity. However, ANN may be advantageous over PLS because it considers the interrelations of the modeled variables. This study focused on the HIV-1 Protease (HIV-1 Pr) inhibitors belonging to the peptidomimetic class of compounds. The main objective was to select molecular descriptors with the best predictive value for antiviral potency (Ki). PLS and ANN were used to predict Ki activity of HIV-1 Pr inhibitors and the results were compared. To address the issue of dimensionality reduction, Genetic Algorithms (GA) were used for variable selection and their performance was compared against that of ANN. Finally, the structure of the optimum ANN achieving the highest Pearson's-R coefficient was determined. On the basis of Pearson's-R, PLS and ANN were compared to determine which exhibits maximum performance. Training and validation of models was performed on 15 random split sets of the master dataset consisted of 231 compounds. For each compound 192 molecular descriptors were considered. The molecular structure and constant of inhibition (Ki) were selected from the NIAID database. Study findings suggested that non-covalent interactions such as hydrophobicity, shape and hydrogen bonding describe well the antiviral activity of the HIV-1 Pr compounds. The significance of lipophilicity and relationship to HIV-1 associated hyperlipidemia and lipodystrophy syndrome warrant further investigation.

Adipose tissue deficiency of hormone-sensitive lipase causes fatty liver in mice

PubMed Central

Yang, Hao; Wang, Shu Pei; Mitchell, Grant A.

2017-01-01

Fatty liver is a major health problem worldwide. People with hereditary deficiency of hormone-sensitive lipase (HSL) are reported to develop fatty liver. In this study, systemic and tissue-specific HSL-deficient mice were used as models to explore the underlying mechanism of this association. We found that systemic HSL deficient mice developed fatty liver in an age-dependent fashion between 3 and 8 months of age. To further explore the mechanism of fatty liver in HSL deficiency, liver-specific HSL knockout mice were created. Surprisingly, liver HSL deficiency did not influence liver fat content, suggesting that fatty liver in HSL deficiency is not liver autonomous. Given the importance of adipose tissue in systemic triglyceride metabolism, we created adipose-specific HSL knockout mice and found that adipose HSL deficiency, to a similar extent as systemic HSL deficiency, causes age-dependent fatty liver in mice. Mechanistic study revealed that deficiency of HSL in adipose tissue caused inflammatory macrophage infiltrates, progressive lipodystrophy, abnormal adipokine secretion and systemic insulin resistance. These changes in adipose tissue were associated with a constellation of changes in liver: low levels of fatty acid oxidation, of very low density lipoprotein secretion and of triglyceride hydrolase activity, each favoring the development of hepatic steatosis. In conclusion, HSL-deficient mice revealed a complex interorgan interaction between adipose tissue and liver: the role of HSL in the liver is minimal but adipose tissue deficiency of HSL can cause age-dependent hepatic steatosis. Adipose tissue is a potential target for treating the hepatic steatosis of HSL deficiency. PMID:29232702

Adipose tissue deficiency of hormone-sensitive lipase causes fatty liver in mice.

PubMed

Xia, Bo; Cai, Guo He; Yang, Hao; Wang, Shu Pei; Mitchell, Grant A; Wu, Jiang Wei

2017-12-01

Fatty liver is a major health problem worldwide. People with hereditary deficiency of hormone-sensitive lipase (HSL) are reported to develop fatty liver. In this study, systemic and tissue-specific HSL-deficient mice were used as models to explore the underlying mechanism of this association. We found that systemic HSL deficient mice developed fatty liver in an age-dependent fashion between 3 and 8 months of age. To further explore the mechanism of fatty liver in HSL deficiency, liver-specific HSL knockout mice were created. Surprisingly, liver HSL deficiency did not influence liver fat content, suggesting that fatty liver in HSL deficiency is not liver autonomous. Given the importance of adipose tissue in systemic triglyceride metabolism, we created adipose-specific HSL knockout mice and found that adipose HSL deficiency, to a similar extent as systemic HSL deficiency, causes age-dependent fatty liver in mice. Mechanistic study revealed that deficiency of HSL in adipose tissue caused inflammatory macrophage infiltrates, progressive lipodystrophy, abnormal adipokine secretion and systemic insulin resistance. These changes in adipose tissue were associated with a constellation of changes in liver: low levels of fatty acid oxidation, of very low density lipoprotein secretion and of triglyceride hydrolase activity, each favoring the development of hepatic steatosis. In conclusion, HSL-deficient mice revealed a complex interorgan interaction between adipose tissue and liver: the role of HSL in the liver is minimal but adipose tissue deficiency of HSL can cause age-dependent hepatic steatosis. Adipose tissue is a potential target for treating the hepatic steatosis of HSL deficiency.

Association of lipin 1 gene polymorphisms with measures of energy and glucose metabolism.

PubMed

Loos, Ruth J F; Rankinen, Tuomo; Pérusse, Louis; Tremblay, Angelo; Després, Jean-Pierre; Bouchard, Claude

2007-11-01

To examine the importance of lipin 1 (LPIN1) gene variation in energy and glucose metabolism. Transgenic animal models have shown that lipin, a protein encoded by the LPIN1 gene, promotes fat synthesis and storage in adipose tissue while decreasing energy expenditure and lipid oxidation in skeletal muscle. Lpin1 was identified as the mutated gene in the fatty liver dystrophy mouse, which exhibits lipin deficiency and features of human lipodystrophy. We genotyped five LPIN1 polymorphisms and tested for association with resting metabolic rate (RMR), fat oxidation, fasting plasma insulin and glucose concentration, and obesity-related phenotypes, including BMI, body fat percentage, sum of six skinfolds, and waist circumference in 712 subjects of the Quebec Family Study. The strongest results were generation-specific. In parents, RMR of the G/G IVS13 + 3333A>G homozygotes was 107 kcal/d higher than in A/A homozygotes and 39 kcal/d higher than in A/G heterozygotes (p = 0.0003). In offspring, carriers of the C allele of the IVS18 + 181C>T variant had significantly higher (p < 0.0003) insulin levels than T/T homozygotes. These associations remained significant after adjusting for multiple testing. Several other associations between body composition measures and the IVS18 + 181C>T variant were significant (p = 0.05 to 0.003), suggesting a strong pattern of relationships. These findings support the hypothesis that sequence variation in the LPIN1 gene contributes to variation in RMR and obesity-related phenotypes potentially in an age-dependent manner.

Incidence and Risk Factors for Prediabetes and Diabetes Mellitus Among HIV-infected Adults on Antiretroviral Therapy: A Systematic Review and Meta-analysis.

PubMed

Nansseu, Jobert Richie; Bigna, Jean Joel; Kaze, Arnaud D; Noubiap, Jean Jacques

2018-05-01

To summarize evidence on the rates and drivers of progression from normoglycemia to prediabetes and/or diabetes mellitus (hereafter "diabetes") in antiretroviral treatment (ART)-exposed HIV-infected people. We searched EMBASE, PubMed, Web of Science, and Global Index Medicus to identify articles published from 1 January 2000 to 30 April 2017. A random-effects model produced a summary estimate of the incidence across studies and heterogeneity was assessed using Cochrane's Q statistic. We included 44 studies, whose methodologic quality was high with only 10 (30%) medium-quality studies and none of low quality. There was substantial heterogeneity between studies in estimates of the incidence of diabetes and prediabetes. The pooled incidence rate of overt diabetes and prediabetes were 13.7 per 1,000 person-years of follow-up (95% CI = 13, 20; I = 98.1%) among 396,496 person-years and 125 per 1,000 person-years (95% CI = 0, 123; I = 99.4) among 1,532 person-years, respectively. The major risk factors for diabetes and prediabetes were aging, family history of diabetes, Black or Hispanic origin, overweight/obesity, central obesity, lipodystrophy/lipoatrophy, dyslipidemia, metabolic syndrome, increased baseline fasting glycemia, and certain ART regimens. These data highlight the important and fast-increasing burden of diabetes and prediabetes among the ART-exposed HIV-infected population. More research is needed to better capture the interplay between prediabetes/diabetes and ART in HIV-infected patients, considering the increasing number of ART-exposed patients subsequent to the World Health Organization's recommendation of initiating ART at HIV infection diagnosis regardless of CD4 count and age.

Ethical issues regarding caring for dermatology patients in the U.S. Department of Veterans Affairs Health Care System.

PubMed

Reich, Reuben; Stevens, Emily; Dellavalle, Robert P

2012-01-01

The U.S. Department of Veterans Affairs (VA) operates the largest integrated health care system within the United States. VA budgets continue to escalate in an environment of heightened financial prudence and accountability. Despite having received many awards in areas from patient satisfaction and safety to product innovations, like any health care system, the VA is not immune to ethical conflict that requires exploration and evaluation. Several VA dermatologists, including section chiefs, were interviewed, and their responses to ethical complexities encountered or anticipated were analyzed in fictional case scenarios. Five morally concerning issues were highlighted. These include (1) providing care in a teaching setting with limited resources to a patient population with few other health care alternatives; (2) stereotyping patients, altogether an uncommon act, is possibly easier to do in the VA and has the potential to negatively affect patient care; (3) service-related disability claim cases often include medical opinion and findings documented in the medical record when judgments are made, thus the VA physician can have a significant effect on the outcome of these claims; (4) whether the VA provides a setting for apathetic physicians to thrive or instead allows for a more meaningful work experience and then how to manage the subpar performer; (5) except for the treatment of HIV lipodystrophy with injectables, primary cosmetic procedures are prohibited at the VA and can lead to difficulties for the VA dermatologist attempting to comply in a era where dermatology is being more closely associated with cosmesis. Published by Elsevier Inc.

Impact of antiretroviral therapy on selected metabolic disorders - pilot study.

PubMed

Bociąga-Jasik, Monika; Polus, Anna; Góralska, Joanna; Raźny, Urszula; Siedlecka, Dominika; Zapała, Barbara; Chrzan, Robert; Garlicki, Aleksander; Mach, Tomasz; Dembińska-Kieć, Aldona

2014-01-01

Taking into consideration the aging of HIV infected individuals, changes in the metabolism aggravated by the antiretroviral therapy significantly impact their health. Mechanisms responsible for lipodystrophy, dyslipidemia and insulin resistance (IR) occurrence have not been completely understood. Only recently, the free fatty acids (FFAs) metabolic turnover has become considered to be the independent risk factor for cardiovascular complications. We designed the follow-up study in which patients were recruited before the introduction of ARV therapy and then observed up to 1 year. The impact of ARV therapy on the development of metabolic complications, inflammation markers and changes in adipokines secretion was investigated. The fasting and postprandial responses of FFAs, triglycerides (TG), glucose, insulin and glucose-dependent insulinotropic peptide (GIP) were measured. Changes in body composition were followed by impedance and a CT scan of adipose tissue volume of the abdomen and thighs. Significant impact of ARV therapy on metabolic disturbances was reported. Not only fasting, but also postprandial levels of FFAs and TG were found to increase during the follow up. The increased concentration of FFAs is suggested to be the triggering event in the development of hypertriglyceridemia and insulin resistance during ARV therapy. Changes in postprandial FFAs and TG during the follow up indicate the increasing risk of cardiovascular diseases. We conclude that modern ARV therapy during the period of 12 months does not induce changes in the fat distribution, although increased limb fat correlated with higher plasma leptin level, which may be the marker of increased risk of metabolic driven cardiovascular complications.

Common variation in the LMNA gene (encoding lamin A/C) and type 2 diabetes: association analyses in 9,518 subjects.

PubMed

Owen, Katharine R; Groves, Christopher J; Hanson, Robert L; Knowler, William C; Shuldiner, Alan R; Elbein, Steven C; Mitchell, Braxton D; Froguel, Philippe; Ng, Maggie C Y; Chan, Juliana C; Jia, Weiping; Deloukas, Panos; Hitman, Graham A; Walker, Mark; Frayling, Timothy M; Hattersley, Andrew T; Zeggini, Eleftheria; McCarthy, Mark I

2007-03-01

Mutations in the LMNA gene (encoding lamin A/C) underlie familial partial lipodystrophy, a syndrome of monogenic insulin resistance and diabetes. LMNA maps to the well-replicated diabetes-linkage region on chromosome 1q, and there are reported associations between LMNA single nucleotide polymorphisms (SNPs) (particularly rs4641; H566H) and metabolic syndrome components. We examined the relationship between LMNA variation and type 2 diabetes (using six tag SNPs capturing >90% of common variation) in several large datasets. Analysis of 2,490 U.K. diabetic case and 2,556 control subjects revealed no significant associations at either genotype or haplotype level: the minor allele at rs4641 was no more frequent in case subjects (allelic odds ratio [OR] 1.07 [95% CI 0.98-1.17], P = 0.15). In 390 U.K. trios, family-based association analyses revealed nominally significant overtransmission of the major allele at rs12063564 (P = 0.01), which was not corroborated in other samples. Finally, genotypes for 2,817 additional subjects from the International 1q Consortium revealed no consistent case-control or family-based associations with LMNA variants. Across all our data, the OR for the rs4641 minor allele approached but did not attain significance (1.07 [0.99-1.15], P = 0.08). Our data do not therefore support a major effect of LMNA variation on diabetes risk. However, in a meta-analysis including other available data, there is evidence that rs4641 has a modest effect on diabetes susceptibility (1.10 [1.04-1.16], P = 0.001).

Relationship of ethnicity and CD4 Count with glucose metabolism among HIV patients on Highly-Active Antiretroviral Therapy (HAART)

PubMed Central

2013-01-01

Background HIV patients on HAART are prone to metabolic abnormalities, including insulin resistance, lipodystrophy and diabetes. This study purports to investigate the relationship of ethnicity and CD4+ T cell count attained after stable highly-active antiretroviral treatment (HAART) with glucose metabolism in hyperrtriglyceridemic HIV patients without a history of diabetes. Methods Demographic, anthropometric, clinical, endocrinologic, energy expenditure and metabolic measures were obtained in 199 multiethnic, healthy but hypertriglyceridemic HIV-infected patients [46% Hispanic, 17% African-American, 37% Non-Hispanic White (NHW)] on stable HAART without a history of diabetes. The relationship of glucose and insulin responses to ethnicity, CD4 strata (low (<300/cc) or moderate-to-high (≥ 300/cc)), and their interaction was determined. Results African-Americans had significantly greater impairment of glucose tolerance (P < 0.05) and HbA1c levels (P < .001) than either Hispanics or NHWs. In multivariate models, after adjusting for confounders (age, sex, HIV/HAART duration, smoking, obesity, glucose, insulin and lipids), African-Americans and Hispanics had significantly higher HbA1c and 2-hour glucose levels than NHW’s. Demonstrating a significant interaction between ethnicity and CD4 count (P = 0.023), African Americans with CD4 <300/cc and Hispanics with CD4 ≥300/cc had the most impaired glucose response following oral glucose challenge. Conclusions Among hypertriglyceridemic HIV patients on HAART, African-Americans and Hispanics are at increased risk of developing diabetes. Ethnicity also interacts with CD4+ T cell count attained on stable HAART to affect post-challenge glycemic response. PMID:23607267

Changes in Body Fat Distribution on Dual-Energy X-Ray Absorptiometry in Black South Africans Starting First-Line Antiretroviral Therapy.

PubMed

Abrahams, Zulfa; Levitt, Naomi; Lesosky, Maia; Maartens, Gary; Dave, Joel

2016-10-01

Long-term use of antiretroviral therapy (ART) increases the risk of developing lipodystrophy. Few studies from Africa have used longitudinal data to assess the development of lipoatrophy and lipohypertrophy. We use clinical anthropometry and dual-energy X-ray absorptiometry (DEXA) to describe changes in body fat distribution over a 24-month period in individuals initiated on ART. A convenience sample of black South Africans (55 men and 132 women) were recruited and followed for 24 months after commencing ART. Body fat distribution was assessed using anthropometric measurements and DEXA scans at baseline and then at 3, 6, 12, 18, and 24 months after commencing ART. DEXA was also used to estimate abdominal visceral adipose tissue (VAT) and subcutaneous adipose tissue (SAT). Women gained more overall weight and more regional fat in all areas analyzed on DEXA scans. Women, not men, experienced a significant increasing trend in trunk fat and a significant decreasing trend in limb fat, when expressed as a percentage of total body fat. In men, the risk of developing lipoatrophy was more than two times greater than that of women, after adjusting for age, baseline body mass index, and ART regimen. Lipohypertrophy occurred similarly in men and women. VAT and SAT increased significantly in men and women, with women gaining considerably more than men. These findings are of great concern as an increased waist circumference is associated with increased mortality in HIV-infected populations. Further investigation is required to understand the mechanisms underlying the sex differences in changes in body fat distribution and its effects on cardiovascular risk.

Effect of Leptin Replacement on PCSK9 in ob/ob Mice and Female Lipodystrophic Patients.

PubMed

Levenson, Amy E; Haas, Mary E; Miao, Ji; Brown, Rebecca J; de Ferranti, Sarah D; Muniyappa, Ranganath; Biddinger, Sudha B

2016-04-01

Leptin treatment has beneficial effects on plasma lipids in patients with lipodystrophy, but the underlying mechanism is unknown. Proprotein convertase subtilisin/kexin type 9 (PCSK9) decreases low-density lipoprotein (LDL) clearance, promotes hypercholesterolemia, and has recently emerged as a novel therapeutic target. To determine the effect of leptin on PCSK9, we treated male and female ob/ob mice with leptin for 4 days via sc osmotic pumps (∼24 μg/d). Leptin reduced body weight and food intake in all mice, but the effects of leptin on plasma PCSK9 and lipids differed markedly between the sexes. In male mice, leptin suppressed PCSK9 but had no effect on plasma triglycerides or cholesterol. In female mice, leptin suppressed plasma triglycerides and cholesterol but had no effect on plasma PCSK9. In parallel, we treated female lipodystrophic patients (8 females, ages 5-23 y) with sc metreleptin injections (∼4.4 mg/d) for 4-6 months. In this case, leptin reduced plasma PCSK9 by 26% (298 ± 109 vs 221 ± 102 ng/mL; n = 8; P = .008), and the change in PCSK9 was correlated with a decrease in LDL cholesterol (r(2) = 0.564, P = .03). In summary, in leptin-deficient ob/ob mice, the effects of leptin on PCSK9 and plasma lipids appeared to be independent of one another and strongly modified by sex. On the other hand, in lipodystrophic females, leptin treatment reduced plasma PCSK9 in parallel with LDL cholesterol.

Effect of Leptin Replacement on PCSK9 in ob/ob Mice and Female Lipodystrophic Patients

PubMed Central

Levenson, Amy E.; Haas, Mary E.; Miao, Ji; Brown, Rebecca J.; de Ferranti, Sarah D.; Muniyappa, Ranganath

2016-01-01

Leptin treatment has beneficial effects on plasma lipids in patients with lipodystrophy, but the underlying mechanism is unknown. Proprotein convertase subtilisin/kexin type 9 (PCSK9) decreases low-density lipoprotein (LDL) clearance, promotes hypercholesterolemia, and has recently emerged as a novel therapeutic target. To determine the effect of leptin on PCSK9, we treated male and female ob/ob mice with leptin for 4 days via sc osmotic pumps (∼24 μg/d). Leptin reduced body weight and food intake in all mice, but the effects of leptin on plasma PCSK9 and lipids differed markedly between the sexes. In male mice, leptin suppressed PCSK9 but had no effect on plasma triglycerides or cholesterol. In female mice, leptin suppressed plasma triglycerides and cholesterol but had no effect on plasma PCSK9. In parallel, we treated female lipodystrophic patients (8 females, ages 5–23 y) with sc metreleptin injections (∼4.4 mg/d) for 4–6 months. In this case, leptin reduced plasma PCSK9 by 26% (298 ± 109 vs 221 ± 102 ng/mL; n = 8; P = .008), and the change in PCSK9 was correlated with a decrease in LDL cholesterol (r2 = 0.564, P = .03). In summary, in leptin-deficient ob/ob mice, the effects of leptin on PCSK9 and plasma lipids appeared to be independent of one another and strongly modified by sex. On the other hand, in lipodystrophic females, leptin treatment reduced plasma PCSK9 in parallel with LDL cholesterol. PMID:26824363

Treatment of diet-induced lipodystrophic C57BL/6J mice with long-acting PASylated leptin normalises insulin sensitivity and hepatic steatosis by promoting lipid utilisation.

PubMed

Bolze, Florian; Bast, Andrea; Mocek, Sabine; Morath, Volker; Yuan, Detian; Rink, Nadine; Schlapschy, Martin; Zimmermann, Anika; Heikenwalder, Mathias; Skerra, Arne; Klingenspor, Martin

2016-09-01

Recombinant leptin offers a viable treatment for lipodystrophy (LD) syndromes. However, due to its short plasma half-life, leptin replacement therapy requires at least daily subcutaneous (s.c.) injections. Here, we optimised this treatment strategy in LD mice by using a novel leptin version with extended plasma half-life using PASylation technology. A long-acting leptin version was prepared by genetic fusion with a 600 residue polypeptide made of Pro, Ala and Ser (PASylation), which enlarges the hydrodynamic volume and, thus, retards renal filtration, allowing less frequent injection. LD was induced in C57BL/6J mice by feeding a diet supplemented with conjugated linoleic acid (CLA). Chronic and acute effects of leptin treatment were assessed by evaluating plasma insulin levels, insulin tolerance, histological liver sections, energy expenditure, energy intake and body composition. In a cohort of female mice, 4 nmol PAS-leptin (applied via four s.c. injections every 3 days) successfully alleviated the CLA-induced LD phenotype, which was characterised by hyperinsulinaemia, insulin intolerance and hepatosteatosis. The same injection regimen had no measurable effect when unmodified recombinant leptin was administered at an equivalent dose. In a cohort of LD males, a single s.c. injection of PAS-leptin did not affect energy expenditure but inhibited food intake and promoted a shift in fuel selection towards preferential fat oxidation, which mechanistically substantiates the metabolic improvements. The excellent pharmacological properties render PASylated leptin an agent of choice for refining both animal studies and therapeutic strategies in the context of LD syndromes and beyond.

[Evaluation and treatment of obesity in clinical practice].

PubMed

Keller, U; van der Werf, H; Stohler, R

1989-05-01

Obesity continues as before to be a widespread condition. Obesity is defined as a body weight of over 120% of the ideal weight, corresponding roughly to the 85th percentile of the weight distribution. According to the "Build Study" (1979), the ideal weight is assumed to be rather higher than formerly; in men it is 8%, in women 6% less than the so-called normal weight. The latter corresponds roughly to the average weight and is defined as: height (cm) minus 100 in kg. In obese subjects both somatic and psychological complications arise; these are related exponentially to the degree of overweight. More recent findings in the Framingham Study show that obesity leads to coronary heart disease and premature death independently of the classical risk factors. Evaluation of the patient should include a personal and familial history of the obesity, together with individual eating habits and the degree of physical activity indulged in. As assessment should be made of the body fat distribution (android or gynoid obesity); android obesity carries a relatively high risk. Complications should be looked for, together with other risk factors for arteriosclerosis. Treatment depends on the severity of the condition and on the motivation. In general, it should consist of a moderate reduction in the caloric value of the food intake together with advice on eating habits and an increase in bodily activity. Group therapy often gives good results on account of the dynamic interactions within groups. Patients with morbid obesity will profit from a very hypocaloric, "ketogenic" diet (ca. 600-700 kcal/day). One of the author's own studies showed that a very hypocaloric diet resulted in mood elevation and a reduction in the need for sleep. Conservative measures such dietary weight reduction, changes in eating habits and encouragement of bodily activity are to be preferred to surgical treatment (eg, gastric stapling). Weight reductions in hospital do not lead to a change in eating habits and

Cross-sectional population associations between detailed adiposity measures and C-reactive protein levels at age 6 years: the Generation R Study.

PubMed

Toemen, L; Gishti, O; Vogelezang, S; Gaillard, R; Hofman, A; Franco, O H; Felix, J F; Jaddoe, V W V

2015-07-01

High body mass index is associated with increased C-reactive protein levels in childhood and adulthood. Little is known about the associations of detailed adiposity measures with C-reactive protein levels in childhood. We examined the associations of general and abdominal adiposity measures with C-reactive protein levels at school age. To gain insight into the direction of causality, we used genetic risk scores based on known genetic variants in adults as proxies for child adiposity measures and C-reactive protein levels. Within a population-based cohort study among 4338 children at the median age of 6.2 years, we measured body mass index, fat mass percentage, android/gynoid fat mass ratio and preperitoneal abdominal fat mass. We also measured C-reactive protein blood levels and defined increased levels as ⩾3.0 mg l(-1). Single-nucleotide polymorphisms (SNPs) for the weighted genetic risk scores were extracted from large genome-wide association studies on adult body mass index, waist-hip ratio and C-reactive protein levels. All fat mass measures were associated with increased C-reactive protein levels, even after adjusting for multiple confounders. Fat mass percentage was most strongly associated with increased C-reactive protein levels (odds ratio 1.46 (95% confidence interval 1.30-1.65) per increase standard deviation scores in fat mass percentage). The association was independent of body mass index. The genetic risk score based on adult body mass index SNPs, but not adult waist-hip ratio SNPs, tended to be associated with increased C-reactive protein levels at school age. The genetic risk score based on adult C-reactive protein level SNPs was not associated with adiposity measures at school age. Our results suggest that higher general and abdominal fat mass may lead to increased C-reactive protein levels at school age. Further studies are needed to replicate these results and explore the causality and long-term consequences.

Estrogen receptor protein content is different in abdominal than gluteal subcutaneous adipose tissue of overweight-to-obese premenopausal women.

PubMed

Gavin, Kathleen M; Cooper, Elizabeth E; Hickner, Robert C

2013-08-01

Premenopausal women demonstrate a distinctive gynoid body fat distribution and circulating estrogen status is associated with the maintenance of this adiposity patterning. Estrogen's role in modulation of regional adiposity may occur through estrogen receptors (ERs), which are present in human adipose tissue. The purpose of this study was to determine regional differences in the protein content of ERα, ERβ, and the G protein-coupled estrogen receptor (GPER) between the abdominal (AB) and gluteal (GL) subcutaneous adipose tissue of overweight-to-obese premenopausal women. Biopsies of the subcutaneous AB and GL adipose tissue were performed in 15 premenopausal women (7 Caucasian/8 African American, 25.1 ± 1.8 years, BMI 29.5 ± 0.5kg/m(2)). Adipose tissue protein content was measured by western blot analysis and correlation analyses were conducted to assess the relationship between ER protein content and anthropometric indices/body composition measurements. We found that ERα protein was higher in AB than GL (AB 1.0 ± 0.2 vs GL 0.67 ± 0.1 arbitrary units [AU], P=0.02), ERβ protein was higher in GL than AB (AB 0.78 ± 0.12 vs GL 1.3 ± 0.2 AU, P=0.002), ERα/ERβ ratio was higher in AB than GL (AB 1.9 ± 0.4 vs GL 0.58 ± 0.08 AU, P=0.007), and GPER protein content was similar in AB and GL (P=0.80) subcutaneous adipose tissue. Waist-to-hip ratio was inversely related to gluteal ERβ (r(2)=0.315, P=0.03) and positively related to gluteal ERα/ERβ ratio (r(2)=0.406, P=0.01). These results indicate that depot specific ER content may be an important underlying determinant of regional effects of estrogen in upper and lower body adipose tissue of overweight-to-obese premenopausal women. Copyright © 2013 Elsevier Inc. All rights reserved.

Regional, but not total, body composition changes in overweight and obese adults consuming a higher protein, energy-restricted diet are sex specific.

PubMed

Tang, Minghua; Leidy, Heather J; Campbell, Wayne W

2013-08-01

Secondary analyses of data from 2 studies were used to assess the effects of protein intake and sex on diet-induced changes in body composition. The primary hypothesis was that the changes of body composition via energy restriction (ie, lean body mass [LBM], fat mass [FM], and bone) would be sex and diet specific. For 12 weeks, 43 male (study 1) and 45 female (study 2) overweight and obese adults consumed an energy-deficit diet (750 kcal/d less than energy needs) containing either 0.8 (normal protein [NP], 21 men and 23 women) or 1.4 g protein∙kg(-1)∙d(-1) (high protein [HP], 22 men and 22 women). Body composition measurements were performed at preintervention and postintervention. Over time, all research participants lost weight, LBM, and FM. Independent of protein intake, the men lost more LBM in the trunk (-0.9 vs -0.5 kg) and less in the legs (-1.5 vs -1.1 kg) compared with the women (P < .05). Independent of sex, the HP group lost less LBM in the trunk and legs than the NP group. These sex and protein intake responses resulted in the NP men losing the most LBM in the legs and the NP women losing the most LBM in the trunk. Over time, men lost more FM (-5.0 vs -3.9 kg) from the trunk and less from legs (-1.7 vs -2.1 kg) than women (P < .05), which resulted in a greater decrease of the android-to-gynoid fat ratio for the men. Protein intake did not influence these sex-specific responses or have any independent effects on changes in FM. In addition, protein intake did not influence bone mineral density responses over time; bone mineral density was reduced in women, but not in men. These findings indicate that higher protein intake during weight loss promotes the retention of LBM in both the trunk and legs despite the sex-specific changes in these body regions. Copyright © 2013 Elsevier Inc. All rights reserved.

Higher Dietary Choline and Betaine Intakes Are Associated with Better Body Composition in the Adult Population of Newfoundland, Canada

PubMed Central

Gao, Xiang; Wang, Yongbo; Randell, Edward; Pedram, Pardis; Yi, Yanqing; Gulliver, Wayne; Sun, Guang

2016-01-01

Background Choline is an essential nutrient and betaine is an osmolyte and methyl donor. Both are important to maintain health including adequate lipid metabolism. Supplementation of dietary choline and betaine increase muscle mass and reduce body fat in animals. However, little data is available regarding the role of dietary choline and betaine on body composition in humans. Objective To investigate the association between dietary choline and betaine intakes with body composition in a large population based cross-sectional study. Design A total of 3214 subjects from the CODING (Complex Disease in Newfoundland population: Environment and Genetics) study were assessed. Dietary choline and betaine intakes were computed from the Willett Food Frequency questionnaire. Body composition was measured using dual-energy X-ray absorptiometry following a 12-hour fast. Major confounding factors including age, sex, total calorie intake and physical activity level were controlled in all analyses. Result Significantly inverse correlations were found between dietary choline and betaine intakes, with all obesity measurements: total percent body fat (%BF), percent trunk fat (%TF), percent android fat (%AF), percent gynoid fat (%GF) and anthropometrics: weight, body mass index, waist circumference, waist-to-hip ratio in both women and men (r range from -0.13 to -0.47 for choline and -0.09 to -0.26 for betaine, p<0.001 for all). Dietary choline intake had stronger association than betaine. Moreover, obese subjects had the lowest dietary choline and betaine intakes, with overweight subjects in the middle, and normal weight subjects consumed the highest dietary choline and betaine (p<0.001). Vice versa, when subjects were ranked according to dietary choline and betaine intakes, subjects with the highest intake of both had the lowest %TF, %AF, %GF, %BF and highest %LM among the groups in both sexes. Conclusion Our findings indicate that high dietary choline and betaine intakes are

Height, adiposity and body fat distribution and breast density in young women.

PubMed

Dorgan, Joanne F; Klifa, Catherine; Shepherd, John A; Egleston, Brian L; Kwiterovich, Peter O; Himes, John H; Gabriel, Kelley; Horn, Linda; Snetselaar, Linda G; Stevens, Victor J; Barton, Bruce A; Robson, Alan M; Lasser, Norman L; Deshmukh, Snehal; Hylton, Nola M

2012-07-13

Breast density is one of the strongest risk factors for breast cancer, but determinants of breast density in young women remain largely unknown. Associations of height, adiposity and body fat distribution with percentage dense breast volume (%DBV) and absolute dense breast volume (ADBV) were evaluated in a cross-sectional study of 174 healthy women, 25 to 29 years old. Adiposity and body fat distribution were measured by anthropometry and dual-energy X-ray absorptiometry (DXA), while %DBV and ADBV were measured by magnetic resonance imaging. Associations were evaluated using linear mixed-effects models. All tests of statistical significance are two-sided. Height was significantly positively associated with %DBV but not ADBV; for each standard deviation (SD) increase in height, %DBV increased by 18.7% in adjusted models. In contrast, all measures of adiposity and body fat distribution were significantly inversely associated with %DBV; a SD increase in body mass index (BMI), percentage fat mass, waist circumference and the android:gynoid fat mass ratio (A:G ratio) was each associated significantly with a 44.4 to 47.0% decrease in %DBV after adjustment for childhood BMI and other covariates. Although associations were weaker than for %DBV, all measures of adiposity and body fat distribution also were significantly inversely associated with ADBV before adjustment for childhood BMI. After adjustment for childhood BMI, however, only the DXA measures of percentage fat mass and A:G ratio remained significant; a SD increase in each was associated with a 13.8 to 19.6% decrease in ADBV. In mutually adjusted analysis, the percentage fat mass and the A:G ratio remained significantly inversely associated with %DBV, but only the A:G ratio was significantly associated with ADBV; a SD increase in the A:G ratio was associated with an 18.5% decrease in ADBV. Total adiposity and body fat distribution are independently inversely associated with %DBV, whereas in mutually adjusted

The Association of Serum Total Peptide YY (PYY) with Obesity and Body Fat Measures in the CODING Study.

PubMed

Cahill, Farrell; Ji, Yunqi; Wadden, Danny; Amini, Peyvand; Randell, Edward; Vasdev, Sudesh; Gulliver, Wayne; Sun, Guang

2014-01-01

PYY is an appetite suppressing hormone. Low circulating PYY has been linked to greater BMI. However data is controversial and this association has not been verified in large human populations. The purpose of this study was to investigate if fasting serum total PYY is associated with obesity status and/or adiposity at the population level. A total of 2094 subjects (Male-523, Female-1571) participated in this investigation. Total PYY was measured in fasting serum by enzyme-linked immunosorbent assay. Obesity status (NW-normal-weight, OW-overweight and OB-obese) was determined by the Bray Criteria according to body fat percentage measured by dual-energy x-ray absorptiometry and the WHO criteria according to BMI. One-way ANOVA and multiple regression was used to assess the adiposity-specific association between PYY and the following; weight, BMI, waist-circumference, hip-circumference, waist-hip ratio, percent body fat (%BF), trunk fat (%TF), android fat (%AF) and gynoid fat (%GF). PYY was not significantly different among NW, OW and OB groups defined by neither %BF nor BMI for both men and women. However among women, fasting PYY was positively associated with adiposity measures. Women with the highest (Top 33%) waist-circumference, %BF and %TF had significantly higher PYY (10.5%, 8.3% and 9.2% respectively) than women with the lowest (Bottom 33%). Age, smoking, medication use and menopause were all positively associated with PYY levels in women but not in men. To our knowledge this is the largest population based study, with the most comprehensive analysis and measures of confounding factors, to explore the relationship of circulating PYY with obesity. Contrary to initial findings in the literature we discovered that PYY was positively associated with body fat measures (waist-circumference, %BF and %TF) in women. Although the effect size of the positive association of PYY with obesity in women is small, and potentially negligible, it may in fact represent a protective

Longitudinal Body Composition Changes in NCAA Division I College Football Players

PubMed Central

Trexler, Eric T.; Smith-Ryan, Abbie E.; Mann, J. Bryan; Ivey, Pat A.; Hirsch, Katie R.; Mock, Meredith G.

2016-01-01

Many athletes seek to optimize body composition to fit the physical demands of their sport. American football requires a unique combination of size, speed, and power. The purpose of the current study was to evaluate longitudinal changes in body composition in Division I collegiate football players. For 57 players (Mean ± SD; Age=19.5 ± 0.9 yrs; Height=186.9 ± 5.7 cm; Weight=107.7 ± 19.1 kg), body composition was assessed via dual-energy x-ray absorptiometry in the off-season (March-Pre), end of off-season (May), mid-July (Pre-Season), and the following March (March-Post). Outcome variables included weight, body fat percentage (BF%), fat mass (FM), lean mass (LM), android (AND) and gynoid (GYN) fat, bone mineral content (BMC), and bone density (BMD). For a subset of athletes (n=13 out of 57), changes over a 4-year playing career were evaluated with measurements taken every March. Throughout a single year, favorable changes were observed for BF% (Δ=−1.3 ± 2.5%), LM (Δ=2.8 ± 2.8 kg), GYN (Δ=−1.5 ± 3.0%), BMC (Δ=0.06 ± 0.14 kg), and BMD (Δ=0.015 ± 0.027g·cm−2; all p<0.05). Across four years, weight increased significantly (Δ=6.6 ± 4.1kg), and favorable changes were observed for LM (Δ=4.3 ± 3.0 kg), BMC (Δ=0.18 ± 0.17 kg), and BMD (Δ=0.033 ± 0.039 g·cm−2; all p<0.05). Similar patterns in body composition changes were observed for linemen and non-linemen. Results indicate that well-trained collegiate football players at high levels of competition can achieve favorable changes in body composition, even late in the career, which may confer benefits for performance and injury prevention. PMID:28005635

Reduction of body fat and improved lipid profile associated with daily consumption of a Puer tea extract in a hyperlipidemic population: a randomized placebo-controlled trial

PubMed Central

Jensen, Gitte S; Beaman, Joni L; He, Yi; Guo, Zhixin; Sun, Henry

2016-01-01

Objective The goal for this study was to evaluate the effects of daily consumption of Puer tea extract (PTE) on body weight, body-fat composition, and lipid profile in a non-Asian population in the absence of dietary restrictions. Materials and methods A randomized, double-blind, placebo-controlled study design was used. A total of 59 overweight or mildly obese subjects were enrolled upon screening to confirm fasting cholesterol level at or above 220 mg/dL (5.7 mmol/dL). After giving informed consent, subjects were randomized to consume PTE (3 g/day) or placebo for 20 weeks. At baseline and at 4-week intervals, blood lipids, C-reactive protein, and fasting blood glucose were evaluated. A dual-energy X-ray absorptiometry scan was performed at baseline and at study exit to evaluate changes to body composition. Appetite and physical and mental energy were scored at each visit using visual analog scales (0–100). Results Consumption of PTE was associated with statistically significant weight loss when compared to placebo (P<0.05). Fat loss was seen for arms, legs, and the gynoid region (hip/belly), as well as for total fat mass. The fat reduction reached significance on within-group analysis, but did not reach between-group significance. Consumption of PTE was associated with improvements to lipid profile, including a mild reduction in cholesterol and the cholesterol:high-density lipoprotein ratio after only 4 weeks, as well as a reduction in triglycerides and very small-density lipoproteins, where average blood levels reached normal range at 8 weeks and remained within normal range for the duration of the study (P<0.08). No significant changes between the PTE group and the placebo group were seen for fasting glucose or C-reactive protein. A transient reduction in appetite was seen in the PTE group when compared to placebo (P<0.1). Conclusion The results from this clinical study showed that the daily consumption of PTE was associated with significant weight loss

Meal replacement based on Human Ration modulates metabolic risk factors during body weight loss: a randomized controlled trial.

PubMed

Alves, Natalia Elizabeth Galdino; Enes, Bárbara Nery; Martino, Hércia Stampini Duarte; Alfenas, Rita de Cássia Gonçalves; Ribeiro, Sônia Machado Rocha

2014-04-01

A meal replacement may be an effective strategy in the management of obesity to increase antioxidant intake, attenuating oxidative stress and inflammation. In the present study, we investigated the efficacy of a new nutritional supplement to reduce metabolic risk parameters in obese women. In a randomized controlled crossover study (2 × 2), 22 women (percentage body fat 40.52 ± 3.75%; body mass index-BMI 28.72 ± 2.87 kg/m²; 35.04 ± 5.6 years old) were allocated into two treatments: hypocaloric diet and drink containing "Human Ration" (HR) consumption (CRHR), and hypocaloric diet and control drink consumption (CR). The study consisted of 2 periods of 5 weeks with 1 week of washout in two orders (CR → CRHR and CRHR → CR). Caloric restriction was 15%, based on estimated energy requirement. Anthropometric, clinical and metabolic risk parameters were assessed at baseline and at the end of each period. Some metabolic risk factors were favorably modulated in both interventions: reduction in body weight (CR -0.74 ± 1.27 kg; p = 0.01; CRHR -0.77 ± 1.3 kg; p = 0.02), body mass index (BMI) (CR -0.27 ± 0.51 kg/m²; p = 0.02; CRHR -0.30 ± 0.52 kg/m²; p = 0.01) and HOMA-IR (CR -0.35 ± 0.82; p = 0.02, CRHR -0.41 ± 0.83; p = 0.03). However, CRHR reduced waist circumference (-2.54 ± 2.74 cm; p < 0.01) and gynoid fat (-0.264 ± 0.28 g; p < 0.01), and increased HDL-c levels (0.08 ± 0.15 mmol/l; p = 0.04). Associated with hypocaloric diet, the intake of a nutritional supplement rich in phytochemicals as a breakfast substitute for 5 weeks had no additional effect on weight reduction than caloric restriction alone, but increased central lipolysis and improved the lipoprotein profile.

Incidence and risk factors for mitochondrial toxicity in treated HIV/HCV-coinfected patients.

PubMed

Laguno, Montse; Milinkovic, Ana; de Lazzari, Elisa; Murillas, Javier; Martínez, Esteban; Blanco, Jose Luis; Loncá, Montse; Biglia, Alejandra; Leon, Agathe; García, Mercedes; Larrousse, Maria; García, Felipe; Miró, Jose Maria; Gatell, Jose Maria; Mallolas, Josep

2005-01-01

Coinfection with hepatitis C virus (HCV) and HIV is not uncommon and therapies for both infections are currently available. A major drawback, however, could be a potentially higher risk for mitochondrial toxicity (MT), defined as the elevation of pancreatic enzymes or lactate levels due to the nucleoside analogue reverse transcriptase inhibitors contained in both therapies. Prospective analyses of clinical and laboratory data, including plasma lactate levels and pancreatic enzymes, of 113 consecutive HIV/HCV-coinfected patients were assigned to receive ribavirin (RBV) plus interferon (IFN)-alpha. Fourteen patients (12%) showed increased levels of amylase/lipase and/or hyperlactataemia. No patient developed clinical pancreatitis. Four patients with hyperlactataemia had clinical symptoms of lactic acidosis and recovered uneventfully by 2 weeks after treatment withdrawal. The variables significantly associated with MT in the univariate analysis were: therapy with didanosine (ddl), ddl plus stavudine (d4T), previous history of diabetes and the baseline lactate level. However, ddl use was the only independent risk factor for MT identified in the multivariate analysis. MT was not associated with gender, age, alcohol consumption, type of IFN, degree of steatosis and fibrosis in liver biopsy, presence of lipodystrophy, CD4+ cell count, HCV or HIV viral load, mitochondrial DNA and COXII-expression in liver tissue, or antiretroviral therapy containing d4T or protease inhibitors. 12% of HIV/HCV-coinfected patients receiving IFN plus RBV concomitantly with highly active antiretroviral therapy developed laboratory markers of MT. Although most of cases were asymptomatic, our study suggests that concomitant use of RBV plus ddl should be avoided, and that routine monitoring of lactate and pancreatic enzymes may be recommended.

Yield of yearly routine physical examination in HIV-1 infected patients is limited: A retrospective cohort study in the Netherlands

PubMed Central

van Amsterdam, Marleen A.; van Assen, Sander; Sprenger, Herman G.; Wilting, Kasper R.; Stienstra, Ymkje

2017-01-01

Background Routine physical examinations might be of value in HIV-infected patients, but the yield is unknown. We determined the diagnoses that would have been missed without performing annual routine physical examinations in HIV-infected patients with stable disease. Methods Data were collected from the medical records of 299 HIV-1-infected patients with CD4 count >350 cells/mm3 if not using combination antiretroviral therapy (cART), or CD4 count >100 cells/mm3 and undetectable viral load if using cART. We defined the diagnoses that would have been missed without performing routine physical examinations on annual check-ups in 2010. Exclusion criteria were hepatitis B/C co-infection, start/ switch of cART < 24 weeks, pregnancy, and transgenderism. Results 215 patients (72%) had positive findings: lipodystrophy (30%), lymphadenopathy (16%) and hypertension (8.4%) were the most common. Two-thirds of all findings were not new or were based on complaints indicating a physical examination even if not routinely scheduled. For 24 patients (8.0%) the routine physical examination led to the finding of a new diagnosis: six—all men who have sex with men (MSM)—had a concurrent sexually transmitted infection, eight had hypertension, and ten others had a large variety of diagnoses. A total atrioventricular block with bradycardia was the most clinically relevant finding. Conclusions Annual physical examinations of HIV-infected patients with stable disease brought few new diagnoses that would have been missed without performing a routine examination. Our results suggest that standard assessments could be restricted to six-monthly measuring blood pressure in all patients and annually performing anogenital and digital rectal examination on MSM. PMID:28636651

Early changes in inflammatory and pro-thrombotic biomarkers in patients initiating antiretroviral therapy with abacavir or tenofovir

PubMed Central

2011-01-01

Background Abacavir has been associated with an increased risk of acute myocardial infarction, but the pathogenic mechanisms remain unknown. We evaluated longitudinal changes in pro-atherosclerotic biomarkers in patients initiating abacavir or tenofovir. Methods Consecutive patients initiating antiretroviral therapy (ART) with abacavir/lamivudine or tenofovir/emtricitabine were included. Plasma levels of high sensitivity C reactive protein (hsCRP), interleukin-6 (IL-6), intercellular adhesion molecule-1, vascular cell adhesion molecule-1 (sVCAM-1) and plasminogen activator inhibitor-1 (PAI-1) were measured at baseline and at different time points throughout 48 weeks. Comparisons were adjusted for age, sex, ART status at inclusion, viral load, lipodystrophy, Framingham score and hepatitis C virus co-infection status. Results 50 patients were analyzed, 28 initiating abacavir and 22 tenofovir. The endothelial biomarker sVCAM-1 declined significantly in both treatment groups. hsCRP tended to increase soon after starting therapy with abacavir, a trend that was not seen in those initiating tenofovir. IL-6 significantly increased only at week 24 from baseline in patients on abacavir (+225%, p < 0.01) although the differences were not significant between groups. The procoagulant biomarker PAI-1 plasma levels increased from baseline at week 12 (+57%; p = 0.017), week 24 (+72%; p = 0.008), and week 48 (+149%; p < 0.001) in patients on tenofovir, but differences between groups were not statistically significant. Conclusion Changes in biomarkers of inflammation, coagulation, and endothelial function are not different in viremic patients starting ART with abacavir/lamivudine or tenofovir/emtricitabine. These changes occur in the early phases of treatment and include anti- and pro-atherosclerotic effects with both drugs. PMID:21294867

Early changes in inflammatory and pro-thrombotic biomarkers in patients initiating antiretroviral therapy with abacavir or tenofovir.

PubMed

Padilla, Sergio; Masiá, Mar; García, Natalia; Jarrin, Inmaculada; Tormo, Consuelo; Gutiérrez, Félix

2011-02-04

Abacavir has been associated with an increased risk of acute myocardial infarction, but the pathogenic mechanisms remain unknown. We evaluated longitudinal changes in pro-atherosclerotic biomarkers in patients initiating abacavir or tenofovir. Consecutive patients initiating antiretroviral therapy (ART) with abacavir/lamivudine or tenofovir/emtricitabine were included. Plasma levels of high sensitivity C reactive protein (hsCRP), interleukin-6 (IL-6), intercellular adhesion molecule-1, vascular cell adhesion molecule-1 (sVCAM-1) and plasminogen activator inhibitor-1 (PAI-1) were measured at baseline and at different time points throughout 48 weeks. Comparisons were adjusted for age, sex, ART status at inclusion, viral load, lipodystrophy, Framingham score and hepatitis C virus co-infection status. 50 patients were analyzed, 28 initiating abacavir and 22 tenofovir. The endothelial biomarker sVCAM-1 declined significantly in both treatment groups. hsCRP tended to increase soon after starting therapy with abacavir, a trend that was not seen in those initiating tenofovir. IL-6 significantly increased only at week 24 from baseline in patients on abacavir (+225%, p < 0.01) although the differences were not significant between groups. The procoagulant biomarker PAI-1 plasma levels increased from baseline at week 12 (+57%; p = 0.017), week 24 (+72%; p = 0.008), and week 48 (+149%; p < 0.001) in patients on tenofovir, but differences between groups were not statistically significant. Changes in biomarkers of inflammation, coagulation, and endothelial function are not different in viremic patients starting ART with abacavir/lamivudine or tenofovir/emtricitabine. These changes occur in the early phases of treatment and include anti- and pro-atherosclerotic effects with both drugs.

Atypical Progeroid Syndrome due to Heterozygous Missense LMNA Mutations

PubMed Central

Garg, Abhimanyu; Subramanyam, Lalitha; Agarwal, Anil K.; Simha, Vinaya; Levine, Benjamin; D'Apice, Maria Rosaria; Novelli, Giuseppe; Crow, Yanick

2009-01-01

Context: Hutchinson-Gilford progeria syndrome (HGPS) and mandibuloacral dysplasia are well-recognized allelic autosomal dominant and recessive progeroid disorders, respectively, due to mutations in lamin A/C (LMNA) gene. Heterozygous LMNA mutations have also been reported in a small number of patients with a less well-characterized atypical progeroid syndrome (APS). Objective: The objective of the study was to investigate the underlying genetic and molecular basis of the phenotype of patients presenting with APS. Results: We report 11 patients with APS from nine families, many with novel heterozygous missense LMNA mutations, such as, P4R, E111K, D136H, E159K, and C588R. These and previously reported patients now reveal a spectrum of clinical features including progeroid manifestations such as short stature, beaked nose, premature graying, partial alopecia, high-pitched voice, skin atrophy over the hands and feet, partial and generalized lipodystrophy with metabolic complications, and skeletal anomalies such as mandibular hypoplasia and mild acroosteolysis. Skin fibroblasts from these patients when assessed for lamin A/C expression using epifluorescence microscopy revealed variable nuclear morphological abnormalities similar to those observed in patients with HGPS. However, these nuclear abnormalities in APS patients could not be rescued with 48 h treatment with farnesyl transferase inhibitors, geranylgeranyl transferase inhibitors or trichostatin-A, a histone deacetylase inhibitor. Immunoblots of cell lysates from fibroblasts did not reveal prelamin A accumulation in any of these patients. Conclusions: APS patients have a few overlapping but some distinct clinical features as compared with HGPS and mandibuloacral dysplasia. The pathogenesis of clinical manifestations in APS patients seems not to be related to accumulation of mutant farnesylated prelamin A. PMID:19875478

Gender differences in GH response to GHRH+ARG in lipodystrophic patients with HIV: a key role for body fat distribution.

PubMed

Brigante, Giulia; Diazzi, Chiara; Ansaloni, Anna; Zirilli, Lucia; Orlando, Gabriella; Guaraldi, Giovanni; Rochira, Vincenzo

2014-05-01

Gender influence on GH secretion in human immunodeficiency virus (HIV)-infected patients is poorly known. To determine the effect of gender, we compared GH response to GH-releasing hormone plus arginine (GHRH+Arg), and body composition in 103 men and 97 women with HIV and lipodystrophy. The main outcomes were IGF1, basal GH, GH peak and area under the curve (AUC) after GHRH+Arg, body composition, visceral adipose tissue (VAT), and subcutaneous adipose tissue (SAT). Men had lower GH peak and AUC than women (P<0.001). Of the study population, 21% of women and 37% of men had biochemical GH deficiency (GHD; GH peak <7.5 μg/l). VAT-to-SAT ratio was higher in men than in women with GHD (P<0.05). Unlike women, VAT, SAT, and trunk fat were greater in men with GHD than in men without GHD. IGF1 was significantly lower in women with GHD than in women without GHD, but not in men. At univariate analysis, BMI, trunk fat mass, VAT, and total adipose tissue were associated with GH peak and AUC in both sexes (P<0.05). BMI was the most significant predictive factor of GH peak, and AUC at multiregression analysis. Overall, abdominal fat had a less pronounced effect on GH in females than in males. These data demonstrate that GH response to GHRH+Arg is significantly lower in HIV-infected males than females, resulting in a higher percentage of GHD in men. Adipose tissue distribution more than fat mass per se seems to account for GH gender differences and for the alteration of GH-IGF1 status in these patients.

Arabidopsis SEIPIN Proteins Modulate Triacylglycerol Accumulation and Influence Lipid Droplet Proliferation[OPEN

PubMed Central

2015-01-01

The lipodystrophy protein SEIPIN is important for lipid droplet (LD) biogenesis in human and yeast cells. In contrast with the single SEIPIN genes in humans and yeast, there are three SEIPIN homologs in Arabidopsis thaliana, designated SEIPIN1, SEIPIN2, and SEIPIN3. Essentially nothing is known about the functions of SEIPIN homologs in plants. Here, a yeast (Saccharomyces cerevisiae) SEIPIN deletion mutant strain and a plant (Nicotiana benthamiana) transient expression system were used to test the ability of Arabidopsis SEIPINs to influence LD morphology. In both species, expression of SEIPIN1 promoted accumulation of large-sized lipid droplets, while expression of SEIPIN2 and especially SEIPIN3 promoted small LDs. Arabidopsis SEIPINs increased triacylglycerol levels and altered composition. In tobacco, endoplasmic reticulum (ER)-localized SEIPINs reorganized the normal, reticulated ER structure into discrete ER domains that colocalized with LDs. N-terminal deletions and swapping experiments of SEIPIN1 and 3 revealed that this region of SEIPIN determines LD size. Ectopic overexpression of SEIPIN1 in Arabidopsis resulted in increased numbers of large LDs in leaves, as well as in seeds, and increased seed oil content by up to 10% over wild-type seeds. By contrast, RNAi suppression of SEIPIN1 resulted in smaller seeds and, as a consequence, a reduction in the amount of oil per seed compared with the wild type. Overall, our results indicate that Arabidopsis SEIPINs are part of a conserved LD biogenesis machinery in eukaryotes and that in plants these proteins may have evolved specialized roles in the storage of neutral lipids by differentially modulating the number and sizes of lipid droplets. PMID:26362606

Adiponectin, Leptin and Inflammatory Markers in HIV-associated Metabolic Syndrome in Children and Adolescents.

PubMed

Espiau, María; Yeste, Diego; Noguera-Julian, Antoni; Soler-Palacín, Pere; Fortuny, Clàudia; Ferrer, Roser; Comas, Immaculada; Martín-Nalda, Andrea; Deyà-Martínez, Ángela; Figueras, Concepció; Carrascosa, Antonio

2017-02-01

Metabolic syndrome (MetS) is more common in HIV-infected adults and children than in the general population. Adipocytokines and inflammatory markers may contribute to the pathophysiology of this condition and could be useful indices for monitoring MetS. The objective of this study was to provide information on the prevalence of MetS and investigate the role of adipocytokines and other biomarkers in this syndrome in HIV-infected pediatric patients. A cross-sectional study was conducted between October 2013 and March 2014 in the outpatient clinics of 2 tertiary pediatric referral hospitals. Fifty-four HIV-infected children and adolescents were included. MetS was defined according to the International Diabetes Federation and modified National Cholesterol Education Program Adult Treatment Panel III criteria. Measurements included anthropometry, waist circumference, blood pressure, fasting lipids, glucose and insulin, adiponectin, leptin, interleukin-6, vitamin D and C-reactive protein and clinical lipodystrophy assessment. Among the total, 3.7% of patients met the International Diabetes Federation criteria for MetS and 7.4% met the National Cholesterol Education Program Adult Treatment Panel III criteria. C-reactive protein and leptin levels were significantly higher and adiponectin level significantly lower in patients with MetS, regardless of the criteria used. Insulin resistance was observed in 40.7% of patients; abnormal quantitative insulin sensitivity check index values were found in 88.9%. Eighteen patients (33.3%) had vitamin D deficiency. The prevalence of MetS was similar to that observed in larger cohorts of HIV-infected patients in our setting. Adipocytokine dysregulation seems to be related to MetS in HIV-infected children. A high percentage of patients showed insulin resistance, which should be strictly monitored.

Arabidopsis SEIPIN Proteins Modulate Triacylglycerol Accumulation and Influence Lipid Droplet Proliferation

DOE PAGES

Cai, Yingqi; Goodman, Joel M.; Pyc, Michal; ...

2015-09-01

The lipodystrophy protein SEIPIN is important for lipid droplet (LD) biogenesis in human and yeast cells. In contrast with the single SEIPIN genes in humans and yeast, there are three SEIPIN homologs in Arabidopsis thaliana, designated SEIPIN1, SEIPIN2, and SEIPIN3. Essentially nothing is known about the functions of SEIPIN homologs in plants. Here, a yeast (Saccharomyces cerevisiae) SEIPIN deletion mutant strain and a plant (Nicotiana benthamiana) transient expression system were used to test the ability of Arabidopsis SEIPINs to influence LD morphology. In both species, expression of SEIPIN1 promoted accumulation of large-sized lipid droplets, while expression of SEIPIN2 and especiallymore » SEIPIN3 promoted small LDs. Arabidopsis SEIPINs increased triacylglycerol levels and altered composition. In tobacco, endoplasmic reticulum (ER)-localized SEIPINs reorganized the normal, reticulated ER structure into discrete ER domains that colocalized with LDs. N-terminal deletions and swapping experiments of SEIPIN1 and 3 revealed that this region of SEIPIN determines LD size. Ectopic overexpression of SEIPIN1 in Arabidopsis resulted in increased numbers of large LDs in leaves, as well as in seeds, and increased seed oil content by up to 10% over wild-type seeds. By contrast, RNAi suppression of SEIPIN1 resulted in smaller seeds and, as a consequence, a reduction in the amount of oil per seed compared with the wild type. Finally, overall, our results indicate that Arabidopsis SEIPINs are part of a conserved LD biogenesis machinery in eukaryotes and that in plants these proteins may have evolved specialized roles in the storage of neutral lipids by differentially modulating the number and sizes of lipid droplets.« less

The lipodystrophic hotspot lamin A p.R482W mutation deregulates the mesodermal inducer T/Brachyury and early vascular differentiation gene networks.

PubMed

Briand, Nolwenn; Guénantin, Anne-Claire; Jeziorowska, Dorota; Shah, Akshay; Mantecon, Matthieu; Capel, Emilie; Garcia, Marie; Oldenburg, Anja; Paulsen, Jonas; Hulot, Jean-Sebastien; Vigouroux, Corinne; Collas, Philippe

2018-04-15

The p.R482W hotspot mutation in A-type nuclear lamins causes familial partial lipodystrophy of Dunnigan-type (FPLD2), a lipodystrophic syndrome complicated by early onset atherosclerosis. Molecular mechanisms underlying endothelial cell dysfunction conferred by the lamin A mutation remain elusive. However, lamin A regulates epigenetic developmental pathways and mutations could perturb these functions. Here, we demonstrate that lamin A R482W elicits endothelial differentiation defects in a developmental model of FPLD2. Genome modeling in fibroblasts from patients with FPLD2 caused by the lamin A R482W mutation reveals repositioning of the mesodermal regulator T/Brachyury locus towards the nuclear center relative to normal fibroblasts, suggesting enhanced activation propensity of the locus in a developmental model of FPLD2. Addressing this issue, we report phenotypic and transcriptional alterations in mesodermal and endothelial differentiation of induced pluripotent stem cells we generated from a patient with R482W-associated FPLD2. Correction of the LMNA mutation ameliorates R482W-associated phenotypes and gene expression. Transcriptomics links endothelial differentiation defects to decreased Polycomb-mediated repression of the T/Brachyury locus and over-activation of T target genes. Binding of the Polycomb repressor complex 2 to T/Brachyury is impaired by the mutated lamin A network, which is unable to properly associate with the locus. This leads to a deregulation of vascular gene expression over time. By connecting a lipodystrophic hotspot lamin A mutation to a disruption of early mesodermal gene expression and defective endothelial differentiation, we propose that the mutation rewires the fate of several lineages, resulting in multi-tissue pathogenic phenotypes.

Gain-of-function KCNJ6 Mutation in a Severe Hyperkinetic Movement Disorder Phenotype.

PubMed

Horvath, Gabriella A; Zhao, Yulin; Tarailo-Graovac, Maja; Boelman, Cyrus; Gill, Harinder; Shyr, Casper; Lee, James; Blydt-Hansen, Ingrid; Drögemöller, Britt I; Moreland, Jacqueline; Ross, Colin J; Wasserman, Wyeth W; Masotti, Andrea; Slesinger, Paul A; van Karnebeek, Clara D M

2018-05-29

Here, we describe a fourth case of a human with a de novo KCNJ6 (GIRK2) mutation, who presented with clinical findings of severe hyperkinetic movement disorder and developmental delay, similar to the Keppen-Lubinsky syndrome but without lipodystrophy. Whole-exome sequencing of the patient's DNA revealed a heterozygous de novo variant in the KCNJ6 (c.512T>G, p.Leu171Arg). We conducted in vitro functional studies to determine if this Leu-to-Arg mutation alters the function of GIRK2 channels. Heterologous expression of the mutant GIRK2 channel alone produced an aberrant basal inward current that lacked G protein activation, lost K + selectivity and gained Ca 2+ permeability. Notably, the inward current was inhibited by the Na + channel blocker QX-314, similar to the previously reported weaver mutation in murine GIRK2. Expression of a tandem dimer containing GIRK1 and GIRK2(p.Leu171Arg) did not lead to any currents, suggesting heterotetramers are not functional. In neurons expressing p.Leu171Arg GIRK2 channels, these changes in channel properties would be expected to generate a sustained depolarization, instead of the normal G protein-gated inhibitory response, which could be mitigated by expression of other GIRK subunits. The identification of the p.Leu171Arg GIRK2 mutation potentially expands the Keppen-Lubinsky syndrome phenotype to include severe dystonia and ballismus. Our study suggests screening for dominant KCNJ6 mutations in the evaluation of patients with severe movement disorders, which could provide evidence to support a causal role of KCNJ6 in neurological channelopathies. Copyright © 2018. Published by Elsevier Ltd.

The juvenile idiopathic inflammatory myopathies: pathogenesis, clinical and autoantibody phenotypes, and outcomes

PubMed Central

Rider, Lisa G.; Nistala, Kiran

2015-01-01

The aim of this review is to summarize recent advances in the understanding of the clinical and autoantibody phenotypes, their associated outcomes, and the pathogenesis of the juvenile idiopathic inflammatory myopathies (JIIMs). The major clinical and autoantibody phenotypes in children have many features similar to those in adults, and each has distinct demographic and clinical features and associated outcomes. The most common myositis autoantibodies in JIIM patients are anti-p155/140, anti-MJ, and anti-MDA5. Higher mortality has been associated with overlap myositis as well as with the presence of anti-synthetase and anti-MDA5 autoantibodies; a chronic illness course and lipodystrophy have been associated with anti-p155/140 autoantibodies; and calcinosis has been associated with anti-MJ autoantibodies. Histologic abnormalities of JIIMs detectable on muscle biopsy have also been correlated with myositis-specific autoantibodies; for example, patients with anti-MDA5 show low levels of inflammatory infiltrate and muscle damage on biopsy. The first genome-wide association study of adult and juvenile dermatomyositis revealed three novel genetic associations, BLK, PLCL1, and CCL21, and confirmed that the human leukocyte antigen region is the primary risk region for juvenile dermatomyositis. Here we review the well-established pathogenic processes in JIIMs, including the type 1 interferon and endoplasmic reticulum stress pathways. Several novel JIIM-associated inflammatory mediators, such as the innate immune system proteins, myeloid-related peptide 8/14, galectin 9, and eotaxin, have emerged as promising biomarkers of disease. Advances in our understanding of the phenotypes and pathophysiology of the JIIMs are leading to better tools to help clinicians stratify and treat these heterogeneous disorders. PMID:27028907

Overcoming subjectivity in assessing facial lipoatrophy: is there a role for three-dimensional laser scans?

PubMed

Benn, P; Ruff, C; Cartledge, J; Sauret, V; Copas, A; Linney, A; Williams, I G; Smith, C; Edwards, S G

2003-10-01

Prevalence and incidence rates of lipodystrophy vary widely and frequently rely upon self- and/or clinician reports. Currently no validated assessment tool for facial lipoatrophy is available. To illustrate that assessment of the severity of facial lipoatrophy by patients and clinicians is subjective. To evaluate the reproducibility of facial three-dimensional surface laser scans. Twenty-three HIV-positive men were recruited from an inner London HIV outpatient clinic in September 2001. CD4 count, viral load, antiretroviral history and body mass index were recorded. Patients and clinicians independently assessed the severity of facial lipoatrophy on a four-point scale and the level agreement was measured. Seventeen of the 23 patients (73.9%) underwent two scans 1 week apart, which were then superimposed. The volume difference (mm3) and mean difference (mm) between the scans for five regions of the face were measured and compared with the self-reported grade of facial lipoatrophy. For each pair of clinicians (P=0.03, 0.005 and 0.0002, respectively), and for one patient-clinician pair (P=0.004), there was a significant systematic difference between the two sets of gradings of facial lipoatrophy. The level of disagreement was generally higher for patients reporting facial lipoatrophy (n=17) compared to those not reporting it (n=6). The mean volume difference and mean difference between any region were within 200 mm3 and 0.25 mm, respectively. Reproducibility was unaffected by the self-reported grade of facial lipoatrophy. Assessment of the severity of facial lipoatrophy by patients and clinicians is subjective. Three-dimensional facial laser scans are reproducible and may provide an objective tool for monitoring changes in facial lipoatrophy.

Yield of yearly routine physical examination in HIV-1 infected patients is limited: A retrospective cohort study in the Netherlands.

PubMed

van Amsterdam, Marleen A; van Assen, Sander; Sprenger, Herman G; Wilting, Kasper R; Stienstra, Ymkje; Bierman, Wouter F W

2017-01-01

Routine physical examinations might be of value in HIV-infected patients, but the yield is unknown. We determined the diagnoses that would have been missed without performing annual routine physical examinations in HIV-infected patients with stable disease. Data were collected from the medical records of 299 HIV-1-infected patients with CD4 count >350 cells/mm3 if not using combination antiretroviral therapy (cART), or CD4 count >100 cells/mm3 and undetectable viral load if using cART. We defined the diagnoses that would have been missed without performing routine physical examinations on annual check-ups in 2010. Exclusion criteria were hepatitis B/C co-infection, start/ switch of cART < 24 weeks, pregnancy, and transgenderism. 215 patients (72%) had positive findings: lipodystrophy (30%), lymphadenopathy (16%) and hypertension (8.4%) were the most common. Two-thirds of all findings were not new or were based on complaints indicating a physical examination even if not routinely scheduled. For 24 patients (8.0%) the routine physical examination led to the finding of a new diagnosis: six-all men who have sex with men (MSM)-had a concurrent sexually transmitted infection, eight had hypertension, and ten others had a large variety of diagnoses. A total atrioventricular block with bradycardia was the most clinically relevant finding. Annual physical examinations of HIV-infected patients with stable disease brought few new diagnoses that would have been missed without performing a routine examination. Our results suggest that standard assessments could be restricted to six-monthly measuring blood pressure in all patients and annually performing anogenital and digital rectal examination on MSM.

Efavirenz-induced gynecomastia in a prepubertal girl with human immunodeficiency virus infection: a case report.

PubMed

van Ramshorst, Mette S; Kekana, Magdeline; Struthers, Helen E; McIntyre, James A; Peters, Remco P H

2013-08-13

Prepubertal gynecomastia is a rare condition and most frequently classified as idiopathic. In HIV-infected adults gynecomastia is a recognised but infrequent side-effect of antiretroviral treatment (ART) and mostly attributed to efavirenz use. Gynecomastia should be distinguished from pseudogynecomastia as part of the lipodystrophy syndrome caused by Nucleoside Reverse Transcriptase Inhibitors (NRTIs) to avoid incorrect substitution of drugs. In the medical literature only five cases of prepubertal gynecomastia in children taking ART are described and underlying pathogenesis was unknown. The occurrence of adverse effects of ART may interfere with therapy adherence and long-term prognosis and for that reason requires attention. We report the first case of prepubertal gynecomastia in a young girl attributed to efavirenz use. A seven-year-old African girl presented with true gynecomastia four months after initiation on ART (abacavir, lamivudine, efavirenz). History, physical examination and laboratory tests excluded known causes of gynecomastia and efavirenz was considered as the most likely cause. Six weeks after withdrawal of efavirenz the breast enlargement had completely resolved. Efavirenz-induced gynecomastia may occur in children as well as in adults. With the increasing access to ART, the possibility of efavirenz-exposure and the potential occurrence of its associated side-effects may be high. In resource-poor settings, empirical change from efavirenz to nevirapine may be considered, providing no other known or alarming cause is identified, as efavirenz-induced gynecomastia can resolve quickly after withdrawal of the drug. Timely recognition of gynecomastia as a side-effect of efavirenz is important in order to intervene while the condition may still be reversible, to sustain adherence to ART and to maintain the sociopsychological health of the child.

Physical activity correlates in people living with HIV/AIDS: a systematic review of 45 studies.

PubMed

Vancampfort, Davy; Mugisha, James; Richards, Justin; De Hert, Marc; Probst, Michel; Stubbs, Brendon

2018-07-01

Understanding barriers and facilitators of physical activity participation in persons living with HIV/AIDS is an essential first step in order to devise effective interventions. The present review provides a systematic quantitative review of the physical activity correlates in people with HIV/AIDS. Major electronic databases were searched till August 2016. Keywords included "physical activity" or "exercise" or "sports" and "AIDS" or "HIV". Out of 55 correlates from 45 studies (N = 13,167; mean age range = 30.5-58.3 years; 63.2% male) five consistent (i.e., reported in four or more studies) correlates were identified. Lower levels of physical activity were consistently associated with older age (6/10 studies), a lower educational level (6/7), a lower number of CD4 cells/μl (7/11), exposure to antiviral therapy (4/6), and the presence of lipodystrophy (4/4). Other important barriers were the presence of bodily pain (2/2), depression (3/3), and opportunistic infections (3/4). Facilitators were a higher cardiorespiratory fitness level (3/3), a higher self-efficacy (2/2), more perceived benefits (2/2), and a better health motivation (3/3). The current review has elucidated that participation in physical activity by people with HIV/AIDS is associated with a range of complex factors which should be considered in rehabilitation programs. Implications for Rehabilitation Health care professionals should consider HIV-related bodily pain and feelings of depression when assisting people living with HIV in inititiating and maintaining an active lifestyle. Interventions to improve self-efficacy and motivation, and to help people living with HIV in understanding the benefits of exercise, may encourage greater participation.

The development of PROQOL-HIV: an international instrument to assess the health-related quality of life of persons living with HIV/AIDS.

PubMed

Duracinsky, Martin; Herrmann, Susan; Berzins, Baiba; Armstrong, Andrew R; Kohli, Rewa; Le Coeur, Sophie; Diouf, Assane; Fournier, Isabelle; Schechter, Mauro; Chassany, Olivier

2012-04-15

Health-related quality of life (HRQL) is an important outcome in HIV/AIDS infection and treatment. However, most existing HIV-HRQL instruments miss important issues (eg, sleeping problems, lipodystrophy). They were developed before highly active antiretroviral therapy (pre-HAART), and in a single language. We sought to develop a contemporary HIV-HRQL instrument (PROQOL-HIV) in multiple languages that accounts for HAART treatment and side effects. This article details the 3-stage content validation phase of PROQOL-HIV. In stage 1, we developed a conceptual model of HIV-HRQL and questionnaire item bank from thematic analysis of 152 patient interviews conducted simultaneously across 9 countries. In stage 2, pilot items were selected by an expert panel to form the pilot instrument. Stage 3 involved linguistic validation and harmonization of selected items to form an equivalent instrument in 9 target languages. Analysis of 3375 pages of interview text revealed 11 underlying themes: general health perception, social relationships, emotions, energy/fatigue, sleep, cognitive functioning, physical and daily activity, coping, future, symptoms, and treatment. Seven issues new to HIV-HRQL measurement were subsumed by these themes: infection fears, future concerns, satisfaction with care, self-esteem problems, sleep problems, work disruption, and treatment issues. Of the 442 theme-related items banked, 70 items met the retention criteria and formed the pilot PROQOL-HIV instrument. HIV patients across 11 countries attributed a wide range of physical, mental, and social issues to their condition, many of which were not measured by existing HIV-HRQL instruments. The pilot PROQOL-HIV instrument captures these issues, is sensitive to sociocultural context, disease stage, and HAART.

Redundant roles of the phosphatidate phosphatase family in triacylglycerol synthesis in human adipocytes.

PubMed

Temprano, Ana; Sembongi, Hiroshi; Han, Gil-Soo; Sebastián, David; Capellades, Jordi; Moreno, Cristóbal; Guardiola, Juan; Wabitsch, Martin; Richart, Cristóbal; Yanes, Oscar; Zorzano, Antonio; Carman, George M; Siniossoglou, Symeon; Miranda, Merce

2016-09-01

In mammals, the evolutionary conserved family of Mg(2+)-dependent phosphatidate phosphatases (PAP1), involved in phospholipid and triacylglycerol synthesis, consists of lipin-1, lipin-2 and lipin-3. While mutations in the murine Lpin1 gene cause lipodystrophy and its knockdown in mouse 3T3-L1 cells impairs adipogenesis, deleterious mutations of human LPIN1 do not affect adipose tissue distribution. However, reduced LPIN1 and PAP1 activity has been described in participants with type 2 diabetes. We aimed to characterise the roles of all lipin family members in human adipose tissue and adipogenesis. The expression of the lipin family was analysed in adipose tissue in a cross-sectional study. Moreover, the effects of lipin small interfering RNA (siRNA)-mediated depletion on in vitro human adipogenesis were assessed. Adipose tissue gene expression of the lipin family is altered in type 2 diabetes. Depletion of every lipin family member in a human Simpson-Golabi-Behmel syndrome (SGBS) pre-adipocyte cell line, alters expression levels of adipogenic transcription factors and lipid biosynthesis genes in early stages of differentiation. Lipin-1 knockdown alone causes a 95% depletion of PAP1 activity. Despite the reduced PAP1 activity and alterations in early adipogenesis, lipin-silenced cells differentiate and accumulate neutral lipids. Even combinatorial knockdown of lipins shows mild effects on triacylglycerol accumulation in mature adipocytes. Overall, our data support the hypothesis of alternative pathways for triacylglycerol synthesis in human adipocytes under conditions of repressed lipin expression. We propose that induction of alternative lipid phosphate phosphatases, along with the inhibition of lipid hydrolysis, contributes to the maintenance of triacylglycerol content to near normal levels.

Recent progress in genetics, epigenetics and metagenomics unveils the pathophysiology of human obesity.

PubMed

Pigeyre, Marie; Yazdi, Fereshteh T; Kaur, Yuvreet; Meyre, David

2016-06-01

In high-, middle- and low-income countries, the rising prevalence of obesity is the underlying cause of numerous health complications and increased mortality. Being a complex and heritable disorder, obesity results from the interplay between genetic susceptibility, epigenetics, metagenomics and the environment. Attempts at understanding the genetic basis of obesity have identified numerous genes associated with syndromic monogenic, non-syndromic monogenic, oligogenic and polygenic obesity. The genetics of leanness are also considered relevant as it mirrors some of obesity's aetiologies. In this report, we summarize ten genetically elucidated obesity syndromes, some of which are involved in ciliary functioning. We comprehensively review 11 monogenic obesity genes identified to date and their role in energy maintenance as part of the leptin-melanocortin pathway. With the emergence of genome-wide association studies over the last decade, 227 genetic variants involved in different biological pathways (central nervous system, food sensing and digestion, adipocyte differentiation, insulin signalling, lipid metabolism, muscle and liver biology, gut microbiota) have been associated with polygenic obesity. Advances in obligatory and facilitated epigenetic variation, and gene-environment interaction studies have partly accounted for the missing heritability of obesity and provided additional insight into its aetiology. The role of gut microbiota in obesity pathophysiology, as well as the 12 genes associated with lipodystrophies is discussed. Furthermore, in an attempt to improve future studies and merge the gap between research and clinical practice, we provide suggestions on how high-throughput '-omic' data can be integrated in order to get closer to the new age of personalized medicine. © 2016 The Author(s). Published by Portland Press Limited on behalf of the Biochemical Society.

Hallermann-Streiff Syndrome: No Evidence for a Link to Laminopathies

PubMed Central

Kortüm, F.; Chyrek, M.; Fuchs, S.; Albrecht, B.; Gillessen-Kaesbach, G.; Mütze, U.; Seemanova, E.; Tinschert, S.; Wieczorek, D.; Rosenberger, G.; Kutsche, K.

2011-01-01

Hallermann-Streiff syndrome (HSS) is a rare inherited disorder characterized by malformations of the cranium and facial bones, congenital cataracts, microphthalmia, skin atrophy, hypotrichosis, proportionate short stature, teeth abnormalities, and a typical facial appearance with prominent forehead, small pointed nose, and micrognathia. The genetic cause of this developmental disorder is presently unknown. Here we describe 8 new patients with a phenotype of HSS. Individuals with HSS present with clinical features overlapping with some progeroid syndromes that belong to the laminopathies, such as Hutchinson-Gilford progeria syndrome (HGPS) and mandibuloacral dysplasia (MAD). HGPS is caused by de novo point mutations in the LMNA gene, coding for the nuclear lamina proteins lamin A and C. MAD with type A and B lipodystrophy are recessive disorders resulting from mutations in LMNA and ZMPSTE24, respectively. ZMPSTE24 in addition to ICMT encode proteins involved in posttranslational processing of lamin A. We hypothesized that HSS is an allelic disorder to HGPS and MAD. As the nuclear shape is often irregular in patients with LMNA mutations, we first analyzed the nuclear morphology in skin fibroblasts of patients with HSS, but could not identify any abnormality. Sequencing of the genes LMNA, ZMPSTE24 and ICMT in the 8 patients with HSS revealed the heterozygous missense mutation c.1930C>T (p.R644C) in LMNA in 1 female. Extreme phenotypic diversity and low penetrance have been associated with the p.R644C mutation. In ZMPSTE24 and ICMT, no pathogenic sequence change was detected in patients with HSS. Together, we found no evidence that HSS is another laminopathy. PMID:22570643

Gender-specific effects of HIV protease inhibitors on body mass in mice.

PubMed

Wilson, Melinda E; Allred, Kimberly F; Kordik, Elizabeth M; Jasper, Deana K; Rosewell, Amanda N; Bisotti, Anthony J

2007-05-01

Protease inhibitors, as part of highly active anti-retroviral therapy (HAART), have significantly increased the lifespan of human immunodeficiency virus (HIV) infected patients. Several deleterious side effects including dyslipidemia and lipodystrophy, however, have been observed with HAART. Women are at a higher risk of developing adipose tissue alterations and these alterations have different characteristics as compared to men. We have previously demonstrated that in mice the HIV protease inhibitor, ritonavir, caused a reduction in weight gain in females, but had no effect on male mice. In the present study, we examined the potential causes of this difference in weight gain. Low-density lipoprotein receptor (LDL-R) null mice or wild-type C57BL/6 mice, were administered 15 mug/ml ritonavir or vehicle (0.01% ethanol) in the drinking water for 6 weeks. The percent of total body weight gained during the treatment period was measured and confirmed that female LDL-R gained significantly less weight with ritonavir treatment than males. In wild type mice, however, there was no effect of ritonavir treatment in either sex. Despite the weight loss in LDL-R null mice, ritonavir increased food intake, but no difference was observed in gonadal fat weight. Serum leptin levels were significantly lower in females. Ritonavir further suppressed leptin levels in (p < 0.05). Ritonavir did not alter serum adiponectin levels in either gender. To determine the source of these differences, female mice were ovariectomized remove the gonadal sex hormones. Ovariectomy prevented the weight loss induced by ritonavir (p < 0.05). Furthermore, leptin levels were no longer suppressed by ritonavir (p < 0.05). This study demonstrates that gonadal factors in females influence the hormonal control of weight gain changes induced by HIV protease inhibitors in an environment of elevated cholesterol.

HIV-1 Vpr Enhances PPARβ/δ-Mediated Transcription, Increases PDK4 Expression, and Reduces PDC Activity

PubMed Central

Shrivastav, Shashi; Zhang, Liyan; Okamoto, Koji; Lee, Hewang; Lagranha, Claudia; Abe, Yoshifusa; Balasubramanyam, Ashok; Lopaschuk, Gary D.; Kino, Tomoshige

2013-01-01

HIV infection and its therapy are associated with disorders of lipid metabolism and bioenergetics. Previous work has suggested that viral protein R (Vpr) may contribute to the development of lipodystrophy and insulin resistance observed in HIV-1–infected patients. In adipocytes, Vpr suppresses mRNA expression of peroxisomal proliferator-activating receptor-γ (PPARγ)-responsive genes and inhibits differentiation. We investigated whether Vpr might interact with PPARβ/δ and influence its transcriptional activity. In the presence of PPARβ/δ, Vpr induced a 3.3-fold increase in PPAR response element-driven transcriptional activity, a 1.9-fold increase in pyruvate dehydrogenase kinase 4 (PDK4) protein expression, and a 1.6-fold increase in the phosphorylated pyruvate dehydrogenase subunit E1α leading to a 47% decrease in the activity of the pyruvate dehydrogenase complex in HepG2 cells. PPARβ/δ knockdown attenuated Vpr-induced enhancement of endogenous PPARβ/δ-responsive PDK4 mRNA expression. Vpr induced a 1.3-fold increase in mRNA expression of both carnitine palmitoyltransferase I (CPT1) and acetyl-coenzyme A acyltransferase 2 (ACAA2) and doubled the activity of β-hydroxylacyl coenzyme A dehydrogenase (HADH). Vpr physically interacted with the ligand-binding domain of PPARβ/δ in vitro and in vivo. Consistent with a role in energy expenditure, Vpr increased state-3 respiration in isolated mitochondria (1.16-fold) and basal oxygen consumption rate in intact HepG2 cells (1.2-fold) in an etomoxir-sensitive manner, indicating that the oxygen consumption rate increase is β-oxidation–dependent. The effects of Vpr on PPAR response element activation, pyruvate dehydrogenase complex activity, and β-oxidation were reversed by specific PPARβ/δ antagonists. These results support the hypothesis that Vpr contributes to impaired energy metabolism and increased energy expenditure in HIV patients. PMID:23842279

POLD1: central mediator of DNA replication and repair, and implication in cancer and other pathologies

PubMed Central

Nicolas, Emmanuelle; Golemis, Erica A.; Arora, Sanjeevani

2016-01-01

The evolutionarily conserved human polymerase delta (POLD1) gene encodes the large p125 subunit which provides the essential catalytic activities of polymerase δ (Polδ), mediated by 5’–3’ DNA polymerase and 3’–5’ exonuclease moieties. POLD1 associates with three smaller subunits (POLD2, POLD3, POLD4), which together with Replication Factor C and Proliferating Nuclear Cell Antigen constitute the polymerase holoenzyme. Polδ function is essential for replication, with a primary role as the replicase for the lagging strand. Polδ also has an important proofreading ability conferred by the exonuclease activity, which is critical for ensuring replicative fidelity, but also serves to repair DNA lesions arising as a result of exposure to mutagens. Polδ has been shown to be important for multiple forms of DNA repair, including nucleotide excision repair, double strand break repair, base excision repair, and mismatch repair. A growing number of studies in the past decade have linked germline and sporadic mutations in POLD1 and the other subunits of Polδ with human pathologies. Mutations in Polδ in mice and humans lead to genomic instability, mutator phenotype and tumorigenesis. The advent of genome sequencing techniques has identified damaging mutations in the proofreading domain of POLD1 as the underlying cause of some inherited cancers, and suggested that mutations in POLD1 may influence therapeutic management. In addition, mutations in POLD1 have been identified in the developmental disorders of mandibular hypoplasia, deafness, progeroid features and lipodystrophy and atypical Werner syndrome, while changes in expression or activity of POLD1 have been linked to senescence and aging. Intriguingly, some recent evidence suggests POLD1 function may also be altered in diabetes. We provide an overview of critical Polδ activities in the context of these pathologic conditions. PMID:27320729

In Vivo Effects of Retrobulbar Bimatoprost Injection on Orbital Fat.

PubMed

Eftekhari, Kian; Vagefi, M Reza; Lee, Vivian; Hui, James Z; Zhu, Menglong; Dine, Kimberly; Anderson, Richard L; Koeberlein, Brigitte; Sulaimankutty, Reas; Shindler, Kenneth S

Recent publications have reported the adverse effects of prostaglandin analogues on the periocular tissues. These medications may cause periorbital lipodystrophy, enophthalmos, and deepening of the superior sulcus deformity. While these effects may have adverse consequences for some patients, the atrophy of the periorbital fat may have a useful role in diseases that lead to orbital and periorbital fat hypertrophy such as thyroid eye disease. In this pilot study, the authors investigated the effects of retrobulbar bimatoprost injection on the intraocular pressure and orbital fat in a rat animal model. Three rats were sedated and intraocular pressure was measured. A 0.1 ml aliquot of bimatoprost was injected into the right orbit of all rats. In the left orbit, 0.1 ml of phosphate-buffered saline was injected as a control. Three weeks later, all rats were sedated and intraocular pressure was measured before euthanizing. Routine histologic staining was performed and thin sections through the intraconal orbital fat were obtained. Density of intraconal adipocytes was measured and adipocyte heterogeneity was determined using a computer image analysis algorithm. The specimens injected with bimatoprost demonstrated atrophy of orbital fat with significantly increased adipocyte density (p = 0.009) and heterogeneity (p = 0.008) when compared with control. Intraocular pressure was not significantly decreased at 3 weeks after injection of retrobulbar bimatoprost. In this pilot study, orbital injection of bimatoprost demonstrated atrophy of intraconal adipocytes when compared with control orbits injected with saline. The orbits injected with bimatoprost were noted to have smaller, more heterogeneous adipocytes that were densely packed in the intraconal space. The study limitations include the small sample size, which limited the ability for us to make conclusions about the effect on intraocular pressure. Nevertheless, the findings presented suggest that retrobulbar

Dyslipidemia and cardiovascular disease risk factor management in HIV-1-infected subjects treated with HAART in the Spanish VACH cohort.

PubMed

Pere, Domingo; Ignacio, Suarez-Lozano; Ramón, Teira; Fernando, Lozano; Alberto, Terrón; Pompeyo, Viciana; Juan, González; M José, Galindo; Paloma, Geijo; Antonio, Vergara; Jaime, Cosín; Esteban, Ribera; Bernardino, Roca; M Luisa, Garcia-Alcalde; Trinitario, Sánchez; Ferran, Torres; Juan Ramón, Lacalle; Myriam, Garrido

2008-01-01

There is increasing evidence that metabolic adverse effects associated with antiretroviral therapy may translate into an increased cardiovascular risk in HIV-1-infected patients. To determine the prevalence of risk factors for cardiovascular disease (CVD) among HIV-1-infected persons, and to investigate any association between them, stage of HIV-1 disease, and use of antiretroviral therapies. Multicentric, cross-sectional analysis of CVD risk factors of treated patients in the VACH cohort. The data collected includes: demographic variables, cigarette smoking, diabetes mellitus, hypertension, dyslipidemia, body mass index, stage of HIV-1 infection, and antiretroviral therapy. The analysis included 2358 patients. More than 18% of the study population was at an age of appreciable risk of CVD. 1.7% had previous CVD and 59.2% were smokers. Increased prevalence of elevated total cholesterol was observed among subjects receiving an NNRTI but no PI [odds ratio (OR), 3.34; 95% confidence interval (CI), 1.77-6.31], PI but no NNRTI (OR, 4.04; 95% CI, 2.12-7.71), or NNRTI + PI (OR, 17.77; 95% CI, 7.24-43.59) compared to patients treated only with nucleoside reverse transcriptase inhibitors (NRTI). Higher CD4 cell count, lower plasma HIV-1 RNA levels, clinical signs of lipodystrophy, longer exposure times to NNRTI and PI, and older age were all also associated with elevated cholesterol levels. The use of lipid lowering agents was very low among our patients. Patients in the VACH cohort present multiple known risk factors for CVD, and a very low rate of lipid lowering therapy use. NNRTI and/or PI-based antiretroviral therapies are associated with the worst lipid profile. This is more frequent in older subjects with greater CD4 counts and controlled HIV-1 replication.

WZB117 (2-Fluoro-6-(m-hydroxybenzoyloxy) Phenyl m-Hydroxybenzoate) Inhibits GLUT1-mediated Sugar Transport by Binding Reversibly at the Exofacial Sugar Binding Site*

PubMed Central

Ojelabi, Ogooluwa A.; Lloyd, Kenneth P.; Simon, Andrew H.; De Zutter, Julie K.; Carruthers, Anthony

2016-01-01

WZB117 (2-fluoro-6-(m-hydroxybenzoyloxy) phenyl m-hydroxybenzoate) inhibits passive sugar transport in human erythrocytes and cancer cell lines and, by limiting glycolysis, inhibits tumor growth in mice. This study explores how WZB117 inhibits the erythrocyte sugar transporter glucose transport protein 1 (GLUT1) and examines the transporter isoform specificity of inhibition. WZB117 reversibly and competitively inhibits erythrocyte 3-O-methylglucose (3MG) uptake with Ki(app) = 6 μm but is a noncompetitive inhibitor of sugar exit. Cytochalasin B (CB) is a reversible, noncompetitive inhibitor of 3MG uptake with Ki(app) = 0.3 μm but is a competitive inhibitor of sugar exit indicating that WZB117 and CB bind at exofacial and endofacial sugar binding sites, respectively. WZB117 inhibition of GLUTs expressed in HEK293 cells follows the order of potency: insulin-regulated GLUT4 ≫ GLUT1 ≈ neuronal GLUT3. This may explain WZB117-induced murine lipodystrophy. Molecular docking suggests the following. 1) The WZB117 binding envelopes of exofacial GLUT1 and GLUT4 conformers differ significantly. 2) GLUT1 and GLUT4 exofacial conformers present multiple, adjacent glucose binding sites that overlap with WZB117 binding envelopes. 3) The GLUT1 exofacial conformer lacks a CB binding site. 4) The inward GLUT1 conformer presents overlapping endofacial WZB117, d-glucose, and CB binding envelopes. Interrogating the GLUT1 mechanism using WZB117 reveals that subsaturating WZB117 and CB stimulate erythrocyte 3MG uptake. Extracellular WZB117 does not affect CB binding to GLUT1, but intracellular WZB117 inhibits CB binding. These findings are incompatible with the alternating conformer carrier for glucose transport but are consistent with either a multisubunit, allosteric transporter, or a transporter in which each subunit presents multiple, interacting ligand binding sites. PMID:27836974

Genetic Ablation of Calcium-independent Phospholipase A2γ Prevents Obesity and Insulin Resistance during High Fat Feeding by Mitochondrial Uncoupling and Increased Adipocyte Fatty Acid Oxidation*

PubMed Central

Mancuso, David J.; Sims, Harold F.; Yang, Kui; Kiebish, Michael A.; Su, Xiong; Jenkins, Christopher M.; Guan, Shaoping; Moon, Sung Ho; Pietka, Terri; Nassir, Fatiha; Schappe, Timothy; Moore, Kristin; Han, Xianlin; Abumrad, Nada A.; Gross, Richard W.

2010-01-01

Phospholipases are critical enzyme mediators participating in many aspects of cellular function through modulating the generation of lipid 2nd messengers, membrane physical properties, and cellular bioenergetics. Here, we demonstrate that mice null for calcium-independent phospholipase A2γ (iPLA2γ−/−) are completely resistant to high fat diet-induced weight gain, adipocyte hypertrophy, hyperinsulinemia, and insulin resistance, which occur in iPLA2γ+/+ mice after high fat feeding. Notably, iPLA2γ−/− mice were lean, demonstrated abdominal lipodystrophy, and remained insulin-sensitive despite having a marked impairment in glucose-stimulated insulin secretion after high fat feeding. Respirometry of adipocyte explants from iPLA2γ−/− mice identified increased rates of oxidation of multiple different substrates in comparison with adipocyte explants from wild-type littermates. Shotgun lipidomics of adipose tissue from wild-type mice demonstrated the anticipated 2-fold increase in triglyceride content after high fat feeding. In sharp contrast, the adipocyte triglyceride content was identical in iPLA2γ−/− mice fed either a standard diet or a high fat diet. Respirometry of skeletal muscle mitochondria from iPLA2γ−/− mice demonstrated marked decreases in state 3 respiration using multiple substrates whose metabolism was uncoupled from ATP production. Shotgun lipidomics of skeletal muscle revealed a decreased content of cardiolipin with an altered molecular species composition thereby identifying the mechanism underlying mitochondrial uncoupling in the iPLA2γ−/− mouse. Collectively, these results identify iPLA2γ as an obligatory upstream enzyme that is necessary for efficient electron transport chain coupling and energy production through its participation in the alterations of cellular bioenergetics that promote the development of the metabolic syndrome. PMID:20817734

From leptin to other adipokines in health and disease: facts and expectations at the beginning of the 21st century.

PubMed

Blüher, Matthias; Mantzoros, Christos S

2015-01-01

This year marks the 20th anniversary of the discovery of leptin, which has tremendously stimulated translational obesity research. The discovery of leptin has led to realizations that have established adipose tissue as an endocrine organ, secreting bioactive molecules including hormones now termed adipokines. Through adipokines, the adipose tissue influences the regulation of several important physiological functions including but not limited to appetite, satiety, energy expenditure, activity, insulin sensitivity and secretion, glucose and lipid metabolism, fat distribution, endothelial function, hemostasis, blood pressure, neuroendocrine regulation, and function of the immune system. Adipokines have a great potential for clinical use as potential therapeutics for obesity, obesity related metabolic, cardiovascular and other diseases. After 20 years of intense research efforts, recombinant leptin and the leptin analog metreleptin are already available for the treatment of congenital leptin deficiency and lipodystrophy. Other adipokines are also emerging as promising candidates for urgently needed novel pharmacological treatment strategies not only in obesity but also other disease states associated with and influenced by adipose tissue size and activity. In addition, prediction of reduced type 2 diabetes risk by high circulating adiponectin concentrations suggests that adipokines have the potential to be used as biomarkers for individual treatment success and disease progression, to monitor clinical responses and to identify non-responders to anti-obesity interventions. With the growing number of adipokines there is an increasing need to define their function, molecular targets and translational potential for the treatment of obesity and other diseases. In this review we present research data on adipose tissue secreted hormones, the discovery of which followed the discovery of leptin 20 years ago pointing to future research directions to unravel mechanisms of action

Should leptin replace insulin as a lifetime monotherapy for diabetes type 1 and 2?

PubMed Central

Kalra, Satya P.

2013-01-01

Evidence accumulated during the last decade has affirmed that adipocyte leptin insufficiency in the hypothalamus is the primary etiological factor in the pathogenesis of diabetes type 1 and 2 and related metabolic morbidities. Leptin insufficiency disrupts the relay of hypothalamic regulatory information along three descending pathways to the organs in the periphery that normally participate in maintenance of glucose homeostasis on a minute-to-minute basis throughout lifetime. Reinstatement of leptin sufficiency in the hypothalamus by either systemic or central injections, or its provision selectively in the hypothalamus with the aid of gene therapy extinguished hyperglycemia and normalized blood glucose stably during the entire course of treatment in a variety of animal models of diabetes type 1 and 2. In follow-up clinical trials, twice daily leptin treatment in leptinopenic and insulinopenic type 1 diabetics and leptinopenic and hyperinsulinemic type 2 diabetics with congenital lipodystrophy or acquired lipoatrophy normalized blood glucose without any discernible adverse effects during the extended course of treatment. Taken together, these findings have amply endorsed the efficacy of leptin therapy to restore glucose homeostasis in insulin-deficient as well as hyperinsulinemic diabetic patients. Consequently, restoration of optimal hypothalmic signaling to reinstate glucose homeostasis with leptin is a highly suitable new therapeutic strategy to ameliorate diabetes type 1 and 2 for the lifetime and to replace the currently in vogue insulin monotherapy. In view of the relentless challenges posed by the worldwide epidemic of diabetes and soaring treatment costs, taken together with the well-known shortcomings of therapies based on restoring insulin signaling, it is highly critical and timely to undertake new clinical trials that ascertain appropriate dosage and route of leptin delivery to the hypothalamus capable of safely sustaining stable glycemia for lifetime

Should leptin replace insulin as a lifetime monotherapy for diabetes type 1 and 2?

PubMed

Kalra, Satya P

2013-10-01

Evidence accumulated during the last decade has affirmed that adipocyte leptin insufficiency in the hypothalamus is the primary etiological factor in the pathogenesis of diabetes type 1 and 2 and related metabolic morbidities. Leptin insufficiency disrupts the relay of hypothalamic regulatory information along three descending pathways to the organs in the periphery that normally participate in maintenance of glucose homeostasis on a minute-to-minute basis throughout lifetime. Reinstatement of leptin sufficiency in the hypothalamus by either systemic or central injections, or its provision selectively in the hypothalamus with the aid of gene therapy extinguished hyperglycemia and normalized blood glucose stably during the entire course of treatment in a variety of animal models of diabetes type 1 and 2. In follow-up clinical trials, twice daily leptin treatment in leptinopenic and insulinopenic type 1 diabetics and leptinopenic and hyperinsulinemic type 2 diabetics with congenital lipodystrophy or acquired lipoatrophy normalized blood glucose without any discernible adverse effects during the extended course of treatment. Taken together, these findings have amply endorsed the efficacy of leptin therapy to restore glucose homeostasis in insulin-deficient as well as hyperinsulinemic diabetic patients. Consequently, restoration of optimal hypothalmic signaling to reinstate glucose homeostasis with leptin is a highly suitable new therapeutic strategy to ameliorate diabetes type 1 and 2 for the lifetime and to replace the currently in vogue insulin monotherapy. In view of the relentless challenges posed by the worldwide epidemic of diabetes and soaring treatment costs, taken together with the well-known shortcomings of therapies based on restoring insulin signaling, it is highly critical and timely to undertake new clinical trials that ascertain appropriate dosage and route of leptin delivery to the hypothalamus capable of safely sustaining stable glycemia for lifetime.

Whipple’s disease: misdiagnosed as sarcoidosis with further tricuspid valve endocarditis and pulmonary embolism – a case report

PubMed Central

Berent, Robert; Auer, Johann; Lassnig, Elisabeth; von Duvillard, Serge P; Crouse, Stephen F; Tuppy, Herwig; Eber, Bernd

2009-01-01

GH Whipple described a 36-year-old physician in 1907 with gradual loss of weight and strength, stools consisting chiefly of neutral fat and fatty acids, indefinite abdominal signs and a peculiar multiple arthritis. The patient died of this progressive illness. Whipple called it intestinal lipodystrophy since he observed accumulation of large masses of neutral fats and fatty acids in the lymph spaces. It was renamed Whipple’s disease in 1949. An infectious aetiology was suspected as early as Whipple’s initial report. However, successful treatment with antibiotics was not reported until 1952, which resulted in dramatic clinical responses. The cause is now known to be Tropheryma whipplei. Light and electron microscopy of infected tissue identified a gram-positive, non-acid-fast, periodic acid-Schiff (PAS) positive bacillus with a characteristic trilamellar plasma membrane resembling that of gram-negative bacteria. Whipple’s disease is extremely rare. It is a systemic infectious disorder affecting mostly middle-aged white men. The clinical presentation is often non-specific, which may make its diagnosis difficult. The four cardinal clinical manifestations are arthralgias, weight loss, diarrhoea and abdominal pain. The frequently vague articular symptoms can precede the diagnosis of Whipple’s disease by an average of 6–8 years. Lymph nodes and other tissues may present diagnostic problems, since the changes in routinely stained sections may mimic those of sarcoidosis. The detection of PAS-positive histiocytes in the small intestine remains the mainstay of the diagnosis, although Whipple’s disease without gastrointestinal involvement is described. We illustrate a case in which, retrospectively, the clinical presentation would have been typical for Whipple’s disease. However, the clinical presentation and the histological examinations of lymph nodes, liver biopsies and ascites initially were misinterpreted as sarcoidosis with consecutive immunosuppressive

Evaluation of Dietary Intake, Leisure-Time Physical Activity, and Metabolic Profile in Women with Mutation in the LMNA Gene.

PubMed

Monteiro, Luciana; Foss-Freitas, Maria Cristina; Navarro, Anderson; Pereira, Francisco; Coeli, Fernanda; Carneseca, Estela; Júnior, Renan Montenegro; Foss, Milton

2017-01-01

Familial partial lipodystrophy (FPL) is a rare genetic disorder characterized by selective lack of subcutaneous fat, which is associated with insulin-resistant diabetes. The Dunnigan variety (FPLD2) is caused by several missense mutations in the lamin A/C (LMNA) gene, most of which are typically located in exon 8 at the codon position 482. The aim of this study was to assess and compare the dietary intake, leisure-time physical activity (LTPA), and biochemical measurements (glucose, A1C, and plasma lipids) in women with FPLD2 and without (control group, CG) and to examine the associations between dietary intake and biochemical measurements (BM). LTPA was measured with a questionnaire and metabolic equivalent (MET) hours per week (hours/week) were calculated. Dietary intake by the 3-day recall method and clinical laboratory parameters were collected. Characteristics of women with FPLD2: 35.8 ± 13.9 years, fat mass = 10 ± 2.3 kg and fat free mass = 41.4 ± 4.5 kg (p < 0.05). Women with FPLD2 showed a smaller intake of energy (kcal), lipids, and carbohydrates and a large intake of protein (p < 0.01) compared to CG. Comparing the 2 groups in terms of LTPA, 78% of women with FPLD2 performed insufficient physical activity. In addition, they had a higher levels of glucose, A1C, and triglycerides (TG) and lower levels of high-density lipoprotein (HDL). There was no correlation between dietary intake and biochemical measurements. Women with FPLD2 have a lower intake of energy (kcal), lipids, and carbohydrates and greater changes in biochemical measurements. Because this is a rare disease, future studies are needed with encouragement of the practice of physical activity and of healthy eating habits, preventing the onset of diseases.

Efavirenz-induced gynecomastia in a prepubertal girl with human immunodeficiency virus infection: a case report

PubMed Central

2013-01-01

Background Prepubertal gynecomastia is a rare condition and most frequently classified as idiopathic. In HIV-infected adults gynecomastia is a recognised but infrequent side-effect of antiretroviral treatment (ART) and mostly attributed to efavirenz use. Gynecomastia should be distinguished from pseudogynecomastia as part of the lipodystrophy syndrome caused by Nucleoside Reverse Transcriptase Inhibitors (NRTIs) to avoid incorrect substitution of drugs. In the medical literature only five cases of prepubertal gynecomastia in children taking ART are described and underlying pathogenesis was unknown. The occurrence of adverse effects of ART may interfere with therapy adherence and long-term prognosis and for that reason requires attention. We report the first case of prepubertal gynecomastia in a young girl attributed to efavirenz use. Case presentation A seven-year-old African girl presented with true gynecomastia four months after initiation on ART (abacavir, lamivudine, efavirenz). History, physical examination and laboratory tests excluded known causes of gynecomastia and efavirenz was considered as the most likely cause. Six weeks after withdrawal of efavirenz the breast enlargement had completely resolved. Conclusions Efavirenz-induced gynecomastia may occur in children as well as in adults. With the increasing access to ART, the possibility of efavirenz-exposure and the potential occurrence of its associated side-effects may be high. In resource-poor settings, empirical change from efavirenz to nevirapine may be considered, providing no other known or alarming cause is identified, as efavirenz-induced gynecomastia can resolve quickly after withdrawal of the drug. Timely recognition of gynecomastia as a side-effect of efavirenz is important in order to intervene while the condition may still be reversible, to sustain adherence to ART and to maintain the sociopsychological health of the child. PMID:23941256

Efficacy of Metreleptin in Obese Patients With Type 2 Diabetes: Cellular and Molecular Pathways Underlying Leptin Tolerance

PubMed Central

Moon, Hyun-Seuk; Matarese, Giuseppe; Brennan, Aoife M.; Chamberland, John P.; Liu, Xiaowen; Fiorenza, Christina G.; Mylvaganam, Geetha H.; Abanni, Luisa; Carbone, Fortunata; Williams, Catherine J.; De Paoli, Alex M.; Schneider, Benjamin E.; Mantzoros, Christos S.

2011-01-01

OBJECTIVE Metreleptin has been efficacious in improving metabolic control in patients with lipodystrophy, but its efficacy has not been tested in obese patients with type 2 diabetes. RESEARCH DESIGN AND METHODS We studied the role of leptin in regulating the endocrine adaptation to long-term caloric deprivation and weight loss in obese diabetic subjects over 16 weeks in the context of a double-blinded, placebo–controlled, randomized trial. We then performed detailed interventional and mechanistic signaling studies in humans in vivo, ex vivo, and in vitro. RESULTS In obese patients with diabetes, metreleptin administration for 16 weeks did not alter body weight or circulating inflammatory markers but reduced HbA1c marginally (8.01 ± 0.93–7.96 ± 1.12, P = 0.03). Total leptin, leptin-binding protein, and antileptin antibody levels increased, limiting free leptin availability and resulting in circulating free leptin levels of ∼50 ng/mL. Consistent with clinical observations, all metreleptin signaling pathways studied in human adipose tissue and peripheral blood mononuclear cells were saturable at ∼50 ng/mL, with no major differences in timing or magnitude of leptin-activated STAT3 phosphorylation in tissues from male versus female or obese versus lean humans in vivo, ex vivo, or in vitro. We also observed for the first time that endoplasmic reticulum (ER) stress in human primary adipocytes inhibits leptin signaling. CONCLUSIONS In obese patients with diabetes, metreleptin administration did not alter body weight or circulating inflammatory markers but reduced HbA1c marginally. ER stress and the saturable nature of leptin signaling pathways play a key role in the development of leptin tolerance in obese patients with diabetes. PMID:21617185

Safety and efficacy of ritonavir and saquinavir in combination with zidovudine and lamivudine.

PubMed

Michelet, C; Bellissant, E; Ruffault, A; Arvieux, C; Delfraissy, J F; Raffi, F; Bazin, C; Renard, I; Sébille, V; Chauvin, J P; Dohin, E; Cartier, F

1999-06-01

Ritonavir is a potent inhibitor of cytochrome P4503A4 that strongly increases saquinavir bioavailability. In this study we assessed the safety and antiretroviral efficacy of the combination of these two compounds in patients pretreated and receiving continued treatment with zidovudine and lamivudine who were protease inhibitor naive and who had a CD4 cell counts below 200/mm3. In this 48-week pilot study, all patients received 600 mg ritonavir and 400 mg saquinavir twice daily. Administration of zidovudine and lamivudine was continued without a change in previous doses. Viral load, CD4 cell count, and the emergence of resistance to the two protease inhibitors were evaluated repeatedly up to week 48. Sixteen patients were included in the study. Previous nucleoside analog treatment duration was 48+/-22 months (mean +/- SD). Two patients quit taking both protease inhibitors within 2 weeks. The ritonavir dose had to be reduced in 10 other patients because of side effects. Between inclusion and week 48, plasma viremia varied from 4.87+/-0.43 to 3.00+/-1.29 log10 copies/mL and CD4 cell counts ranged from 98+/-61 to 250+/-139/mm3. Ten patients (63%) had viral loads below 200 copies/mL and 7 (44%) had viral loads below 50 copies/mL. A single key mutation that conferred ritonavir resistance I84V and V82A/V developed in two patients. A mutation at codon 54 developed in another patient. These mutations were associated with repeated cessations of antiretroviral treatment. No lipodystrophy was observed. Ritonavir and saquinavir in combination are quite well tolerated and induce a high and sustained antiretroviral efficacy. A four-drug combination that includes these two protease inhibitors should be considered as a first line of treatment in patients with low CD4 cell counts.

Leptin may enhance hepatic insulin sensitivity in children and women born small for gestational age

PubMed Central

Kistner, Anna; Vanpée, Mireille; Hall, Kerstin

2013-01-01

Objective Children born small for gestational age (SGA) are at risk for developing type 2 diabetes. Lipodystrophy leads to early type 2 diabetes and leptin reverses the metabolic consequences of the disease. Low IGF-binding protein 1 (IGFBP1) can predict the development of type 2 diabetes. The aim of this study was to determine leptin, insulin, and IGFBP1 in children and adult women born preterm or SGA to evaluate the role of leptin as a compensatory mechanism in insulin resistance development. Methods Seventy-six children (8.5–10 years, 41 girls and 35 boys) and 45 women (23–30 years) were studied. The children comprised subjects born appropriate for gestational age (<30 gestational weeks) (n=22), born SGA at term (n=23), and full-term normal-weight controls (n=31). Among the women, the corresponding figures were, n=10, n=18, and n=17 respectively. Fasting levels of IGFBP1, leptin, insulin, and IGF1 were determined and total adiponectin only in women. Results In girls and women, term SGA subjects had higher leptin levels in relation to BMI SDS (P=0.042 and P=0.03 respectively). More than half of IGFBP1 variability was explained by leptin and insulin in children. In term SGA women, IGFBP1 level was lower compared with controls (P=0.012) and the regression line of IGFBP1 on insulin was suppressed below −1 s.d. of a reference material. Conclusion Leptin levels were elevated in term SGA girls and women, in particular in adult women, but not found in preterm girls and women. IGFBP1 was lower in term SGA women. In children, leptin and insulin were strong suppressors of IGFBP1. We speculate that higher leptin levels could be a protective event to enhance hepatic insulin sensitivity. PMID:23781317

Ultrasound Detection of Soft Tissue Abscesses Performed by Non-Physician U.S. Army Medical Providers Naïve to Diagnostic Sonography.

PubMed

LaDuke, Mike; Monti, Jon; Cronin, Aaron; Gillum, Bart

2017-03-01

Patients commonly present to emergency rooms and primary care clinics with cellulitic skin infections with or without abscess formation. In military operational units, non-physician medical personnel provide most primary and initial emergency medical care. The objective of this study was to determine if, after minimal training, Army physician assistants and medics could use portable ultrasound (US) machines to detect superficial soft tissue abscesses. This was a single-blinded, randomized, prospective observational study conducted over the course of 2 days at a military installation. Active duty military physician assistants and medics with little or no US experience were recruited as participants. They received a short block of training on abscess detection using both clinical examination skills (inspection/palpation) and US examination. The participants were then asked to provide a yes/no answer regarding abscess presence in a chicken tissue model. Results were analyzed to assess the participants' abilities to detect abscesses, compare the diagnostic accuracy of their clinical examinations with their US examinations, and assess how often US results changed treatment plans initially on the basis of clinical examination findings alone. 22 participants performed a total of 220 clinical examinations and 220 US scans on 10 chicken tissue abscess models. Clinical examination for abscess detection yielded a sensitivity of 73.5% (95% confidence interval [CI], 65.3-80.3%) and a specificity of 77.2% (95% CI, 67.4-84.9%), although US examination for abscess detection yielded a sensitivity of 99.2% (95% CI, 95.4-99.9%) and a specificity of 95.5% (95% CI, 88.5-98.6%). Clinical examination yielded a diagnostic accuracy of 75.0% (95% CI, 68.9-80.3) although US examination yielded a diagnostic accuracy of 97.7% (95% CI, 94.6-99.2%), a difference in accuracy of 22.7% favoring US (p < 0.01). US changed the diagnosis in 56 of 220 cases (25.4% of all cases, p = 0.02). Of these 56

Comparison of regional fat measurements by dual-energy X-ray absorptiometry and conventional anthropometry and their association with markers of diabetes and cardiovascular disease risk

PubMed Central

Vasan, S K; Osmond, C; Canoy, D; Christodoulides, C; Neville, M J; Di Gravio, C; Fall, C H D; Karpe, F

2018-01-01

Background/Objectives: Fat distribution is a strong and independent predictor of type 2 diabetes (T2D) and cardiovascular disease (CVD) and is usually determined using conventional anthropometry in epidemiological studies. Dual-energy X-ray absorptiometry (DXA) can measure total and regional adiposity more accurately. Nonetheless, whether DXA provides more precise estimates of cardiovascular risk in relation to total and regional adiposity is not known. We determined the strength of the associations between DXA- and conventional anthropometry determined fat distribution and T2D and CVD risk markers. Subjects/Methods: Waist (WC) and hip circumference (HC) and DXA was used to measure total and regional adiposity in 4950 (2119 men) participants aged 29–55 years from the Oxford Biobank without pre-existing T2D or CVD. Cross-sectional associations were compared between WC and HC vs. DXA-determined regional adiposity (all z-score normalised) with impaired fasting glucose, hypertriglyceridemia, hypertension and insulin resistance (IR). Results: Following adjustment for total adiposity, upper body adiposity measurements showed consistently increased risk of T2D and CVD risk markers except for abdominal subcutaneous fat in both sexes, and arm fat in men, which showed protective associations. Among upper adiposity depots, visceral fat mass showed stronger odds ratios (OR) ranging from 1.69 to 3.64 compared with WC 1.07–1.83. Among lower adiposity depots, HC showed modest protection for IR in both sexes (men: OR 0.80 (95% confidence interval 0.67, 0.96); women: 0.69 (0.56, 0.86)), whereas gynoid fat and in particular leg fat showed consistent and strong protective effects for all outcomes in both men and women. The differential effect of body fat distribution on CVD and T2D were more pronounced at higher levels of total adiposity. Conclusions: Compared with DXA, conventional anthropometry underestimates the associations of regional adiposity with T2D and CVD risk markers

Asymptomatic Achilles tendon pathology is associated with a central fat distribution in men and a peripheral fat distribution in women: a cross sectional study of 298 individuals

PubMed Central

2010-01-01

Background Adiposity is a modifiable factor that has been implicated in tendinopathy. As tendon pain reduces physical activity levels and can lead to weight gain, associations between tendon pathology and adiposity must be studied in individuals without tendon pain. Therefore, the purpose of this study was to determine whether fat distribution was associated with asymptomatic Achilles tendon pathology. Methods The Achilles tendons of 298 individuals were categorised as normal or pathological using diagnostic ultrasound. Fat distribution was determined using anthropometry (waist circumference, waist hip ratio [WHR]) and dual-energy x-ray absorptiometry. Results Asymptomatic Achilles tendon pathology was more evident in men (13%) than women (5%) (p = 0.007). Men with tendon pathology were older (50.9 ± 10.4, 36.3 ± 11.3, p < 0.001), had greater WHR (0.926 ± 0.091, 0.875 ± 0.065, p = 0.039), higher android/gynoid fat mass ratio (0.616 ± 0.186, 0.519 ± 0.142, p = 0.014) and higher upper-body/lower body fat mass ratio (2.346 ± 0.630, 2.022 ± 0.467, p = 0.013). Men older than 40 years with a waist circumference >83 cm had the greatest prevalence of tendon pathology (33%). Women with tendon pathology were older (47.4 ± 10.0, 36.0 ± 10.3, p = 0.008), had less total fat (17196 ± 3173 g, 21626 ± 7882 g, p = 0.009), trunk fat (7367 ± 1662 g, 10087 ± 4152 g, p = 0.003) and android fat (1117 ± 324 g, 1616 ± 811 g, p = 0.005). They had lower central/peripheral fat mass ratios (0.711 ± 0.321 g, 0.922 ± 0.194 g, p = 0.004) than women with normal tendons. Women with tendon pathology were more often menopausal (63%, 13%, p = 0.002). Conclusions Men with Achilles tendon pathology were older and had a central fat distribution. Women with tendon pathology were older and had a peripheral fat distribution. An interaction between age and waist circumference was observed among men. PMID:20196870

HIV lipodystrophy in participants randomised to lopinavir/ritonavir (LPV/r) +2-3 nucleoside/nucleotide reverse transcriptase inhibitors (N(t)RTI) or LPV/r + raltegravir as second-line antiretroviral therapy.

PubMed

Martin, Allison; Moore, Cecilia L; Mallon, Patrick W G; Hoy, Jennifer F; Emery, Sean; Belloso, Waldo H; Phanuphak, Praphan; Ferret, Samuel; Cooper, David A; Boyd, Mark A

2013-01-01

To compare changes over 48 weeks in body fat, lipids, Metabolic Syndrome and cardiovascular disease risk between patients randomised 1:1 to lopinavir/ritonavir (r/LPV) plus raltegravir (RAL) compared to r/LPV plus 2-3 nucleoside/nucleotide reverse transcriptase inhibitors (N(t)RTIs) as second-line therapy. Participants were HIV-1 positive (>16 years) failing first-line treatment (2 consecutive HIV RNA >500 copies/mL) of NNRTI +2N(t)RTI. Whole body dual energy x-ray absorptiometry was performed at baseline and week 48. Data were obtained to calculate the Metabolic Syndrome and Framingham cardiovascular disease (CVD) risk score. Linear regression was used to compare mean differences between arms. Logistic regression compared incidence of metabolic syndrome. Associations between percent limb fat changes at 48 weeks with baseline variables were assessed by backward stepwise multivariate linear regression. Analyses were adjusted for gender, body mass index and smoking status. 210 participants were randomised. The mean (95% CI) increase in limb fat over 48 weeks was 15.7% (5.3, 25.9) or 0.9 kg (0.2, 1.5) in the r/LPV+N(t)RTI arm and 21.1% (11.1, 31,1) or 1.3 kg (0.7, 1.9) in the r/LPV+RAL arm, with no significant difference between treatment arms (-5.4% [-0.4 kg], p>0.1). Increases in total body fat mass (kg) and trunk fat mass (kg) were also similar between groups. Total:HDL cholesterol ratio was significantly higher in the RAL arm (mean difference -0.4 (1.4); p = 0.03), there were no other differences in lipid parameters between treatment arms. There were no statistically significant differences in CVD risk or incidence of Metabolic Syndrome between the two treatment arms. The baseline predictors of increased limb fat were high viral load, high insulin and participant's not taking lipid lowering treatment. In patients switching to second line therapy, r/LPV combined with RAL demonstrated similar improvements in limb fat as an N(t)RTI + r/LPV regimen, but a worse total:HDL cholesterol ratio over 48 weeks. This clinical trial is registered on Clinicaltrials.gov, registry number NCT00931463 http://clinicaltrials.gov/ ct2/show/NCT00931463?term = NCT00931463&rank = 1.

WZB117 (2-Fluoro-6-(m-hydroxybenzoyloxy) Phenyl m-Hydroxybenzoate) Inhibits GLUT1-mediated Sugar Transport by Binding Reversibly at the Exofacial Sugar Binding Site.

PubMed

Ojelabi, Ogooluwa A; Lloyd, Kenneth P; Simon, Andrew H; De Zutter, Julie K; Carruthers, Anthony

2016-12-23

WZB117 (2-fluoro-6-(m-hydroxybenzoyloxy) phenyl m-hydroxybenzoate) inhibits passive sugar transport in human erythrocytes and cancer cell lines and, by limiting glycolysis, inhibits tumor growth in mice. This study explores how WZB117 inhibits the erythrocyte sugar transporter glucose transport protein 1 (GLUT1) and examines the transporter isoform specificity of inhibition. WZB117 reversibly and competitively inhibits erythrocyte 3-O-methylglucose (3MG) uptake with K i (app) = 6 μm but is a noncompetitive inhibitor of sugar exit. Cytochalasin B (CB) is a reversible, noncompetitive inhibitor of 3MG uptake with K i (app) = 0.3 μm but is a competitive inhibitor of sugar exit indicating that WZB117 and CB bind at exofacial and endofacial sugar binding sites, respectively. WZB117 inhibition of GLUTs expressed in HEK293 cells follows the order of potency: insulin-regulated GLUT4 ≫ GLUT1 ≈ neuronal GLUT3. This may explain WZB117-induced murine lipodystrophy. Molecular docking suggests the following. 1) The WZB117 binding envelopes of exofacial GLUT1 and GLUT4 conformers differ significantly. 2) GLUT1 and GLUT4 exofacial conformers present multiple, adjacent glucose binding sites that overlap with WZB117 binding envelopes. 3) The GLUT1 exofacial conformer lacks a CB binding site. 4) The inward GLUT1 conformer presents overlapping endofacial WZB117, d-glucose, and CB binding envelopes. Interrogating the GLUT1 mechanism using WZB117 reveals that subsaturating WZB117 and CB stimulate erythrocyte 3MG uptake. Extracellular WZB117 does not affect CB binding to GLUT1, but intracellular WZB117 inhibits CB binding. These findings are incompatible with the alternating conformer carrier for glucose transport but are consistent with either a multisubunit, allosteric transporter, or a transporter in which each subunit presents multiple, interacting ligand binding sites. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

HIV-associated fatigue in the era of highly active antiretroviral therapy: novel biological mechanisms?

PubMed

Payne, B A I; Hateley, C L; Ong, E L C; Premchand, N; Schmid, M L; Schwab, U; Newton, J L; Price, D A

2013-04-01

The aim of the study was to determine the prevalence and risk factors for HIV-associated fatigue in the era of highly active antiretroviral therapy (HAART). A cross-sectional survey of 100 stable HIV-infected out-patients was carried out. Severity of fatigue was measured using the Fatigue Impact Scale (FIS). Symptoms of orthostatic intolerance (dysautonomia) were evaluated using the Orthostatic Grading Scale (OGS). Data for HIV-infected patients were compared with those for 166 uninfected controls and 74 patients with chronic fatigue syndrome (CFS)/myalgic encephalomyelitis (encephalopathy) (ME). Ninety-one per cent of HIV-infected patients were on HAART and 78% had suppressed plasma HIV viral load (≤ 40 HIV-1 RNA copies/mL). Fifty-one per cent of HIV-infected patients reported excessive symptomatic fatigue (FIS ≥ 40), and 28% reported severe fatigue symptoms (FIS ≥ 80). The mean FIS score among HIV-infected patients was 50.8 [standard deviation (SD) 41.9] compared with 13.0 (SD 17.6) in uninfected control subjects, and 92.9 (SD 29.0) in CFS patients (P < 0.001 for comparison of HIV-infected patients and uninfected controls). Among HIV-infected patients, fatigue severity was not significantly associated with current or nadir CD4 lymphocyte count, HIV plasma viral load, or whether on HAART. Prior dideoxynucleoside analogue (d-drug) exposure (P = 0.016) and the presence of clinical lipodystrophy syndrome (P = 0.011) were associated with fatigue. Additionally, fatigue severity correlated strongly with symptomatic orthostatic intolerance (r = 0.65; P < 0.001). Fatigue is very common and often severe in HIV-infected out-patients, despite viral suppression and good immune function. In a subgroup of patients, prior d-drug exposure may contribute to fatigue, suggesting a metabolic basis. Dysautonomia may also drive fatigue associated with HIV infection, as in other chronic diseases, and CFS/ME, and should be further evaluated with the potential for a shared

Adipose Tissue Is a Neglected Viral Reservoir and an Inflammatory Site during Chronic HIV and SIV Infection

PubMed Central

Damouche, Abderaouf; Huot, Nicolas; Dejucq-Rainsford, Nathalie; Satie, Anne-Pascale; Mélard, Adeline; David, Ludivine; Gommet, Céline; Ghosn, Jade; Noel, Nicolas; Pourcher, Guillaume; Martinez, Valérie; Benoist, Stéphane; Béréziat, Véronique; Cosma, Antonio; Favier, Benoit; Vaslin, Bruno; Rouzioux, Christine; Capeau, Jacqueline; Müller-Trutwin, Michaela; Dereuddre-Bosquet, Nathalie; Le Grand, Roger; Lambotte, Olivier; Bourgeois, Christine

2015-01-01

Two of the crucial aspects of human immunodeficiency virus (HIV) infection are (i) viral persistence in reservoirs (precluding viral eradication) and (ii) chronic inflammation (directly associated with all-cause morbidities in antiretroviral therapy (ART)-controlled HIV-infected patients). The objective of the present study was to assess the potential involvement of adipose tissue in these two aspects. Adipose tissue is composed of adipocytes and the stromal vascular fraction (SVF); the latter comprises immune cells such as CD4+ T cells and macrophages (both of which are important target cells for HIV). The inflammatory potential of adipose tissue has been extensively described in the context of obesity. During HIV infection, the inflammatory profile of adipose tissue has been revealed by the occurrence of lipodystrophies (primarily related to ART). Data on the impact of HIV on the SVF (especially in individuals not receiving ART) are scarce. We first analyzed the impact of simian immunodeficiency virus (SIV) infection on abdominal subcutaneous and visceral adipose tissues in SIVmac251 infected macaques and found that both adipocytes and adipose tissue immune cells were affected. The adipocyte density was elevated, and adipose tissue immune cells presented enhanced immune activation and/or inflammatory profiles. We detected cell-associated SIV DNA and RNA in the SVF and in sorted CD4+ T cells and macrophages from adipose tissue. We demonstrated that SVF cells (including CD4+ T cells) are infected in ART-controlled HIV-infected patients. Importantly, the production of HIV RNA was detected by in situ hybridization, and after the in vitro reactivation of sorted CD4+ T cells from adipose tissue. We thus identified adipose tissue as a crucial cofactor in both viral persistence and chronic immune activation/inflammation during HIV infection. These observations open up new therapeutic strategies for limiting the size of the viral reservoir and decreasing low-grade chronic

Nuclear lamina genetic variants, including a truncated LAP2, in twins and siblings with nonalcoholic fatty liver disease.

PubMed

Brady, Graham F; Kwan, Raymond; Ulintz, Peter J; Nguyen, Phirum; Bassirian, Shirin; Basrur, Venkatesha; Nesvizhskii, Alexey I; Loomba, Rohit; Omary, M Bishr

2018-05-01

Nonalcoholic fatty liver disease (NAFLD) is becoming the major chronic liver disease in many countries. Its pathogenesis is multifactorial, but twin and familial studies indicate significant heritability, which is not fully explained by currently known genetic susceptibility loci. Notably, mutations in genes encoding nuclear lamina proteins, including lamins, cause lipodystrophy syndromes that include NAFLD. We hypothesized that variants in lamina-associated proteins predispose to NAFLD and used a candidate gene-sequencing approach to test for variants in 10 nuclear lamina-related genes in a cohort of 37 twin and sibling pairs: 21 individuals with and 53 without NAFLD. Twelve heterozygous sequence variants were identified in four lamina-related genes (ZMPSTE24, TMPO, SREBF1, SREBF2). The majority of NAFLD patients (>90%) had at least one variant compared to <40% of controls (P < 0.0001). When only insertions/deletions and changes in conserved residues were considered, the difference between the groups was similarly striking (>80% versus <25%; P < 0.0001). Presence of a lamina variant segregated with NAFLD independently of the PNPLA3 I148M polymorphism. Several variants were found in TMPO, which encodes the lamina-associated polypeptide-2 (LAP2) that has not been associated with liver disease. One of these, a frameshift insertion that generates truncated LAP2, abrogated lamin-LAP2 binding, caused LAP2 mislocalization, altered endogenous lamin distribution, increased lipid droplet accumulation after oleic acid treatment in transfected cells, and led to cytoplasmic association with the ubiquitin-binding protein p62/SQSTM1. Several variants in nuclear lamina-related genes were identified in a cohort of twins and siblings with NAFLD; one such variant, which results in a truncated LAP2 protein and a dramatic phenotype in cell culture, represents an association of TMPO/LAP2 variants with NAFLD and underscores the potential importance of the nuclear lamina in NAFLD

Paradoxical adipose hyperplasia secondary to cryolipolysis: An underreported entity?

PubMed

Singh, Selina M; Geddes, Elizabeth R C; Boutrous, Sean G; Galiano, Robert D; Friedman, Paul M

2015-08-01

avoided, or even utilized as a therapeutic alternative for the treatment of congenital or acquired lipodystrophy. © 2015 Wiley Periodicals, Inc.

Prokineticin Receptor‐1 Is a New Regulator of Endothelial Insulin Uptake and Capillary Formation to Control Insulin Sensitivity and Cardiovascular and Kidney Functions

PubMed Central

Dormishian, Mojdeh; Turkeri, Gulen; Urayama, Kyoji; Nguyen, Thu Lan; Boulberdaa, Mounia; Messaddeq, Nadia; Renault, Gilles; Henrion, Daniel; Nebigil, Canan G.

2013-01-01

Background Reciprocal relationships between endothelial dysfunction and insulin resistance result in a vicious cycle of cardiovascular, renal, and metabolic disorders. The mechanisms underlying these impairments are unclear. The peptide hormones prokineticins exert their angiogenic function via prokineticin receptor‐1 (PKR1). We explored the extent to which endothelial PKR1 contributes to expansion of capillary network and the transcapillary passage of insulin into the heart, kidney, and adipose tissues, regulating organ functions and metabolism in a specific mice model. Methods and Results By combining cellular studies and studies in endothelium‐specific loss‐of‐function mouse model (ec‐PKR1−/−), we showed that a genetically induced PKR1 loss in the endothelial cells causes the impaired capillary formation and transendothelial insulin delivery, leading to insulin resistance and cardiovascular and renal disorders. Impaired insulin delivery in endothelial cells accompanied with defective expression and activation of endothelial nitric oxide synthase in the ec‐PKR1−/− aorta, consequently diminishing endothelium‐dependent relaxation. Despite having a lean body phenotype, ec‐PKR1−/− mice exhibited polyphagia, polydipsia, polyurinemia, and hyperinsulinemia, which are reminiscent of human lipodystrophy. High plasma free fatty acid levels and low leptin levels further contribute to the development of insulin resistance at the later age. Peripheral insulin resistance and ectopic lipid accumulation in mutant skeletal muscle, heart, and kidneys were accompanied by impaired insulin‐mediated Akt signaling in these organs. The ec‐PKR1−/− mice displayed myocardial fibrosis, low levels of capillary formation, and high rates of apoptosis, leading to diastolic dysfunction. Compact fibrotic glomeruli and high levels of phosphate excretion were found in mutant kidneys. PKR1 restoration in ec‐PKR1−/− mice reversed the decrease in capillary

A pharmacovigilance study of adults on highly active antiretroviral therapy, South Africa: 2007 - 2011.

PubMed

Dube, Nomathemba Michell; Summers, Robert; Tint, Khin-San; Mayayise, Guistee

2012-01-01

Of the 1.6 million South African people infected with human immunodeficiency virus (HIV), approximately 970,000 (55%) have been initiated on HAART. Despite these numbers, very little has been published about the safety profile of antiretroviral (ARV) medicines in the country. This study was performed at the Medunsa National Pharmacovigilance Centre and aimed to describe the demographic characteristics of patients enrolled in the pharmacovigilance surveillance study; highly active antiretroviral therapy (HAART) initiation regimen patterns; reasons for regimen changes; and adverse effects of ARV medicines. A cohort study of HIV-infected individuals aged 15 years or older who were on ARV medicines was conducted at four sentinel sites. After HAART initiation, with an average lapse of 17.8 months (range: 0 - 83.8 months), 2,815 patients were enrolled into the study. Results show that patients were observed for 1,606.2 person-years for pharmacy visits (collection of ARV medicines) and 817.1 person-years for clinical visits (consultation with the doctor). Females constituted 69.6% (1,958/2,815) of the study population. Almost all patients initiated HAART on first-line regimens (2,801/2,815). Some patients (6.7%, 190/2,815) dropped out of the study after HAART initiation. Reasons for regimen changes were not recorded for 2.5% (22/891) of the patients who changed regimens. The primary reason for regimen changes was drug-related toxicity (76.1%, 678/891), mostly evident in patients taking first-line regimens. Adverse effects experienced by patients were polyneuropathy (24.0%, 163/678); lipodystrophy (23.9%, 162/678); neuropathy (10.6%, 72/678); and suspected lactic acidosis (3.8%, 26/678). The majority of prescribers complied with the HAART guidelines and initiated most patients on first-line regimens. However, adverse effects are evident in patients taking first-line regimens. We recommend that the Department of Health should introduce less toxic first-line ARV regimens

Antiretroviral therapy related adverse effects: Can sub-Saharan Africa cope with the new "test and treat" policy of the World Health Organization?

PubMed

Nansseu, Jobert Richie N; Bigna, Jean Joel R

2017-02-15

Recent studies have shown that early antiretroviral therapy (ART) initiation results in significant HIV transmission reduction. This is the rationale behind the "test and treat" policy of the World Health Organization (WHO). Implementation of this policy will lead to an increased incidence of ART-related adverse effects, especially in sub-Saharan Africa (SSA). Is the region yet ready to cope with such a challenging issue? The introduction and widespread use of ART have drastically changed the natural history of HIV/AIDS, but exposure to ART leads to serious medication-related adverse effects mainly explained by mitochondrial toxicities, and the situation will get worse in the near future. Indeed, ART is associated with an increased risk of developing cardiovascular disease, lipodystrophy, prediabetes and overt diabetes, insulin resistance and hyperlactatemia/lactic acidosis. The prevalence of these disorders is already high in SSA, and the situation will be exacerbated by the implementation of the new WHO recommendations. Most SSA countries are characterized by (extreme) poverty, very weak health systems, inadequate and low quality of health services, inaccessibility to existing health facilities, lack of (qualified) health personnel, lack of adequate equipment, inaccessibility and unaffordability of medicines, and heavy workload in a context of a double burden of disease. Additionally, there is dearth of data on the incidence and predictive factors of ART-related adverse effects in SSA, to anticipate on strategies that should be put in place to prevent the occurrence of these conditions or properly estimate the upcoming burden and prepare an adequate response plan. These are required if we are to anticipate and effectively prevent this upcoming burden. While SSA would be the first region to experience the huge benefits of implementing the "test and treat" policy of the WHO, the region is not yet prepared to manage the consequential increased burden of ART

HIV replication enhances production of free fatty acids, low density lipoproteins and many key proteins involved in lipid metabolism: a proteomics study.

PubMed

Rasheed, Suraiya; Yan, Jasper S; Lau, Alex; Chan, Arvan S

2008-08-20

HIV-infected patients develop multiple metabolic abnormalities including insulin resistance, lipodystrophy and dyslipidemia. Although progression of these disorders has been associated with the use of various protease inhibitors and other antiretroviral drugs, HIV-infected individuals who have not received these treatments also develop lipid abnormalities albeit to a lesser extent. How HIV alters lipid metabolism in an infected cell and what molecular changes are affected through protein interaction pathways are not well-understood. Since many genetic, epigenetic, dietary and other factors influence lipid metabolism in vivo, we have chosen to study genome-wide changes in the proteomes of a human T-cell line before and after HIV infection in order to circumvent computational problems associated with multiple variables. Four separate experiments were conducted including one that compared 14 different time points over a period of >3 months. By subtractive analyses of protein profiles overtime, several hundred differentially expressed proteins were identified in HIV-infected cells by mass spectrometry and each protein was scrutinized for its biological functions by using various bioinformatics programs. Herein, we report 18 HIV-modulated proteins and their interaction pathways that enhance fatty acid synthesis, increase low density lipoproteins (triglycerides), dysregulate lipid transport, oxidize lipids, and alter cellular lipid metabolism. We conclude that HIV replication alone (i.e. without any influence of antiviral drugs, or other human genetic factors), can induce novel cellular enzymes and proteins that are significantly associated with biologically relevant processes involved in lipid synthesis, transport and metabolism (p = <0.0002-0.01). Translational and clinical studies on the newly discovered proteins may now shed light on how some of these proteins may be useful for early diagnosis of individuals who might be at high risk for developing lipid

Identifying sex-specific risk factors for low bone mineral density in adolescent runners.

PubMed

Tenforde, Adam Sebastian; Fredericson, Michael; Sayres, Lauren Carter; Cutti, Phil; Sainani, Kristin Lynn

2015-06-01

Adolescent runners may be at risk for low bone mineral density (BMD) associated with sports participation. Few prior investigations have evaluated bone health in young runners, particularly males. To characterize sex-specific risk factors for low BMD in adolescent runners. Cross-sectional study; Level of evidence, 3. Training characteristics, fracture history, eating behaviors and attitudes, and menstrual history were measured using online questionnaires. A food frequency questionnaire was used to identify dietary patterns and measure calcium intake. Runners (female: n = 94, male: n = 42) completed dual-energy x-ray absorptiometry (DXA) to measure lumbar spine (LS) and total body less head (TBLH) BMD and body composition values, including android-to-gynoid (A:G) fat mass ratio. The BMD was standardized to Z-scores using age, sex, and race/ethnicity reference values. Questionnaire values were combined with DXA values to determine risk factors associated with differences in BMD Z-scores in LS and TBLH and low bone mass (defined as BMD Z-score ≤-1). In multivariable analyses, risk factors for lower LS BMD Z-scores in girls included lower A:G ratio, being shorter, and the combination of (interaction between) current menstrual irregularity and a history of fracture (all P < .01). Later age of menarche, lower A:G ratio, lower lean mass, and drinking less milk were associated with lower TBLH BMD Z-scores (P < .01). In boys, lower body mass index (BMI) Z-scores and the belief that being thinner improves performance were associated with lower LS and TBLH BMD Z-scores (all P < .05); lower A:G ratio was additionally associated with lower TBLH Z-scores (P < .01). Thirteen girls (14%) and 9 boys (21%) had low bone mass. Girls with a BMI ≤17.5 kg/m(2) or both menstrual irregularity and a history of fracture were significantly more likely to have low bone mass. Boys with a BMI ≤17.5 kg/m(2) and belief that thinness improves performance were significantly more likely to have

Serum Adipokines and Adipose Tissue Distribution in Rheumatoid Arthritis and Ankylosing Spondylitis. A Comparative Study

PubMed Central

Toussirot, Éric; Grandclément, Émilie; Gaugler, Béatrice; Michel, Fabrice; Wendling, Daniel; Saas, Philippe; Dumoulin, Gilles

2013-01-01

Rheumatoid arthritis (RA) and ankylosing spondylitis (AS) are inflammatory rheumatic diseases that may modify body composition. Adipose tissue has the ability to release a wide range of products involved in physiologic functions, but also in various pathological processes, including the inflammatory/immune response. RA and AS are both associated with the development of cardiovascular complications. It is has been established that central/abdominal, and particularly intra-abdominal or visceral adiposity is closely linked to cardiovascular events. Thus, in this study, we aimed to evaluate the body composition of patients with RA or AS compared to healthy controls (HC), with a special emphasis on the visceral region. In parallel, we measured adipose products or adipokines, namely leptin, adiponectin and its high molecular weight (HMW) isoform, resistin, and ghrelin, a gastric peptide that plays a role in energetic balance. The homeostasis model assessment for insulin resistance (HOMA-IR) and atherogenic index were used to evaluate cardiovascular risk. One hundred and twelve subjects were enrolled (30 patients with RA, 31 with AS, and 51 HC). Body composition was measured using dual-energy X-ray absorptiometry to determine total fat mass and lean mass, adiposity, fat in the android and gynoid regions, and visceral fat. Patients and HC did not differ in terms of body mass index. On the contrary, adiposity was increased in RA (p = 0.01) while visceral fat was also increased, but only in women (p = 0.01). Patients with AS tended to have lower total fat mass (p = 0.07) and higher lean mass compared to HC (p = 0.07). Leptin and leptin/fat mass were decreased in male patients with AS (p < 0.01), while total adiponectin and the ratio of HMW to total adiponectin were both increased in RA (p < 0.01). There were no changes in serum resistin and ghrelin in any group of patients. HOMA-IR and the atherogenic index were not modified in RA and AS. These

Serum adipokines and adipose tissue distribution in rheumatoid arthritis and ankylosing spondylitis. A comparative study.

PubMed

Toussirot, Eric; Grandclément, Emilie; Gaugler, Béatrice; Michel, Fabrice; Wendling, Daniel; Saas, Philippe; Dumoulin, Gilles

2013-01-01

Rheumatoid arthritis (RA) and ankylosing spondylitis (AS) are inflammatory rheumatic diseases that may modify body composition. Adipose tissue has the ability to release a wide range of products involved in physiologic functions, but also in various pathological processes, including the inflammatory/immune response. RA and AS are both associated with the development of cardiovascular complications. It is has been established that central/abdominal, and particularly intra-abdominal or visceral adiposity is closely linked to cardiovascular events. Thus, in this study, we aimed to evaluate the body composition of patients with RA or AS compared to healthy controls (HC), with a special emphasis on the visceral region. In parallel, we measured adipose products or adipokines, namely leptin, adiponectin and its high molecular weight (HMW) isoform, resistin, and ghrelin, a gastric peptide that plays a role in energetic balance. The homeostasis model assessment for insulin resistance (HOMA-IR) and atherogenic index were used to evaluate cardiovascular risk. One hundred and twelve subjects were enrolled (30 patients with RA, 31 with AS, and 51 HC). Body composition was measured using dual-energy X-ray absorptiometry to determine total fat mass and lean mass, adiposity, fat in the android and gynoid regions, and visceral fat. Patients and HC did not differ in terms of body mass index. On the contrary, adiposity was increased in RA (p = 0.01) while visceral fat was also increased, but only in women (p = 0.01). Patients with AS tended to have lower total fat mass (p = 0.07) and higher lean mass compared to HC (p = 0.07). Leptin and leptin/fat mass were decreased in male patients with AS (p < 0.01), while total adiponectin and the ratio of HMW to total adiponectin were both increased in RA (p < 0.01). There were no changes in serum resistin and ghrelin in any group of patients. HOMA-IR and the atherogenic index were not modified in RA and AS. These

Impact of Vitamin D Supplementation during Lactation on Vitamin D Status and Body Composition of Mother-Infant Pairs: A MAVID Randomized Controlled Trial

PubMed Central

Czech-Kowalska, Justyna; Latka-Grot, Julita; Bulsiewicz, Dorota; Jaworski, Maciej; Pludowski, Pawel; Wygledowska, Grazyna; Chazan, Bogdan; Pawlus, Beata; Zochowska, Anna; Borszewska-Kornacka, Maria K.; Karczmarewicz, Elzbieta; Czekuc-Kryskiewicz, Edyta; Dobrzanska, Anna

2014-01-01

Objective The optimal vitamin D intake for nursing women is controversial. Deterioration, at least in bone mass, is reported during lactation. This study evaluated whether vitamin D supplementation during lactation enhances the maternal and infant’s vitamin D status, bone mass and body composition. Design and Methods After term delivery, 174 healthy mothers were randomized to receive 1200 IU/d (800 IU/d+400 IU/d from multivitamins) or 400 IU/d (placebo+400 IU/d from multivitamins) of cholecalciferol for 6 months while breastfeeding. All infants received 400 IU/d of cholecalciferol. Serum 25-hydroxyvitamin D [25(OH)D], iPTH, calcium, urinary calcium, and densitometry were performed in mother-offspring pairs after delivery, and at 3 and 6 months later. Results A total of 137 (79%) (n = 70; 1200 IU/d, n = 67; 400 IU/d) completed the study. 25(OH)D was similar in both groups at baseline (13.7 ng/ml vs. 16.1 ng/ml; P = 0.09) and at 3 months (25.7 ng/ml vs. 24.5 ng/ml; P = 0.09), but appeared higher in the 1200 IU/d group at 6 months of supplementation (25.6 ng/ml vs. 23.1 ng/ml; P = 0.009). The prevalence of 25(OH)D <20 ng/ml was comparable between groups at baseline (71% vs. 64%, P = 0.36) but lower in the 1200 IU/d group after 3 months (9% vs. 25%, P = 0.009) and 6 months (14% vs. 30%, P = 0.03). Maternal and infants’ iPTH, calciuria, bone mass and body composition as well as infants’ 25(OH)D levels were not significantly different between groups during the study. Significant negative correlations were noted between maternal 25(OH)D and fat mass (R = −0.49, P = 0.00001), android fat mass (R = −0.53, P = 0.00001), and gynoid fat mass (R = −0.43, P = 0.00001) after 6 months of supplementation. Conclusions Vitamin D supplementation at a dose of 400 IU/d was not sufficient to maintain 25(OH)D >20 ng/ml in nursing women, while 1200 IU/d appeared more effective, but had no effect on breastfed offspring

Treatment of metabolic syndrome.

PubMed

Wagh, Arati; Stone, Neil J

2004-03-01

should be considered in those with at least a 10% risk of a coronary event over 10 years. Finally, three related conditions, nonalcoholic fatty liver disease, polycystic ovary syndrome and protease inhibitor associated lipodystrophy improve with therapeutic lifestyle change. Although metformin is shown to be useful with polycystic ovary syndrome, the data supporting drug therapy for the other syndromes is less convincing. More robust studies are needed before any firm recommendations can be made.

Indian Adolescent Living with HIV-AIDS: Current Clinical Scenario.

PubMed

Joshi, Kavita S; Bhaware, Bhushan D; Pazare, Amar R

2017-07-01

count. Indian adolescent receiving long term ART, Lipodystrophy is not a troubling issue. Indian adolescent seems to be more tolerance of ART than the other parts of world.

Lipid-lowering therapy in HIV-infected patients: relationship with antiretroviral agents and impact of substance-related disorders

PubMed Central

Bednasz, Cindy; Zingman, Barry S.; Luque, Amneris E.; Fischl, Margaret A.; Gripshover, Barbara M.; Venuto, Charles S.; Gu, Jie; Feng, Zekun; DiFrancesco, Robin; Morse, Gene D.; Ma, Qing

2016-01-01

BACKGROUND The use of combination antiretroviral therapy (cART) has significantly decreased the morbidity and mortality associated with HIV infection. Lipid disorders, including lipodystrophy, hypertriglyceridemia, hypercholesterolemia, and dyslipidemia, remain the most commonly reported metabolic disorders among those treated with long-term cART. Mounting evidence suggests an association between drug abuse and poor glycemic control and diabetes complications. Substance related disorders (SRD) may increase the risk of metabolic syndrome. MATERIALS AND METHODS The aim of this retrospective cohort study was to examine the relationship between SRD, cART, and lipid-lowering agent use in an HIV infected population. A total of 276 subjects with HIV infection were included, 90 (33%) received lipid-lowering agents, and 31 (34%) had SRD. Patients received efavirenz or protease inhibitor-based cART for at least 6 months. Prescription information was retrieved from the medical records. The primary outcome was the use of lipid-lowering agents including statins, fibrates and fish oil. The impact of SRD and cART was assessed on the lipid-lowering agent use. RESULTS Smoking was prevalent among subjects with SRD (84% vs. 15%, p<0.001). Statins were the mainstay for the management of dyslipidemia (66%), followed by the fibrates (24%), omega-3 fatty acids (5%), nicotinic acid (3%) and the cholesterol absorption inhibitors (3%). Use of statins or fibrates was significantly higher among subjects without SRD than those with (40% vs. 23%, p=0.005). The type of cART, including efavirenz and protease inhibitors, appeared to have no significant impact on the use pattern of lipid-lowering agents. Lopinavir/r was mostly prescribed for subjects with SRD (25% vs. 8%, p=0.02). CONCLUSIONS Among HIV-infected patients, statins remain the mainstay for the management of dyslipidemia in routine clinical care, followed by fibrates. A significant high risk of metabolic disorders among patients with

Lipid-Lowering Therapy in HIV-Infected Patients: Relationship with Antiretroviral Agents and Impact of Substance-Related Disorders.

PubMed

Bednasz, Cindy; Luque, Amneris E; Zingman, Barry S; Fischl, Margaret A; Gripshover, Barbara M; Venuto, Charles S; Gu, Jie; Feng, Zekun; DiFrancesco, Robin; Morse, Gene D; Ma, Qing

2016-01-01

The use of combination antiretroviral therapy (cART) has significantly decreased the morbidity and mortality associated with human immunodeficiency virus (HIV) infection. Lipid disorders, including lipodystrophy, hypertriglyceridemia, and hypercholesterolemia, remain the most commonly reported metabolic disorders among those treated with long-term cART. Mounting evidence suggests an association between drug abuse and poor glycemic control and diabetes complications. Substance related disorders (SRD) may increase the risk of metabolic syndrome. The aim of this retrospective cohort study was to examine the relationship between SRD, cART, and lipid-lowering agent use in an HIV infected population. Patients received efavirenz or protease inhibitor-based cART for at least 6 months. Prescription information was retrieved from the medical records. The primary outcome was the use of lipid-lowering agents including statins, fibrates and fish oil. The impact of SRD and cART was assessed on the lipid-lowering agent use. A total of 276 subjects with HIV infection were included, 90 (33%) received lipid-lowering agents, and 31 (34%) had SRD. Smoking was prevalent among subjects with SRD (84 vs 15%, p<0.001). Statins were the mainstay for the management of dyslipidemia (66%), followed by the fibrates (24%), omega-3 fatty acids (5%), nicotinic acid (3%) and the cholesterol absorption inhibitors (3%). Use of statins or fibrates was significantly higher among subjects without SRD than those with (40 vs 23%, p=0.005). The type of cART, including efavirenz and protease inhibitors, appeared to have no significant impact on the use pattern of lipid-lowering agents. Lopinavir/ritonavir (lopinavir/r) was mostly prescribed for subjects with SRD (25 vs 8%, p=0.02). Among HIV-infected patients, statins remain the mainstay for the management of dyslipidemia in routine clinical care, followed by fibrates. A significant high risk of metabolic disorders among patients with SRD is implicated by

Esthetic and cosmetic dermatology.

PubMed

Wollina, Uwe; Goldman, Alberto; Berger, Uwe; Abdel-Naser, Mohammed Badawy

2008-01-01

The field of esthetic and cosmetic dermatology has gained remarkable interest all over the world. The major advantage of recent years is the high scientific levels of the most significant new developments in techniques and pharmacotherapy and other nonsurgical approaches. The present paper reviews selected fields of interest under this view. Sexual hormones are involved in the aging process of men and women. Skin function, in particular the epidermal barrier, is affected by a loss of endocrine activity. Hormone replacement therapy has only recently been introduced in treatment of aging males. This is an area of gender-medicine in dermatology with a strong well-aging attempt. Botulinum toxin therapy for hyperfunctional lines has become not only well-established but evidence-based medicine on its highest level. Recent advantages were gained in objective evaluation and monitoring the effect. Digital imaging techniques with various facets have been introduced to assess the achievements of treatment in the most objective way. This may become an example for other techniques as peeling, laser therapy, or radiofrequency in esthetic and cosmetic dermatology. Botulinum toxin has become a valuable tool for brow lifts. Details of the technique are discussed. Cellulite is a strongly female gender-related condition. During the past decades numerous treatments had been recommended but only recently a more critical scientific approach led to improvements in therapy of this common and disfiguring condition. Three major approaches are developed: (a) skin loosing with techniques such as subcision, (b) skin tightening with radiofrequency and other approaches, and (c) improving circulation in blood and lymphatic microvasculature using both physical treatments and pharmacotherapy. The last two chapters are devoted to body sculpturing by lipotransfer and lipolysis. Lipotransfer for facial or body sculpturing has a history of about 100 years. Nevertheless, recently the role of adult stem

Is methicillin-resistant Staphylococcus aureus an emerging community pathogen? A review of the literature

PubMed Central

Gardam, Michael A

2000-01-01

OBJECTIVES: To discuss the historical epidemiology of methicillin-resistant Staphylococcus aureus (MRSA) and review the literature suggesting that MRSA has become a community pathogen. DATA SOURCES: A search of the MEDLINE database was performed, encompassing all English or French language citations from 1966 to 1999 and containing the subjects and/or text words: 'Staphylococcus aureus', 'methicillin resistance', 'endocarditis', 'cellulites', 'pneumonia' and 'community-acquired'. Articles published in other languages that provided English or French abstracts were included. All relevant references cited in articles obtained from the MEDLINE database and book chapters were also included. DATA EXTRACTION: All articles obtained from the above sources were examined and were included in the review if a laboratory or epidemiological study of community-acquired MRSA was presented. DATA SYNTHESIS AND CONCLUSIONS: MRSA has emerged over the past 30 years to become a worldwide nosocomial pathogen and has recently been reported as a cause of community-acquired infections. The changing epidemiology of MRSA is likely because of two mechanisms: the movement of nosocomial MRSA strains into the community and the de novo appearance of community strains resulting from the transfer of genetic material from methicillin-resistant Gram-positive organisms to sensitive S aureus strains. The emergence of MRSA as a community pathogen has occurred at a slower rate than it did for penicillin-resistant S aureus (PRSA) in the 1950s and 1960s, possibly because the mechanism of methicillin resistance does not exhibit the same ease of transferability as that of penicillin resistance. Four case reports, seven case series, 10 case-control studies and two cohort studies on community-acquired MRSA were analyzed. Determining whether these reports involve new community-acquired strains rather than previously acquired nosocomial strains can be problematic. It appears, however, that MRSA strains of both

Mutations in Known Monogenic High Bone Mass Loci Only Explain a Small Proportion of High Bone Mass Cases

PubMed Central

Wheeler, Lawrie; Hardcastle, Sarah A; Appleton, Louise H; Addison, Kathryn A; Brugmans, Marieke; Clark, Graeme R; Ward, Kate A; Paggiosi, Margaret; Stone, Mike; Thomas, Joegi; Agarwal, Rohan; Poole, Kenneth ES; McCloskey, Eugene; Fraser, William D; Williams, Eleanor; Bullock, Alex N; Davey Smith, George; Brown, Matthew A; Tobias, Jon H; Duncan, Emma L

2015-01-01

ABSTRACT High bone mass (HBM) can be an incidental clinical finding; however, monogenic HBM disorders (eg, LRP5 or SOST mutations) are rare. We aimed to determine to what extent HBM is explained by mutations in known HBM genes. A total of 258 unrelated HBM cases were identified from a review of 335,115 DXA scans from 13 UK centers. Cases were assessed clinically and underwent sequencing of known anabolic HBM loci: LRP5 (exons 2, 3, 4), LRP4 (exons 25, 26), SOST (exons 1, 2, and the van Buchem's disease [VBD] 52‐kb intronic deletion 3′). Family members were assessed for HBM segregation with identified variants. Three‐dimensional protein models were constructed for identified variants. Two novel missense LRP5 HBM mutations ([c.518C>T; p.Thr173Met], [c.796C>T; p.Arg266Cys]) were identified, plus three previously reported missense LRP5 mutations ([c.593A>G; p.Asn198Ser], [c.724G>A; p.Ala242Thr], [c.266A>G; p.Gln89Arg]), associated with HBM in 11 adults from seven families. Individuals with LRP5 HBM (∼prevalence 5/100,000) displayed a variable phenotype of skeletal dysplasia with increased trabecular BMD and cortical thickness on HRpQCT, and gynoid fat mass accumulation on DXA, compared with both non‐LRP5 HBM and controls. One mostly asymptomatic woman carried a novel heterozygous nonsense SOST mutation (c.530C>A; p.Ser177X) predicted to prematurely truncate sclerostin. Protein modeling suggests the severity of the LRP5‐HBM phenotype corresponds to the degree of protein disruption and the consequent effect on SOST‐LRP5 binding. We predict p.Asn198Ser and p.Ala242Thr directly disrupt SOST binding; both correspond to severe HBM phenotypes (BMD Z‐scores +3.1 to +12.2, inability to float). Less disruptive structural alterations predicted from p.Arg266Cys, p.Thr173Met, and p.Gln89Arg were associated with less severe phenotypes (Z‐scores +2.4 to +6.2, ability to float). In conclusion, although mutations in known HBM loci may be asymptomatic, they only

The impact of testosterone imbalance on depression and women's health.

PubMed

Rohr, Uwe D

2002-04-15

Women suffer more often from depression than males, indicating that hormones might be involved in the etiology of this disease. Low as well as high testosterone (T) levels are related to depression and well-being in women, T plasma levels correlate to depression in a parabolic curve: at about 0.4-0.6 ng/ml plasma free T a minimum of depression is detected. Lower levels are related to depression, osteoporosis, declining libido, dyspareunia and an increase in total body fat mass. Androgen levels in women decrease continuously to about 50% before menopause compared to a 20-year-old women. Androgen levels even decline 70% within 24 h when women undergo surgical removal of the ovaries. Conventional oral contraception or HRT cause a decline in androgens because of higher levels of SHBG. Hyperandrogenic states exist, like hirsutism, acne and polycystic ovary syndrome. Social research suggests high androgen levels cause aggressive behavior in men and women and as a consequence may cause depression. Higher androgen values are more pronounced at young ages and before and after delivery of a baby and might be responsible for the "baby blues". It was found that depression in pubertal girls correlated best with an increase in T levels in contrast to the common belief that "environmental factors" during the time of growing up might be responsible for emotional "up and downs". T replacement therapy might be useful in perimenopausal women suffering from hip obesity, also named gynoid obesity. Abdominal obesity in men and women is linked to type 2 diabetes and coronary heart diseases. Testosterone replacement therapy in hypoandrogenic postmenopausal women might not only protect against obesity but also reduce the risk of developing these diseases. Antiandrogenic progestins might be useful for women suffering from hyperandrogenic state in peri- and postmenopause. Individual dosing schemes balancing side effects and beneficial effects are absolutely necessary. Substantial

High plasma apolipoprotein B identifies obese subjects who best ameliorate white adipose tissue dysfunction and glucose-induced hyperinsulinemia after a hypocaloric diet.

PubMed

Bissonnette, Simon; Saint-Pierre, Nathalie; Lamantia, Valerie; Leroux, Catherine; Provost, Viviane; Cyr, Yannick; Rabasa-Lhoret, Remi; Faraj, May

2018-06-18

To optimize the prevention of type 2 diabetes (T2D), high-risk obese subjects with the best metabolic recovery after a hypocaloric diet should be targeted. Apolipoprotein B lipoproteins (apoB lipoproteins) induce white adipose tissue (WAT) dysfunction, which in turn promotes postprandial hypertriglyceridemia, insulin resistance (IR), and hyperinsulinemia. The aim of this study was to explore whether high plasma apoB, or number of plasma apoB lipoproteins, identifies subjects who best ameliorate WAT dysfunction and related risk factors after a hypocaloric diet. Fifty-nine men and postmenopausal women [mean ± SD age: 58 ± 6 y; body mass index (kg/m2): 32.6 ± 4.6] completed a prospective study with a 6-mo hypocaloric diet (-500 kcal/d). Glucose-induced insulin secretion (GIIS) and insulin sensitivity (IS) were measured by 1-h intravenous glucose-tolerance test (IVGTT) followed by a 3-h hyperinsulinemic-euglycemic clamp, respectively. Ex vivo gynoid WAT function (i.e., hydrolysis and storage of 3H-triolein-labeled triglyceride-rich lipoproteins) and 6-h postprandial plasma clearance of a 13C-triolein-labeled high-fat meal were measured in a subsample (n = 25). Postintervention first-phase GIISIVGTT and total C-peptide secretion decreased in both sexes, whereas second-phase and total GIISIVGTT and clamp IS were ameliorated in men (P < 0.05). Baseline plasma apoB was associated with a postintervention increase in WAT function (r = 0.61) and IS (glucose infusion rate divided by steady state insulin (M/Iclamp) r = 0.30) and a decrease in first-phase, second-phase, and total GIISIVGTT (r = -0.30 to -0.35) without sex differences. The association with postintervention amelioration in WAT function and GIISIVGTT was independent of plasma cholesterol (total, LDL, and HDL), sex, and changes in body composition. Subjects with high baseline plasma apoB (1.2 ± 0.2 g/L) showed a significant increase in WAT function (+105%; P = 0.012) and a decrease in total

Different origin of adipogenic stem cells influences the response to antiretroviral drugs

DOE Office of Scientific and Technical Information (OSTI.GOV)

Gibellini, Lara; De Biasi, Sara; Nasi, Milena

Lipodystrophy (LD) is a main side effect of antiretroviral therapy for HIV infection, and can be provoked by nucleoside reverse transcriptase inhibitors (NRTIs) and protease inhibitors (PIs). LD exists in different forms, characterized by fat loss, accumulation, or both, but its pathogenesis is still unclear. In particular, few data exist concerning the effects of antiretroviral drugs on adipocyte differentiation. Adipose tissue can arise either from mesenchymal stem cells (MSCs), that include bone marrow-derived MSCs (hBM-MSCs), or from ectodermal stem cells, that include dental pulp stem cells (hDPSCs). To analyze whether the embryonal origin of adipocytes might impact the occurrence ofmore » different phenotypes in LD, we quantified the effects of several antiretroviral drugs on the adipogenic differentiation of hBM-MSCs and hDPSCs. hBM-MSCs and hDPSCs were isolated from healthy donors. Cells were treated with 10 and 50 μM stavudine (d4T), efavirenz (EFV), atazanavir (ATV), ritonavir (RTV), and ATV-boosted RTV. Viability and adipogenesis were evaluated by staining with propidium iodide, oil red, and adipoRed; mRNA levels of genes involved in adipocyte differentiation, i.e. CCAAT/enhancer-binding protein alpha (CEBPα) and peroxisome proliferator-activated receptor gamma (PPARγ), and in adipocyte functions, i.e. fatty acid synthase (FASN), fatty acid binding protein-4 (FABP4), perilipin-1 (PLIN1) and 1-acylglycerol-3-phosphate O-acyltransferase-2 (AGPAT2), were quantified by real time PCR. We found that ATV, RTV, EFV, and ATV-boosted RTV, but not d4T, caused massive cell death in both cell types. EFV and d4T affected the accumulation of lipid droplets and induced changes in mRNA levels of genes involved in adipocyte functions in hBM-MSCs, while RTV and ATV had little effects. All drugs stimulated the accumulation of lipid droplets in hDPSCs. Thus, the adipogenic differentiation of human stem cells can be influenced by antiretroviral drugs, and depends, at

[The quality of life if HIV/AIDS patients in Iasi Romania].

PubMed

Manciuc, Carmen; Largu, Alexandra; Vâţă, A; Nicolau, Cristina; Prisacaru, L; Stoica, Daniela; Dorobăţ, Carmen

2011-01-01

Quality of life in relation to health is a consequence of disease and treatment on the patient's perception of his ability to have a full and useful life. Due to its nature, the quality of life is a multidimensional and subjective construct, based on the patient's experience. We operationalized the quality of life using the following parameters: CD4 count and HIV viral levels in the patient's blood, the number of days of hospitalization, number of antiretroviral plans, types of side effects and their frequency, psychological issues (anxiety, depression, and neurotic tendencies). We centralized data from a total of 600 patients from the Regional Center in Iaşi in 2010-2011. Side effects accused by the patients emerged from discussions with the infectious disease doctor and psychologist, and psychological aspects were measured by specific instruments (PA Inventory, Beck Depression Scale). Most patients enrolled in the study were male (59%) with mean age of 21.1 years. 34% of them came from rural areas. Average schooling level was 6 primary classes, with extremes between the two classes of primary and higher education. Only 14% of patients had a job, while the rest did not have a stable job or were not employed. 38% came from broken homes or foster care. 85% of patients were in therapy at the time of data centralization. 55% were in the second, third or fourth regimen. 25% were at their first scheme, while 10% in the seventh - eighth scheme. The mean CD4 count ranged between 13 and 269/mmc, while the average viral load varied between 1730 and 3.180.000/mmc. The average number of days of hospitalization was 4. Among the antiretroviral side effects patients complained nausea and vomiting in 85% of cases, lipodystrophy symptoms in 25% of cases, diarrhea 15%. With regard to psychological aspects, 65% of patients showed an above average level of anxiety, 40% showed depressive symptoms, while 10% had specific obsessions-compulsions, and 10% neurotic and hysterical

Abacavir, zidovudine, or stavudine as paediatric tablets for African HIV-infected children (CHAPAS-3): an open-label, parallel-group, randomised controlled trial.

PubMed

Mulenga, Veronica; Musiime, Victor; Kekitiinwa, Adeodata; Cook, Adrian D; Abongomera, George; Kenny, Julia; Chabala, Chisala; Mirembe, Grace; Asiimwe, Alice; Owen-Powell, Ellen; Burger, David; McIlleron, Helen; Klein, Nigel; Chintu, Chifumbe; Thomason, Margaret J; Kityo, Cissy; Walker, A Sarah; Gibb, Diana M

2016-02-01

NRTIs had low toxicity and good clinical, immunological, and virological responses. Clinical and subclinical lipodystrophy was not noted in those younger than 5 years and anaemia was no more frequent with zidovudine than with the other drugs. Absence of hypersensitivity reactions, superior resistance profile and once-daily dosing favours abacavir for African children, supporting WHO 2013 guidelines. European Developing Countries Clinical Trials Partnership. Copyright © 2016 Walker et al. Open Access article distributed under the terms of CC BY. Published by Elsevier Ltd.. All rights reserved.

Abacavir, zidovudine, or stavudine as paediatric tablets for African HIV-infected children (CHAPAS-3): an open-label, parallel-group, randomised controlled trial

PubMed Central

Mulenga, Veronica; Musiime, Victor; Kekitiinwa, Adeodata; Cook, Adrian D; Abongomera, George; Kenny, Julia; Chabala, Chisala; Mirembe, Grace; Asiimwe, Alice; Owen-Powell, Ellen; Burger, David; McIlleron, Helen; Klein, Nigel; Chintu, Chifumbe; Thomason, Margaret J; Kityo, Cissy; Walker, A Sarah; Gibb, Diana M

2016-01-01

-experienced children maintained suppression (p=1·00). Interpretation All NRTIs had low toxicity and good clinical, immunological, and virological responses. Clinical and subclinical lipodystrophy was not noted in those younger than 5 years and anaemia was no more frequent with zidovudine than with the other drugs. Absence of hypersensitivity reactions, superior resistance profile and once-daily dosing favours abacavir for African children, supporting WHO 2013 guidelines. Funding European Developing Countries Clinical Trials Partnership. PMID:26481928

[Neurologic disorders in Whipple's disease].

PubMed

Jović, N S; Jović, J Z

1996-01-01

The disease is named after George H. Whipple who, in 1907, was the first to describe an intestinal "lipodystrophy". Although Whipple's disease is generally recognized as a multisystem chronic granulomatous disease, primarily involving the digestive system, it can also appear as a primary neurological disorder in rare cases. Most often it is manifested with loss of weight, diarrhea, malabsorption, abdominal pain, lymphadenopathy, cardiopathy, hyperpigmentation and hypotension. The presence of periodic acid-Schiff (PAS)-positive macrophages in biopsy specimens (not only jejunal) and demonstration of "Whipple's bacilli" visible by electron microscopy, are diagnostic signs of active Whipple's disease. Whipple's disease confined to the CNS is rare. It is rarely found in the differential diagnosis of patients with progressive neurological deterioration. The most common neurological picture includes progressive dementia, external ophalmoplegia, myoclonus, seizures, ataxia, hypothalamic dysfunction (sleep disorders, hyperphagia, polydipsia) and meningitis. Oculofacial-skeletal myorhythmia as a movement disorder, associated with Whipple's disease, is reported. Fulminant course of cerebral Whipple's disease is unusual and unfavourable. The confusing and nonspecific clinical appearance is typical for primary CNS involvement. It has recently been suggested that CNS involvement occurs in all cases, although only 10-20% of patients may show it. The CNS is the most common site of disease relapse. The CT scans and MRI of the brain are often normal, but may show cortical/subcortical atrophy, hydrocephalus, focal or intracerebral mass lesions. The cerebrospinal fluid can sometimes contain PAS-positive macrophages. Brain biopsy is suggested as a diagnostic method in cases of high suspicion of CNS Whipple's disease. However, the lesions are frequently inaccessible and false negative. Without extended antibiotic therapy, the course of Whipple's disease is lethal. Now, the prognosis is

[Overweight, obesity and underweight in HIV infected patients].

PubMed

Kwiatkowska, Wiesława; Knysz, Brygida; Drelichowska-Durawa, Justyna; Czarnecki, Marcin; Gasiorowski, Jacek; Biłyk, Ewa; Karczewski, Maciej; Witkiewicz, Wojciech

2013-01-01

The history of HIV infection has always been associated with patient nutritional problems, initially in the form of wasting syndrome, and since the introduction of highly active antiretroviral therapy such metabolic disorders as lipodystrophy, obesity, insulin resistance, dyslipidemia that are risk factors for cardiovascular diseases have been observed. evaluation of nutritional disorders in HIV infected patients using anthropometric parameters: waist circumference, BMI (body mass index) and WHR (waist-hip ratio). the study included 72 HIV infected patients (48 men, 24 women, average age 39.4). The control group comprised 27 not infected subjects, matched for age and sex. Physical examination with measurements of body mass, height, waist and hip circumference was performed and the values of two anthropometric parameters--body mass index and waist/hip ratio were calculated. BMI in the group of HIV infected patients was significantly lower than in the control group (23.6 vs. 25.6 kg/m2, p = 0.01). These BMI values are normal, but significantly lower in HIV-infected men compared with not infected, and no differences were found between women. Infected men are less likely to be overweight and obese than not infected ones. Underweight was noted in 6.8% of patients from the study group (6% of men and 4% of women). WHR was significantly higher in the study group comparing with the healthy subjects (0.92 vs. 0.86 p = 0.002), which resulted from significantly lower hip circumference among the infected patients (93.0 vs. 98.3, p = 0.002). Waist circumference was similar in both groups (85.1 vs. 84.0). The WHR value in the infected women was a result of insignificantly higher waist circumference and lower hip circumference. HIV infected women have significantly more often too large waist circumference comparing with not infected ones (46% vs 0%, p = 0.01). In the group of infected men, the WHR value was significantly affected only by low hip circumference, and larger waist

Aspects of constitutive and acquired antibioresistance in Aeromonas hydrophila strains isolated from water sources.

PubMed

Balotescu, Carmen; Israil, Anca; Radu, Roxana; Alexandru, Ionela; Dobre, Georgeta

2003-01-01

Over the last three decades, the literature pointed out the implications of Aeromonas species in human pathology. These species were described as being involved in intestinal (several outbreaks of acute gastroenteritis of choleric/dysenteric form or chronic diarrhoea, ulcerative colitis, etc.) in normal adults or children, as well as in extraintestinal infections in immunocompromised hosts. This last aspect included a large range of cutaneous injuries (micronecrosis, abscesses, bums, cellulites, furunculosis), joint, bones, respiratory, urinary tract, ocular infections up to meningitis, endocarditis, peritonitis, hepatobilliary disease, endotoxic shock and septicemia (as consequence of leech microvascular surgery). During the last decade, the literature reported a high mortality in Aeromonas infections determined by certain phenospecies (A. hydrophila and A. veronii) especially in extraintestinal infections in immunocompromised patients. In microbiologists' opinion this high rate of mortality was probably due to poor knowledge concerning the aspects of antibioresistance in Aeromonas strains, to empiric treatments with antibiotics to which these bacteria exhibiting constitutive resistance lead to insuccessful results, and at last to the increasing trend of aeromonads resistance to certain antibiotics after 1996. The literature mentioned also that for a great number of Beta-lactamase producing Aeromonas strains, the use of microdilution method (by comparison to disk diffusion in agar medium) giving false results made more difficult the true knowledge of Aeromonas antibioresistance patterns. At the same time, in 2002, the literature mentioned 4 ecological compartments considered as "reservoirs for dissemination and transfer of microbial antibioresistance i.e. humans, animals, plants and natural soil and water. In the last time, more and more data of the literature revealed that some bacteria with role of reservoir of antibioresistance in the natural environment, even

Interactions of Fat and Carbohydrate Metabolism—New Aspects and Therapies

PubMed Central

Lawrence, R. D.

1941-01-01

��Diabetic obesity” is very common and is often seen in the earliest stages and again after insulin treatment. It seems probable that hyperglycæmia causes this obesity and this has been clearly established by observations on an unusual case of lipæmia, diabetes and lipodystrophy. Lipæcmia may occur in two opposite phases of metabolism, one anabolic—when fat is on its way to storage, the other catabolic—when it is flowing from stores to the liver. The latter is the usual condition obvious in disease. Work has also been done which suggests that other lipotropic factors—choline, lipocaic, &c., exert an influence on carbohydrate-fat balance, more specifically the glycogen-fat balance in the liver. In America attention has been drawn to the frequent and persistenzt occurrence of fatty enlargement of the liver in diabetic children. The author has seen many diabetic children (usually in a state of chronic ketosis) with enlarged livers, but such enlargement has rapidly disappeared with better management of the diabetes. Only two out of some 500 diabetic children have clearly shown the unmistakable syndrome of “hepatomegalic dwarfism ”. In these two cases choline and lipocaic were given over prolonged periods without any effect: the liver, however, of one of these cases has since become normal by the addition of zinc protamine insulin. PMID:19992415

Efficacy, safety, bone and metabolic effects of HIV nucleoside reverse transcriptase inhibitor BMS-986001 (AI467003): a phase 2b randomised, controlled, partly blinded trial.

PubMed

Gupta, Samir K; McComsey, Grace A; Lombaard, John; Echevarría, Juan; Orrell, Catherine; Avihingsanon, Anchalee; Osiyemi, Olayemi; Santoscoy, Mario; Ray, Neelanjana; Stock, David A; Joshi, Samit R; Hanna, George J; Lataillade, Max

2016-01-01

%) of 65 patients for whom there were data in the 100 mg group, 54 (81%) of 67 in the 200 mg group, 62 (94%) of 66 in the 400 mg group achieved HIV-1 RNA less than 50 copies per mL, compared with 88 (89%) of 99 in the tenofovir disoproxil fumarate group (modified intention-to-treat population). BMS-986001 was generally well tolerated through week 48. Two patients had BMS-986001-related serious adverse events (atypical drug eruption and thrombocytopenia) and two in the tenofovir disoproxil fumarate group had study drug-related serious adverse events (potential drug-induced liver injury and depression or lipodystrophy) that led to discontinuation. NRTI resistance-associated mutations were reported in four (2%) of 198 patients, and non-NRTI mutations in 17 (9%) of 198 patients receiving BMS-986001 versus none of 99 and one (1%) of 99 patients receiving tenofovir disoproxil fumarate, respectively. Compared with tenofovir disoproxil fumarate, individuals in the BMS-986001 groups showed a smaller decrease in lumbar spine and hip bone mineral density but greater accumulation of limb and trunk fat, subcutaneous and visceral adipose tissue, and increased total cholesterol. BMS-986001 had similar efficacy to that of tenofovir disoproxil fumarate and was associated with a smaller decrease in bone mineral density; however, greater resistance and gains in both peripheral and central fat accumulation were recorded for the investigational drug. Bristol-Myers Squibb has discontinued its involvement in the development of BMS-986001, and future decisions on development will be made by Oncolys BioPharma. Bristol-Myers Squibb. Copyright © 2016 Elsevier Ltd. All rights reserved.

[Psychopathology of the misuse of Subutex®: The Popeye syndrome].

PubMed

Békaert, J; Podevin, G

2015-06-01

High dose buprenorphine (HDB), commonly known as Subutex(®), is nowadays largely prescribed as a replacement therapy for major opiate dependence. Its sublingual administration allows a decrease in the withdrawal syndrome accompanying opiate abuse cessation. Over the past few decades, epidemiological data on people on replacement therapy have emphasized an increase in the misuse of Subutex(®) and more specifically intravenous injections of HDB. These growing practices pave the way to major physical consequences or even death. Several studies have highlighted the infectious, vascular, venous and arterial (pseudo-aneurysm) complications stemming from this habit. Among the possible vascular complications, we can notice the presence of abscess, venous thrombosis, phlegmons, skin necrosis, cellulite, and profound and superficial thrombophlebitis at injection sites. These can evolve into chronic edemas of the tips and subcutaneous nodules. The Popeye syndrome is one of the possible complications of this misuse. This syndrome is characterized by the swelling of both sides of the forearms and hands. These edemas tend to become persistent and to be paired with tissue changes such as skin thickening. Besides, the increase in the hands volume can occur bilaterally or sometimes in an asymmetrical way, accentuated on the hand of the non-dominant limb. This syndrome does not decrease, or just a little, after the stoppage of injections. It can have a psychological, social, psychopathological and esthetic impact. In this article, we will focus on the clinical case of a 43-year-old man, who is hospitalized in an addictology unit for massive injections of HDB. This patient suffers from a Popeye syndrome as well as from an alcoholic dependence. Following the description of psychopathological disorders, our analysis will originate from a clarification relative to the specificities of the practice of intravenous HDB injection to better sharpen the understanding of these misuses in

Impact of protease inhibitor substitution with efavirenz in HIV-infected children: results of the First Pediatric Switch Study.

PubMed

McComsey, Grace; Bhumbra, Nasreen; Ma, Jen-Fu; Rathore, Mobeen; Alvarez, Ana

2003-03-01

Simplification of antiretroviral regimen in human immunodeficiency virus (HIV)-infected children has not yet been investigated. In general, children have a more difficult time maintaining viral suppression because of many factors, including frequent nonadherence and less availability of antiretrovirals in palatable forms. In addition, many serious metabolic complications have emerged in HIV-infected adults and are believed to be attributable to antiretroviral therapy. Some of these complications--hypercholesterolemia, hypertriglyceridemia, and insulin resistance--are believed to be the result of the use of protease inhibitor (PI) therapy, whereas the cause of others, such as lipodystrophy, remains undetermined. Recent reports underline that children experience long-term metabolic abnormalities in the same manner that adults do, and perhaps these consequences are even more worrisome in children secondary to long-term expected survival. We report here the results of the first open-label PI-switch study in HIV-infected children. Seventeen children, 24 to 160 months of age (median: 120), were enrolled into the study. All were receiving a stable PI-containing antiretroviral regimen that containing 2 to 3 nucleoside analogue reverse transcriptase inhibitors (NRTIs) in addition to 1 to 2 PIs for a median duration of 21 months (range: 5-50) before study entry. All children had HIV-1 RNA <400 copies/mL at screening; their baseline plasma HIV-1 RNA level had been <400 copies/mL for a median of 13 months (range: 4-55) before study entry. All patients were naïve to nonnucleoside reverse transcriptase inhibitor therapy. Their protease inhibitor(s) was switched to efavirenz while their NRTI therapy was maintained. All children were heavily pretreated; 88% of the patients had previous NRTIs, and 41% had previous PI use. The most common PI at study entry was nelfinavir (47%), followed by ritonavir (29%), then amprenavir (18%); only 1 was on saquinavir/ritonavir. At study entry