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Sample records for fat alters pulmonary

  1. High-fat diet enhances mammary tumorigenesis and pulmonary metastasis and alters inflammatory and angiogenic profiles in MMTV-PyMT mice

    USDA-ARS?s Scientific Manuscript database

    The MMTV-PyMT transgenic mouse model is commonly used to study luminal B breast cancer, which has a lower prevalence but a worse prognosis. The objective of the present study was to determine whether an obesogenic, high-fat diet enhances primary tumorigenesis and pulmonary metastasis in female MMTV...

  2. [Pulmonary alterations in Hodgkin lymphoma].

    PubMed

    Jóna, Ádám; Illés, Árpád; Szemes, Katalin; Miltényi, Zsófia

    2016-01-31

    Most of Hodgkin lymphoma patients survive due to combined chemo/radiotherapy. Improved survival brings long-term side effects to the front, which may determine the patients' subsequent quality of life and expected lifetime. This manuscript aims to analyze lung manifestations of Hodgkin lymphoma and treatment related pulmonary complications, demonstrated with own cases. The lung involvement in Hodgkin lymphoma is often secondary, and primary pulmonary involvement is very rare. The authors found 8-12% of lung involvement among their patients. Side effects of treatment consist of pulmonary infections in conjuction with immunosuppression, while on the other hand bleomycin and chest irradiation as part of current standard of care induced pneumonitis and fibrosis are reported. The pulmonary involvement in Hodgkin lymphoma may cause differential diagnostic difficulty. Lung involvement could modify stage and consequently treatment, and the development of side effects might determine later quality of life and expected lifetime. Therefore, identification of lung involvement is crucial.

  3. Factors that Alter Body Fat, Body Mass, and Fat-Free Mass in Pediatric Obesity.

    ERIC Educational Resources Information Center

    LeMura, Linda M.; Maziekas, Michael T.

    2002-01-01

    Investigated the effects of exercise programs on changes in body mass, fat-free mass, and body fat in obese children and adolescents. Research review indicated that exercise effectively helped reduce children's and adolescents' body composition variables. The most favorable body alterations occurred with low- intensity, long-duration exercise;…

  4. Factors that Alter Body Fat, Body Mass, and Fat-Free Mass in Pediatric Obesity.

    ERIC Educational Resources Information Center

    LeMura, Linda M.; Maziekas, Michael T.

    2002-01-01

    Investigated the effects of exercise programs on changes in body mass, fat-free mass, and body fat in obese children and adolescents. Research review indicated that exercise effectively helped reduce children's and adolescents' body composition variables. The most favorable body alterations occurred with low- intensity, long-duration exercise;…

  5. High-fat feeding alters the clock synchronization to light.

    PubMed

    Mendoza, Jorge; Pévet, Paul; Challet, Etienne

    2008-12-15

    High-fat feeding in rodents leads to metabolic abnormalities mimicking the human metabolic syndrome, including obesity and insulin resistance. These metabolic diseases are associated with altered temporal organization of many physiological functions. The master circadian clock located in the suprachiasmatic nuclei controls most physiological functions and metabolic processes. Furthermore, under certain conditions of feeding (hypocaloric diet), metabolic cues are capable of altering the suprachiasmatic clock's responses to light. To determine whether high-fat feeding (hypercaloric diet) can also affect resetting properties of the suprachiasmatic clock, we investigated photic synchronization in mice fed a high-fat or chow (low-fat) diet for 3 months, using wheel-running activity and body temperature rhythms as daily phase markers (i.e. suprachiasmatic clock's hands). Compared with the control diet, mice fed with the high-fat diet exhibited increased body mass index, hyperleptinaemia, higher blood glucose, and increased insulinaemia. Concomitantly, high-fat feeding led to impaired adjustment to local time by photic resetting. At the behavioural and physiological levels, these alterations include slower rate of re-entrainment of behavioural and body temperature rhythms after 'jet-lag' test (6 h advanced light-dark cycle) and reduced phase-advancing responses to light. At a molecular level, light-induced phase shifts have been correlated, within suprachiasmatic cells, with a high induction of c-FOS, the protein product of immediate early gene c-fos, and phosphorylation of the extracellular signal-regulated kinases I/II (P-ERK). In mice fed a high-fat diet, photic induction of both c-FOS and P-ERK in the suprachiasmatic nuclei was markedly reduced. Taken together, the present data demonstrate that high-fat feeding modifies circadian synchronization to light.

  6. Posttraumatic lung injury after pulmonary contusion and fat embolism: factors determining abnormal gas exchange.

    PubMed

    Whelan, Daniel B; Byrick, Robert J; Mazer, C David; Kay, Colin; Richards, Robin R; Zdero, Rad; Schemitsch, Emil H

    2010-09-01

    The objective was to investigate changes in pulmonary blood flow after lung contusion and fat embolism. Eighteen mongrel dogs were randomly assigned to three groups: fat embolism alone (n = 7); moderate unilateral pulmonary contusion followed by fat embolism (n = 6); and severe unilateral pulmonary contusion followed by fat embolism (n = 5). Fat embolism was produced by intramedullary reaming of left femur and tibia followed by canal pressurization using bone cement. Outcome measures were systemic blood pressure, pulmonary artery pressure, pulmonary artery occluded pressure, cardiac output (CO), and partial pressures of arterial and mixed venous oxygen (Pao2, PvO2). Samples were taken from contused and noncontused contralateral lung to calculate regional pulmonary blood flow. After the fat embolism, pulmonary artery pressure and pulmonary vascular resistance increased significantly (p < 0.05) in all groups, whereas Pao2 decreased in groups 2 and 3 and at 30 minutes in group 1. CO decreased significantly in group 3. Group 3 also demonstrated a greater initial decrease in Pao2 and PvO2 from baseline and a larger increase in pulmonary vascular resistance. In those animals that underwent contusion, regional pulmonary blood flow was not found to be different between contused and noncontused lung segments. After contusion, flow decreased significantly in contused and noncontused segments in group 3 only. Gas exchange deteriorates because of decreased CO. For any preexisting intrapulmonary shunt, the decrease of PvO2 will cause worsening of Pao2.

  7. Incidence of pulmonary fat embolism at autopsy: an undiagnosed epidemic.

    PubMed

    Eriksson, Evert Austin; Pellegrini, Daniela C; Vanderkolk, Wayne E; Minshall, Christian T; Fakhry, Samir M; Cohle, Stephen D

    2011-08-01

    To determine the incidence, time course, and severity of pulmonary fat embolism (PFE) and cerebral fat embolism (CFE) in trauma and nontrauma patients at the time of autopsy. Prospectively, consecutive patients presenting for autopsy were evaluated for evidence pulmonary and brain fat embolism. The lung sections were obtained from the upper and lower lobe of the patients' lungs on the right and left and brain tissue. This tissue was prepared with osmium tetroxide for histologic evaluation. The number of fat droplets per high power field was counted for all sections. The autopsy reports and medical records were used to determine cause of death, time to death, injuries, if cardiopulmonary resuscitation (CPR) was attempted, sex, height, weight, and age. Fifty decedents were evaluated for PFE and CFE. The average age was 45.8 years ± 17.4 years, average body mass index was 30.1 kg/cm² ± 7.0 kg/cm², and 68% of the patients were men. The cause of death was determined to be trauma in 68% (34/50) of decedents, with 88% (30/34) blunt and 12% (4/34) penetrating. CPR was performed on 30% (15/50), and PFE was present in 76% (38/50) of all patients. Subjects with PFE had no difference with respect to sex, trauma, mechanism of injury, CPR, external contusions, fractures, head, spine, chest, abdominal, pelvic, and extremity injuries. However, subjects without PFE had significantly increased weight (109 ± 29 kg vs. 86 ± 18 kg; p = 0.023) but no difference in height or body mass index. PFE was present in 82% (28/34) of trauma patents and 63% (10/16) nontrauma patients. Eighty-eight percent of nontrauma patients and 86% of trauma patients who received CPR had PFE. Trauma patients with PFE showed no significant difference in any group. Eighty-eight percent of trauma patients died within 1 hour of injury, and 80% (24/30) of them had PFE at the time of autopsy. CFE was present only in one patient with a severe head and cervical spine injury. PFE is common in trauma patients. CPR

  8. Load Carriage Induced Alterations of Pulmonary Function

    DTIC Science & Technology

    1989-01-01

    pulmonar , function reductions are directh’ related to the backpack load carried due to the mechanical constraint it imposes on the thoracic cage.2 To...and Fish- man. A.P.. 1965. The regulation of venttlation in diffuse Agostor. E.. D’Angelc, E. and Piolini, M., 1978. Breathing pulmonary fibrosis . J

  9. Parental dietary fat intake alters offspring microbiome and immunity1

    PubMed Central

    Myles, Ian A.; Vithayathil, Paul J.; Segre, Julia A.; Datta, Sandip K.

    2013-01-01

    Mechanisms underlying modern increases in prevalence of human inflammatory diseases remain unclear. The hygiene hypothesis postulates that decreased microbial exposure has, in part, driven this immune dysregulation. However, dietary fatty acids also influence immunity, partially through modulation of responses to microbes. Prior reports have described the direct effects of high fat diets on the gut microbiome and inflammation, and some have additionally shown metabolic consequences for offspring. Our study sought to expand on these previous observations to identify the effects of parental diet on offspring immunity using mouse models to provide insights into challenging aspects of human health. To test the hypothesis that parental dietary fat consumption during gestation and lactation influences offspring immunity, we compared pups of mice fed either a Western diet fatty acid profile or a standard low fat diet. All pups were weaned onto the control diet to specifically test the effects of early developmental fat exposure on immune development. Pups from Western diet breeders were not obese or diabetic, but still had worse outcomes in models of infection, autoimmunity, and allergic sensitization. They had heightened colonic inflammatory responses, with increased circulating bacterial lipopolysaccharide (LPS) and muted systemic LPS responsiveness. These deleterious impacts of the Western diet were associated with alterations of the offspring gut microbiome. These results indicate that parental fat consumption can leave a “lard legacy” impacting offspring immunity and suggest inheritable microbiota may contribute to the modern patterns of human health and disease. PMID:23935191

  10. Lipoprotein alterations, abdominal fat distribution and breast cancer.

    PubMed

    Schreier, L E; Berg, G A; Basilio, F M; Lopez, G I; Etkin, A E; Wikinski, R L

    1999-04-01

    Plasma lipid profile and abdominal obesity have been associated with breast cancer risk, however published results have been inconsistent. To clarify these associations we studied lipid and lipoprotein alterations, obesity degree and body fat distribution, in 30 newly diagnosed breast cancer patients without treatment and 30 controls matched by age and menopausal status. Both pre and postmenopausal breast cancer patients presented higher body mass index, waist/hip ratio and insulin levels than their matched controls. An increase in triglycerides and a decrease in HDL-cholesterol, especially in the HDL2 subfraction, were observed in patients with breast cancer. Besides, HDL particle from these patients showed increased apo A1/HDL-cholesterol ratio. These alterations were correlated with waist/hip ratio. The association between lipoprotein alterations and abdominal obesity independent of menopausal status, in untreated newly diagnosed breast cancer patients is reported for the first time in this study.

  11. Pulmonary hamartomas: CT pixel analysis for fat attenuation using radiologic-pathologic correlation.

    PubMed

    Gleeson, Tadhg; Thiessen, Rennae; Hannigan, Ailish; Murphy, Darra; English, John C; Mayo, John R

    2013-10-01

    To assess the accuracy of CT pixel analysis for fat attenuation in pulmonary hamartomas. Retrospective review identified 32 patients in three separate groups; pathologically proven hamartoma (n = 11), hamartoma diagnosed on imaging (n = 9) and a control group (n = 14) of pathology-proven non-hamartomatous smoothly marginated solitary pulmonary nodules. All lesions were assessed using: visual assessment for fat, pixel analysis of the inner 2/3rds and mean attenuation of the entire lesion, using an internal reference for fat. Fat percentages on CT and at histology were compared. Visual assessment for macroscopic fat was the most reliable method for diagnosing pulmonary hamartoma. Combining percentage of fat-attenuation pixels in the inner 2/3rds of the lesion improved specificity to 100%. Mean attenuation or pixel analysis in isolation were not helpful in lesional characterization. Combining percentage fat-attenuating pixels in the inner 2/3rds with visual assessment for macroscopic fat improves specificity for diagnosing pulmonary hamartomas. © 2013 The Royal Australian and New Zealand College of Radiologists.

  12. High-fat diet alters gut microbiota physiology in mice

    PubMed Central

    Daniel, Hannelore; Gholami, Amin Moghaddas; Berry, David; Desmarchelier, Charles; Hahne, Hannes; Loh, Gunnar; Mondot, Stanislas; Lepage, Patricia; Rothballer, Michael; Walker, Alesia; Böhm, Christoph; Wenning, Mareike; Wagner, Michael; Blaut, Michael; Schmitt-Kopplin, Philippe; Kuster, Bernhard; Haller, Dirk; Clavel, Thomas

    2014-01-01

    The intestinal microbiota is known to regulate host energy homeostasis and can be influenced by high-calorie diets. However, changes affecting the ecosystem at the functional level are still not well characterized. We measured shifts in cecal bacterial communities in mice fed a carbohydrate or high-fat (HF) diet for 12 weeks at the level of the following: (i) diversity and taxa distribution by high-throughput 16S ribosomal RNA gene sequencing; (ii) bulk and single-cell chemical composition by Fourier-transform infrared- (FT-IR) and Raman micro-spectroscopy and (iii) metaproteome and metabolome via high-resolution mass spectrometry. High-fat diet caused shifts in the diversity of dominant gut bacteria and altered the proportion of Ruminococcaceae (decrease) and Rikenellaceae (increase). FT-IR spectroscopy revealed that the impact of the diet on cecal chemical fingerprints is greater than the impact of microbiota composition. Diet-driven changes in biochemical fingerprints of members of the Bacteroidales and Lachnospiraceae were also observed at the level of single cells, indicating that there were distinct differences in cellular composition of dominant phylotypes under different diets. Metaproteome and metabolome analyses based on the occurrence of 1760 bacterial proteins and 86 annotated metabolites revealed distinct HF diet-specific profiles. Alteration of hormonal and anti-microbial networks, bile acid and bilirubin metabolism and shifts towards amino acid and simple sugars metabolism were observed. We conclude that a HF diet markedly affects the gut bacterial ecosystem at the functional level. PMID:24030595

  13. High-fat diet alters gut microbiota physiology in mice.

    PubMed

    Daniel, Hannelore; Gholami, Amin Moghaddas; Berry, David; Desmarchelier, Charles; Hahne, Hannes; Loh, Gunnar; Mondot, Stanislas; Lepage, Patricia; Rothballer, Michael; Walker, Alesia; Böhm, Christoph; Wenning, Mareike; Wagner, Michael; Blaut, Michael; Schmitt-Kopplin, Philippe; Kuster, Bernhard; Haller, Dirk; Clavel, Thomas

    2014-02-01

    The intestinal microbiota is known to regulate host energy homeostasis and can be influenced by high-calorie diets. However, changes affecting the ecosystem at the functional level are still not well characterized. We measured shifts in cecal bacterial communities in mice fed a carbohydrate or high-fat (HF) diet for 12 weeks at the level of the following: (i) diversity and taxa distribution by high-throughput 16S ribosomal RNA gene sequencing; (ii) bulk and single-cell chemical composition by Fourier-transform infrared- (FT-IR) and Raman micro-spectroscopy and (iii) metaproteome and metabolome via high-resolution mass spectrometry. High-fat diet caused shifts in the diversity of dominant gut bacteria and altered the proportion of Ruminococcaceae (decrease) and Rikenellaceae (increase). FT-IR spectroscopy revealed that the impact of the diet on cecal chemical fingerprints is greater than the impact of microbiota composition. Diet-driven changes in biochemical fingerprints of members of the Bacteroidales and Lachnospiraceae were also observed at the level of single cells, indicating that there were distinct differences in cellular composition of dominant phylotypes under different diets. Metaproteome and metabolome analyses based on the occurrence of 1760 bacterial proteins and 86 annotated metabolites revealed distinct HF diet-specific profiles. Alteration of hormonal and anti-microbial networks, bile acid and bilirubin metabolism and shifts towards amino acid and simple sugars metabolism were observed. We conclude that a HF diet markedly affects the gut bacterial ecosystem at the functional level.

  14. Postural alterations and pulmonary function of mouth-breathing children.

    PubMed

    Silveira, Waleska da; Mello, Fernanda Carvalho de Queiroz; Guimarães, Fernando Silva; Menezes, Sara Lucia Siveira de

    2010-01-01

    Mouth-breathing children have changes in their stomatognathic system, which result in head projection, stress increase in the scapular belt muscles and postural adaptations. Although thoracic shape and posture can influence ventilatory dynamics, we didn't find studies addressing pulmonary function of mouth-breathing children. this study aimed at analyzing the posture of mouth-breathing children, and studying the existence of correlations between posture and pulmonary volumes. prospective, observational and cross-sectional study, where the posture and pulmonary function of 17 mouth-breathing children and of 17 nasal-breathing children were evaluated by means of photogrammetry and forced spirometry. when compared to nasal-breathing, mouth-breathing subjects presented an increment in head projection and cervical lordosis, forwarded gravity center and reduced pulmonary volumes. There was an association between head projection and forced vital capacity, and between postural alterations and age. mouth-breathing children have postural alterations which increases with age and also reduced spirometry values. The vital capacity reduction correlates negatively with head projection.

  15. Cerebral fat embolism: pulmonary contusion is a more important etiology than long bone fractures.

    PubMed

    Aydin, M D; Akçay, F; Aydin, N; Gündogdu, C

    2005-01-01

    Lipid embolism is a serious and life-threatening problem and usually arises as a complication of severe trauma associated with long bone or pelvic fractures. It is generally thought that fat droplets enter the circulation at the site of fracture. In the systemic circulation, they become emboli to brain, kidney and other areas. Lipids are absorbed from the intestinal tract and transported into pulmonary tissue via thoracic duct and exposed to first catabolic procedures in the lungs. We have predicted that systemic lipid embolism may not occur unless bone fractures lead to pulmonary injury. This study was planned to investigate this hypothesis with respect to the role of pulmonary contusion and long bone fractures in the formation of cerebral fat embolism. Twenty male hybrid rabbits were included in this study. Pulmonary contusion was performed on half of the rabbits (n = 10) and femur fracture was applied to the remaining ones (n = 10). Ten days after procedure, all rabbits were sacrificed. Brain specimens were taken by frozen-section method and stained with Sudan black. Intraarteriolar lipid particles in the brain were examined microscopically. Cerebral fat embolism was detected in seven animals exposed to pulmonary contusion and only in one animal exposed to femur fracture. The mean number of branches of middle cerebral artery at midparietal level occluded with fat particles were higher in the pulmonary contusion group than in the long bone fracture group. In conclusion, we found that pulmonary contusion had more deleterious effects than long bone fracture in the formation of cerebral fat embolism.

  16. Does heat stress alter the pig's response to dietary fat?

    PubMed

    Kellner, T A; Baumgard, L H; Prusa, K J; Gabler, N K; Patience, J F

    2016-11-01

    PFTN; = 0.624). Jowl IV at market increased with increasing degree of unsaturation of the dietary fat (68.5 g/100 g for CNTR, 68.2 g/100 g for TAL, and 71.5 g/100 g for CO; < 0.001). Heat stress decreased mRNA abundance of and ( ≤ 0.041). Heat stress and CO increased mRNA abundance of ( ≤ 0.047), and CO increased abundance of ( = 0.011). In conclusion, HS does not alter the pig's response to dietary fat. However, HS leads to reduced ADG, ADFI, G:F, and caloric efficiency and a suppression of mRNA abundance of genes involved in the lipolytic cascade, which resulted in a phenotype that was fatter than PFTN.

  17. Detection of pulmonary fat embolism with dual-energy CT: an experimental study in rabbits.

    PubMed

    Tang, Chun Xiang; Zhou, Chang Sheng; Zhao, Yan E; Schoepf, U Joseph; Mangold, Stefanie; Ball, B Devon; Han, Zong Hong; Qi, Li; Zhang, Long Jiang; Lu, Guang Ming

    2017-04-01

    To evaluate the use of dual-energy CT imaging of the lung perfused blood volume (PBV) for the detection of pulmonary fat embolism (PFE). Dual-energy CT was performed in 24 rabbits before and 1 hour, 1 day, 4 days and 7 days after artificial induction of PFE via the right ear vein. CT pulmonary angiography (CTPA) and lung PBV images were evaluated by two radiologists, who recorded the presence, number, and location of PFE on a per-lobe basis. Sensitivity, specificity, and accuracy of CTPA and lung PBV for detecting PFE were calculated using histopathological evaluation as the reference standard. A total of 144 lung lobes in 24 rabbits were evaluated and 70 fat emboli were detected on histopathological analysis. The overall sensitivity, specificity and accuracy were 25.4 %, 98.6 %, and 62.5 % for CTPA, and 82.6 %, 76.0 %, and 79.2 % for lung PBV. Higher sensitivity (p < 0.001) and accuracy (p < 0.01), but lower specificity (p < 0.001), were found for lung PBV compared with CTPA. Dual-energy CT can detect PFE earlier than CTPA (all p < 0.01). Dual-energy CT provided higher sensitivity and accuracy in the detection of PFE as well as earlier detection compared with conventional CTPA in this animal model study. • Fat embolism occurs commonly in patients with traumatic bone injury. • Dual-energy CT improves diagnostic performance for pulmonary fat embolism detection. • Dual-energy CT can detect pulmonary fat embolism earlier than CTPA.

  18. Effects of a high-fat meal on pulmonary function in healthy subjects.

    PubMed

    Rosenkranz, Sara K; Townsend, Dana K; Steffens, Suzanne E; Harms, Craig A

    2010-06-01

    Obesity has important health consequences, including elevating risk for heart disease, diabetes, and cancer. A high-fat diet is known to contribute to obesity. Little is known regarding the effect of a high-fat diet on pulmonary function, despite the dramatic increase in the prevalence of respiratory ailments (e.g., asthma). The purpose of our study was to determine whether a high-fat meal (HFM) would increase airway inflammation and decrease pulmonary function in healthy subjects. Pulmonary function tests (PFT) (forced expiratory volume in 1-s, forced vital capacity, forced expiratory flow at 25-75% of vital capacity) and exhaled nitric oxide (eNO; airway inflammation) were performed in 20 healthy (10 men, 10 women), inactive subjects (age 21.9 +/- 0.4 years) pre and 2 h post HFM (1 g fat/1 kg body weight; 74.2 +/- 4.1 g fat). Total cholesterol, triglycerides, and C-reactive protein (CRP; systemic inflammation) were determined via a venous blood sample pre and post HFM. Body composition was measured via dual energy X-ray absorptiometry. The HFM significantly increased total cholesterol by 4 +/- 1%, and triglycerides by 93 +/- 3%. ENO also increased (p < 0.05) due to the HFM by 19 +/- 1% (pre 17.2 +/- 1.6; post 20.6 +/- 1.7 ppb). ENO and triglycerides were significantly related at baseline and post-HFM (r = 0.82, 0.72 respectively). Despite the increased eNO, PFT or CRP did not change (p > 0.05) with the HFM. These results demonstrate that a HFM, which leads to significant increases in total cholesterol, and especially triglycerides, increases exhaled NO. This suggests that a high-fat diet may contribute to chronic inflammatory diseases of the airway and lung.

  19. Dietary fat-dependent transcriptional architecture and copy number alterations associated with modifiers of mammary cancer metastasis

    PubMed Central

    Gordon, Ryan R; La Merrill, Michele; Hunter, Kent W; Sørensen, Peter; Threadgill, David W; Pomp, Daniel

    2015-01-01

    Breast cancer is a complex disease resulting from a combination of genetic and environmental factors. Among environmental factors, body composition and intake of specific dietary components like total fat are associated with increased incidence of breast cancer and metastasis. We previously showed that mice fed a high-fat diet have shorter mammary cancer latency, increased tumor growth and more pulmonary metastases than mice fed a standard diet. Subsequent genetic analysis identified several modifiers of metastatic mammary cancer along with widespread interactions between cancer modifiers and dietary fat. To elucidate diet-dependent genetic modifiers of mammary cancer and metastasis risk, global gene expression profiles and copy number alterations from mammary cancers were measured and expression quantitative trait loci (eQTL) identified. Functional candidate genes that colocalized with previously detected metastasis modifiers were identified. Additional analyses, such as eQTL by dietary fat interaction analysis, causality and database evaluations, helped to further refine the candidate loci to produce an enriched list of genes potentially involved in the pathogenesis of metastatic mammary cancer. PMID:20354763

  20. Do pulmonary artery catheters alter outcome in trauma patients?

    PubMed

    Kirton, O C; Civetta, J M

    1997-08-01

    To review the literature addressing the use of the pulmonary artery catheter (PAC) in victims of blunt and penetrating trauma and examine the available evidence that supports or refutes the claim that PAC use alters outcome in this patient population. Furthermore, to determine what additional research should be done in this area. All pertinent English language articles dealing with pulmonary artery catheterization in trauma patients were retrieved from 1979 through 1996. Clinical studies were considered if PACs were used to establish a cardiopulmonary diagnosis, optimize or achieve endpoints of oxygen transport and utilization indices, or guide and/or determine response to therapy. Emphasis was placed on prospective, randomized, controlled trials. However, descriptive case series and retrospectively-analyzed, uncontrolled reviews comprise the majority of available literature. From these selective studies, information was obtained regarding patient demographics, therapeutic endpoints, and achieved outcome. Insufficient evidence exists to support a true survival benefit. However, recommendations for indications can be proposed where a reduction in morbidity or improvement in functional outcome is suggested. Hemodynamic data obtained from the PAC appear to be beneficial for the following indications: a) to ascertain the status of underlying cardiovascular performance and/or the need for improvement; b) to direct therapy when noninvasive monitoring may be inadequate, misleading, or the endpoints of resuscitation difficult to define; c) to assess response to resuscitation; d) to potentially decrease secondary injury when severe closed-head or acute spinal cord injuries are components of multisystem trauma; e) to augment clinical decision-making when major trauma is complicated by severe adult respiratory distress syndrome, progressive oliguria/anuria, myocardial ischemia, congestive heart failure, or major thermal injury; and f) to establish futility of care.

  1. The Effects of Aquaporin-1 in Pulmonary Edema Induced by Fat Embolism Syndrome

    PubMed Central

    Zhang, Yiwei; Tian, Kun; Wang, Yan; Zhang, Rong; Shang, Jiawei; Jiang, Wei; Wang, Aizhong

    2016-01-01

    This study was designed to investigate the role of aquaporin1 (AQP1) in the pathologic process of pulmonary edema induced by fat embolism syndrome (FES) and the effects of a free fatty acid (FFA) mixture on AQP1 expression in pulmonary microvascular endothelial cells (PMVECs). In vivo, edema was more serious in FES mice compared with the control group. The expression of AQP1 and the wet-to-dry lung weight ratio (W/D) in the FES group were significantly increased compared with the control group. At the same time, inhibition of AQP1 decreased the pathological damage resulting from pulmonary edema. Then we performed a study in vitro to investigate whether AQP1 was induced by FFA release in FES. The mRNA and protein level of AQP1 were increased by FFAs in a dose- and time-dependent manner in PMVECs. In addition, the up-regulation of AQP1 was blocked by the inhibitor of p38 kinase, implicating the p38 MAPK pathway as involved in the FFA-induced AQP1 up-regulation in PMVECs. Our results demonstrate that AQP1 may play important roles in pulmonary edema induced by FES and can be regarded as a new therapy target for treatment of pulmonary edema induced by FES. PMID:27455237

  2. The Effects of Aquaporin-1 in Pulmonary Edema Induced by Fat Embolism Syndrome.

    PubMed

    Zhang, Yiwei; Tian, Kun; Wang, Yan; Zhang, Rong; Shang, Jiawei; Jiang, Wei; Wang, Aizhong

    2016-07-21

    This study was designed to investigate the role of aquaporin1 (AQP1) in the pathologic process of pulmonary edema induced by fat embolism syndrome (FES) and the effects of a free fatty acid (FFA) mixture on AQP1 expression in pulmonary microvascular endothelial cells (PMVECs). In vivo, edema was more serious in FES mice compared with the control group. The expression of AQP1 and the wet-to-dry lung weight ratio (W/D) in the FES group were significantly increased compared with the control group. At the same time, inhibition of AQP1 decreased the pathological damage resulting from pulmonary edema. Then we performed a study in vitro to investigate whether AQP1 was induced by FFA release in FES. The mRNA and protein level of AQP1 were increased by FFAs in a dose- and time-dependent manner in PMVECs. In addition, the up-regulation of AQP1 was blocked by the inhibitor of p38 kinase, implicating the p38 MAPK pathway as involved in the FFA-induced AQP1 up-regulation in PMVECs. Our results demonstrate that AQP1 may play important roles in pulmonary edema induced by FES and can be regarded as a new therapy target for treatment of pulmonary edema induced by FES.

  3. Fat adaptation science: low-carbohydrate, high- fat diets to alter fuel utilization and promote training adaptation.

    PubMed

    Hawley, John A

    2011-01-01

    The effect of manipulating an individual's habitual diet on skeletal muscle fuel utilization has been of longstanding interest to scientists, and it is now well established that changes in dietary intake that alter the concentration of blood-borne substrates and hormones cause substantial perturbations in the macronutrient storage profile of muscle and exert profound effects on rates of substrate oxidation during exercise. Only recently, however, has it become appreciated that nutrient-exercise interventions can modulate many contraction- induced responses in muscle, and that fuel availability per se provides a 'trigger' for adaptation. Consumption of low-carbohydrate, high- fat diets in the face of endurance training alters patterns of fuel utilization and subsequent exercise responses. Human studies show how low-carbohydrate, fat-rich diets interact with specific contractile stimulus to modulate many of the acute responses to exercise, thereby promoting or inhibiting subsequent training adaptation. Copyright © 2011 S. Karger AG, Basel.

  4. Pregnancy Complicated by Obesity Induces Global Transcript Expression Alterations in Visceral and Subcutaneous Fat

    PubMed Central

    Bashiri, Asher; Heo, Hye J.; Ben-Avraham, Danny; Mazor, Moshe; Budagov, Temuri; Einstein, Francine H.; Atzmon, Gil

    2014-01-01

    Maternal obesity is a significant risk factor for development of both maternal and fetal metabolic complications. Increase in visceral fat and insulin resistance is a metabolic hallmark of pregnancy, yet little is known how obesity alters adipose cellular function and how this may contribute to pregnancy morbidities. We sought to identify alterations in genome-wide transcription expression in both visceral (omental) and abdominal subcutaneous fat deposits in pregnancy complicated by obesity. Visceral and abdominal subcutaneous fat deposits were collected from normal weight and obese pregnant women (n=4/group) at time of scheduled uncomplicated cesarean section. A genome-wide expression array (Affymetrix Human Exon 1.0 st platform), validated by quantitative real-time PCR, was utilized to establish the gene transcript expression profile in both visceral and abdominal subcutaneous fat in normal weight and obese pregnant women. Global alteration in gene expression was identified in pregnancy complicated by obesity. These regions of variations lead to identification of indolethylamine N-methyltransferase (INMT), tissue factor pathway inhibitor-2 (TFPI-2), and ephrin type-B receptor 6 (EPHB6), not previously associated with fat metabolism during pregnancy. In addition, subcutaneous fat of obese pregnant women demonstrated increased coding protein transcripts associated with apoptosis compared to lean counterparts. Global alteration of gene expression in adipose tissue may contribute to adverse pregnancy outcomes associated with obesity. PMID:24696292

  5. The Relationship between Small Pulmonary Vascular Alteration and Aortic Atherosclerosis in Chronic Obstructive Pulmonary Disease: Quantitative CT Analysis

    PubMed Central

    Matsuoka, Shin; Yamashiro, Tsuneo; Diaz, Alejandro; Estépar, Raúl San José; Ross, James C.; Silverman, Edwin K.; Kobayashi, Yasuyuki; Dransfield, Mark T.; Bartholmai, Brian J.; Hatabu, Hiroto; Washko, George R.

    2010-01-01

    Rationale and Objectives The relationship between chronic obstructive pulmonary disease (COPD) and atherosclerosis has been suggested; this association may relate to systemic inflammation and endothelial dysfunction, which can lead to alteration of small pulmonary vessels. The relationship between atherosclerosis and small pulmonary vessel alteration, however, has not been assessed in COPD patients. We tested the hypothesis that the severity of thoracic aortic calcification measured by computed tomography (CT) would be associated with the total cross-sectional area of small pulmonary vessels (CSA) on CT images. Materials and Methods The study was approved by the institutional review board and was HIPAA compliant. Informed consent was waived. For 51 COPD patients enrolled in the NHBLI Lung Tissue Research Consortium (LTRC), we calculated the percentage of total CSAs of less than 5 mm2 for the total lung area (%CSA<5). Thoracic aortic calcification, quantified by modified Agatston score, was measured. The correlations between thoracic aortic calcification score and %CSA<5, pulmonary function, and extent of emphysema were evaluated. Multiple linear regression analysis using aortic calcification score as the dependent outcome was also performed. Results The %CSA<5 had a significant negative correlation with the thoracic aortic calcification score (r=−0.566, p<0.0001). Multiple linear regression analysis showed significant correlation between the aortic calcification score and %CSA<5 (p<0.0001) independent of age, pack-years, extent of emphysema, and FEV1%. Conclusions Atherosclerosis, assessed by aortic calcification, is associated with the small pulmonary vascular alteration in COPD. Systemic inflammation and endothelial dysfunction may cause the close relationship between atherosclerosis and small pulmonary vessel alteration. PMID:20947389

  6. Potential to alter the content and composition of milk fat through nutrition.

    PubMed

    Ashes, J R; Gulati, S K; Scott, T W

    1997-09-01

    Nutritional manipulation of the rumen ecosystem provides a strategy to alter the content and composition of milk fat. Dietary fat supplements affect the content and composition of milk fat. The magnitude of changes is influenced by the degree of protection; as protection increases, the deleterious effects fatty acids on microbial activity decreases, and biohydrogenation of C18 unsaturated fatty acids is reduced. In addition, change is influenced by the transfer of dietary fat into milk, which is related to fatty acid composition, degree of ruminal metabolism, and efficiency of digestion. A cascade of metabolic events involving specific nutrients (e.g., trans fatty acids and cyclopropene acids) occurs that regulates the activity of key enzymes in pathways of endogenous fat synthesis within the mammary gland. When cattle are fed oilseeds (e.g., canola and cotton) with > 75% protection from biohydrogenation, the proportion of saturated to unsaturated fatty acids is changed, and the fat content of milk is increased. Human consumption of dairy products containing elevated proportions of C18 mono- and polyunsaturated fatty acids reduces the content of cholesterol in plasma low density lipoproteins. These fat-modified dairy products are more susceptible to autoxidation, which can be controlled by including vitamin E in the diet of lactating cow. These products also have much less solid fat, which improves spreadability of butter. By protecting different oilseeds from ruminal metabolism, demands for energy can be satisfied while producing milk fat that can be designed for consumer and manufacturing requirements.

  7. Fat emulsion composition alters intake and the effects of baclofen.

    PubMed

    Wang, Y; Wilt, D C; Wojnicki, F H E; Babbs, R K; Coupland, J N; Corwin, R L C

    2011-12-01

    Thickened oil-in-water emulsions are useful model foods in rat studies due to their high acceptance and similarity to foods consumed by humans. Previous work from this laboratory used oil-in-water emulsions thickened with a biopolymer blend containing starch. Intake and effects of baclofen, a GABA-B agonist that decreases fat intake and drug self-administration, were reported, but the contribution of starch was not assessed. In the present study, intake and effects of baclofen were assessed in rats using emulsions prepared with two fat types (32% vegetable shortening, 32% corn oil) and thickened with three biopolymer blends. One biopolymer blend contained starch and the other two did not. Daily 1-h intake of the vegetable shortening emulsion containing starch was significantly greater than the other emulsions. When starch was added to the emulsions originally containing no starch, intake significantly increased. Baclofen generally reduced intake of all emulsions regardless of starch content and stimulated intake of chow. However, effects were more often significant for vegetable shortening emulsions. This report: (1) demonstrates that products used to prepare thickened oil-in-water emulsions have significant effects on rat ingestive behavior, and (2) confirms the ability of baclofen to reduce consumption of fatty foods, while simultaneously stimulating intake of chow. Copyright © 2011 Elsevier Ltd. All rights reserved.

  8. FAT EMULSION COMPOSITION ALTERS INTAKE AND THE EFFECTS OF BACLOFEN

    PubMed Central

    Wang, Y; Wilt, DC; Wojnicki, FHE; Babbs, RK; Coupland, JN; Corwin, RLC

    2011-01-01

    Thickened oil-in-water emulsions are useful model foods in rat studies due to their high acceptance and similarity to foods consumed by humans. Previous work from this laboratory used oil-in-water emulsions thickened with a biopolymer blend containing starch. Intake and effects of baclofen, a GABA-B agonist that decreases fat intake and drug self-administration, were reported, but the contribution of starch was not assessed. In the present study, intake and effects of baclofen were assessed in rats using emulsions prepared with two fat types (32% vegetable shortening, 32% corn oil) and thickened with three biopolymer blends. One biopolymer blend contained starch and the other two did not. Daily 1-h intake of the vegetable shortening emulsion containing starch was significantly greater than the other emulsions. When starch was added to the emulsions originally containing no starch, intake significantly increased. Baclofen generally reduced intake of all emulsions regardless of starch content and stimulated intake of chow. However, effects were more often significant for vegetable shortening emulsions. This report: 1) demonstrates that products used to prepare thickened oil-in-water emulsions have significant effects on rat ingestive behavior, and 2) confirms the ability of baclofen to reduce consumption of fatty foods, while simultaneously stimulating intake of chow. PMID:21855586

  9. A minimally invasive technique for the detection and analysis of pulmonary fat embolism: a feasibility study.

    PubMed

    Filograna, Laura; Bolliger, Stephan A; Kneubuehl, Beat; Jackowski, Christian; Hatch, Gary M; Thali, Michael J

    2012-09-01

    We investigated the feasibility of postmortem percutaneous needle biopsy (PNB) for obtaining pulmonary samples adequate for the study of pulmonary fat embolism (PFE). Samples of both lungs were obtained from 26 cadavers via two different methods: (i) PNB and (ii) the double-edged knife technique, the gold standard at our institute. After water storage and Sudan III staining, six forensic pathologists independently examined all samples for the presence and severity of PFE. The results were compared and analyzed in each case regarding the vitality of the PFE and its relationship to the cause of death. The results showed that PFE was almost identically diagnosed and graded on the samples obtained via both methods. The discrepancies between the two techniques did not affect the diagnoses of vitality or cause of death related to PFE. This study demonstrates the feasibility of the PNB sampling method for the diagnosis and interpretation of PFE in the postmortem setting.

  10. Pulmonary Embolization of Fat and Bone Marrow in Cynomolgus Macaques (Macaca fascicularis)

    PubMed Central

    Fong, Derek L.; Murnane, Robert D.; Hotchkiss, Charlotte E.; Green, Damian J.; Hukkanen, Renee R.

    2011-01-01

    Fat embolization (FE), the introduction of bone marrow elements into circulation, is a known complication of bone fractures. Although FE has been described in other animal models, this study represents the first reported cases of FE and bone marrow embolism in nonhuman primates. Histopathologic findings from cynomolgus macaques (Macaca fascicularis) indicated that in all 5 cases, fat and bone marrow embolization occurred subsequent to multiple bone marrow biopsies. In the most severe case, extensive embolization was associated pulmonary damage consistent with acute respiratory distress syndrome. Fat embolism syndrome (FES) is an infrequent clinical outcome of FE and is triggered by systemic biochemical and mechanical responses to fat in circulation. Although clinical criteria diagnostic of FES were not investigated at the time of death, this severe case may represent the fulminant form of FES, which occurs within 12 h after trauma. Bone marrow biopsy as an etiology of FES has been reported only once in humans. In addition, the association of embolization with bone marrow biopsies suggests that nonhuman primates may be a useful animal model of FE. FE and FES represent important research confounders and FES should be considered as a differential diagnosis for clinical complications subsequent to skeletal trauma. PMID:21819686

  11. Combined Pulmonary Fibrosis and Emphysema Alters Physiology but Has Similar Mortality to Pulmonary Fibrosis Without Emphysema

    PubMed Central

    Rounds, Sharon

    2010-01-01

    Studies have described individuals with combined pulmonary fibrosis and emphysema (CPFE), with preserved lung volumes, significant reductions in gas exchange, and high prevalence of pulmonary hypertension. While physiologic changes in CPFE are well documented, there is little mortality data in the CPFE population compared to appropriate controls. A study was performed to determine the features and outcomes of a group of individuals with imaging and/or pathologic evidence of CPFE to determine if individuals with combined pulmonary fibrosis and emphysema have different features and survival than individuals with pulmonary fibrosis alone. We conducted a retrospective study at a Veterans Affairs Medical Center. Included in the study were individuals hospitalized over a 5-year period who were given a clinical diagnosis of pulmonary fibrosis. Individuals with confirmed imaging or pathologic evidence of pulmonary fibrosis were divided into a study group with concomitant emphysema (CPFE group, n = 20) and a control group without emphysema (isolated pulmonary fibrosis (PF) group, n = 24). The CPFE group, all current or former cigarette smokers, had significantly larger lung volumes, more expiratory airflow obstruction, and worse gas exchange than the isolated pulmonary fibrosis group. Mortality did not differ between the groups. Combined pulmonary fibrosis and emphysema results in unique physiologic features but no difference in survival compared with a group with pulmonary fibrosis alone. PMID:20614219

  12. Inflammatory and Metabolic Alterations of Kager's Fat Pad in Chronic Achilles Tendinopathy.

    PubMed

    Pingel, Jessica; Petersen, M Christine H; Fredberg, Ulrich; Kjær, Søren G; Quistorff, Bjørn; Langberg, Henning; Hansen, Jacob B

    2015-01-01

    Achilles tendinopathy is a painful inflammatory condition characterized by swelling, stiffness and reduced function of the Achilles tendon. Kager's fat pad is an adipose tissue located in the area anterior to the Achilles tendon. Observations reveal a close physical interplay between Kager's fat pad and its surrounding structures during movement of the ankle, suggesting that Kager's fat pad may stabilize and protect the mechanical function of the ankle joint. The aim of this study was to characterize whether Achilles tendinopathy was accompanied by changes in expression of inflammatory markers and metabolic enzymes in Kager's fat pad. A biopsy was taken from Kager's fat pad from 31 patients with chronic Achilles tendinopathy and from 13 healthy individuals. Gene expression was measured by reverse transcription-quantitative PCR. Focus was on genes related to inflammation and lipid metabolism. Expression of the majority of analyzed inflammatory marker genes was increased in patients with Achilles tendinopathy compared to that in healthy controls. Expression patterns of the patient group were consistent with reduced lipolysis and increased fatty acid β-oxidation. In the fat pad, the pain-signaling neuropeptide substance P was found to be present in one third of the subjects in the Achilles tendinopathy group but in none of the healthy controls. Gene expression changes in Achilles tendinopathy patient samples were consistent with Kager's fat pad being more inflamed than in the healthy control group. Additionally, the results indicate an altered lipid metabolism in Kager's fat pad of Achilles tendinopathy patients.

  13. Dietary fat alters the response of hypothalamic neuropeptide Y to subsequent energy intake in broiler chickens.

    PubMed

    Wang, Xiao J; Xu, Shao H; Liu, Lei; Song, Zhi G; Jiao, Hong C; Lin, Hai

    2017-02-15

    Dietary fat affects appetite and appetite-related peptides in birds and mammals; however, the effect of dietary fat on appetite is still unclear in chickens faced with different energy statuses. Two experiments were conducted to investigate the effects of dietary fat on food intake and hypothalamic neuropeptides in chickens subjected to two feeding states or two diets. In Experiment 1, chickens were fed a high-fat (HF) or low-fat (LF) diet for 35 days, and then subjected to fed (HF-fed, LF-fed) or fasted (HF-fasted, LF-fasted) conditions for 24 h. In Experiment 2, chickens that were fed a HF or LF diet for 35 days were fasted for 24 h and then re-fed with HF (HF-RHF, LF-RHF) or LF (HF-RLF, LF-RLF) diet for 3 h. The results showed that chickens fed a HF diet for 35 days had increased body fat deposition despite decreasing food intake even when the diet was altered during the re-feeding period (P<0.05). LF diet (35 days) promoted agouti-related peptide (AgRP) expression compared with HF diet (P<0.05) under both fed and fasted conditions. LF-RHF chickens had lower neuropeptide Y (NPY) expression compared with LF-RLF chickens; conversely, HF-RHF chickens had higher NPY expression than HF-RLF chickens (P<0.05). These results demonstrate: (1) that HF diet decreases food intake even when the subsequent diet is altered; (2) the orexigenic effect of hypothalamic AgRP; and (3) that dietary fat alters the response of hypothalamic NPY to subsequent energy intake. These findings provide a novel view of the metabolic perturbations associated with long-term dietary fat over-ingestion in chickens.

  14. Altered Immune Phenotype in Peripheral Blood Cells of Patients with Scleroderma-Associated Pulmonary Hypertension

    PubMed Central

    Risbano, Michael G; Meadows, Christina A; Coldren, Christopher D; Jenkins, Tiffany J.; Edwards, Michael G; Collier, David; Huber, Wendy; Mack, Douglas G; Fontenot, Andrew P; Geraci, Mark W; Bull, Todd M

    2010-01-01

    Pulmonary arterial hypertension is a common and fatal complication of scleroderma that may involve inflammatory and autoimmune mechanisms. Alterations in the gene expression of peripheral blood mononuclear cells have been previously described in patients with pulmonary arterial hypertension. Our goal is to identify differentially expressed genes in peripheral blood mononuclear cells in scleroderma patients with and without pulmonary hypertension as biomarkers of disease. Gene expression analysis was performed on a Microarray Cohort of scleroderma patients with (n=10) and without (n=10) pulmonary hypertension. Differentially expressed genes were confirmed in the Microarray Cohort and validated in a Validation Cohort of scleroderma patients with (n=15) and without (n=19) pulmonary hypertension by RT-qPCR. We identified inflammatory and immune-related genes including interleukin-7 receptor (IL-7R) and chemokine receptor 7 as differentially expressed in patients with scleroderma-associated pulmonary hypertension. Flow cytometry confirmed decreased expression of IL-7R on circulating CD4+ T-cells from scleroderma patients with pulmonary hypertension. Differences exist in the expression of inflammatory and immune-related genes in peripheral blood cells from patients with scleroderma-related pulmonary hypertension compared to those with normal pulmonary artery pressures. These findings may have implications as biomarkers to screen at-risk populations for early diagnosis and provide insight into mechanisms of scleroderma-related pulmonary hypertension. PMID:20973920

  15. High-fat-induced intestinal permeability dysfunction associated with altered fecal bile acids

    PubMed Central

    Stenman, Lotta K; Holma, Reetta; Korpela, Riitta

    2012-01-01

    AIM: To investigate whether high-fat-feeding is associated with increased intestinal permeability via alterations in bile acid metabolism. METHODS: Male C57Bl/6J mice were fed on a high-fat (n = 26) or low-fat diet (n = 24) for 15 wk. Intestinal permeability was measured from duodenum, jejunum, ileum and colon in an Ussing chamber system using 4 kDa FITC-labeled dextran as an indicator. Fecal bile acids were analyzed with gas chromatography. Segments of jejunum and colon were analyzed for the expression of farnesoid X receptor (FXR) and tumor necrosis factor (TNF). RESULTS: Intestinal permeability was significantly increased by high-fat feeding in jejunum (median 0.334 for control vs 0.393 for high-fat, P = 0.03) and colon (0.335 for control vs 0.433 for high-fat, P = 0.01), but not in duodenum or ileum. The concentration of nearly all identified bile acids was significantly increased by high-fat feeding (P < 0.001). The proportion of ursodeoxycholic acid (UDCA) in all bile acids was decreased (1.4% ± 0.1% in high-fat vs 2.8% ± 0.3% in controls, P < 0.01) and correlated inversely with intestinal permeability (r = -0.72, P = 0.01). High-fat feeding also increased jejunal FXR expression, as well as TNF expression along the intestine, especially in the colon. CONCLUSION: High-fat-feeding increased intestinal permeability, perhaps by a mechanism related to bile acid metabolism, namely a decreased proportion of fecal UDCA and increased FXR expression. PMID:22408351

  16. Pulmonary alterations associated with inhalation of occupational and environmental irritants.

    PubMed

    Castranova, V; Frazer, D G; Manley, L K; Dey, R D

    2002-02-01

    Many gases, vapors, or particles found in occupational and/or environmental settings can act as irritants. In the present study, sensory irritants are characterized by the stimulation of neuropeptide release from sensory nerves in the nasal mucosa, while pulmonary irritants are characterized by recruitment of PMN into bronchoalveolar airspaces, elevation of breathing frequency, and neuropeptide release from sensory fibers innervating the epithelium of the conducting airways. A review of data from our laboratory as well as results from others indicate that asphalt fume is a sensory irritant; toluene diisocyanate (TDI), methyl isocyanate, and machining fluid act as both sensory and pulmonary irritants; while cotton dust, agricultural dusts, microbial products, leather conditioner, and ozone exhibit responses characteristic of pulmonary irritants.

  17. High-fat diet alters the dopamine and opioid systems: effects across development

    PubMed Central

    Reyes, T M

    2012-01-01

    Consumption of a high-fat diet has been linked to obesity, dyslipidemia and cardiovascular disease. Less well appreciated are adverse effects on the brain and behavior. Recent research has shown that consumption of a high-fat diet can alter gene expression within the brain, and the dopamine and opioid neurotransmitter systems appear to be vulnerable to dysregulation. This review will focus on recent reports in both humans and animal models that describe adverse effects of high-fat diet consumption on the central reward circuitry. In addition, the importance of different development windows will be discussed, with effects observed in both the prenatal/perinatal time period and with chronic high-fat diet consumption in adulthood. PMID:27152150

  18. Role of Survival Time and Injury Severity in Fatal Pulmonary Fat Embolism.

    PubMed

    Jarmer, Juliane; Ampanozi, Garyfalia; Thali, Michael J; Bolliger, Stephan A

    2017-03-01

    Pulmonary fat embolism (PFE) is frequent in blunt trauma and may occasionally lead to death. A correlation between fracture grade and severity and PFE grade has been described before, but no correlation between PFE and survival time, fat crushing extent, fat crush grade, or number of body regions with fractures could be noted in this small study. To further examine this, we decided to examine the aforementioned points in a far larger study group.Autopsy protocols of 188 nonresuscitated fatalities with blunt trauma and without right heart injury, which underwent whole body dissection, were retrospectively reviewed concerning the presence and the severity of PFE, injuries, survival time, age, sex, and the body mass index.The fracture grade, the fracture severity, and the number of the fractured regions correlated very well with the grade of PFE, but the crushed regions, crush grade, and crush severity did not. We observed a time correlation between survival time and PFE only in the sense that very rapid deaths were often PFE negative. High-grade PFE was observed most often in patients having died less than 6 hours after the incident, and PFE grades of 2 or more were occasionally noted even after 48 hours.

  19. Coronary Artery Calcification, Epicardial Fat Burden, and Cardiovascular Events in Chronic Obstructive Pulmonary Disease

    PubMed Central

    Schwarz, Esther I.; Possner, Mathias; Stehli, Julia; Sievi, Noriane A.; Clarenbach, Christian F.; Dey, Damini; Slomka, Piotr J.; Kaufmann, Philipp A.; Kohler, Malcolm

    2015-01-01

    Rationale Patients with chronic obstructive pulmonary disease (COPD) suffer from significantly more cardiovascular comorbidity and mortality than would be anticipated from conventional risk factors. The aim of this study was to determine whether COPD patients have a higher coronary artery calcium score (CACS) and epicardial fat burden, compared to control subjects, and their association with cardiovascular events. Methods From a registry of 1906 patients 81 patients with clinically diagnosed COPD were one-to-one matched to 81 non-COPD control subjects with a smoking history, according to their age, sex, and the number of classic cardiovascular risk factors (arterial hypertension, diabetes mellitus, dyslipidemia, family history of premature coronary artery disease). CACS, epicardial fat, and subsequent major adverse cardiovascular events (MACE) during follow-up were compared between groups. Results Patients with COPD (Global Initiative for Chronic Obstructive Lung Disease-classification I: 5%, II: 23%, III: 16% and IV: 56%) showed no difference in CACS (median difference 68 Agatston Units [95% confidence interval -176.5 to 192.5], p=0.899) or epicardial fat volume (mean difference -0.5 cm3 [95% confidence interval -20.9 to 21.9], p=0.961) compared with controls. After a median follow-up of 42.6 months a higher incidence of MACE was observed in COPD patients (RR=2.80, p=0.016) compared with controls. Cox proportional hazard regression identified cardiac ischemias and CACS as independent predictors for MACE. Conclusion COPD patients experienced a higher MACE incidence compared to controls despite no baseline differences in coronary calcification and epicardial fat burden. Other mechanisms such as undersupply of medication seem to account for an excess cardiovascular comorbidity in COPD patients. PMID:26011039

  20. Acute exposure to a high-fat diet alters meal patterns and body composition

    PubMed Central

    Melhorn, Susan J; Krause, Eric G; Scott, Karen A; Mooney, Marie R; Johnson, Jeffrey D; Woods, Stephen C; Sakai, Randall R

    2009-01-01

    Weight gain and adiposity are often attributed to the overconsumption of unbalanced, high-fat diets however, the pattern of consumption can also contribute to associated body weight and compositional changes. The present study explored the rapid alterations in meal patterns of normal-weight rats given continuous access to high-fat diet and examined body weight and composition changes compared to chow fed controls. Ten Long-Evans rats were implanted with subcutaneous microchips for meal pattern analysis. Animals were body weight-matched and separated into two groups: high-fat or chow fed. Each group was maintained on their assigned diet for nine days and monitored for 22-hours each day for meal pattern behavior. Body weight was evaluated every other day, and body composition measures were taken prior and following diet exposure. High-fat fed animals gained more weight and adipose tissue than chow fed controls and displayed a reduced meal frequency and increased meal size. Furthermore, meal size was significantly correlated with the gain of adipose tissue. Together, these results suggest that consumption of a high-fat diet can rapidly alter meal patterns, which in turn contribute to the development of adiposity. PMID:19835896

  1. Analysis of visceral fat in patients with chronic obstructive pulmonary disease (COPD).

    PubMed

    Lenártová, Petra; Habánová, Marta; Mrázová, Jana; Chlebo, Peter; Wyka, Joanna

    2016-01-01

    Cigarette smoking is a major public health problem, which leads to the formation of chronic obstructive pulmonary disease (COPD) and is one of the main causes of avoidable death and disability worldwide. The aim of study was analysis and comparison of the visceral fat in the body of the three groups of subjects (non-smokers, smokers and COPD patients) by Tanita Viscan 140. The control group was composed of: (1) non-smokers (n=30), consisted of 13 males (43.4%) and 17 women (56.6%) - the average age was 52 ± 6.51 years and (2) smokers (n=30), consisted of 12 men (40%) and 18 women (60%) - the average age 46.53 ± 9.22 years. Study group consisted of patients with COPD (n=60), which consisted of 48 men (80%) and 12 women (20%). Mean age was 69.25 ± 9.90 years. The measurement of visceral fat by Tanita Viscan device 140, which uses bioelectrical impedance analysis to measure fat in the abdomen of the patient in the supine position. High levels of visceral fat (women from 36.9% to 52.3% and more, men from 27.1% to 40.3% or more) were observed in 19 patients (3 women and 16 men), with 19 smokers (10 women and 9 men) and non-smokers in 22 subjects (10 women and 12 men). The average value of waist circumference measured with a Tanita Viscan 140 was in the group of patients 96.38 ± 12.27 cm, in the group of smokers 95.23 ± 10.12 cm and in group of non-smokers 96.86 ± 10.88 cm. The results of our work are of great importance for the health assessment not only among patients with COPD but also in the group of smokers. Therefore it would be appropriate to remind the general public, eg. by campaign for chronic obstructive pulmonary disease and its serious complications and reduce the life quality of these patients and thus help protect human health and in particular young people from the harmful effects of tobacco products.

  2. Altered autophagy and sympathetic innervation in salivary glands from high-fat diet mice.

    PubMed

    de Carvalho, Polliane Morais; Gavião, Maria Beatriz Duarte; Carpenter, Guy Howard

    2017-03-01

    to investigate the effects of a high fat diet (HFD) on salivary glands in vivo, in a mouse model. In particular, whether it will induce the appearance of fat cells in salivary glands, alterations related to autophagy, mTOR pathway and sympathetic innervation. 27 adult female ICR mice were separated in six groups. Three groups fed with (HFD) containing 55% fat, for one, two and three month and another three groups fed with normal diet (2.7% of fat), for the same time periods. The submandibular glands and liver were dissected and part homogenized for protein analyses and part fixed in formalin for histological analyses. After three months the HFD fed mice total body weight fold change increased compared to controls. The Oil Red O staining showed no fat cells deposit in salivary gland however a large increase was observed in liver after three months of HFD. Adiponectin levels were significantly decreased in the HFD group after three months. The group fed with HFD for three months showed increased conversion of the LC3 autophagy marker in salivary gland. mTOR showed no activation regarding the time point studied. Tyrosine hydroxylase significantly decreased after two and three month of HFD. HFD caused several changes after three months however the earliest change was noticed after two months regarding sympathetic innervation. This suggests neural alteration may drive other diet induced changes in salivary glands. These early changes may be the starting point for longer term alterations of salivary glands with alterations in diet. Copyright © 2016 Elsevier Ltd. All rights reserved.

  3. Inflammatory and Metabolic Alterations of Kager's Fat Pad in Chronic Achilles Tendinopathy

    PubMed Central

    Fredberg, Ulrich; Kjær, Søren G.; Quistorff, Bjørn; Langberg, Henning; Hansen, Jacob B.

    2015-01-01

    Background Achilles tendinopathy is a painful inflammatory condition characterized by swelling, stiffness and reduced function of the Achilles tendon. Kager’s fat pad is an adipose tissue located in the area anterior to the Achilles tendon. Observations reveal a close physical interplay between Kager’s fat pad and its surrounding structures during movement of the ankle, suggesting that Kager’s fat pad may stabilize and protect the mechanical function of the ankle joint. Aim The aim of this study was to characterize whether Achilles tendinopathy was accompanied by changes in expression of inflammatory markers and metabolic enzymes in Kager’s fat pad. Methods A biopsy was taken from Kager’s fat pad from 31 patients with chronic Achilles tendinopathy and from 13 healthy individuals. Gene expression was measured by reverse transcription-quantitative PCR. Focus was on genes related to inflammation and lipid metabolism. Results Expression of the majority of analyzed inflammatory marker genes was increased in patients with Achilles tendinopathy compared to that in healthy controls. Expression patterns of the patient group were consistent with reduced lipolysis and increased fatty acid β-oxidation. In the fat pad, the pain-signaling neuropeptide substance P was found to be present in one third of the subjects in the Achilles tendinopathy group but in none of the healthy controls. Conclusion Gene expression changes in Achilles tendinopathy patient samples were consistent with Kager’s fat pad being more inflamed than in the healthy control group. Additionally, the results indicate an altered lipid metabolism in Kager’s fat pad of Achilles tendinopathy patients. PMID:25996876

  4. Pulmonary vascular-bronchial interactions: acute reduction in pulmonary blood flow alters lung mechanics

    PubMed Central

    Schulze-Neick, I; Penny, D; Derrick, G; Dhillon, R; Rigby, M; Kelleher, A; Bush, A; Redington, A

    2000-01-01

    BACKGROUND—Postoperative pulmonary hypertension in children after congenital heart surgery is a risk factor for death and is associated with severe acute changes in both pulmonary vascular resistance and lung mechanics.
OBJECTIVE—To examine the impact of changes in pulmonary blood flow on lung mechanics in preoperative children with congenital heart disease, in order to assess the cause-effect relation of pulmonary vascular-bronchial interactions.
DESIGN—Prospective, cross sectional study.
SETTING—Cardiac catheterisation laboratory, general anaesthesia with mechanical ventilation.
INTERVENTIONS—Variation of pulmonary blood flow (Qp) by either balloon occlusion of an atrial septal defect before interventional closure, or by complete occlusion of the pulmonary artery during balloon pulmonary valvuloplasty for pulmonary valve stenosis.
MAIN OUTCOME MEASURES—Ventilatory tidal volume (Vt), dynamic respiratory system compliance (Cdyn), respiratory system resistance (Rrs).
RESULTS—28 occlusions were examined in nine patients with atrial septal defect (median age 9.5 years) and 22 in eight patients with pulmonary stenosis (median age 1.2 years). Normalisation of Qp during balloon occlusion of atrial septal defect caused no significant change in airway pressures and Rrs, but there was a small decrease in Vt (mean (SD): 9.61 (0.85) to 9.52 (0.97) ml/kg; p < 0.05) and Cdyn (0.64 (0.11) to 0.59 (0.10) ml/cm H2O*kg; p < 0.01). These changes were more pronounced when there was complete cessation of Qp during balloon valvuloplasty in pulmonary stenosis, with a fall in Vt (9.71 (2.95) to 9.32 (2.84) ml/kg; p < 0.05) and Cdyn (0.72 (0.29) to 0.64 (0.26) ml/cm H2O*kg; p < 0.001), and there was also an increase in Rrs (25.1 (1.7) to 28.8 (1.6) cm H2O/litre*s; p < 0.01). All these changes exceeded the variability of the baseline measurements more than threefold.
CONCLUSIONS—Acute changes in pulmonary blood flow are associated

  5. The effects of body fat distribution on pulmonary function tests in the overweight and obese.

    PubMed

    Ceylan, Emel; Cömlekçi, Abdurrahman; Akkoçlu, Atila; Ceylan, Cengiz; Itil, Oya; Ergör, Gül; Yeşil, Sena

    2009-01-01

    To determine the predominant pulmonary function abnormality in overweight and moderately obese subjects and to evaluate the correlation between the severity of lung function impairment and the degree of obesity. Fifty-three volunteers underwent physical examination, skin fold measurements, and standardized pulmonary function tests. Thirty-one women and 22 men with a mean age of 40.2 (18-66) years were studied. The reduction in functional residual capacity (FRC) and expiratory reserve volume (ERV) were the most common abnormalities in overweight and obese subjects. The reduction in static lung volume was correlated with the degree of obesity in women and men. Stepwise multiple regression coefficients were obtained separately for women and men. Subscapular skinfold was the best predictor in women for FRC and waist-to-hip ratio (WHR) and BMI were found the best for ERV. WHR was found predictive for forced vital capacity, total lung capacity, and FRC in men. The lung volumes are substantially affected in our overweight and obese subjects. This influence is focused on different parameters of respiratory functions in men and women in relation to body fat distribution.

  6. Experimental pulmonary fat embolism: computed tomography and pathologic findings of the sequential changes.

    PubMed

    Woo, Ok Hee; Yong, Hwan Seok; Oh, Yu-Whan; Shin, Bong Kyung; Kim, Han Kyeom; Kang, Eun-Young

    2008-08-01

    This study was done to demonstrate the computed tomography (CT) and pathologic findings of the sequential changes for experimental pulmonary fat embolism (PFE), and to correlate the CT and pathologic findings of rabbit lung. PFE was induced by an intravenous injection of 0.2 mL linoleic acid in 24 rabbits. The rabbits were divided into 4 groups of 6 rabbits each. CT scans were obtained sequentially at 2 hr (n= 24), day 1 (n=18), day 3 (n=12) and day 7 (n=6) after fat embolization. The pathologic findings were analyzed and CT-pathologic correlation was done. CT scans showed bilateral ground-glass opacity (GGO), consolidation and nodule in all cases. The findings of PFE at 2 hr after fat embolization were areas of decreased attenuation, GGO, consolidation and nodule. These findings were aggravated on the follow- up CT after 1 day and 3 days. The follow-up CT revealed linear density in the subpleural lungs after 7 days. On CT-pathology correlation, wedge-shaped ischemic necrosis in the subpleural lungs correlated with nodule at 2 hr. GGO and consolidation at day 1 on CT correlated with congestion and edema, and these findings at day 3 were correlated with inflammation and hemorrhagic edema. The linear density in the subpleural lungs correlated with interstitial fibrosis and pleural contraction at day 7. In conclusion, PFE was caused by using linoleic acid which is kind of free fatty acid and this study served as one model of the occurrence of nontraumatic PFE. CT accurately depicted the natural evolution of PFE in the serial followup, and this correlated well with the pathologic findings.

  7. Changes of Dietary Fat and Carbohydrate Content Alter Central and Peripheral Clock in Humans.

    PubMed

    Pivovarova, Olga; Jürchott, Karsten; Rudovich, Natalia; Hornemann, Silke; Ye, Lu; Möckel, Simona; Murahovschi, Veronica; Kessler, Katharina; Seltmann, Anne-Cathrin; Maser-Gluth, Christiane; Mazuch, Jeannine; Kruse, Michael; Busjahn, Andreas; Kramer, Achim; Pfeiffer, Andreas F H

    2015-06-01

    The circadian clock coordinates numerous metabolic processes with light-dark and feeding regimens. However, in humans it is unknown whether dietary patterns influence circadian rhythms. We examined the effects of switching from a high-carbohydrate, low-fat diet to a low-carbohydrate, high fat (LC/HFD) isocaloric diet on the central and peripheral circadian clocks in humans. Diurnal patterns of salivary cortisol and gene expression were analyzed in blood monocytes of 29 nonobese healthy subjects before and 1 and 6 weeks after the dietary switch. For this, we established a method of rhythm prediction by 3-time point data. The centrally driven cortisol rhythm showed a phase delay 1 and 6 weeks after the dietary switch to a LC/HFD as well as an amplitude increase. The dietary switch altered diurnal oscillations of core clock genes (PER1, PER2, PER3, and TEF) and inflammatory genes (CD14, CD180, NFKBIA, and IL1B). The LC/HFD also affected the expression of nonoscillating genes contributing to energy metabolism (SIRT1) and fat metabolism (ACOX3 and IDH3A). Expression of clock genes but not of salivary cortisol in monocytes tightly correlated with levels of blood lipids and with expression of metabolic and inflammatory genes. Our results suggest that the modulation of the dietary fat and carbohydrate content alters the function of the central and peripheral circadian clocks in humans.

  8. Alteration of pulmonary artery integrin levels in chronic hypoxia and monocrotaline-induced pulmonary hypertension.

    PubMed

    Umesh, Anita; Paudel, Omkar; Cao, Yuan-Ning; Myers, Allen C; Sham, James S K

    2011-01-01

    Pulmonary hypertension is associated with vascular remodeling and increased extracellular matrix (ECM) deposition. While the contribution of ECM in vascular remodeling is well documented, the roles played by their receptors, integrins, in pulmonary hypertension have received little attention. Here we characterized the changes of integrin expression in endothelium-denuded pulmonary arteries (PAs) and aorta of chronic hypoxia as well as monocrotaline-treated rats. Immunoblot showed increased α(1)-, α(8)- and α(v)-integrins, and decreased α(5)-integrin levels in PAs of both models. β(1)- and β(3)-integrins were reduced in PAs of chronic hypoxia and monocrotaline-treated rats, respectively. Integrin expression in aorta was minimally affected. Differential expression of α(1)- and α(5)-integrins induced by chronic hypoxia was further examined. Immunostaining showed that they were expressed on the surface of PA smooth muscle cells (PASMCs), and their distribution was unaltered by chronic hypoxia. Phosphorylation of focal adhesion kinase was augmented in PAs of chronic hypoxia rats, and in chronic hypoxia PASMCs cultured on the α(1)-ligand collagen IV. Moreover, α(1)-integrin binding hexapeptide GRGDTP elicited an enhanced Ca(2+) response, whereas the response to α(5)-integrin binding peptide GRGDNP was reduced in CH-PASMCs. Integrins in PASMCs are differentially regulated in pulmonary hypertension, and the dynamic integrin-ECM interactions may contribute to the vascular remodeling accompanying disease progression. Copyright © 2011 S. Karger AG, Basel.

  9. Alteration of Pulmonary Artery Integrin Levels in Chronic Hypoxia and Monocrotaline-Induced Pulmonary Hypertension

    PubMed Central

    Umesh, Anita; Paudel, Omkar; Cao, Yuan-Ning; Myers, Allen C.; Sham, James S.K.

    2011-01-01

    Background Pulmonary hypertension is associated with vascular remodeling and increased extracellular matrix (ECM) deposition. While the contribution of ECM in vascular remodeling is well documented, the roles played by their receptors, integrins, in pulmonary hypertension have received little attention. Here we characterized the changes of integrin expression in endothelium-denuded pulmonary arteries (PAs) and aorta of chronic hypoxia as well as monocrotaline-treated rats. Methods and Results Immunoblot showed increased α1-, α8- and αv-integrins, and decreased α5-integrin levels in PAs of both models. β1- and β3-integrins were reduced in PAs of chronic hypoxia and monocrotaline-treated rats, respectively. Integrin expression in aorta was minimally affected. Differential expression of α1- and α5-integrins induced by chronic hypoxia was further examined. Immunostaining showed that they were expressed on the surface of PA smooth muscle cells (PASMCs), and their distribution was unaltered by chronic hypoxia. Phosphorylation of focal adhesion kinase was augmented in PAs of chronic hypoxia rats, and in chronic hypoxia PASMCs cultured on the α1-ligand collagen IV. Moreover, α1-integrin binding hexapeptide GRGDTP elicited an enhanced Ca2+ response, whereas the response to α5-integrin binding peptide GRGDNP was reduced in CH-PASMCs. Conclusion Integrins in PASMCs are differentially regulated in pulmonary hypertension, and the dynamic integrin-ECM interactions may contribute to the vascular remodeling accompanying disease progression. PMID:21829038

  10. Pulmonary Ozone Exposure Alters Essential Metabolic Pathways involved in Glucose Homeostasis in the Liver

    EPA Science Inventory

    Pulmonary Ozone Exposure Alters Essential Metabolic Pathways involved in Glucose Homeostasis in the Liver D.B. Johnson, 1 W.O. Ward, 2 V.L. Bass, 2 M.C.J. Schladweiler, 2A.D. Ledbetter, 2 D. Andrews, and U.P. Kodavanti 2 1 Curriculum in Toxicology, UNC School of Medicine, Cha...

  11. Pulmonary Ozone Exposure Alters Essential Metabolic Pathways involved in Glucose Homeostasis in the Liver

    EPA Science Inventory

    Pulmonary Ozone Exposure Alters Essential Metabolic Pathways involved in Glucose Homeostasis in the Liver D.B. Johnson, 1 W.O. Ward, 2 V.L. Bass, 2 M.C.J. Schladweiler, 2A.D. Ledbetter, 2 D. Andrews, and U.P. Kodavanti 2 1 Curriculum in Toxicology, UNC School of Medicine, Cha...

  12. Use of free subcutaneous fat pad for reduction of intraoperative air leak in thoracoscopic pulmonary resection cases with lung cancer.

    PubMed

    Shintani, Yasushi; Inoue, Masayoshi; Nakagiri, Tomoyuki; Okumura, Meinoshin

    2014-08-01

    Intraoperative alveolar air leaks occur in patients with non-small-cell lung cancer (NSCLC) following a pulmonary resection using thoracoscopic surgery. We showed the efficacy of covering damaged lung tissue with a subcutaneous fat pad for preventing postoperative air leak. Thoracoscopic surgery was performed for NSCLC patients with three incisions along with a 3-4 cm anterior utility incision. When an air leak originated from deep within the pulmonary parenchyma or was large, a subcutaneous fat pad ∼2 × 2 cm in size was harvested from the utility incision and placed on the damaged lung tissue with fibrin glue and 2-3 mattress sutures. Subcutaneous fat pads were used for 50 patients with NSCLC during thoracoscopic surgery procedures. There were no intraoperative complications in any of the patients. A prolonged air leak (>7 days) was noted in 3 (6%) of the 50 patients. Air leak was diminished at 1.5 ± 2.6 postoperative days and the chest tubes removed at 3.2 ± 2.8 postoperative days. Reinforcement of damaged lung tissues by use of subcutaneous free fat pads is a safe and intriguing procedure in NSCLC patients who underwent a pulmonary resection in thoracoscopic surgery.

  13. Maternal High Fat Diet Alters Skeletal Muscle Mitochondrial Catalytic Activity in Adult Male Rat Offspring

    PubMed Central

    Pileggi, Chantal A.; Hedges, Christopher P.; Segovia, Stephanie A.; Markworth, James F.; Durainayagam, Brenan R.; Gray, Clint; Zhang, Xiaoyuan D.; Barnett, Matthew P. G.; Vickers, Mark H.; Hickey, Anthony J. R.; Reynolds, Clare M.; Cameron-Smith, David

    2016-01-01

    A maternal high-fat (HF) diet during pregnancy can lead to metabolic compromise, such as insulin resistance in adult offspring. Skeletal muscle mitochondrial dysfunction is one mechanism contributing to metabolic impairments in insulin resistant states. Therefore, the present study aimed to investigate whether mitochondrial dysfunction is evident in metabolically compromised offspring born to HF-fed dams. Sprague-Dawley dams were randomly assigned to receive a purified control diet (CD; 10% kcal from fat) or a high fat diet (HFD; 45% kcal from fat) for 10 days prior to mating, throughout pregnancy and during lactation. From weaning, all male offspring received a standard chow diet and soleus muscle was collected at day 150. Expression of the mitochondrial transcription factors nuclear respiratory factor-1 (NRF1) and mitochondrial transcription factor A (mtTFA) were downregulated in HF offspring. Furthermore, genes encoding the mitochondrial electron transport system (ETS) respiratory complex subunits were suppressed in HF offspring. Moreover, protein expression of the complex I subunit, NDUFB8, was downregulated in HF offspring (36%), which was paralleled by decreased maximal catalytic linked activity of complex I and III (40%). Together, these results indicate that exposure to a maternal HF diet during development may elicit lifelong mitochondrial alterations in offspring skeletal muscle. PMID:27917127

  14. Fasting and high-fat diet alter histone deacetylase expression in the medial hypothalamus.

    PubMed

    Funato, Hiromasa; Oda, Satoko; Yokofujita, Junko; Igarashi, Hiroaki; Kuroda, Masaru

    2011-04-15

    Increasing attention is now being given to the epigenetic regulation of animal and human behaviors including the stress response and drug addiction. Epigenetic factors also influence feeding behavior and metabolic phenotypes, such as obesity and insulin sensitivity. In response to fasting and high-fat diets, the medial hypothalamus changes the expression of neuropeptides regulating feeding, metabolism, and reproductive behaviors. Histone deacetylases (HDACs) are involved in the epigenetic control of gene expression and alter behavior in response to a variety of environmental factors. Here, we examined the expression of HDAC family members in the medial hypothalamus of mice in response to either fasting or a high-fat diet. In response to fasting, HDAC3 and -4 expression levels increased while HDAC10 and -11 levels decreased. Four weeks on a high-fat diet resulted in the increased expression of HDAC5 and -8. Moreover, fasting decreased the number of acetylated histone H3- and acetylated histone H4-positive cells in the ventrolateral subdivision of the ventromedial hypothalamus. Therefore, HDACs may be implicated in altered gene expression profiles in the medial hypothalamus under different metabolic states.

  15. Fasting and High-Fat Diet Alter Histone Deacetylase Expression in the Medial Hypothalamus

    PubMed Central

    Funato, Hiromasa; Oda, Satoko; Yokofujita, Junko; Igarashi, Hiroaki; Kuroda, Masaru

    2011-01-01

    Increasing attention is now being given to the epigenetic regulation of animal and human behaviors including the stress response and drug addiction. Epigenetic factors also influence feeding behavior and metabolic phenotypes, such as obesity and insulin sensitivity. In response to fasting and high-fat diets, the medial hypothalamus changes the expression of neuropeptides regulating feeding, metabolism, and reproductive behaviors. Histone deacetylases (HDACs) are involved in the epigenetic control of gene expression and alter behavior in response to a variety of environmental factors. Here, we examined the expression of HDAC family members in the medial hypothalamus of mice in response to either fasting or a high-fat diet. In response to fasting, HDAC3 and −4 expression levels increased while HDAC10 and −11 levels decreased. Four weeks on a high-fat diet resulted in the increased expression of HDAC5 and −8. Moreover, fasting decreased the number of acetylated histone H3- and acetylated histone H4-positive cells in the ventrolateral subdivision of the ventromedial hypothalamus. Therefore, HDACs may be implicated in altered gene expression profiles in the medial hypothalamus under different metabolic states. PMID:21526203

  16. Altered carnitine homeostasis is associated with decreased mitochondrial function and altered nitric oxide signaling in lambs with pulmonary hypertension

    PubMed Central

    Sharma, Shruti; Sud, Neetu; Wiseman, Dean A.; Carter, A. Lee; Kumar, Sanjiv; Hou, Yali; Rau, Thomas; Wilham, Jason; Harmon, Cynthia; Oishi, Peter; Fineman, Jeffrey R.; Black, Stephen M.

    2008-01-01

    Utilizing aortopulmonary vascular graft placement in the fetal lamb, we have developed a model (shunt) of pulmonary hypertension that mimics congenital heart disease with increased pulmonary blood flow. Our previous studies have identified a progressive development of endothelial dysfunction in shunt lambs that is dependent, at least in part, on decreased nitric oxide (NO) signaling. The purpose of this study was to evaluate the possible role of a disruption in carnitine metabolism in shunt lambs and to determine the effect on NO signaling. Our data indicate that at 2 wk of age, shunt lambs have significantly reduced expression (P < 0.05) of the key enzymes in carnitine metabolism: carnitine palmitoyltransferases 1 and 2 as well as carnitine acetyltransferase (CrAT). In addition, we found that CrAT activity was inhibited due to increased nitration. Furthermore, free carnitine levels were significantly decreased whereas acylcarnitine levels were significantly higher in shunt lambs (P < 0.05). We also found that alterations in carnitine metabolism resulted in mitochondrial dysfunction, since shunt lambs had significantly decreased pyruvate, increased lactate, and a reduced pyruvate/lactate ratio. In pulmonary arterial endothelial cells cultured from juvenile lambs, we found that mild uncoupling of the mitochondria led to a decrease in cellular ATP levels and a reduction in both endothelial NO synthase-heat shock protein 90 (eNOS-HSP90) interactions and NO signaling. Similarly, in shunt lambs we found a loss of eNOS-HSP90 interactions that correlated with a progressive decrease in NO signaling. Our data suggest that mitochondrial dysfunction may play a role in the development of endothelial dysfunction and pulmonary hypertension and increased pulmonary blood flow. PMID:18024721

  17. Alterations in immunoglobulin & complement levels in chronic obstructive pulmonary disease.

    PubMed

    Chauhan, S; Gupta, M K; Goyal, A; Dasgupta, D J

    1990-08-01

    Thirty patients of chronic obstructive pulmonary disease (COPD; all smokers) and an equal number of controls (15 smokers) were studied. The COPD patients were further divided into group A (predominantly emphysema) and group B (predominantly bronchitis) of 15 patients each. Serum and sputum IgG, IgA and IgM and serum C3 and C4 were estimated. IgG, IgA, IgM and C3 and C4 were similar in smoker and non-smoker controls. Mean (+/- SD) serum IgG (IU/ml) was significantly higher in COPD patients (207.78 +/- 62.73) than in control (177.25 +/- 43.5; P less than 0.05), serum IgA (IU/ml) was also significantly higher in COPD (205.04 +/- 46.56) than in control (108.21 +/- 33.3; P less than 0.01). IgM was similar in the 2 groups. Sputum IgA (IU/ml) was higher in COPD (4.68 +/- 3.51) than in control (2.25 +/- 1.03; P less than 0.05). IgG and IgM were similar in the 2 groups. Both serum C3 (IU) and C4 (IU) were lower in COPD patients (C3 = 95.9 +/- 33.11, C4 = 113.6 +/- 62.4) than in control (C3 = 167.3 +/- 25.42, C4 = 205 +/- 76.5; P less than 0.05). Serum IgA in type B COPD (212.25 +/- 50.06) was higher than in type A (197.52 +/- 43.3; P less than 0.05) IgG and IgM were similar in these 2 groups. In COPD patients, immunoglobulins were either normal or higher indicating that deficiency of immunoglobulin is not a predisposing factor in development of COPD. Similar immunoglobulin values in smoker and nonsmoker controls indicated that smoking was not the cause of rise of immunoglobulins in COPD.(ABSTRACT TRUNCATED AT 250 WORDS)

  18. Biological features of core networks that result from a high-fat diet in hepatic and pulmonary tissues in mammary tumour-bearing, obesity-resistant mice.

    PubMed

    Kim, Eun Ji; Oh, Hea Young; Heo, Hyoung-Sam; Hong, Ji Eun; Jung, Sung-Jae; Lee, Ki Won; Park, Jong Hoon; Hur, Cheol-Goo; Park, Jung Han Yoon

    2013-07-28

    We previously demonstrated that the chronic consumption of a high-fat diet (HFD) promotes lung and liver metastases of 4T1 mammary carcinoma cells in obesity-resistant BALB/c mice. To examine early transcriptional responses to tumour progression in the liver and lungs of HFD-fed mice, 4-week-old female BALB/c mice were divided into four groups: sham-injected, control diet (CD)-fed; sham-injected, HFD-fed (SH); 4T1 cell-injected, CD-fed (TC); 4T1 cell-injected, HFD-fed (TH). Following 16 weeks of either a CD or HFD, 4T1 cells were injected into the mammary fat pads of mice in the TC and TH groups and all mice were continuously fed identical diets. At 14 d post-injection, RNA was isolated from hepatic and pulmonary tissues for microarray analysis of mRNA expression. Functional annotation and core network analyses were conducted for the TH/SH Unique gene set. Inflammation in hepatic tissues and cell mitosis in pulmonary tissues were the most significant biological functions in the TH/SH Unique gene set. The biological core networks of the hepatic TH/SH Unique gene set were characterised as those genes involved in the activation of acute inflammatory responses (Orm1, Lbp, Hp and Cfb), disordered lipid metabolism and deregulated cell cycle progression. Networks of the pulmonary Unique gene set displayed the deregulation of cell cycle progression (Cdc20, Cdk1 and Bub1b). These HFD-influenced alterations may have led to favourable conditions for the formation of both pro-inflammatory and pro-mitotic microenvironments in the target organs that promote immune cell infiltration and differentiation, as well as the infiltration and proliferation of metastatic tumour cells.

  19. MicroRNA Expression Signature Is Altered in the Cardiac Remodeling Induced by High Fat Diets.

    PubMed

    Guedes, Elaine Castilho; França, Gustavo Starvaggi; Lino, Caroline Antunes; Koyama, Fernanda Christtanini; Moreira, Luana do Nascimento; Alexandre, Juliana Gomes; Barreto-Chaves, Maria Luiza M; Galante, Pedro Alexandre Favoretto; Diniz, Gabriela Placoná

    2016-08-01

    Recent studies have revealed the involvement of microRNAs (miRNAs) in the control of cardiac hypertrophy and myocardial function. In addition, several reports have demonstrated that high fat (HF) diet induces cardiac hypertrophy and remodeling. In the current study, we investigated the effect of diets containing different percentages of fat on the cardiac miRNA expression signature. To address this question, male C57Bl/6 mice were fed with a low fat (LF) diet or two HF diets, containing 45 kcal% fat (HF45%) and 60 kcal% fat (HF60%) for 10 and 20 weeks. HF60% diet promoted an increase on body weight, fasting glycemia, insulin, leptin, total cholesterol, triglycerides, and induced glucose intolerance. HF feeding promoted cardiac remodeling, as evidenced by increased cardiomyocyte transverse diameter and interstitial fibrosis. RNA sequencing analysis demonstrated that HF feeding induced distinct miRNA expression patterns in the heart. HF45% diet for 10 and 20 weeks changed the abundance of 64 and 26 miRNAs in the heart, respectively. On the other hand, HF60% diet for 10 and 20 weeks altered the abundance of 27 and 88 miRNAs in the heart, respectively. Bioinformatics analysis indicated that insulin signaling pathway was overrepresented in response to HF diet. An inverse correlation was observed between cardiac levels of GLUT4 and miRNA-29c. Similarly, we found an inverse correlation between expression of GSK3β and the expression of miRNA-21a-3p, miRNA-29c-3p, miRNA-144-3p, and miRNA-195a-3p. In addition, miRNA-1 overexpression prevented cardiomyocyte hypertrophy. Taken together, our results revealed differentially expressed miRNA signatures in the heart in response to different HF diets. J. Cell. Physiol. 231: 1771-1783, 2016. © 2015 Wiley Periodicals, Inc.

  20. Deregulation of the Protocadherin Gene FAT1 Alters Muscle Shapes: Implications for the Pathogenesis of Facioscapulohumeral Dystrophy

    PubMed Central

    Caruso, Nathalie; Herberth, Balàzs; Bartoli, Marc; Puppo, Francesca; Dumonceaux, Julie; Zimmermann, Angela; Denadai, Simon; Lebossé, Marie; Roche, Stephane; Geng, Linda; Magdinier, Frederique; Attarian, Shahram; Bernard, Rafaelle; Maina, Flavio; Levy, Nicolas; Helmbacher, Françoise

    2013-01-01

    Generation of skeletal muscles with forms adapted to their function is essential for normal movement. Muscle shape is patterned by the coordinated polarity of collectively migrating myoblasts. Constitutive inactivation of the protocadherin gene Fat1 uncoupled individual myoblast polarity within chains, altering the shape of selective groups of muscles in the shoulder and face. These shape abnormalities were followed by early onset regionalised muscle defects in adult Fat1-deficient mice. Tissue-specific ablation of Fat1 driven by Pax3-cre reproduced muscle shape defects in limb but not face muscles, indicating a cell-autonomous contribution of Fat1 in migrating muscle precursors. Strikingly, the topography of muscle abnormalities caused by Fat1 loss-of-function resembles that of human patients with facioscapulohumeral dystrophy (FSHD). FAT1 lies near the critical locus involved in causing FSHD, and Fat1 mutant mice also show retinal vasculopathy, mimicking another symptom of FSHD, and showed abnormal inner ear patterning, predictive of deafness, reminiscent of another burden of FSHD. Muscle-specific reduction of FAT1 expression and promoter silencing was observed in foetal FSHD1 cases. CGH array-based studies identified deletion polymorphisms within a putative regulatory enhancer of FAT1, predictive of tissue-specific depletion of FAT1 expression, which preferentially segregate with FSHD. Our study identifies FAT1 as a critical determinant of muscle form, misregulation of which associates with FSHD. PMID:23785297

  1. Altering the fatty acids in milk fat by including canola seed in dairy cattle diets.

    PubMed

    Chichlowski, M W; Schroeder, J W; Park, C S; Keller, W L; Schimek, D E

    2005-09-01

    The objective was to evaluate the effects of feeding ground canola seed on the fatty acid profile, yield, and composition of milk from dairy cows. Twenty-four multiparous Holstein cows (548.3 +/- 11.9 kg body weight and 28 +/- 9 d in lactation) were randomly assigned to 1 of 2 treatments: Control (CON) or ground canola seed treatment (GCS) with 14% [of diet dry matter (DM)] of the total ration as ground canola seed containing 34% lipid. Diets contained 20% crude protein, but varied in net energy as a result of fat content differences of 2.5% and 6.4% (DM) for CON and GCS, respectively. Diets were composed of corn, corn silage, alfalfa (50:50 ground hay and haylage, DM basis), soybean and blood meal, and vitamins and minerals. Mechanically extruded canola meal was used in the CON diet to adjust for the protein from canola seed in the GCS diet. Cows were housed in tie-stalls and fed and milked twice daily for 10 wk. The inclusion of ground canola seed did not alter DM intake, weight gain, or body condition score of cows. Milk fat from GCS cows had greater proportions of long-chain fatty acids (> or = 18 carbons) and a lower ratio of n-6 to n-3 fatty acids. Feeding GCS reduced the proportion of short- and medium-chain fatty acids. Milk fat from cows fed GCS had a greater proportion of vaccenic acid and tended to have a higher proportion of cis-9,trans-11 conjugated linoleic acid. Actual and 3.5% fat-corrected milk yields were similar between treatments. The milk fat and protein percentages were lower for GCS cows, but total yield of these components was similar between treatments. Milk urea nitrogen was lower and serum urea nitrogen tended to be lower in cows fed canola seed. Serum glucose, insulin, and nonesterified fatty acids were not altered, but serum triglycerides were higher in GCS cows. Ammonia and total volatile fatty acids tended to be lower in ruminal fluid from GCS cows; rumen pH was unchanged. Feeding canola seed to lactating dairy cows resulted in milk

  2. Functional properties of butter oil made from bovine milk with experimentally altered fat composition.

    PubMed

    Ortiz-Gonzalez, G; Jimenez-Flores, R; Bremmer, D R; Clark, J H; DePeters, E J; Schmidt, S J; Drackley, J K

    2007-11-01

    Modification of milk fat composition might be desirable to alter manufacturing characteristics or produce low saturated fat dairy products that more closely meet consumer dietary preferences. The aim of this research was to evaluate functional properties of butter oil obtained from milks with fat composition modified by altering the profile of long-chain fatty acids (FA) absorbed from the small intestine of cows. A control and 5 mixtures of long-chain free FA were infused into the abomasum of lactating dairy cows in a 6 x 6 Latin square design with 21-d periods. Treatments were 1) control (no FA infused), 2) mostly saturated FA (C16:C18 = 0.72), 3) low-linoleic palm FA (C16:C18 = 0.85), 4) palm FA (C16:C18 = 0.72), 5) soy FA (C16:C18 = 0.10), and 6) high-palmitic soy FA (C16:C18 = 0.68). All treatments included meat solubles and Tween 80 as emulsifiers. Solid fat content (from 0 to 40 degrees C), melting point, and force at fracture were determined in butter oil. Milk fat from cows infused with palm FA (treatment 4) exhibited functionality equal to or better than control butter oil. Infusion with palm FA increased amounts of triglyceride (TG) fractions with 48, 52, and 54 carbon numbers but decreased TG with 32, 34, 36, and 42 carbon numbers. Infusion with soy FA increased TG with 26, 38, 40, 52, and 54 carbon numbers but decreased TG with 34, 42, and 46 carbons. Infusion of the mostly saturated FA increased TG with 38, 50, 52, and 54 carbon numbers but decreased TG with 32, 34, and 42 carbon numbers. These TG groups were consistently correlated with functional properties of butter oils from different treatments. The content of palmitic acid is important for maintaining functionality in the presence of increased polyunsaturated FA. The composition of milk fat may be able to be optimized through nutritional manipulation of diets for dairy cows if the optimal composition of FA and TG is defined for a particular dairy product.

  3. The relation of fat-free mass to maximum exercise performance in patients with chronic obstructive pulmonary disease.

    PubMed

    Kobayashi, A; Yoneda, T; Yoshikawa, M; Ikuno, M; Takenaka, H; Fukuoka, A; Narita, N; Nezu, K

    2000-01-01

    To assess the factors determining maximum exercise performance in patients with chronic obstructive pulmonary disease (COPD), we examined nutritional status with special reference to body composition and pulmonary function in 50 stable COPD patients. Nutritional status was evaluated by body weight and body composition, including fat mass (FM) and fat-free mass (FFM) assessed by bioelectrical impedance analysis (BIA). Exercise performance was evaluated by maximum oxygen uptake (Vo(2max)) on a cycle ergometer. A total of 50 patients (FEV(1) = 0.98 L) was divided randomly into either a study group (group A, n = 25) or validation group (group B, n = 25). Stepwise regression analysis was performed in group A to determine the best predictors of Vo(2max) from measurements of pulmonary function and nutritional status. Stepwise regression analysis revealed that Vo(2max) was predicted best by the following equation in group A: Vo(2max) (mL/min) = 10.223 x FFM (kg) + 4.188 x MVV (L/min) + 9.952 x DL(co) (mL/min/mmHg) - 127.9 (r = 0.84, p < 0. 001). This equation was then cross-validated in group B: Measured Vo(2max) (mL/min) = 1.554 x Predicted Vo(2max) (mL/min) - 324.0 (r = 0.87, p < 0.001). We conclude that FFM is an important factor in determining maximum exercise performance, along with pulmonary function parameters, in patients with COPD.

  4. Circulating cytokines in sarcoidosis: Phenotype-specific alterations for fibrotic and non-fibrotic pulmonary disease

    PubMed Central

    Patterson, Karen C.; Franek, Beverly S.; Müller-Quernheim, Joachim; Sperling, Anne I.; Sweiss, Nadera J.; Niewold, Timothy B.

    2013-01-01

    Aims Sarcoidosis is a granulomatous disease of unknown etiology marked by tremendous clinical heterogeneity. Many patients enter remission with good long-term outcomes. Yet, chronic disease is not uncommon, and this important phenotype remains understudied. Identified alterations in local and circulating cytokines—specifically targeted for study, and often in the acute phase of disease—have informed our growing understanding of the immunopathogenesis of sarcoidosis. Our aim was to evaluate a broad panel of circulating cytokines in patients with chronic sarcoidosis. Among those with chronic disease, pulmonary fibrosis occurs in only a subset. To gain more insight into the determinants of the fibrotic response, we also determined if the phenotypes of fibrotic and non-fibrotic pulmonary sarcoidosis have distinct cytokine profiles. Results In patients with sarcoidosis compared to controls, IL-5 was decreased, and IL-7 was increased. Both of these comparisons withstood rigorous statistical correction for multiple comparisons. GM-CSF met a nominal level of significance. We also detected an effect of phenotype, where IL-5 was significantly decreased in non-fibrotic compared to fibrotic pulmonary sarcoidosis, and compared to controls. Compared to controls, there was a trend towards a significant increase in IL-7 in fibrotic, but not in non-fibrotic pulmonary sarcoidosis. In contrast, compared to controls, there was a trend towards a significant increase in GM-CSF in non-fibrotic, but not in fibrotic pulmonary sarcoidosis. Conclusions In a comprehensive evaluation of circulating cytokines in sarcoidosis, we found IL-5, IL-7, and GM-CSF to be altered. These findings provide a window into the immunopathogenesis of sarcoidosis. IL-7 is a novel sarcoidosis cytokine and, as a master regulator of lymphocytes, is an attractive target for further studies. By observing an effect of phenotype upon cytokine patterns, we also identify specific immune alterations which may

  5. Alteration of tight junctions in pulmonary microvascular endothelial cells in bleomycin-treated rats.

    PubMed

    Yin, Qian; Nan, Haiyan; Yan, Linfeng; Huang, Xiaofeng; Wang, Wei; Cui, Guangbin; Wei, Jingguo

    2012-01-01

    Macrophages and eosinophils that infiltrate the lung interstitium are active promoters of bleomycin (BLM)-induced pulmonary fibrosis. Leukocyte infiltration indicates disrupted barrier function in endothelial cells. The aims of this study were to investigate tight junctions (TJs) and their regulation of zonula occludens-1 (ZO-1) proteins in pulmonary microvascular endothelial cells (PMVECs) during BLM-induced pulmonary fibrosis and to compare the BLM model with the pneumococcus-induced pneumonia model of lung injury. The results revealed that the majority of PMVEC TJs were in an open state in BLM-treated tissue, where PMVEC paracellular permeability remained consistently higher than in controls. Macrophage accumulation in the lung interstitium was also significantly higher than in controls. Alteration of ZO-1 protein expression further supported the apparent disruption in PMVEC TJs in tissues from BLM-treated rats. These changes were markedly different from the concurrent changes in pneumococcus-infected rats. The findings suggest that changes in the ZO-1 proteins of PMVECs underlie the sustained disruption of TJs in BLM-treated animal models of pulmonary fibrosis. This dysfunction of paracellular barriers directly leads to the sustained infiltration of leukocytes and corresponding cytokine secretion, proliferation of fibroblasts, and progression of pulmonary fibrosis. Crown Copyright © 2010. Published by Elsevier GmbH. All rights reserved.

  6. Maternal high-fat diet alters anxiety behavior and glucocorticoid signaling in adolescent offspring.

    PubMed

    Sasaki, A; de Vega, W; Sivanathan, S; St-Cyr, S; McGowan, P O

    2014-07-11

    Maternal obesity and overconsumption of saturated fats during pregnancy have profound effects on offspring health, ranging from metabolic to behavioral disorders in later life. The influence of high-fat diet (HFD) exposure on the development of brain regions implicated in anxiety behavior is not well understood. We previously found that maternal HFD exposure is associated with an increase in anxiety behavior and alterations in the expression of several genes involved in inflammation via the glucocorticoid signaling pathway in adult rat offspring. During adolescence, the maturation of feedback systems mediating corticosteroid sensitivity is incomplete, and therefore distinct from adulthood. In this study, we examined the influence of maternal HFD on several measures of anxiety behavior and gene expression in adolescent offspring. We examined the expression of corticosteroid receptors and related inflammatory processes, as corticosteroid receptors are known to regulate circulating corticosterone levels during basal and stress conditions in addition to influencing inflammatory processes in the hippocampus and amygdala. We found that adolescent animals perinatally exposed to HFD generally showed decreased anxiety behavior accompanied by a selective alteration in the expression of the glucocorticoid receptor and several downstream inflammatory genes in the hippocampus and amygdala. These data suggest that adolescence constitutes an additional period when the effects of developmental programming may modify mental health trajectories. Copyright © 2014 IBRO. Published by Elsevier Ltd. All rights reserved.

  7. Vascular smooth muscle cell alterations triggered by mice adipocytes: role of high-fat diet.

    PubMed

    El Akoum, Souhad; Cloutier, Isabelle; Tanguay, Jean-François

    2012-01-01

    Inherent mechanisms leading to vascular smooth muscle cells (VSMC) alterations in obesitylinked type 2 diabetes (T2D) situation remain to be clarified. This study evaluates the impact of supernatant of adipocytes extracted from mice fed high-fat-diets (HFD) on the proliferation and apoptosis of VSMC. Adipocytes were extracted from visceral white fat pads of male and female C57Bl6 mice showing different stages of metabolic alterations after 20 weeks of vegetal or animal HFD feeding. These cells were stimulated or not with insulin or glucose to condition VSMC media. After 24h of stimulation with adipocyte supernatants (AdS), VSMC proliferation and sustainability were assessed in the absence and presence of AdS. CD36 and insulin receptor mRNA levels were also evaluated. Proliferation and viability of VSMC were significantly modulated by the nature of the AdS used and the gender of mice from which adipocytes have been extracted. The most extensive effects on VSMC were triggered by adipocytes from males fed animal HFD and females fed vegetal HFD. These effects were concurrent with increased leptin concentration and decreased adiponectin levels in AdS. In addition, adipocytes of HFD-fed mice increased caspase-3 activity and apoptosis in VSMC. Significant up-regulation of CD36 mRNA was also found in these cells. Adipocytes of HFD-fed mice induce VSMC alterations. These changes involved mouse gender, most probably correlated to the diet-induced adipocyte secretion profile. Greater sensitivity to AdS effects in VSMC raises concerns about the more frequent cardiovascular events associated with obesity in the presence of T2D, which impairs adipocyte activity.

  8. Composition of Dietary Fat Source Shapes Gut Microbiota Architecture and Alters Host Inflammatory Mediators in Mouse Adipose Tissue

    PubMed Central

    Huang, Edmond; Leone, Vanessa; Devkota, Suzanne; Wang, Yunwei; Brady, Matthew; Chang, Eugene

    2013-01-01

    Background Growing evidence shows that dietary factors can dramatically alter the gut microbiome in ways that contribute to metabolic disturbance and progression of obesity. In this regard, mesenteric adipose tissue has been implicated in mediating these processes through the elaboration of pro-inflammatory adipokines. In this study, we examined the relationship of these events by determining the effects of dietary fat content and source on gut microbiota, as well as the effects on adipokine profiles of mesenteric and peripheral adipocytes. Methods Adult male C57Bl/6 mice were fed milk fat-, lard-(SFA sources), or safflower oil (PUFA)- based high fat diets for four weeks. Body mass and food consumption were measured. Stool 16S rRNA was isolated and analyzed via T-RFLP as well as variable V3-4 sequence tags via next gen sequencing. Mesenteric and gonadal adipose samples were analyzed for both lipogenic and inflammatory mediators via qRT-PCR. Results High-fat feedings caused more weight gain with concomitant increases in caloric consumption relative to low-fat diets. Additionally, each of the high fat diets induced dramatic and specific 16S rRNA phylogenic profiles that were associated with different inflammatory and lipogenic mediator profile of mesenteric and gonadal fat depots. Conclusions Our findings support the notion that dietary fat composition can both reshape the gut microbiota as well as alter host adipose tissue inflammatory/lipogenic profiles. They also demonstrate the interdependency of dietary fat source, commensal gut microbiota, and inflammatory profile of mesenteric fat that can collectively impact the host metabolic state. PMID:23639897

  9. Rate of alteration of hepatic mixed-function oxidase system in rats fed different dietary fats.

    PubMed

    Ammouche, A; Dinh, L; Youyou, A; Clément, M; Bourre, J M

    1993-01-01

    Studies were carried out to evaluate and relate the rate of alteration in mixed-function oxidase system with the changes of the fatty acid composition of rat microsomes induced by different dietary lipids. Male weanling rats were fed from day 21 to 120 with a commercial rat diet or a semisynthetic diet containing no fat or 10% fat consisting of peanut-rapeseed oil, sunflower oil, or salmon oil. In rats fed a fat-free diet, the cytochrome P-450 concentration and aniline hydroxylase, aminopyrine N-demethylase, and NADPH-cytochrome-c reductase activities of liver microsomes at 120 days were, respectively, 26, 16, 10, and 24% lesser than those of rats fed the control diet. However, cytochrome b5 concentration and NADH-cytochrome-b5 reductase activity were, respectively, 33 and 43% higher than those of the control group at the same time. When rats were fed the sunflower oil diet, the cytochrome P-450 concentration and NADH-cytochrome-b5 reductase activity at 120 days were, respectively, 11 and 23% lesser than those of control group. But the cytochrome b5 concentration was 10% higher than that of the control group. In rats fed the fish oil diet, the cytochrome P-450 concentration and NADPH-cytochrome-c reductase, aniline hydroxylase, and aminopyrine N-demethylase activities at 120 days were, respectively, 30, 48, 41, and 31% higher than those of rats fed the control diet. These enzymes were correlated very well (0.84 < r < 0.93), P < 0.05 with dietary sigma polyunsaturated fatty acids (n-3).(ABSTRACT TRUNCATED AT 250 WORDS)

  10. High-fat diet alters protein composition of detergent-resistant membrane microdomains.

    PubMed

    Uyy, Elena; Ivan, Luminita; Boteanu, Raluca Maria; Suica, Viorel Iulian; Antohe, Felicia

    2013-12-01

    A high-lipid diet is one of the main risk factors in atherosclerosis and can induce changes in the composition of plasma membrane microdomains. In response, important functions such as vesicle trafficking, protein docking, signaling and receptor recognition are significantly altered. In particular, interactions of heat-shock proteins (Hsps), acting as danger signals, with components of the membrane microdomains can influence signaling pathways and the inflammatory response of cells. Our study focuses on the composition of detergent-resistant membrane (DRM) isolated from ApoE-/- mice fed a standard or high-fat diet with and without fluvastatin treatment versus appropriate controls. Biochemical studies, immunoblotting and liquid chromatography mass spectrometric analysis were performed to investigate whether the structural components (such as caveolin and cavin) of the detergent-resistant microdomains were correlated with the expression and secretion of stress-inducible Hsps (Hsp70 and Hsp90) and AKT phosphorylation in experimental atherosclerosis. ApoE-/- mice challenged with a high-fat diet developed extensive atherosclerotic plaques in lesion-prone areas. DRM harvested from hyperlipidemic animals showed a modified biochemical composition with cholesterol, glycerolipids, caveolin-1 and phospho-AKT being up-regulated, whereas cavin-1 and dynamin were down-regulated. The data also demonstrated the co-fractionation of Hsps with caveolin-1 in isolated DRM, expression being positively correlated with their secretion into blood serum. Statin therapy significantly attenuated the processes induced by the development of atherosclerosis in ApoE-/- mice under a high-fat diet. Thus, high-lipid stress induces profound changes in DRM biochemistry and modifies the cellular response, supporting the systemic inflammatory onset of atherosclerosis.

  11. Altering the sex determination pathway in Drosophila fat body modifies sex-specific stress responses

    PubMed Central

    Neckameyer, Wendi S.

    2014-01-01

    The stress response in Drosophila melanogaster reveals sex differences in behavior, similar to what has been observed in mammals. However, unlike mammals, the sex determination pathway in Drosophila is well established, making this an ideal system to identify factors involved in the modulation of sex-specific responses to stress. In this study, we show that the Drosophila fat body, which has been shown to be important for energy homeostasis and sex determination, is a dynamic tissue that is altered in response to stress in a sex and time-dependent manner. We manipulated the sex determination pathway in the fat body via targeted expression of transformer and transformer-2 and analyzed these animals for changes in their response to stress. In the majority of cases, manipulation of transformer or transformer-2 was able to change the physiological output in response to starvation and oxidative stress to that of the opposite sex. Our data also uncover the possibility of additional downstream targets for transformer and transformer-2 that are separate from the sex determination pathway and can influence behavioral and physiological responses. PMID:24789992

  12. Association between abdominal fat distribution, adipocytokines and metabolic alterations in obese low-birth-weight children.

    PubMed

    Domínguez Hernández, C; Klünder Klünder, M; Huang, F; Flores Armas, E M; Velázquez-López, L; Medina-Bravo, P

    2016-08-01

    In addition to obesity, low birth weight (LBW) has been proposed as another independent risk factor associated with cardiovascular disease and type 2 diabetes mellitus. This study aimed to evaluate the influence of birth weight on abdominal fat distribution, adipocytokine levels and associated metabolic alterations in obese children. A cross-sectional study was conducted in 92 children. Children were divided into three groups according to their body mass index and birth weight. Glucose and insulin (0 and 120 min), lipid profile and adipocytokines were measured. Abdominal fat distribution was assessed by magnetic resonance imaging. Obese LBW children had higher fasting glucose (P = 0.054) and insulin (P < 0.001), and 120 min glucose (P < 0.001) and insulin levels (P < 0.001), such as increased HOMA-IR (homeostasis model assessment of insulin resistance index) (P < 0.001). Obesity and LBW were associated with lower concentrations of high molecular weight (HMW) adiponectin (-2.38 [IC 95% -4.27; -0.42, P = 0.018]) and higher subcutaneous adipose tissue (SAT) (28.05 [IC 95% 0.40; 55.7, P = 0.047]) compared with NBW obese children, independent of age or sex. LBW in obese children is associated with lower HMW adiponectin, increased insulin resistance and greater SAT. © 2015 World Obesity.

  13. In utero and postnatal exposure to arsenic alters pulmonary structure and function

    SciTech Connect

    Lantz, R. Clark Chau, Binh; Sarihan, Priyanka; Witten, Mark L.; Pivniouk, Vadim I.; Chen, Guan Jie

    2009-02-15

    In addition to cancer endpoints, arsenic exposures can also lead to non-cancerous chronic lung disease. Exposures during sensitive developmental time points can contribute to the adult disease. Using a mouse model, in utero and early postnatal exposures to arsenic (100 ppb or less in drinking water) were found to alter airway reactivity to methacholine challenge in 28 day old pups. Removal of mice from arsenic exposure 28 days after birth did not reverse the alterations in sensitivity to methacholine. In addition, adult mice exposed to similar levels of arsenic in drinking water did not show alterations. Therefore, alterations in airway reactivity were irreversible and specific to exposures during lung development. These functional changes correlated with protein and gene expression changes as well as morphological structural changes around the airways. Arsenic increased the whole lung levels of smooth muscle actin in a dose dependent manner. The level of smooth muscle mass around airways was increased with arsenic exposure, especially around airways smaller than 100 {mu}m in diameter. This increase in smooth muscle was associated with alterations in extracellular matrix (collagen, elastin) expression. This model system demonstrates that in utero and postnatal exposure to environmentally relevant levels of arsenic can irreversibly alter pulmonary structure and function in the adults.

  14. In Utero and Postnatal Exposure to Arsenic Alters Pulmonary Structure and Function

    PubMed Central

    Lantz, R. Clark; Chau, Binh; Sarihan, Priyanka; Witten, Mark L.; Pivniouk, Vadim I.; Chen, Guan Jie

    2009-01-01

    In addition to cancer endpoints, arsenic exposures can also lead to non-cancerous chronic lung disease. Exposures during sensitive developmental time points can contribute to the adult disease. Using a mouse model, in utero and early postnatal exposures to arsenic (100 ppb or less in drinking water) were found to alter airway reactivity to methacholine challenge in 28 day old pups. Removal of mice from arsenic exposure 28 days after birth did not reverse the alterations in sensitivity to methacholine. In addition, adult mice exposed to similar levels of arsenic in drinking water did not show alterations. Therefore, alterations in airway reactivity were irreversible and specific to exposures during lung development. These functional changes correlated with protein and gene expression changes as well as morphological structural changes around the airways. Arsenic increased the whole lung levels of smooth muscle actin in a dose dependent manner. The level of smooth muscle mass around airways was increased with arsenic exposure, especially around airways smaller than 100 μm in diameter. This increase in smooth muscle was associated with alterations in extracellular matrix (collagen, elastin) expression. This model system demonstrates that in utero and postnatal exposure to environmentally relevant levels of arsenic can irreversibly alter pulmonary structure and function in the adults. PMID:19095001

  15. Prebiotics Reduce Body Fat and Alter Intestinal Microbiota in Children Who Are Overweight or With Obesity.

    PubMed

    Nicolucci, Alissa C; Hume, Megan P; Martínez, Inés; Mayengbam, Shyamchand; Walter, Jens; Reimer, Raylene A

    2017-09-01

    interleukin 6 from baseline (decrease of 15%) compared with the placebo group (increase of 25%). There was a significant decrease in serum triglycerides (decrease of 19%) in the OI group. Quantitative polymerase chain reaction showed a significant increase in Bifidobacterium spp. in the OI group compared with controls. 16S rRNA sequencing revealed significant increases in species of the genus Bifidobacterium and decreases in Bacteroides vulgatus within the group who consumed OI. In fecal samples, levels of primary bile acids increased in the placebo group but not in the OI group over the 16-week study period. In a placebo-controlled, randomized trial, we found a prebiotic (OI) to selectively alter the intestinal microbiota and significantly reduce body weight z-score, percent body fat, percent trunk fat, and serum level of interleukin 6 in children with overweight or obesity (Clinicaltrials.gov no: NCT02125955). Copyright © 2017 AGA Institute. Published by Elsevier Inc. All rights reserved.

  16. Interleukin-22 protects against non-typeable Haemophilus influenzae infection: alteration during chronic obstructive pulmonary disease.

    PubMed

    Sharan, R; Perez-Cruz, M; Kervoaze, G; Gosset, Pierre; Weynants, V; Godfroid, F; Hermand, P; Trottein, F; Pichavant, M; Gosset, P

    2017-01-01

    Chronic obstructive pulmonary disease is a major health problem becoming a leading cause of morbidity and mortality worldwide. A large part of these disorders is associated with acute exacerbations resulting from infection by bacteria, such as non-typeable Haemophilus influenzae (NTHi). Our understanding of the pathogenesis of these exacerbations is still elusive. We demonstrate herein that NTHi infection of mice chronically exposed to cigarette smoke (CS), an experimental model of chronic obstructive pulmonary disease (COPD), not only causes acute pulmonary inflammation but also impairs the production of interleukin (IL)-22, a cytokine with potential anti-bacterial activities. We also report that mice lacking IL-22, as well as mice exposed to CS, have a delayed clearance of NTHi bacteria and display enhanced alveolar wall thickening and airway remodeling compared with controls. Supplementation with IL-22 not only boosted bacterial clearance and the production of anti-microbial peptides but also limited lung damages induced by infection both in IL-22(-/-) and CS-exposed mice. In vitro exposure to CS extract altered the NTHi-induced IL-22 production by spleen cells. This study shows for the first time that a defect in IL-22 is involved in the acute exacerbation induced by NTHi infection during experimental COPD and opens the way to innovative therapeutic strategies.

  17. Switching Adolescent High-Fat Diet to Adult Control Diet Restores Neurocognitive Alterations

    PubMed Central

    Boitard, Chloé; Parkes, Shauna L.; Cavaroc, Amandine; Tantot, Frédéric; Castanon, Nathalie; Layé, Sophie; Tronel, Sophie; Pacheco-Lopez, Gustavo; Coutureau, Etienne; Ferreira, Guillaume

    2016-01-01

    In addition to metabolic and cardiovascular disorders, obesity is associated with adverse cognitive and emotional outcomes. Its growing prevalence in adolescents is particularly alarming since this is a period of ongoing maturation for brain structures (including the hippocampus and amygdala) and for the hypothalamic-pituitary-adrenal (HPA) stress axis, which is required for cognitive and emotional processing. We recently demonstrated that adolescent, but not adult, high-fat diet (HF) exposure leads to impaired hippocampal function and enhanced amygdala function through HPA axis alteration (Boitard et al., 2012, 2014, 2015). Here, we assessed whether the effects of adolescent HF consumption on brain function are permanent or reversible. After adolescent exposure to HF, switching to a standard control diet restored levels of hippocampal neurogenesis and normalized enhanced HPA axis reactivity, amygdala activity and avoidance memory. Therefore, while the adolescent period is highly vulnerable to the deleterious effects of diet-induced obesity, adult exposure to a standard diet appears sufficient to reverse alterations of brain function. PMID:27917115

  18. Effect of physical training on fat-free mass in patients with chronic obstructive pulmonary disease (COPD).

    PubMed

    Emtner, Margareta; Hallin, Runa; Arnardottir, Ragnheiður Harpa; Janson, Christer

    2015-03-01

    Weight loss and depletion of fat-free mass are common problems in patients with chronic obstructive pulmonary disease (COPD) and are related to muscular weakness and exercise intolerance. Physical training of COPD patients has good effect on exercise tolerance and quality of life. The aim of this study was to examine factors that affect change in fat-free mass after physical training, in patients with COPD. Patients were examined before and after a 4-month exercise period. Weight and height were measured, and bioelectrical impedance was performed. Fat-free mass (FFM) was calculated, by a three-compartment model, and fat-free mass index (FFMI) was calculated as FFM kg/m(2) and body mass index (BMI) as kg/m(2). A symptom-limited ramp ergometer test and 12-minute walk test (12MWT) were performed. Dyspnoea score of daily activities was determined by Chronic Respiratory Disease Questionnaire (CRDQ). Blood was taken for analyses of C-reactive protein (CRP) and fibrinogen. Patients with a BMI <21 kg/m(2) were given nutritional support during the training period. A total of 27 patients completed the training (64 years, FEV1 31% of predicted). Patients with low FFMI gained 1.2 kg, whereas those with normal FFMI lost 0.7 kg (p = 0.04). In multivariate analyses high age (p = 0.03), low FEV1 (p = 0.02), and a high level of dyspnoea (p = 0.01) at baseline were found to be negative predictors for increase in FFM. Difficulties in increasing the fat-free mass in COPD patients by physical training seem to be associated with dyspnoea in daily life and impaired lung function (FEV1).

  19. Neuromuscular electrical stimulation improves exercise tolerance in chronic obstructive pulmonary disease patients with better preserved fat-free mass

    PubMed Central

    Nápolis, Lara Maris; Corso, Simone Dal; Neder, José Alberto; Malaguti, Carla; Gimenes, Ana Cristina Oliveira; Nery, Luiz Eduardo

    2011-01-01

    BACKGROUND: High-frequency neuromuscular electrical stimulation increases exercise tolerance in patients with advanced chronic obstructive pulmonary disease (COPD patients). However, it is conceivable that its benefits are more prominent in patients with better-preserved peripheral muscle function and structure. OBJECTIVE: To investigate the effects of high-frequency neuromuscular electrical stimulation in COPD patients with better-preserved peripheral muscle function. Design: Prospective and cross-over study. METHODS: Thirty COPD patients were randomly assigned to either home-based, high-frequency neuromuscular electrical stimulation or sham stimulation for six weeks. The training intensity was adjusted according to each subject's tolerance. Fat-free mass, isometric strength, six-minute walking distance and time to exercise intolerance (Tlim) were assessed. RESULTS: Thirteen (46.4%) patients responded to high-frequency neuromuscular electrical stimulation; that is, they had a post/pre ΔTlim >10% after stimulation (unimproved after sham stimulation). Responders had a higher baseline fat-free mass and six-minute walking distance than their seventeen (53.6%) non-responding counterparts. Responders trained at higher stimulation intensities; their mean amplitude of stimulation during training was significantly related to their fat-free mass (r  =  0.65; p<0.01). Logistic regression revealed that fat-free mass was the single independent predictor of Tlim improvement (odds ratio [95% CI]  =  1.15 [1.04-1.26]; p<0.05). CONCLUSIONS: We conclude that high-frequency neuromuscular electrical stimulation improved the exercise capacity of COPD patients with better-preserved fat-free mass because they tolerated higher training stimulus levels. These data suggest that early training with high-frequency neuromuscular electrical stimulation before tissue wasting begins might enhance exercise tolerance in patients with less advanced COPD. PMID:21552662

  20. Effect of high-fructose and high-fat diets on pulmonary sensitivity, motor activity, and body composition of brown Norway rats exposed to ozone

    EPA Pesticide Factsheets

    pulmonary parameters, BALF biomarkers, body composition, motor activity data collected from rats exposed to ozone after high fructose or high fat diets.This dataset is associated with the following publication:Gordon , C., P. Phillips , A. Johnstone , T. Beasley , A. Ledbetter , M. Schladweiler , S. Snow, and U. Kodavanti. Effect of High Fructose and High Fat Diets on Pulmonary Sensitivity, Motor Activity, and Body Composition of Brown Norway Rats Exposed to Ozone. INHALATION TOXICOLOGY. Taylor & Francis, Inc., Philadelphia, PA, USA, 28(5): 203-15, (2016).

  1. Elevated pulmonary arterial pressure and altered expression of Ddah1 and Arg1 in mice lacking cavin-1/PTRF

    PubMed Central

    Swärd, Karl; Sadegh, Mardjaneh K; Mori, Michiko; Erjefält, Jonas S; Rippe, Catarina

    2013-01-01

    Caveolae are invaginations in the plasma membrane that depend on caveolins and cavins for maturation. Here, we investigated the pulmonary phenotype in mice lacking cavin-1. Bright field and electron-microscopy showed that the cavin-1-deficient mice lacked caveolae in the lung, had an increased lung tissue density, and exhibited hypertrophic remodeling of pulmonary arteries. The right ventricle of the heart moreover had an increased mass and the right ventricular pressure was elevated. A microarray analysis revealed upregulation of Arg1 and downregulation of Ddah1, molecules whose altered expression has previously been associated with pulmonary arterial hypertension. Taken together, this work demonstrates vascular remodeling and increased pulmonary blood pressure in cavin-1 deficient mice and associates this phenotype with altered expression of Arg1 and Ddah1. PMID:24303100

  2. A high-fat diet is associated with altered adipokine production and a more aggressive esophageal adenocarcinoma phenotype in vivo.

    PubMed

    Fowler, Aaron J; Richer, Amanda L; Bremner, Ross M; Inge, Landon J

    2015-04-01

    Obesity has been linked to esophageal adenocarcinoma (EAC). We hypothesize that adipokines, which are altered by obesity, could affect EAC growth rates and potentially serve as biomarkers of disease and targets for treatment. We have developed a potential murine model to investigate the effects of obesity-altered adipokines on EAC in vivo. Severe combined immune-deficient mice were fed either a high-fat diet (HFD) containing 60% animal fat, or a control diet with 10% animal fat, and monitored for weight gain for 5 weeks. All mice were subcutaneously implanted with EAC cells (OE33), and tumor volume was monitored for an additional 4 weeks by direct measurement and uptake of fluorescently labeled 2-D-deoxyglucose. At sacrifice, serum triglyceride levels and abdominal fat-pad weight were measured to assess obesity state. Adipokine levels were measured within abdominal fat of tumor-bearing mice. Mice fed the HFD displayed increased body weight, visceral fat, and serum leptin and triglycerides. All mice developed tumors; OE33 EAC cells in HFD mice displayed increased growth rates, proliferation, and metabolic activity relative to tumors of EAC in control diet mice. Adipokine expression in the abdominal fat revealed distinct changes associated with the HFD and increased body weight. Ad libitum feeding of the HFD was correlated with more-proliferative EAC tumors in vivo. This phenotype was associated with alterations to secreted adipokines, representing a potential mechanism for our observations. Further studies are necessary to explore findings, as they have potential to improve treatment of EAC. Copyright © 2015 The American Association for Thoracic Surgery. Published by Elsevier Inc. All rights reserved.

  3. Altered Hypoxic-Adenosine Axis and Metabolism in Group III Pulmonary Hypertension.

    PubMed

    Garcia-Morales, Luis J; Chen, Ning-Yuan; Weng, Tingting; Luo, Fayong; Davies, Jonathan; Philip, Kemly; Volcik, Kelly A; Melicoff, Ernestina; Amione-Guerra, Javier; Bunge, Raquel R; Bruckner, Brian A; Loebe, Matthias; Eltzschig, Holger K; Pandit, Lavannya M; Blackburn, Michael R; Karmouty-Quintana, Harry

    2016-04-01

    Group III pulmonary hypertension (PH) is a highly prevalent and deadly lung disorder with limited treatment options other than transplantation. Group III PH affects patients with ongoing chronic lung injury, such as idiopathic pulmonary fibrosis (IPF). Between 30 and 40% of patients with IPF are diagnosed with PH. The diagnosis of PH has devastating consequences to these patients, leading to increased morbidity and mortality, yet the molecular mechanisms involved in the development of PH in patients with chronic lung disease remain elusive. Our hypothesis was that the hypoxic-adenosinergic system is enhanced in patients with group III PH compared with patients with IPF with no PH. Explanted lung tissue was analyzed for markers of the hypoxic-adenosine axis, including expression levels of hypoxia-inducible factor (HIF)-1A, adenosine A2B receptor, CD73, and equilibrative nucleotide transporter-1. In addition, we assessed whether altered mitochondrial metabolism was present in these samples. Increased expression of HIF-1A was observed in tissues from patients with group III PH. These changes were consistent with increased evidence of adenosine accumulation in group III PH. A novel observation of our study was of evidence suggesting altered mitochondrial metabolism in lung tissue from group III PH leading to increased succinate levels that are able to further stabilize HIF-1A. Our data demonstrate that the hypoxic-adenosine axis is up-regulated in group III PH and that subsequent succinate accumulation may play a part in the development of group III PH.

  4. Androgen Deficiency Exacerbates High-Fat Diet-Induced Metabolic Alterations in Male Mice.

    PubMed

    Dubois, Vanessa; Laurent, Michaël R; Jardi, Ferran; Antonio, Leen; Lemaire, Katleen; Goyvaerts, Lotte; Deldicque, Louise; Carmeliet, Geert; Decallonne, Brigitte; Vanderschueren, Dirk; Claessens, Frank

    2016-02-01

    Androgen deficiency is associated with obesity, metabolic syndrome, and type 2 diabetes mellitus in men, but the mechanisms behind these associations remain unclear. In this study, we investigated the combined effects of androgen deficiency and high-fat diet (HFD) on body composition and glucose homeostasis in C57BL/6J male mice. Two models of androgen deficiency were used: orchidectomy (ORX) and androgen receptor knockout mice. Both models displayed higher adiposity and serum leptin levels upon HFD, whereas no differences were seen on a regular diet. Fat accumulation in HFD ORX animals was accompanied by increased sedentary behavior and occurred in spite of reduced food intake. HFD ORX mice showed white adipocyte hypertrophy, correlated with decreased mitochondrial content but not function as well as increased lipogenesis and decreased lipolysis suggested by the up-regulation of fatty acid synthase and the down-regulation of hormone-sensitive lipase. Both ORX and androgen receptor knockout exacerbated HFD-induced glucose intolerance by impairing insulin action in liver and skeletal muscle, as evidenced by the increased triglyceride and decreased glycogen content in these tissues. In addition, serum IL-1β levels were elevated, and pancreatic insulin secretion was impaired after ORX. Testosterone but not dihydrotestosterone supplementation restored the castration effects on body composition and glucose homeostasis. We conclude that sex steroid deficiency in combination with HFD exacerbates adiposity, insulin resistance, and β-cell failure in 2 preclinical male mouse models. Our findings stress the importance of a healthy diet in a clinical context of androgen deficiency and may have implications for the prevention of metabolic alterations in hypogonadal men.

  5. Caffeine ingestion does not alter carbohydrate or fat metabolism in human skeletal muscle during exercise

    PubMed Central

    Graham, Terry E; Helge, Jorn W; MacLean, David A; Kiens, Bente; Richter, Erik A

    2000-01-01

    This study examined the effect of ingesting caffeine (6 mg kg−1) on muscle carbohydrate and fat metabolism during steady-state exercise in humans. Young male subjects (n = 10) performed 1 h of exercise (70 % maximal oxygen consumption (V̇O2,max)) on two occasions (after ingestion of placebo and caffeine) and leg metabolism was quantified by the combination of direct Fick measures and muscle biopsies. Following caffeine ingestion serum fatty acid and glycerol concentration increased (P ≤ 0.05) at rest, suggesting enhanced adipose tissue lipolysis. In addition circulating adrenaline concentration was increased (P ≤ 0.05) at rest following caffeine ingestion and this, as well as leg noradrenaline spillover, was elevated (P ≤ 0.05) above placebo values during exercise. Caffeine resulted in a modest increase (P ≤ 0.05) in leg vascular resistance, but no difference was found in leg blood flow. Arterial lactate and glucose concentrations were increased (P ≤ 0.05) by caffeine, while the rise in plasma potassium was dampened (P ≤ 0.05). There were no differences in respiratory exchange ratio or in leg glucose uptake, net muscle glycogenolysis, leg lactate release or muscle lactate, or glucose 6-phosphate concentration. Similarly there were no differences between treatments in leg fatty acid uptake, glycerol release or muscle acetyl CoA concentration. These findings indicate that caffeine ingestion stimulated the sympathetic nervous system but did not alter the carbohydrate or fat metabolism in the monitored leg. Other tissues must have been involved in the changes in circulating potassium, fatty acids, glucose and lactate. PMID:11118510

  6. Array comparative genomic hybridization-based characterization of genetic alterations in pulmonary neuroendocrine tumors.

    PubMed

    Voortman, Johannes; Lee, Jih-Hsiang; Killian, Jonathan Keith; Suuriniemi, Miia; Wang, Yonghong; Lucchi, Marco; Smith, William I; Meltzer, Paul; Wang, Yisong; Giaccone, Giuseppe

    2010-07-20

    The goal of this study was to characterize and classify pulmonary neuroendocrine tumors based on array comparative genomic hybridization (aCGH). Using aCGH, we performed karyotype analysis of 33 small cell lung cancer (SCLC) tumors, 13 SCLC cell lines, 19 bronchial carcinoids, and 9 gastrointestinal carcinoids. In contrast to the relatively conserved karyotypes of carcinoid tumors, the karyotypes of SCLC tumors and cell lines were highly aberrant. High copy number (CN) gains were detected in SCLC tumors and cell lines in cytogenetic bands encoding JAK2, FGFR1, and MYC family members. In some of those samples, the CN of these genes exceeded 100, suggesting that they could represent driver alterations and potential drug targets in subgroups of SCLC patients. In SCLC tumors, as well as bronchial carcinoids and carcinoids of gastrointestinal origin, recurrent CN alterations were observed in 203 genes, including the RB1 gene and 59 microRNAs of which 51 locate in the DLK1-DIO3 domain. These findings suggest the existence of partially shared CN alterations in these tumor types. In contrast, CN alterations of the TP53 gene and the MYC family members were predominantly observed in SCLC. Furthermore, we demonstrated that the aCGH profile of SCLC cell lines highly resembles that of clinical SCLC specimens. Finally, by analyzing potential drug targets, we provide a genomics-based rationale for targeting the AKT-mTOR and apoptosis pathways in SCLC.

  7. Low carbohydrate/high-fat diet attenuates cardiac hypertrophy, remodeling, and altered gene expression in hypertension

    USDA-ARS?s Scientific Manuscript database

    The effects of dietary fat intake on the development of left ventricular hypertrophy and accompanying structural and molecular remodeling in response to hypertension are not understood. The present study compared the effects of a high-fat versus a low-fat diet on development of left ventricular hype...

  8. Randomized trial comparing pulmonary alterations after conventional with venovenous bypass versus piggyback liver transplantation.

    PubMed

    Isern, Maria Rita Montenegro; Massarollo, Paulo Celso Bosco; de Carvalho, Eliane Maria; Baía, Carlos Eduardo Sandoli; Kavakama, Jorge; de Andrade Lima, Poliana; Mies, Sérgio

    2004-03-01

    During the anhepatic phase of conventional liver transplantation (LT), the inferior vena cava (IVC) is cross-clamped and venovenous bypass (VVB) is usually indicated for diversion of IVC and portal blood flow. VVB can theoretically lead to pulmonary complications due to the contact of the blood with the surfaces of the circuit. In the piggyback method, preservation of the IVC avoids VVB. The aim of this study is to compare pulmonary alterations after conventional with VVB versus piggyback LT. Sixty-seven patients were randomized for conventional VVB (n = 34) or piggyback (n = 33) LT. Pulmonary static compliance (C(st)) and Pa(O2)/F(IO2) ratio were measured pre- and post-LT. Chest X-rays were obtained daily from the 1st to the 5th postoperative day. Pre- and post-LT C(st) were 73.4 +/- 36.0 mL/cm H(2)O and 59.7 +/- 22.0 mL/cm H(2)O in the conventional group and 69.1 +/- 20.0 mL/cm H(2)O and 58.7 +/- 27.1 mL/cmH(2)O in the piggyback group. The difference between the two groups was not significant (P =.702). C(st) significantly decreased after LT (P =.008). The pre- and post-LT Pa(O2)/F(IO2) were 455.6 +/- 126.6 mm Hg and 463.1 +/- 105.9 mm Hg in the conventional group and 468.9 +/- 114.1 mm Hg and 483.3 +/- 119.8 mm Hg in the piggyback group. The difference among the two groups was not significant (P = 0.331). There was no significant difference after LT (P =.382). Upon the radiological evaluation, piggyback group presented a higher frequency of pulmonary infiltrates (80.6% vs. 50.0%; P =.025). In conclusion, piggyback LT recipients have a higher rate of pulmonary infiltrates when compared to those operated upon using the conventional VVB method.

  9. Prolonged High Fat Diet Reduces Dopamine Reuptake without Altering DAT Gene Expression

    PubMed Central

    Cone, Jackson J.; Chartoff, Elena H.; Potter, David N.; Ebner, Stephanie R.; Roitman, Mitchell F.

    2013-01-01

    The development of diet-induced obesity (DIO) can potently alter multiple aspects of dopamine signaling, including dopamine transporter (DAT) expression and dopamine reuptake. However, the time-course of diet-induced changes in DAT expression and function and whether such changes are dependent upon the development of DIO remains unresolved. Here, we fed rats a high (HFD) or low (LFD) fat diet for 2 or 6 weeks. Following diet exposure, rats were anesthetized with urethane and striatal DAT function was assessed by electrically stimulating the dopamine cell bodies in the ventral tegmental area (VTA) and recording resultant changes in dopamine concentration in the ventral striatum using fast-scan cyclic voltammetry. We also quantified the effect of HFD on membrane associated DAT in striatal cell fractions from a separate group of rats following exposure to the same diet protocol. Notably, none of our treatment groups differed in body weight. We found a deficit in the rate of dopamine reuptake in HFD rats relative to LFD rats after 6 but not 2 weeks of diet exposure. Additionally, the increase in evoked dopamine following a pharmacological challenge of cocaine was significantly attenuated in HFD relative to LFD rats. Western blot analysis revealed that there was no effect of diet on total DAT protein. However, 6 weeks of HFD exposure significantly reduced the 50 kDa DAT isoform in a synaptosomal membrane-associated fraction, but not in a fraction associated with recycling endosomes. Our data provide further evidence for diet-induced alterations in dopamine reuptake independent of changes in DAT production and demonstrates that such changes can manifest without the development of DIO. PMID:23516454

  10. Metformin prevents vascular prostanoid release alterations induced by a high-fat diet in rats.

    PubMed

    Lee, H J; Cantú, S M; Donoso, A S; Choi, M R; Peredo, H A; Puyó, A M

    2017-06-01

    Perivascular adipose tissue dysfunction induced by high-fat feeding leads to alterations in the modulation of inflammation, contractile activity of the vascular smooth muscle and endothelial function, all risk factors in the development of hypertension. Metformin, an activator of AMP-activated protein kinase (AMPK), is currently the first-line drug treatment for type 2 diabetes (T2DM) and metabolic syndrome. Besides its glucose-lowering effect, there is an interest in actions of this drug with potential relevance in cardiovascular diseases. The high-fat (HF) diet is an experimental model that resembles human metabolic syndrome. We have previously reported an altered pattern of prostanoid release in mesenteric vessels in this model. The aim of this study was to analyse the effects of metformin on mesenteric vascular bed prostanoid release, adiposity index and its relation to blood pressure in Sprague-Dawley rats fed a HF diet for 8 and 12 weeks. Eight groups were used: control (C8, C1), HF diet (HF8, HF12, 50% w/w bovine fat), metformin-treated (CMf8, CMf12, 500 mg/kg/day) and metformin-treated HF diet (HFMf8, HFMf12, both treatments). HF diet increased mesenteric vascular bed adiposity index (%, HF8: 1.7±0.1 vs C8: 0.9±0.04 and HF12: 1.8±0.1 vs C12: 0.8±0.1, P<.001); systolic blood pressure (SBP, mm Hg, HF8: 145±6 vs C8: 118±4, P<.01 and HF12: 151±1 vs C12: 121±3, P<.001). We found a positive correlation between these two parameters. Moreover HF diet increased the release of vasoconstrictor prostanoids such as thromboxane (TX) B2 (ng PR/mg of tissue, HF8: 117±6 vs C8: 66±2 and HF12: 123±6 vs C12: 62±5, P<.001) and prostaglandin (PG) F2α (ng/mg, HF8: 153±9 vs C8: 88±3 and HF12: 160±11 vs C12: 83±5, P<.001). We also found that this increase in the release of vasoconstrictor prostanoids positively correlates with the elevation of SBP. In addition, HF diet increases the release of PGE2 and decreases the prostacyclin (PGI2 )/TXA2 release ratio at 8 and

  11. Altered lymphatics in an ovine model of congenital heart disease with increased pulmonary blood flow.

    PubMed

    Datar, Sanjeev A; Johnson, Eric G; Oishi, Peter E; Johengen, Michael; Tang, Eric; Aramburo, Angela; Barton, Jubilee; Kuo, Hsuan-Chang; Bennett, Stephen; Xoinis, Konstantine; Reel, Bhupinder; Kalkan, Gokhan; Sajti, Eniko; Osorio, Oscar; Raff, Gary W; Matthay, Michael A; Fineman, Jeffrey R

    2012-03-15

    Abnormalities of the lymphatic circulation are well recognized in patients with congenital heart defects. However, it is not known how the associated abnormal blood flow patterns, such as increased pulmonary blood flow (PBF), might affect pulmonary lymphatic function and structure. Using well-established ovine models of acute and chronic increases in PBF, we cannulated the efferent lymphatic duct of the caudal mediastinal node and collected and analyzed lymph effluent from the lungs of lambs with acutely increased PBF (n = 6), chronically increased PBF (n = 6), and age-matched normal lambs (n = 8). When normalized to PBF, we found that lymph flow was unchanged following acute increases in PBF but decreased following chronic increases in PBF. The lymph:plasma protein ratio decreased with both acute and chronic increases in PBF. Lymph bioavailable nitric oxide increased following acute increases in PBF but decreased following chronic increases in PBF. In addition, we found perturbations in the transit kinetics of contrast material through the pleural lymphatics of lambs with chronic increases in PBF. Finally, there were structural changes in the pulmonary lymphatic system in lambs with chronic increases in PBF: lymphatics from these lambs were larger and more dilated, and there were alterations in the expression of vascular endothelial growth factor-C, lymphatic vessel endothelial hyaluronan receptor-1, and Angiopoietin-2, proteins known to be important for lymphatic growth, development, and remodeling. Taken together these data suggest that chronic increases in PBF lead to both functional and structural aberrations of lung lymphatics. These findings have important therapeutic implications that warrant further study.

  12. The unique alterations of hippocampus and cognitive impairment in chronic obstructive pulmonary disease

    PubMed Central

    2013-01-01

    Background Cognitive impairment has been found in chronic obstructive pulmonary disease (COPD) patients. However, the structural alteration of the brain and underlying mechanisms are poorly understood. Methods Thirty-seven mild-to-moderate COPD patients, forty-eight severe COPD patients, and thirty-one control subjects were recruited for cognitive test and neuroimaging studies. Serum levels of S100B,pulmonary function and arterial blood gas levels were also evaluated in each subject. Results The hippocampal volume was significantly smaller in COPD patients compared to the control group. It is positively correlated with a mini mental state examination (MMSE) score, SaO2 in mild-to-moderate COPD patients, the levels of PaO2 in both mild-to-moderate and severe COPD patients. Higher S100B concentrations were observed in mild-to-moderate COPD patients, while the highest S100B level was found in severe COPD patients when compared to the control subjects. S100B levels are negatively associated with MMSE in both mild-to-moderate and severe COPD patients and also negatively associated with the hippocampal volume in the total COPD patients. Conclusions Hippocampal atrophy based on quantitative assessment by magnetic resonance imaging does occur in COPD patients, which may be associated with cognitive dysfunction and the most prevalent mechanism accountable for hippocampal atrophy is chronic hypoxemia in COPD. Higher serum S100B levels may be peripheral biochemical marker for cognitive impairment in COPD. PMID:24359080

  13. POSTWEANING EXPOSURE TO A HIGH FAT DIET IS ASSOCIATED WITH ALTERATIONS TO THE HEPATIC HISTONE CODE IN JAPANESE MACAQUES

    PubMed Central

    Suter, Melissa A.; Takahashi, Diana; Grove, Kevin L.; Aagaard, Kjersti M.

    2013-01-01

    Background Expression of the circadian gene, Npas2, is altered in fetal life with maternal high fat diet exposure by virtue of alterations in the fetal histone code. We postulated that these disruptions would persist postnatally. Methods Pregnant macaques were fed a control (CTR) or high fat (HF) diet and delivered at term. When offspring were weaned, they were placed on either CTR or HF diet for a period of 5 months to yield four exposure models (in utero diet/postweaning diet: CTR/CTR n = 5; CTR/HF n = 4; HF/CTR n = 4; HF/HF n = 5). Liver specimens were obtained at necropsy at one year of age. Results Hepatic trimethylation of lysine 4 of histone H3 is decreased, (CTR/HF 0.87-fold, P = 0.038; HF/CTR 0.84-fold, P = 0.038) while hepatic methyltransferase activity increased by virtue of diet exposure (HF/HF 1.3-fold, P = 0.019). Using chromatin immunoprecipitation to determine Npas2 promoter occupancy, we found alterations of both repressive and permissive histone modifications specifically with postweaning high fat diet exposure. Conclusion We find altered Npas2 expression corresponds with a change in the histone code within the Npas2 promoter. PMID:23788059

  14. Alteration of Aging-dependent MicroRNAs in Idiopathic Pulmonary Fibrosis (IPF)

    PubMed Central

    Nho, Richard Seonghun

    2015-01-01

    Idiopathic Pulmonary Fibrosis (IPF) is the most severe fibrotic lung disease and characterized by the accumulation of (myo)fibroblasts and collagen within the alveolar wall resulting in obliteration of the gas-exchange surface. Although the detailed pathogenesis is not understood, recent studies have found that several microRNAs (miRNAs) are associated with the progression of lung diseases including IPF. IPF is an age-associated disease and, accordingly, frequently found in an aged population. In this review, the functional roles of miRNAs that are deregulated in IPF progression are discussed together with how aging affects the miRNA signature, altering the fibroblast phenotype and promoting lung fibrosis. Finally, the possibility of targeting miRNAs as a therapeutic approach for the treatment of IPF is discussed. PMID:26303294

  15. Pulmonary fat embolism--a prospective study within the forensic autopsy collective of the Republic of Iceland.

    PubMed

    Voisard, Matthias X; Schweitzer, Wolf; Jackowski, Christian

    2013-01-01

    In the last century, studies established the origin of pulmonary fat embolism (PFE) and identified mechanical trauma as main source for PFE. This prospective study focused on determining a possible influence of cardiopulmonary resuscitation (CPR), in the context of an aging population, on the occurrence of PFE. Lung tissue samples from 256 bodies were examined using the twin-edged knife technique without preliminary fixation but after staining with Sudan III. PFE grading was determined according to Falzi and performed at a 10× magnification. For statistical analysis, bodies were grouped by age, gender, and putrefaction and categorized following whether they had experienced trauma, CPR, the combination of both, or no mechanical impact. There was a significant correlation of trauma, CPR, and the combination of both to PFE but no noticeable influence of gender or putrefaction. An age over 70 years promotes a PFE due to resuscitation.

  16. Prenatal nicotine increases pulmonary α7 nicotinic receptor expression and alters fetal lung development in monkeys

    PubMed Central

    Sekhon, Harmanjatinder S.; Jia, Yibing; Raab, Renee; Kuryatov, Alexander; Pankow, James F.; Whitsett, Jeffrey A.; Lindstrom, Jon; Spindel, Eliot R.

    1999-01-01

    It is well established that maternal smoking during pregnancy is a leading preventable cause of low birth weight and prematurity. Less appreciated is that maternal smoking during pregnancy is also associated with alterations in pulmonary function at birth and greater incidence of respiratory illnesses after birth. To determine if this is the direct result of nicotine interacting with nicotinic cholinergic receptors (nAChRs) during lung development, rhesus monkeys were treated with 1 mg/kg/day of nicotine from days 26 to 134 of pregnancy. Nicotine administration caused lung hypoplasia and reduced surface complexity of developing alveoli. Immunohistochemistry and in situ α-bungarotoxin (αBGT) binding showed that α7 nAChRs are present in the developing lung in airway epithelial cells, cells surrounding large airways and blood vessels, alveolar type II cells, free alveolar macrophages, and pulmonary neuroendocrine cells (PNEC). As detected both by immunohistochemistry and by αBGT binding, nicotine administration markedly increased α7 receptor subunit expression and binding in the fetal lung. Correlating with areas of increased α7 expression, collagen expression surrounding large airways and vessels was significantly increased. Nicotine also significantly increased numbers of type II cells and neuroendocrine cells in neuroepithelial bodies. These findings demonstrate that nicotine can alter fetal monkey lung development by crossing the placenta to interact directly with nicotinic receptors on non-neuronal cells in the developing lung, and that similar effects likely occur in human infants whose mothers smoke during pregnancy. J. Clin. Invest. 103:637–647 (1999) PMID:10074480

  17. High-fat taste challenge reveals altered striatal response in women recovered from bulimia nervosa: A pilot study

    PubMed Central

    RADELOFF, DANIEL; WILLMANN, KATHRIN; OTTO, LISA; LINDNER, MICHAEL; PUTNAM, KAREN; VAN LEEUWEN, SARA; KAYE, WALTER H; POUSTKA, FRITZ; WAGNER, ANGELA

    2015-01-01

    Objectives Individuals with anorexia nervosa (AN) and bulimia nervosa (BN) tend to have disordered thinking and eating behaviours in regards to fat containing foods. This is the first study to investigate neuronal pathways that may contribute to altered fat consumption in eating disordered patients. Methods We used functional magnetic resonance imaging (fMRI) to compare responses to a high-fat cream stimulus, water, and a non-caloric viscous stimulus (CMC) to control for response to viscosity in individuals recovered from AN (N = 15), BN (N = 14) and a healthy control sample (CW, N = 18). Results An interaction analysis (ANOVAR) comparing the three groups (AN, BN, CW) and the three conditions (cream, CMC, water) revealed significant differences in the left anterior ventral striatum (AVS). A post hoc analysis displayed a higher magnitude of response for the contrast cream/water in BN compared to AN or CW and for the contrast CMC/water in BN compared to AN. Conclusions BN showed an exaggerated AVS response for the cream/water contrast in comparison to AN or CW. Moreover, BN showed an exaggerated AVS response for the CMC/water contrast in comparison to AN. These findings support the possibility that BN have an altered hedonic and/or motivational drive to consume fats. PMID:22540408

  18. Ct Anatomy of Buccal Fat Pad and its Role in Volumetric Alterations of Face

    NASA Astrophysics Data System (ADS)

    Guryanov, R. A.; Guryanov, A. S.

    2015-05-01

    The aim of our study is the revision of the anatomy of buccal fat pad and its role in a volumetric pattern of face. Bichat fat pad is a fatty anatomical structure with body and numerous process enclosed between the bony and muscular structures in temporal, pterygopalatine fossae and extents to the cheek area. Nevertheless, the opinion about its structure and role in forming of volume pattern of face sometimes could be controversial. The Bichat fat pad consists on predominately hormone insensitive fat tissue with underdeveloped stroma, this leads to the stability of the fat pad volume and lesser radiodensity in contrast to the subcutaneous fat. Moreover, the buccal fat pad is delimited from the subcutaneous fat of cheek area by the strong capsule. This feature allows us to use CT to divide the Bichat fat pad from the surrounding tissues. The thorough embryological data provide the distinction of Bichat fat pad from the subcutaneous fat of cheek area even at the stage of development. On the other hand, the border between the masticatory muscles and the processes of the fat pad is not evident and resembles cellular spaces in the other anatomical areas. To elicit the role of the buccal fat pad in volume pattern of face and its function we have performed the several experiments, analyzed the postoperative results after Bichat fat pad resection using surface scanner and CT data. At first, we have performed the gravity test: the patient's face photogrammetry scanning in horizontal and vertical position of head and it revealed the excess of volume in temporal area in horizontal position. To exclude mechanism of overflowing of the skin and subcutaneous fat over the zygomatic arch we have placed the markers on the skin surface at the different areas of face including the projection of ligaments and found out that the migration of soft tissue over the zygomatic arch is about 3-5 mm and almost the same in temporal area. However, the acquired result was unsatisfying because

  19. Ozone-induced injury and oxidative stress in bronchiolar epithelium are associated with altered pulmonary mechanics.

    PubMed

    Sunil, Vasanthi R; Vayas, Kinal N; Massa, Christopher B; Gow, Andrew J; Laskin, Jeffrey D; Laskin, Debra L

    2013-06-01

    In these studies, we analyzed the effects of ozone on bronchiolar epithelium. Exposure of rats to ozone (2 ppm, 3 h) resulted in rapid (within 3 h) and persistent (up to 72 h) histological changes in the bronchiolar epithelium, including hypercellularity, loss of cilia, and necrotizing bronchiolitis. Perivascular edema and vascular congestion were also evident, along with a decrease in Clara cell secretory protein in bronchoalveolar lavage, which was maximal 24 h post-exposure. Ozone also induced the appearance of 8-hydroxy-2'-deoxyguanosine, Ym1, and heme oxygenase-1 in the bronchiolar epithelium. This was associated with increased expression of cleaved caspase-9 and beclin-1, indicating initiation of apoptosis and autophagy. A rapid and persistent increase in galectin-3, a regulator of epithelial cell apoptosis, was also observed. Following ozone exposure (3-24 h), increased expression of cyclooxygenase-2, inducible nitric oxide synthase, and arginase-1 was noted in bronchiolar epithelium. Ozone-induced injury and oxidative stress in bronchiolar epithelium were linked to methacholine-induced alterations in pulmonary mechanics. Thus, significant increases in lung resistance and elastance, along with decreases in lung compliance and end tidal volume, were observed at higher doses of methacholine. This indicates that ozone causes an increase in effective stiffness of the lung as a consequence of changes in the conducting airways. Collectively, these studies demonstrate that bronchiolar epithelium is highly susceptible to injury and oxidative stress induced by acute exposure to ozone; moreover, this is accompanied by altered lung functioning.

  20. Ozone-Induced Injury and Oxidative Stress in Bronchiolar Epithelium Are Associated with Altered Pulmonary Mechanics

    PubMed Central

    Sunil, Vasanthi R.

    2013-01-01

    In these studies, we analyzed the effects of ozone on bronchiolar epithelium. Exposure of rats to ozone (2 ppm, 3h) resulted in rapid (within 3h) and persistent (up to 72h) histological changes in the bronchiolar epithelium, including hypercellularity, loss of cilia, and necrotizing bronchiolitis. Perivascular edema and vascular congestion were also evident, along with a decrease in Clara cell secretory protein in bronchoalveolar lavage, which was maximal 24h post-exposure. Ozone also induced the appearance of 8-hydroxy-2′-deoxyguanosine, Ym1, and heme oxygenase-1 in the bronchiolar epithelium. This was associated with increased expression of cleaved caspase-9 and beclin-1, indicating initiation of apoptosis and autophagy. A rapid and persistent increase in galectin-3, a regulator of epithelial cell apoptosis, was also observed. Following ozone exposure (3–24h), increased expression of cyclooxygenase-2, inducible nitric oxide synthase, and arginase-1 was noted in bronchiolar epithelium. Ozone-induced injury and oxidative stress in bronchiolar epithelium were linked to methacholine-induced alterations in pulmonary mechanics. Thus, significant increases in lung resistance and elastance, along with decreases in lung compliance and end tidal volume, were observed at higher doses of methacholine. This indicates that ozone causes an increase in effective stiffness of the lung as a consequence of changes in the conducting airways. Collectively, these studies demonstrate that bronchiolar epithelium is highly susceptible to injury and oxidative stress induced by acute exposure to ozone; moreover, this is accompanied by altered lung functioning. PMID:23492811

  1. Modulation of polyamine metabolic flux in adipose tissue alters the accumulation of body fat by affecting glucose homeostasis.

    PubMed

    Liu, Chunli; Perez-Leal, Oscar; Barrero, Carlos; Zahedi, Kamyar; Soleimani, Manoocher; Porter, Carl; Merali, Salim

    2014-03-01

    The continued rise in obesity despite public education, awareness and policies indicates the need for mechanism-based therapeutic approaches to help control the disease. Our data, in conjunction with other studies, suggest an unexpected role for the polyamine catabolic enzyme spermidine/spermine-N1-acetyltransferase (SSAT) in fat homeostasis. Our previous studies showed that deletion of SSAT greatly exaggerates weight gain and that the transgenic overexpression suppresses weight gain in mice on a high-fat diet. This discovery is substantial but the underlying molecular linkages are only vaguely understood. Here, we used a comprehensive systems biology approach, on white adipose tissue (WAT), to discover that the partition of acetyl-CoA towards polyamine catabolism alters glucose homeostasis and hence, fat accumulation. Comparative proteomics and antibody-based expression studies of WAT in SSAT knockout, wild type and transgenic mice identified nine proteins with an increasing gradient across the genotypes, all of which correlate with acetyl-CoA consumption in polyamine acetylation. Adipose-specific SSAT knockout mice and global SSAT knockout mice on a high-fat diet exhibited similar growth curves and proteomic patterns in their WAT, confirming that attenuated consumption of acetyl-CoA in acetylation of polyamines in adipose tissue drives the obese phenotype of these mice. Analysis of protein expression indicated that the identified changes in the levels of proteins regulating acetyl-CoA consumption occur via the AMP-activated protein kinase pathway. Together, our data suggest that differential expression of SSAT markedly alters acetyl-CoA levels, which in turn trigger a global shift in glucose metabolism in adipose tissue, thus affecting the accumulation of body fat.

  2. Modulation of polyamine metabolic flux in adipose tissue alters the accumulation of body fat by affecting glucose homeostasis

    PubMed Central

    Liu, Chunli; Perez-Leal, Oscar; Barrero, Carlos; Zahedi, Kamyar; Soleimani, Manoocher; Porter, Carl

    2013-01-01

    The continued rise in obesity despite public education, awareness and policies indicates the need for mechanism-based therapeutic approaches to help control the disease. Our data, in conjunction with other studies, suggest an unexpected role for the polyamine catabolic enzyme spermidine/spermine-N1-acetyltransferase (SSAT) in fat homeostasis. Our previous studies showed that deletion of SSAT greatly exaggerates weight gain and that the transgenic overexpression suppresses weight gain in mice on a high-fat diet. This discovery is substantial but the underlying molecular linkages are only vaguely understood. Here, we used a comprehensive systems biology approach, on white adipose tissue (WAT), to discover that the partition of acetyl-CoA towards polyamine catabolism alters glucose homeostasis and hence, fat accumulation. Comparative proteomics and antibody-based expression studies of WAT in SSAT knockout, wild type and transgenic mice identified nine proteins with an increasing gradient across the genotypes, all of which correlate with acetyl-CoA consumption in polyamine acetylation. Adipose-specific SSAT knockout mice and global SSAT knockout mice on a high-fat diet exhibited similar growth curves and proteomic patterns in their WAT, confirming that attenuated consumption of acetyl-CoA in acetylation of polyamines in adipose tissue drives the obese phenotype of these mice. Analysis of protein expression indicated that the identified changes in the levels of proteins regulating acetyl-CoA consumption occur via the AMP-activated protein kinase pathway. Together, our data suggest that differential expression of SSAT markedly alters acetyl-CoA levels, which in turn trigger a global shift in glucose metabolism in adipose tissue, thus affecting the accumulation of body fat. PMID:23881108

  3. Plasma Metabolomics Implicates Modified Transfer RNAs and Altered Bioenergetics in the Outcomes of Pulmonary Arterial Hypertension

    PubMed Central

    Rhodes, Christopher J.; Ghataorhe, Pavandeep; Wharton, John; Rue-Albrecht, Kevin C.; Hadinnapola, Charaka; Watson, Geoffrey; Bleda, Marta; Haimel, Matthias; Coghlan, Gerry; Corris, Paul A.; Howard, Luke S.; Kiely, David G.; Peacock, Andrew J.; Pepke-Zaba, Joanna; Toshner, Mark R.; Wort, S. John; Gibbs, J. Simon R.; Lawrie, Allan; Gräf, Stefan; Morrell, Nicholas W.

    2017-01-01

    Background: Pulmonary arterial hypertension (PAH) is a heterogeneous disorder with high mortality. Methods: We conducted a comprehensive study of plasma metabolites using ultraperformance liquid chromatography mass spectrometry to identify patients at high risk of early death, to identify patients who respond well to treatment, and to provide novel molecular insights into disease pathogenesis. Results: Fifty-three circulating metabolites distinguished well-phenotyped patients with idiopathic or heritable PAH (n=365) from healthy control subjects (n=121) after correction for multiple testing (P<7.3e-5) and confounding factors, including drug therapy, and renal and hepatic impairment. A subset of 20 of 53 metabolites also discriminated patients with PAH from disease control subjects (symptomatic patients without pulmonary hypertension, n=139). Sixty-two metabolites were prognostic in PAH, with 36 of 62 independent of established prognostic markers. Increased levels of tRNA-specific modified nucleosides (N2,N2-dimethylguanosine, N1-methylinosine), tricarboxylic acid cycle intermediates (malate, fumarate), glutamate, fatty acid acylcarnitines, tryptophan, and polyamine metabolites and decreased levels of steroids, sphingomyelins, and phosphatidylcholines distinguished patients from control subjects. The largest differences correlated with increased risk of death, and correction of several metabolites over time was associated with a better outcome. Patients who responded to calcium channel blocker therapy had metabolic profiles similar to those of healthy control subjects. Conclusions: Metabolic profiles in PAH are strongly related to survival and should be considered part of the deep phenotypic characterization of this disease. Our results support the investigation of targeted therapeutic strategies that seek to address the alterations in translational regulation and energy metabolism that characterize these patients. PMID:27881557

  4. In utero tobacco smoke exposure alters pulmonary responses of newborn rats to ozone.

    PubMed

    Han, Sung Gu; Bhoopalan, Vanitha; Akinbiyi, Tolulola; Gairola, C Gary; Bhalla, Deepak K

    2011-01-01

    Prenatal tobacco smoke (TS) exposure has been implicated in various adverse health outcomes in the offspring, including poor development of lung and immune system, which in turn can alter the response of neonates to environmental challenges. This study was performed to determine whether in utero exposure to TS influences the pulmonary response of newborn rat pups to ozone (O₃). Timed pregnant Sprague-Dawley (SD) rats were exposed to TS or air for 3 h/d from gestation d 7 through 21. The pulmonary response of pups was assessed following a single 3-h exposure to air or 0.6 ppm O₃ on d 13 after birth. In all, 4 exposure groups were evaluated: (1) Air/Air (in utero air and postnatal air), (2) Air/O₃ (in utero air and postnatal O₃), (3) TS/Air (in utero TS and postnatal air), and (4) TS/O₃ (in utero TS and postnatal O₃). Bronchoalveolar lavage (BAL) was performed, and BAL cells and fluid were analyzed. Data revealed a significant increase in polymorphonuclear leukocytes (PMN) and total BALF protein in the Air/O₃ group compared to the Air/Air control, reflecting the inflammatory and cytotoxic effects of O₃. However, in utero exposure to TS attenuated PMN infiltration into the air spaces for recovery in the BAL of TS/O₃ pups. Lung tissue myeloperoxidase activity significantly increased only in the TS/O₃ group but not in Air/O₃ pups, thus suggesting that PMN are sequestered in the lung tissue and that the in utero TS likely inhibits O₃-mediated influx of PMN into the air spaces. Lung tissue analyses further showed a significant rise in manganese superoxide dismutase (SOD) protein and a decrease in extracellular SOD protein in the Air/O₃ group, suggesting oxidative effects of O₃. Interestingly, in utero TS exposure again suppressed these effects in the TS/O₃ group. Overall, results suggest that in utero exposure to TS alone produced minimal acute pulmonary effects in newborn rats, but modulated adverse effects of postnatal O₃ exposure. The

  5. Background diet and fat type alters plasma lipoprotein response but not aortic cholesterol accumulation in F1B golden syrian hamsters

    USDA-ARS?s Scientific Manuscript database

    Dietary modification alters plasma lipoprotein profiles and atherosclerotic lesion progression in humans and some animal models. Variability in response to diet induced atherosclerosis has been reported in hamsters. Assessed was the interaction between background diet composition and dietary fat typ...

  6. Impacts of fat from ruminants' meat on cardiovascular health and possible strategies to alter its lipid composition.

    PubMed

    Vargas-Bello-Pérez, Einar; Larraín, Rafael E

    2017-05-01

    In the last few decades there has been increased consumer interest in the fatty acid (FA) composition of ruminant meat due to its content of saturated FAs, which have been implicated in diseases associated with modern life. However, recent studies have questioned the recommendations to reduce intake of fat, saturated FAs and cholesterol as a means of reducing the risk of cardiovascular disease. Interestingly, ruminant meat has some bioactive lipids such as C18:1t11 and C18:2 c9, t11 which have been reported to have positive effects on human health. In order to improve muscle fat composition from a human health standpoint, oilseeds, plant oils and marine oils can be used in ruminant diets. On the other hand, molecular mechanisms play an important role in the alteration of the FA composition of muscle fat. Genetics offer a wide range of possibilities for improvement of muscle fat composition by identifying different loci underlying the expression of quantitative traits. While significant progress has been made in characterizing the influence of diet on the FA composition of ruminant meat, the use of genetic tools can favor genotypes that could maximize their genetic potential through the diet. © 2016 Society of Chemical Industry. © 2016 Society of Chemical Industry.

  7. Meal pattern alterations associated with intermittent fasting for weight loss are normalized after high-fat diet re-feeding.

    PubMed

    Gotthardt, Juliet D; Bello, Nicholas T

    2017-05-15

    Alternate day, intermittent fasting (IMF) can be an effective weight loss strategy. However, the effects of IMF on eating behaviors are not well characterized. We investigated the acute and residual effects of IMF for weight loss on meal patterns in adult obese male C57BL/6 mice. After 8weeks of ad libitum high-fat diet to induce diet-induced obesity (DIO), mice were either continued on ad libitum high-fat diet (HFD) or placed on one of 5 diet strategies for weight loss: IMF of high-fat diet (IMF-HFD), pair-fed to IMF-HFD group (PF-HFD), ad libitum low-fat diet (LFD), IMF of low-fat diet (IMF-LFD), or pair-fed to IMF-LFD group (PF-LFD). After the 4-week diet period, all groups were refed the high-fat diet for 6weeks. By the end of the diet period, all 5 groups had lost weight compared with HFD group, but after 6weeks of HFD re-feeding all groups had similar body weights. On (Day 2) of the diet period, IMF-HFD had greater first meal size and faster eating rate compared with HFD. Also, first meal duration was greater in LFD and IMF-LFD compared with HFD. At the end of the diet period (Day 28), the intermittent fasting groups (IMF-HFD and IMF-LFD) had greater first meal sizes and faster first meal eating rate compared with their respective ad libitum fed groups on similar diets (HFD and LFD). Also, average meal duration was longer on Day 28 in the low-fat diet groups (LFD and IMF-LFD) compared with high-fat diet groups (HFD and IMF-HFD). After 6weeks of HFD re-feeding (Day 70), there were no differences in meal patterns in groups that had previously experienced intermittent fasting compared with ad libitum fed groups. These findings suggest that meal patterns are only transiently altered during alternate day intermittent fasting for weight loss in obese male mice. Copyright © 2017 Elsevier Inc. All rights reserved.

  8. Alterations in cardiomyocyte function after pulmonary treatment with stainless steel welding fume in rats.

    PubMed

    Popstojanov, Risto; Antonini, James M; Salmen, Rebecca; Ye, Morgan; Zheng, Wen; Castranova, Vincent; Fekedulegn, Desta B; Kan, Hong

    2014-01-01

    Welding fume is composed of a complex of different metal particulates. Pulmonary exposure to different welding fumes may exert a negative impact on cardiac function, although the underlying mechanisms remain unclear. To explore the effect of welding fumes on cardiac function, Sprague-Dawley rats were exposed by intratracheal instillation to 2 mg/rat of manual metal arc hard surfacing welding fume (MMA-HS) once per week for 7 wk. Control rats received saline. Cardiomyocytes were isolated enzymatically at d 1 and 7 postexposure. Intracellular calcium ([Ca(2+)]i) transients (fluorescence ratio) were measured on the stage of an inverted phase-contrast microscope using a myocyte calcium imaging/cell length system. Phosphorylation levels of cardiac troponin I (cTnI) were determined by Western blot. The levels of nonspecific inflammatory marker C-reactive protein (CRP) and proinflammatory cytokine interleukin-6 (IL-6) in serum were measured by enzyme-linked immunosorbent assay (ELISA). Contraction of isolated cardiomyocytes was significantly reduced at d 1 and d 7 postexposure. Intracellular calcium levels were decreased in response to extracellular calcium stimulation at d 7 postexposure. Changes of intracellular calcium levels after isoprenaline hydrochloride (ISO) stimulation were not markedly different between groups at either time point. Phosphorylation levels of cTnI in the left ventricle were significantly lower at d 1 postexposure. The serum levels of CRP were not markedly different between groups at either time point. Serum levels of IL-6 were not detectable in both groups. Cardiomyocyte alterations observed after welding fume treatment were mainly due to alterations in intracellular calcium handling and phosphorylation levels of cTnI.

  9. Aged mice display an altered pulmonary host response to Francisella tularensis live vaccine strain (LVS) infections

    PubMed Central

    CA, Mares; SS, Ojeda; Q, Li; EG, Morris; JJ, Coalson; JM, Teale

    2012-01-01

    Aging is a complex phenomenon that has been shown to affect many organ systems including the innate and adaptive immune systems. The current study was designed to examine the potential effect of immunosenescence on the pulmonary immune response using a Francisella tularensis live vaccine strain (LVS) inhalation infection model. F. tularensis is a gram-negative intracellular pathogen that can cause a severe pneumonia.In this study both young (8-12 week old) and aged (20-24 month old) mice were infected intranasally with LVS. Lung tissues from young and aged mice were used to assess pathology, recruitment of immune cell types and cytokine expression levels at various times post infection. Bacterial burdens were also assessed. Interestingly, the lungs of aged animals harbored fewer organisms at early time points of infection (day 1, day 3) compared with their younger counterparts. In addition, only aged animals displayed small perivascular aggregates at these early time points that appeared mostly mononuclear in nature. However, the kinetics of infiltrating polymorphonuclear neutrophils (PMNs) and increased cytokine levels measured in the bronchial alveolar lavage fluid (BALF) were delayed in infected aged animals relative to young infected animals with neutrophils appearing at day 5 post infection (PI) in the aged animals as opposed to day 3 PI in the young infected animals. Also evident were alterations in the ratios of mononuclear to PMNs at distinct post infection times. The above evidence indicates that aged mice elicit an altered immune response in the lung to respiratory Francisella tularensis LVS infections compared to their younger counterparts. PMID:19825409

  10. ALTERATIONS IN CARDIOMYOCYTE FUNCTION AFTER PULMONARY TREATMENT WITH STAINLESS STEEL WELDING FUME IN RATS

    PubMed Central

    Popstojanov, Risto; Antonini, James M.; Salmen, Rebecca; Ye, Morgan; Zheng, Wen; Castranova, Vincent; Fekedulegn, Desta B.; Kan, Hong

    2015-01-01

    Welding fume is composed of a complex of different metal particulates. Pulmonary exposure to different welding fumes may exert a negative impact on cardiac function, although the underlying mechanisms remain unclear. To explore the effect of welding fumes on cardiac function, Sprague-Dawley rats were exposed by intratracheal instillation to 2 mg/rat of manual metal arc hard surfacing welding fume (MMA-HS) once per week for 7 wk. Control rats received saline. Cardiomyocytes were isolated enzymatically at d 1 and 7 postexposure. Intracellular calcium ([Ca2+]i) transients (fluorescence ratio) were measured on the stage of an inverted phase-contrast microscope using a myocyte calcium imaging/cell length system. Phosphorylation levels of cardiac troponin I (cTnI) were determined by Western blot. The levels of nonspecific inflammatory marker C-reactive protein (CRP) and proinflammatory cytokine interleukin-6 (IL-6) in serum were measured by enzyme-linked immunosorbent assay (ELISA). Contraction of isolated cardiomyocytes was significantly reduced at d 1 and d 7 postexposure. Intracellular calcium levels were decreased in response to extracellular calcium stimulation at d 7 postexposure. Changes of intracellular calcium levels after isoprenaline hydrochloride (ISO) stimulation were not markedly different between groups at either time point. Phosphorylation levels of cTnI in the left ventricle were significantly lower at d 1 post-exposure. The serum levels of CRP were not markedly different between groups at either time point. Serum levels of IL-6 were not detectable in both groups. Cardiomyocyte alterations observed after welding fume treatment were mainly due to alterations in intracellular calcium handling and phosphorylation levels of cTnI. PMID:24786677

  11. Effectiveness of a low-fat vegetarian diet in altering serum lipids in healthy premenopausal women.

    PubMed

    Barnard, N D; Scialli, A R; Bertron, P; Hurlock, D; Edmonds, K; Talev, L

    2000-04-15

    Few controlled trials have studied cholesterol-lowering diets in premenopausal women. None has examined the cholesterol-lowering effect of a low-fat vegetarian diet, which, in other population groups, leads to marked reductions in serum cholesterol concentrations and, in combination with other life-style changes, a regression of atherosclerosis. We tested the hypothesis that a low-fat, vegetarian diet significantly reduces serum total and low-density lipoprotein (LDL) cholesterol concentrations in premenopausal women. In a crossover design, 35 women, aged 22 to 48, followed a low-fat vegetarian diet deriving approximately 10% of energy from fat for 2 menstrual cycles. For 2 additional cycles, they followed their customary diet while also taking a "supplement" (placebo) pill. Serum lipid concentrations were assessed at baseline and during each intervention phase. Mean serum LDL, high-density lipoprotein (HDL), and total cholesterol concentrations decreased 16. 9%, 16.5%, and 13.2%, respectively, from baseline to the intervention diet phase (p<0.001), whereas mean serum triacylglycerol concentration increased 18.7% (p<0.01). LDL/HDL ratio remained unchanged. Thus, in healthy premenopausal women, a low-fat vegetarian diet led to rapid and sizable reductions in serum total, LDL, and HDL cholesterol concentrations.

  12. Alterations in welding process voltage affect the generation of ultrafine particles, fume composition, and pulmonary toxicity.

    PubMed

    Antonini, James M; Keane, Michael; Chen, Bean T; Stone, Samuel; Roberts, Jenny R; Schwegler-Berry, Diane; Andrews, Ronnee N; Frazer, David G; Sriram, Krishnan

    2011-12-01

    The goal was to determine if increasing welding voltage changes the physico-chemical properties of the fume and influences lung responses. Rats inhaled 40 mg/m³ (3 h/day × 3 days) of stainless steel (SS) welding fume generated at a standard voltage setting of 25 V (regular SS) or at a higher voltage (high voltage SS) of 30 V. Particle morphology, size and composition were characterized. Bronchoalveolar lavage was performed at different times after exposures to assess lung injury. Fumes collected from either of the welding conditions appeared as chain-like agglomerates of nanometer-sized primary particles. High voltage SS welding produced a greater number of ultrafine-sized particles. Fume generated by high voltage SS welding was higher in manganese. Pulmonary toxicity was more substantial and persisted longer after exposure to the regular SS fume. In summary, a modest raise in welding voltage affected fume size and elemental composition and altered the temporal lung toxicity profile.

  13. Molecular Alterations in Patients with Pulmonary Adenocarcinoma Presenting with Malignant Pleural Effusion at the First Diagnosis.

    PubMed

    Rodriguez, Erika F; Shabihkhani, Maryam; Carter, Jamal; Maleki, Zahra

    2017-01-01

    The aim of this study was to report cytologic and molecular features of pulmonary adenocarcinoma patients presenting with a malignant pleural effusion at the first diagnosis. Patients who had a cytopathologic diagnosis conclusive for lung adenocarcinoma for the first time on their pleural fluid specimen, and molecular testing done, were studied. The control group consisted of patients with a malignant pleural effusion that developed during disease progression. We identified 18 patients (9 males and 9 females). Micropapillary and/or solid adenocarcinoma type features predominated among cytologic specimens (n = 15), while acinar patterns predominated in controls. Survival was not significantly different from that of the control group (mean 13.8 vs. 13.9 months, respectively; p = 0.61). Ten (55%) cases had mutations in EGFR (n = 6; 60%), KRAS (n = 3; 30%), or ALK translocation (n = 1; 10%). No mutations were identified in BRAF, AKT, ERBB2, NRAS, or PIK3CA (tested in 7 patients). Patients positive for the tested mutations had a better overall survival than patients negative for the mutations (mean survival 16.2 vs. 6.05 months, respectively; p = 0.006, log-rank test). Ten (84%) control patients were positive for mutations in EGFR (n = 5; 42%), KRAS (n = 4; 34%), or ALK translocation (n = 1; 8.4%). In our series, a micropapillary-like and solid-like morphology, common in cytologic specimens, and alterations in EGFR were the most frequent identifiable molecular changes. © 2017 S. Karger AG, Basel.

  14. Early High-Fat Feeding Induces Alteration of Trace Element Content in Tissues of Juvenile Male Wistar Rats.

    PubMed

    Tinkov, Alexey A; Gatiatulina, Eugenia R; Popova, Elizaveta V; Polyakova, Valentina S; Skalnaya, Anastasia A; Agletdinov, Eduard F; Nikonorov, Alexandr A; Skalny, Anatoly V

    2017-02-01

    The primary objective of the current study was to assess the influence of early high-fat feeding on tissue trace element content in young male Wistar rats. Twenty weanling male Wistar rats were divided into two groups fed standard (STD) or high-fat diet (HFD) containing 10 and 31.6 % of total calories from fat, respectively, for 1 month. Serum lipid spectrum, apolipoproteins, glucose, insulin, adiponectin, and leptin levels were assessed. The level of trace elements was estimated using inductively coupled plasma mass spectrometry. High-fat feeding significantly increased epidydimal (EDAT) and retroperitoneal adipose tissue (RPAT), as well as total adipose tissue mass by 34, 103, and 59 %, respectively. Serum leptin levels in HFD animals were twofold higher than those in the control rats. No significant difference in serum lipid spectrum, apolipoproteins, glucose, adiponectin, and insulin was detected between the groups. HFD significantly altered tissue trace element content. In particular, HFD-fed animals were characterized by significantly lower levels of Cu, I, Mn, Se, and Zn in the liver; Cr, V, Co, Cu, Fe, and I content of EDAT; Co, Cu, I, Cr, V, Fe, and Zn concentration in RPAT samples. At the same time, only serum Cu was significantly depressed in HFD-fed animals as compared to the control ones. Hair Co, Mn, Si, and V levels were significantly increased in comparison to the control values, whereas Se and I content was decreased. HFD feeding induced excessive adiposity and altered tissue trace element content in rats without insulin resistance, adiponectin deficiency, and proatherogenic state. Hypothetically, trace element disbalance may precede obesity-associated metabolic disturbances.

  15. Prediabetes in obese youth: a syndrome of impaired glucose tolerance, severe insulin resistance, and altered myocellular and abdominal fat partitioning

    PubMed Central

    Weiss, Ram; Dufour, Sylvie; Taksali, Sara E; Tambortlane, William V; Petersen, Kitt F; Bonadonna, Riccardo C; Boselli, Linda; Barbetta, Gina; Alle, Karin; Rife, Francis; Savoye, Mary; Dziura, James; Sherwin, Robert; Shulman, Gerald I; Caprio, Sonia

    2010-01-01

    Summary Background Impaired glucose tolerance is common among obese adolescents, but the changes in insulin sensitivity and secretion that lead to this prediabetic state are unknown. We investigated whether altered partitioning of myocellular and abdominal fat relates to abnormalities in glucose homoeostasis in obese adolescents with prediabetes. Methods We studied 14 obese children with impaired glucose tolerance and 14 with normal glucose tolerance, of similar ages, sex distribution, and degree of obesity. Insulin sensitivity and secretion were assessed by the euglycaemichyperinsulinaemic clamp and the hyperglycaemic clamp. Intramyocellular lipid was assessed by proton nuclear magnetic resonance spectroscopy and abdominal fat distribution by magnetic resonance imaging. Findings Peripheral glucose disposal was significantly lower in individuals with impaired than in those with normal glucose tolerance (mean 35·4 [SE 4·0] vs 60·6 [7·2] μmoles per kg lean body mass per min; p=0·023) owing to a reduction in non-oxidative glucose disposal metabolism (storage). Individuals with impaired glucose tolerance had higher intramyocellular lipid content (3·04 [0·43] vs 1·99 [0·19]%, p=0·03), lower abdominal subcutaneous fat (460 [47] vs 626 [39] cm2, p=0·04), and slightly higher visceral fat than the controls (70 [11] vs 47 [6] cm2, p=0·065), resulting in a higher ratio of visceral to subcutaneous fat (0·15 [0·02] vs 0·07 [0·01], p=0·002). Intramyocellular and visceral lipid contents were inversely related to the glucose disposal and non-oxidative glucose metabolism and positively related to the 2 h plasma glucose concentration. Interpretation In obese children and adolescents with prediabetes, intramyocellular and intra-abdominal lipid accumulation is closely linked to the development of severe peripheral insulin resistance. PMID:14511928

  16. Prediabetes in obese youth: a syndrome of impaired glucose tolerance, severe insulin resistance, and altered myocellular and abdominal fat partitioning.

    PubMed

    Weiss, Ram; Dufour, Sylvie; Taksali, Sara E; Tamborlane, William V; Petersen, Kitt F; Bonadonna, Riccardo C; Boselli, Linda; Barbetta, Gina; Allen, Karin; Rife, Francis; Savoye, Mary; Dziura, James; Sherwin, Robert; Shulman, Gerald I; Caprio, Sonia

    2003-09-20

    Impaired glucose tolerance is common among obese adolescents, but the changes in insulin sensitivity and secretion that lead to this prediabetic state are unknown. We investigated whether altered partitioning of myocellular and abdominal fat relates to abnormalities in glucose homoeostasis in obese adolescents with prediabetes. We studied 14 obese children with impaired glucose tolerance and 14 with normal glucose tolerance, of similar ages, sex distribution, and degree of obesity. Insulin sensitivity and secretion were assessed by the euglycaemic-hyperinsulinaemic clamp and the hyperglycaemic clamp. Intramyocellular lipid was assessed by proton nuclear magnetic resonance spectroscopy and abdominal fat distribution by magnetic resonance imaging. Peripheral glucose disposal was significantly lower in individuals with impaired than in those with normal glucose tolerance (mean 35.4 [SE 4.0] vs 60.6 [7.2] micromoles per kg lean body mass per min; p=0.023) owing to a reduction in non-oxidative glucose disposal metabolism (storage). Individuals with impaired glucose tolerance had higher intramyocellular lipid content (3.04 [0.43] vs 1.99 [0.19]%, p=0.03), lower abdominal subcutaneous fat (460 [47] vs 626 [39] cm2, p=0.04), and slightly higher visceral fat than the controls (70 [11] vs 47 [6] cm2, p=0.065), resulting in a higher ratio of visceral to subcutaneous fat (0.15 [0.02] vs 0.07 [0.01], p=0.002). Intramyocellular and visceral lipid contents were inversely related to the glucose disposal and non-oxidative glucose metabolism and positively related to the 2 h plasma glucose concentration. In obese children and adolescents with prediabetes, intramyocellular and intra-abdominal lipid accumulation is closely linked to the development of severe peripheral insulin resistance.

  17. High-fat diet feeding alters olfactory-, social-, and reward-related behaviors of mice independent of obesity.

    PubMed

    Takase, Kenkichi; Tsuneoka, Yousuke; Oda, Satoko; Kuroda, Masaru; Funato, Hiromasa

    2016-04-01

    High-fat diet (HFD) consumption causes obesity, which is associated with well-known increased health risks. Moreover, obesity has been associated with altered sensorimotor and emotional behaviors of humans and mice. This study attempted to dissociate the influence of HFD-induced obesity on behaviors from the influence of HFD consumption itself. C57BL male mice were randomly allocated to a low-fat diet (LFD) group, an HFD-induced obesity (DIO) group, or a pair-fed HFD-feeding nonobese (HFD) group. A comprehensive behavioral test battery was performed on all three groups to assess sensorimotor functions, anxiety- and depression-like behaviors, reward-related behaviors, social behaviors, and learning/memory functions. Both the DIO and HFD groups exhibited disturbed olfaction, blunted ethanol preference, and enhanced social interactions. The DIO group exhibited blunted sucrose preference, shorter latency before falling off during the rotarod test, and a lower response to mechanical stimuli. The HFD-fed nonobese mice showed altered behaviors related to olfaction, social interactions, and rewards that were similar to those of the DIO mice. This finding suggests that HFD consumption alters a variety of behaviors independent of obesity. © 2016 The Obesity Society.

  18. Clinical usefulness of free subcutaneous fat pad for reduction of intraoperative air leakage during thoracoscopic pulmonary resection in lung cancer cases.

    PubMed

    Shintani, Yasushi; Inoue, Masayoshi; Funaki, Soichiro; Kawamura, Tomohiro; Minami, Masato; Okumura, Meinoshin

    2015-10-01

    Intraoperative alveolar air leaks remain a significant problem in thoracoscopic surgery (TS) cases. We examined the usefulness of covering damaged lung tissue with a subcutaneous fat pad for preventing postoperative air leakage in patients with non-small cell lung cancer (NSCLC). Patients with NSCLC underwent a thoracoscopic lobectomy or segmentectomy. When alveolar air leakage from the superficial pulmonary parenchyma was found, fibrin glue in combination with an absorbable mesh sheet was applied (S group; n = 100). When leakage originated from deep within the pulmonary parenchyma, a subcutaneous fat pad about 2 × 2 cm in size was harvested from the utility incision and placed on the damaged lung tissue with fibrin glue and sutures (F group; n = 66). Patient characteristics, air leak duration, and chest-tube removal time were analyzed. The homogeneity of each group was consistent, with no statistical differences for age, respiratory function, surgical procedures, pathologic stage, and histological type. The air leak duration was significantly shorter (p = 0.015), and the chest tube was removed significantly earlier (p = 0.002) in patients in the F group. Use of a free subcutaneous fat pad during pulmonary resection for TS patients with NSCLC reduced the duration of air leakage and chest tube drainage. The present method is easy, safe, and effective for repairing an air leak from remaining lung tissues in such cases.

  19. Methyl donor supplementation alters cognitive performance and motivation in female offspring from high-fat diet-fed dams.

    PubMed

    McKee, Sarah E; Grissom, Nicola M; Herdt, Christopher T; Reyes, Teresa M

    2017-02-16

    During gestation, fetal nutrition is entirely dependent on maternal diet. Maternal consumption of excess fat during pregnancy has been linked to an increased risk of neurologic disorders in offspring, including attention deficit/hyperactivity disorder, autism, and schizophrenia. In a mouse model, high-fat diet (HFD)-fed offspring have cognitive and executive function deficits as well as whole-genome DNA and promoter-specific hypomethylation in multiple brain regions. Dietary methyl donor supplementation during pregnancy or adulthood has been used to alter DNA methylation and behavior. Given that extensive brain development occurs during early postnatal life-particularly within the prefrontal cortex (PFC), a brain region critical for executive function-we examined whether early life methyl donor supplementation (e.g., during adolescence) could ameliorate executive function deficits observed in offspring that were exposed to maternal HFD. By using operant testing, progressive ratio, and the PFC-dependent 5-choice serial reaction timed task (5-CSRTT), we determined that F1 female offspring (B6D2F1/J) from HFD-fed dams have decreased motivation (decreased progressive ratio breakpoint) and require a longer stimulus length to complete the 5-CSRTT task successfully, whereas early life methyl donor supplementation increased motivation and shortened the minimum stimulus length required for a correct response in the 5-CSRTT. Of interest, we found that expression of 2 chemokines, CCL2 and CXCL10, correlated with the median stimulus length in the 5-CSRTT. Furthermore, we found that acute adult supplementation of methyl donors increased motivation in HFD-fed offspring and those who previously received supplementation with methyl donors. These data point to early life as a sensitive time during which dietary methyl donor supplementation can alter PFC-dependent cognitive behaviors.-McKee, S. E., Grissom, N. M., Herdt, C. T., Reyes, T. M. Methyl donor supplementation alters

  20. High-fat maternal diet during pregnancy persistently alters the offspring microbiome in a primate model

    PubMed Central

    Ma, Jun; Prince, Amanda L.; Bader, David; Hu, Min; Ganu, Radhika; Baquero, Karalee; Blundell, Peter; Harris, R. Alan; Frias, Antonio E.; Grove, Kevin L.; Aagaard, Kjersti M.

    2014-01-01

    The intestinal microbiome is a unique ecosystem and an essential mediator of metabolism and obesity in mammals. However, studies investigating the impact of the diet on the establishment of the gut microbiome early in life are generally lacking, and most notably so in primate models. Here we report that a high-fat maternal or postnatal diet, but not obesity per se, structures the offspring’s intestinal microbiome in Macaca fuscata (Japanese macaque). The resultant microbial dysbiosis is only partially corrected by a low-fat, control diet after weaning. Unexpectedly, early exposure to a high-fat diet diminished the abundance of non-pathogenic Campylobacter in the juvenile gut, suggesting a potential role for dietary fat in shaping commensal microbial communities in primates. Our data challenge the concept of an obesity-causing gut microbiome, and rather provide evidence for a contribution of the maternal diet in establishing the microbiota, which in turn affects intestinal maintenance of metabolic health. PMID:24846660

  1. High Fat Diet Produces Brain Insulin Resistance, Synaptodendritic Abnormalities and Altered Behavior in Mice

    PubMed Central

    Arnold, Steven E.; Lucki, Irwin; Brookshire, Bethany R.; Carlson, Gregory C.; Browne, Carolyn A.; Kazi, Hala; Bang, Sookhee; Choi, Bo-Ran; Chen, Yong; McMullen, Mary F.; Kim, Sangwon F.

    2014-01-01

    Insulin resistance and other features of the metabolic syndrome are increasingly recognized for their effects on cognitive health. To ascertain mechanisms by which this occurs, we fed mice a very high fat diet (60% kcal by fat) for 17 days or a moderate high fat diet (HFD, 45% kcal by fat) for 8 weeks and examined changes in brain insulin signaling responses, hippocampal synaptodendritic protein expression, and spatial working memory. Compared to normal control diet mice, cerebral cortex tissues of HFD mice were insulin-resistant as evidenced by failed activation of Akt, S6 and GSK3β with ex-vivo insulin stimulation. Importantly, we found that expression of brain IPMK, which is necessary for mTOR/Akt signaling, remained decreased in HFD mice upon activation of AMPK. HFD mouse hippocampus exhibited increased expression of serine-phosphorylated insulin receptor substrate 1 (IRS1-pS616), a marker of insulin resistance, as well as decreased expression of PSD-95, a scaffolding protein enriched in post-synaptic densities, and synaptopodin, an actin-associated protein enriched in spine apparatuses. Spatial working memory was impaired as assessed by decreased spontaneous alternation in a T-maze. These findings indicate that HFD is associated with telencephalic insulin resistance and deleterious effects on synaptic integrity and cognitive behaviors. PMID:24686304

  2. Abdominal Fat and Sarcopenia in Women Significantly Alter Osteoblasts Homeostasis In Vitro by a WNT/β-Catenin Dependent Mechanism

    PubMed Central

    Wannenes, Francesca; Papa, Vincenza; Greco, Emanuela A.; Fornari, Rachele; Marocco, Chiara; Di Luigi, Luigi; Donini, Lorenzo M.; Lenzi, Andrea

    2014-01-01

    Obesity and sarcopenia have been associated with mineral metabolism derangement and low bone mineral density (BMD). We investigated whether imbalance of serum factors in obese or obese sarcopenic patients could affect bone cell activity in vitro. To evaluate and characterize potential cellular and molecular changes of human osteoblasts, cells were exposed to sera of four groups of patients: (1) affected by obesity with normal BMD (O), (2) affected by obesity with low BMD (OO), (3) affected by obesity and sarcopenia (OS), and (4) affected by obesity, sarcopenia, and low BMD (OOS) as compared to subjects with normal body weight and normal BMD (CTL). Patients were previously investigated and characterized for body composition, biochemical and bone turnover markers. Then, sera of different groups of patients were used to incubate human osteoblasts and evaluate potential alterations in cell homeostasis. Exposure to OO, OS, and OOS sera significantly reduced alkaline phosphatase, osteopontin, and BMP4 expression compared to cells exposed to O and CTL, indicating a detrimental effect on osteoblast differentiation. Interestingly, sera of all groups of patients induced intracellular alteration in Wnt/β-catenin molecular pathway, as demonstrated by the significant alteration of specific target genes expression and by altered β-catenin cellular compartmentalization and GSK3β phosphorylation. In conclusion our results show for the first time that sera of obese subjects with low bone mineral density and sarcopenia significantly alter osteoblasts homeostasis in vitro, indicating potential detrimental effects of trunk fat on bone formation and skeletal homeostasis. PMID:24963291

  3. Abdominal Fat and Sarcopenia in Women Significantly Alter Osteoblasts Homeostasis In Vitro by a WNT/ β -Catenin Dependent Mechanism.

    PubMed

    Wannenes, Francesca; Papa, Vincenza; Greco, Emanuela A; Fornari, Rachele; Marocco, Chiara; Baldari, Carlo; Di Luigi, Luigi; Emerenziani, Gian Pietro; Poggiogalle, Eleonora; Guidetti, Laura; Donini, Lorenzo M; Lenzi, Andrea; Migliaccio, Silvia

    2014-01-01

    Obesity and sarcopenia have been associated with mineral metabolism derangement and low bone mineral density (BMD). We investigated whether imbalance of serum factors in obese or obese sarcopenic patients could affect bone cell activity in vitro. To evaluate and characterize potential cellular and molecular changes of human osteoblasts, cells were exposed to sera of four groups of patients: (1) affected by obesity with normal BMD (O), (2) affected by obesity with low BMD (OO), (3) affected by obesity and sarcopenia (OS), and (4) affected by obesity, sarcopenia, and low BMD (OOS) as compared to subjects with normal body weight and normal BMD (CTL). Patients were previously investigated and characterized for body composition, biochemical and bone turnover markers. Then, sera of different groups of patients were used to incubate human osteoblasts and evaluate potential alterations in cell homeostasis. Exposure to OO, OS, and OOS sera significantly reduced alkaline phosphatase, osteopontin, and BMP4 expression compared to cells exposed to O and CTL, indicating a detrimental effect on osteoblast differentiation. Interestingly, sera of all groups of patients induced intracellular alteration in Wnt/ β -catenin molecular pathway, as demonstrated by the significant alteration of specific target genes expression and by altered β -catenin cellular compartmentalization and GSK3 β phosphorylation. In conclusion our results show for the first time that sera of obese subjects with low bone mineral density and sarcopenia significantly alter osteoblasts homeostasis in vitro, indicating potential detrimental effects of trunk fat on bone formation and skeletal homeostasis.

  4. Pulmonary neuroendocrine cells, airway innervation, and smooth muscle are altered in Cftr null mice.

    PubMed

    Pan, Jie; Luk, Catherine; Kent, Geraldine; Cutz, Ernest; Yeger, Herman

    2006-09-01

    The amine- and peptide-producing pulmonary neuroendocrine cells (PNEC) are widely distributed within the airway mucosa of mammalian lung as solitary cells and innervated clusters, neuroepithelial bodies (NEB), which function as airway O2 sensors. These cells express Cftr and hence could play a role in the pathophysiology of cystic fibrosis (CF) lung disease. We performed confocal microscopy and morphometric analysis on lung sections from Cftr-/- (null), Cftr+/+, and Cftr+/- (control) mice at developmental stages E20, P5, P9, and P30 to determine the distribution, frequency, and innervation of PNEC/NEB, innervation and cell mass of airway smooth muscle, and neuromuscular junctions using synaptic vesicle protein 2, smooth muscle actin, and synaptophysin markers, respectively. The mean number of PNEC/NEB in Cftr-/- mice was significantly reduced compared with control mice at E20, whereas comparable or increased numbers were observed postnatally. NEB cells in Cftr null mice showed a significant reduction in intracorpuscular nerve endings compared with control mice, which is consistent with an intrinsic abnormality of the PNEC system. The airways of Cftr-/- mice showed reduced density (approximately 20-30%) of smooth muscle innervation, decreased mean airway smooth muscle mass (approximately 35%), and reduced density (approximately 20%) of nerve endings compared with control mice. We conclude that the airways of Cftr-/- mice exhibit heretofore unappreciated structural alterations affecting cellular and neural components of the PNEC system and airway smooth muscle and its innervation resulting in blunted O2 sensing and reduced airway tonus. Cftr could play a role in the development of the PNEC system, lung innervation, and airway smooth muscle.

  5. Severe pulmonary hypertension is associated with altered right ventricle metabolic substrate uptake

    PubMed Central

    Kumar, Rahul; Mickael, Claudia; Sanders, Linda; Gebreab, Liya; Huber, Kendra M.; Perez, Mario; Smith-Jones, Peter; Serkova, Natalie J.; Tuder, Rubin M.

    2015-01-01

    In severe pulmonary hypertension (SPH), prior studies have shown an increase in right ventricle (RV) uptake of glucose, but it is unclear whether there is a change in the relative utilization of fatty acids. We hypothesized that in the RV in SPH, as in left ventricular (LV) failure, there is altered substrate utilization, with increased glucose uptake and decreased fatty acid uptake. SPH was induced in rats by treatment with the VEGF receptor inhibitor SU5416 and 3 wk of hypoxia (10% FiO2), followed by an additional 4 wk of normoxia (SU-Hx group). Control rats were treated with carboxymethylcellulose vehicle and 7 wk of normoxia (CMC-Nx group). The rodents then underwent positron emission tomography with sequential administration of two radiotracers, 2-deoxy-2-[18F]fluoroglucose (18F-FDG) and 14-(R,S)-[18F]fluoro-6-thia-heptadecanoic acid (18F-FTHA), analogs of glucose and fatty acid, respectively. Five CMC-Nx and 3 SU-Hx rats completed the entire experimental protocol. In the RV, there was a mild increase in 18F-FDG uptake (1.35-fold, P = 0.085) and a significant decrease in 18F-FTHA uptake (−2.1-fold, P < 0.05) in the SU-Hx rats relative to the CMC-Nx rats. In the LV, SU-Hx rats had less uptake of both radiotracers compared with CMC-Nx rats. Less RV fatty acid uptake in SPH was corroborated by decreased fatty acid transporters and enzymes in the RV tissue, and specifically a decrease in lipoprotein lipase. In the RV in rats with SPH, there is a major shift in metabolic substrate preference, largely due to decreased fatty acid uptake. PMID:26115672

  6. High-fat diet transition reduces brain DHA levels associated with altered brain plasticity and behaviour.

    PubMed

    Sharma, Sandeep; Zhuang, Yumei; Gomez-Pinilla, Fernando

    2012-01-01

    To assess how the shift from a healthy diet rich in omega-3 fatty acids to a diet rich in saturated fatty acid affects the substrates for brain plasticity and function, we used pregnant rats fed with omega-3 supplemented diet from their 2nd day of gestation period as well as their male pups for 12 weeks. Afterwards, the animals were randomly assigned to either a group fed on the same diet or a group fed on a high-fat diet (HFD) rich in saturated fats for 3 weeks. We found that the HFD increased vulnerability for anxiety-like behavior, and that these modifications harmonized with changes in the anxiety-related NPY1 receptor and the reduced levels of BDNF, and its signalling receptor pTrkB, as well as the CREB protein. Brain DHA contents were significantly associated with the levels of anxiety-like behavior in these rats.

  7. High-fat diet transition reduces brain DHA levels associated with altered brain plasticity and behaviour

    PubMed Central

    Sharma, Sandeep; Zhuang, Yumei; Gomez-Pinilla, Fernando

    2012-01-01

    To assess how the shift from a healthy diet rich in omega-3 fatty acids to a diet rich in saturated fatty acid affects the substrates for brain plasticity and function, we used pregnant rats fed with omega-3 supplemented diet from their 2nd day of gestation period as well as their male pups for 12 weeks. Afterwards, the animals were randomly assigned to either a group fed on the same diet or a group fed on a high-fat diet (HFD) rich in saturated fats for 3 weeks. We found that the HFD increased vulnerability for anxiety-like behavior, and that these modifications harmonized with changes in the anxiety-related NPY1 receptor and the reduced levels of BDNF, and its signalling receptor pTrkB, as well as the CREB protein. Brain DHA contents were significantly associated with the levels of anxiety-like behavior in these rats. PMID:22666534

  8. Soluble metals in residual oil fly ash alter innate and adaptive pulmonary immune responses to bacterial infection in rats

    SciTech Connect

    Roberts, Jenny R. . E-mail: jur6@cdc.gov; Young, Shih-Houng; Castranova, Vincent; Antonini, James M.

    2007-06-15

    The soluble metals of the pollutant, residual oil fly ash (ROFA), have been shown to alter pulmonary bacterial clearance in rats. The goal of this study was to determine the potential effects on both the innate and adaptive lung immune responses after bacterial infection in rats pre-exposed to the soluble metals in ROFA. Sprague-Dawley rats were intratracheally dosed (i.t.) at day 0 with ROFA (R-Total) (1.0 mg/100 g body weight), the soluble fraction of ROFA (R-Soluble), the soluble sample subject to a chelator (R-Chelex), or phosphate-buffered saline (Saline). On day 3, rats were administered an i.t. dose of 5 x 10{sup 4} Listeria monocytogenes. On days 6, 8, and 10, bacterial pulmonary clearance was monitored and bronchoalveolar lavage (BAL) was performed on days 3 (pre-infection), 6, 8, and 10. A concentrated first fraction of lavage fluid was retained for analysis of lactate dehydrogenase and albumin to assess lung injury. BAL cell number, phenotype, and production of reactive oxygen (ROS) and nitrogen species (RNS) were assessed, and a variety of cytokines were measured in the BAL fluid. Rats pre-treated with R-Soluble showed elevated lung injury/cytotoxicity and increased cellular influx into the lungs. R-Soluble-treatment also altered ROS, RNS, and cytokine levels, and caused a degree of macrophage and T cell inhibition. These effects of R-Soluble result in increased pulmonary bacterial burden after infection. The results suggest that soluble metals in ROFA increase lung injury and inflammation, and alter both innate and adaptive pulmonary immune responses.

  9. Altered vasoreactivity in neonatal rats with pulmonary hypertension associated with bronchopulmonary dysplasia: Implication of both eNOS phosphorylation and calcium signaling

    PubMed Central

    Quignard, Jean-François; Freund-Michel, Véronique; Courtois, Arnaud; Marthan, Roger; Muller, Bernard; Guibert, Christelle; Dubois, Mathilde

    2017-01-01

    Bronchopulmonary dysplasia (BPD) consists of an arrest of pulmonary vascular and alveolar growth, with persistent hypoplasia of the pulmonary microvasculature and alveolar simplification. In 25 to 40% of the cases, BPD is complicated by pulmonary hypertension (BPD-PH) that significantly increases the risk of morbidity. In vivo studies suggest that increased pulmonary vascular tone could contribute to late PH in BPD. Nevertheless, an alteration in vasoreactivity as well as the mechanisms involved remain to be confirmed. The purpose of this study was thus to assess changes in pulmonary vascular reactivity in a murine model of BPD-PH. Newborn Wistar rats were exposed to either room air (normoxia) or 90% O2 (hyperoxia) for 14 days. Exposure to hyperoxia induced the well-known features of BPD-PH such as elevated right ventricular systolic pressure, right ventricular hypertrophy, pulmonary vascular remodeling and decreased pulmonary vascular density. Intrapulmonary arteries from hyperoxic pups showed decreased endothelium-dependent relaxation to acetylcholine without any alteration of relaxation to the NO-donor sodium nitroprusside. This functional alteration was associated with a decrease of lung eNOS phosphorylation at the Ser1177 activating site. In pups exposed to hyperoxia, serotonin and phenylephrine induced exacerbated contractile responses of intrapulmonary arteries as well as intracellular calcium response in pulmonary arterial smooth muscle cells (PASMC). Moreover, the amplitude of the store-operated Ca2+ entry (SOCE), induced by store depletion using a SERCA inhibitor, was significantly greater in PASMC from hyperoxic pups. Altogether, hyperoxia-induced BPD-PH alters the pulmonary arterial reactivity, with effects on both endothelial and smooth muscle functions. Reduced activating eNOS phosphorylation and enhanced Ca2+ signaling likely account for alterations of pulmonary arterial reactivity. PMID:28235094

  10. A High-Fat High-Sucrose Diet Rapidly Alters Muscle Integrity, Inflammation and Gut Microbiota in Male Rats

    PubMed Central

    Collins, Kelsey H.; Paul, Heather A.; Hart, David A.; Reimer, Raylene A.; Smith, Ian C.; Rios, Jaqueline L.; Seerattan, Ruth A.; Herzog, Walter

    2016-01-01

    The chronic low-level inflammation associated with obesity is known to deleteriously affect muscle composition. However, the manner in which obesity leads to muscle loss has not been explored in detail or in an integrated manner following a short-term metabolic challenge. In this paper, we evaluated the relationships between compromised muscle integrity, diet, systemic inflammatory mediators, adipose tissue, and gut microbiota in male Sprague-Dawley rats. We show that intramuscular fat, fibrosis, and the number of pro-inflammatory cells increased by 3-days and was sustained across 28-days of high-fat high-sugar feeding compared to control-diet animals. To understand systemic contributors to muscle damage, dynamic changes in gut microbiota and serum inflammatory markers were evaluated. Data from this study links metabolic challenge to persistent compromise in muscle integrity after just 3-days, a finding associated with altered gut microbiota and systemic inflammatory changes. These data contribute to our understanding of early consequences of metabolic challenge on multiple host systems, which are important to understand as obesity treatment options are developed. Therefore, intervention within this early period of metabolic challenge may be critical to mitigate these sustained alterations in muscle integrity. PMID:27853291

  11. Table grape consumption reduces adiposity and markers of hepatic lipogenesis and alters gut microbiota in butter fat-fed mice.

    PubMed

    Baldwin, Jessie; Collins, Brian; Wolf, Patricia G; Martinez, Kristina; Shen, Wan; Chuang, Chia-Chi; Zhong, Wei; Cooney, Paula; Cockrell, Chase; Chang, Eugene; Gaskins, H Rex; McIntosh, Michael K

    2016-01-01

    Our objective was to determine if consuming table grapes reduces adiposity and its metabolic consequences and alters gut microbiota in mice fed a high-fat (HF), butter-rich diet. C57BL/6J mice were fed a low-fat (LF) diet or HF diet with 3% or 5% grapes for 11weeks. Total body and inguinal fat were moderately but significantly reduced in mice fed both levels of grapes compared to their controls. Mice fed 5% grapes had lower liver weights and triglyceride levels and decreased expression of glycerol-3-phosphate acyltransferase (Gpat1) compared to the 5% controls. Mice fed 3% grapes had lower hepatic mRNA levels of peroxisome proliferator-activated receptor gamma 2, sterol-CoA desaturase 1, fatty-acid binding protein 4 and Gpat1 compared to the 3% controls. Although grape feeding had only a minor impact on markers of inflammation or lipogenesis in adipose tissue or intestine, 3% of grapes decreased the intestinal abundance of sulfidogenic Desulfobacter spp. and the Bilophila wadsworthia-specific dissimilatory sulfite reductase gene and tended to increase the abundance of the beneficial bacterium Akkermansia muciniphila compared to controls. In addition, Bifidobacterium, Lactobacillus, Allobaculum and several other genera correlated negatively with adiposity. Allobaculum in particular was increased in the LF and 3% grapes groups compared to the HF-fed controls. Notably, grape feeding attenuated the HF-induced impairment in epithelial localization of the intestinal tight junction protein zonula occludens. Collectively, these data indicate that some of the adverse health consequences of consuming an HF diet rich in saturated fat can be attenuated by table grape consumption.

  12. Table grape consumption reduces adiposity and markers of hepatic lipogenesis and alters gut microbiota in butter fat-fed mice

    PubMed Central

    Baldwin, Jessie; Collins, Brian; Wolf, Patricia G.; Martinez, Kristina; Shen, Wan; Chuang, Chia-Chi; Zhong, Wei; Cooney, Paula; Cockrell, Chase; Chang, Eugene; Gaskins, H. Rex; McIntosh, Michael K.

    2016-01-01

    Our objective was to determine if consuming table grapes reduces adiposity and its metabolic consequences and alters gut microbiota in mice fed a high fat (HF), butter-rich diet. C57BL/6J mice were fed a low fat (LF) diet or HF diet with 3% or 5% grapes for 11 weeks. Total body and inguinal fat were moderately, but significantly reduced in mice fed both levels of grapes compared to their controls. Mice fed 5% grapes had lower liver weights and triglyceride levels, and decreased expression of glycerol-3-phosphate acyltransferase (Gpat1) compared to the 5% controls. Mice fed 3% grapes had lower hepatic mRNA levels of peroxisome proliferator-activated receptor gamma 2, sterol-CoA desaturase 1, fatty-acid binding protein 4, and Gpat1 compared to the 3% controls. Although grape feeding had only a minor impact on markers of inflammation or lipogenesis in adipose tissue or intestine, 3% grapes decreased the intestinal abundance of sulfidogenic Desulfobacter spp., and the Bilophila wadsworthia-specific dissimilatory sulfite reductase gene (dsrA-Bw), and tended to increase the abundance of the beneficial bacterium Akkermansia muciniphila compared to controls. Additionally, Bifidobacterium, Lactobacillus, Allobaculum, and several other genera correlated negatively with adiposity. Allobaculum in particular was increased in the LF and 3% grapes groups compared to the HF-fed controls. Notably, grape feeding attenuated the HF-induced impairment in epithelial localization of the intestinal tight junction protein zonula occludens. Collectively, these data indicate that some of the adverse health consequences of consuming a HF diet rich in saturated fat can be attenuated by table grape consumption. PMID:26423887

  13. High fat and/or high salt intake during pregnancy alters maternal meta‐inflammation and offspring growth and metabolic profiles

    PubMed Central

    Reynolds, Clare M.; Vickers, Mark H.; Harrison, Claudia J.; Segovia, Stephanie A.; Gray, Clint

    2014-01-01

    Abstract A high intake of fat or salt during pregnancy perturbs placental function, alters fetal development, and predisposes offspring to metabolic disease in adult life. Despite its relevance to modern dietary habits, the developmental programming effects of excessive maternal fat and salt, fed in combination, have not been examined. We investigated the effects of moderately high maternal fat and/or salt intake on maternal metainflammation and its consequences on fetal and weanling growth and metabolic profile. Female Sprague–Dawley rats were fed a standard control diet (CD), 4% salt diet (SD), 45% fat diet (HF) or 4% salt/45% fat combined diet (HFSD) 3 weeks prior to and throughout pregnancy and lactation. Plasma and tissue samples were collected at day 18 of pregnancy from mother and fetus, and at postnatal day 24 in weanlings. Markers of adipose tissue inflammation, macrophage infiltration, lipogenesis, nutrient transport, and storage were altered in pregnant dams receiving high‐fat and/or ‐salt diets. This was accompanied by increased fat mass in high‐fat groups and differential hepatic lipid and glucose homeostasis. Offspring of high fat‐fed mothers had reduced fetal weight, displayed catch‐up growth, increased fat mass, and altered metabolic profiles at weaning. Maternal diets high in fat and/or salt affect maternal metabolic parameters, fetal growth and development, metabolic status, and adipoinsular axis in the weanling. Results presented here highlight the importance of diet in expectant mothers or women considering pregnancy. Furthermore, the potential for maternal nutritional intervention strategies may be employed to modify the metabolic disease risk in adult offspring during later life. PMID:25096554

  14. Neonatal Pulmonary Macrophage Depletion Coupled to Defective Mucus Clearance Increases Susceptibility to Pneumonia and Alters Pulmonary Immune Responses

    PubMed Central

    Wilkinson, Kristen J.; Terrell, Kristy A.; Burns, Kimberlie A.; Livraghi-Butrico, Alessandra; Doerschuk, Claire M.; O’Neal, Wanda K.; Boucher, Richard C.

    2016-01-01

    Resident immune cells (e.g., macrophages [MΦs]) and airway mucus clearance both contribute to a healthy lung environment. To investigate interactions between pulmonary MΦ function and defective mucus clearance, a genetic model of lysozyme M (LysM) promoter–mediated MΦ depletion was generated, characterized, and crossed with the sodium channel β subunit transgenic (Scnn1b-Tg) mouse model of defective mucus clearance. Diphtheria toxin A–mediated depletion of LysM+ pulmonary MΦs in wild-type mice with normal mucus clearance resulted in lethal pneumonia in 24% of neonates. The pneumonias were dominated by Pasteurella pneumotropica and accompanied by emaciation, neutrophilic inflammation, and elevated Th1 cytokines. The incidence of emaciation and pneumonia reached 51% when LysM+ MΦ depletion was superimposed on the airway mucus clearance defect of Scnn1b-Tg mice. In LysM+ MΦ-depleted Scnn1b-Tg mice, pneumonias were associated with a broader spectrum of bacterial species and a significant reduction in airway mucus plugging. Bacterial burden (CFUs) was comparable between Scnn1b-Tg and nonpneumonic LysM+ MΦ-depleted Scnn1b-Tg mice. However, the nonpneumonic LysM+ MΦ-depleted Scnn1b-Tg mice exhibited increased airway inflammation, the presence of neutrophilic infiltration, and increased levels of inflammatory cytokines in bronchoalveolar lavage fluid compared with Scnn1b-Tg mice. Collectively, these data identify key MΦ–mucus clearance interactions with respect to both infectious and inflammatory components of muco-obstructive lung disease. PMID:26121027

  15. Neonatal Pulmonary Macrophage Depletion Coupled to Defective Mucus Clearance Increases Susceptibility to Pneumonia and Alters Pulmonary Immune Responses.

    PubMed

    Saini, Yogesh; Wilkinson, Kristen J; Terrell, Kristy A; Burns, Kimberlie A; Livraghi-Butrico, Alessandra; Doerschuk, Claire M; O'Neal, Wanda K; Boucher, Richard C

    2016-02-01

    Resident immune cells (e.g., macrophages [MΦs]) and airway mucus clearance both contribute to a healthy lung environment. To investigate interactions between pulmonary MΦ function and defective mucus clearance, a genetic model of lysozyme M (LysM) promoter-mediated MΦ depletion was generated, characterized, and crossed with the sodium channel β subunit transgenic (Scnn1b-Tg) mouse model of defective mucus clearance. Diphtheria toxin A-mediated depletion of LysM(+) pulmonary MΦs in wild-type mice with normal mucus clearance resulted in lethal pneumonia in 24% of neonates. The pneumonias were dominated by Pasteurella pneumotropica and accompanied by emaciation, neutrophilic inflammation, and elevated Th1 cytokines. The incidence of emaciation and pneumonia reached 51% when LysM(+) MΦ depletion was superimposed on the airway mucus clearance defect of Scnn1b-Tg mice. In LysM(+) MΦ-depleted Scnn1b-Tg mice, pneumonias were associated with a broader spectrum of bacterial species and a significant reduction in airway mucus plugging. Bacterial burden (CFUs) was comparable between Scnn1b-Tg and nonpneumonic LysM(+) MΦ-depleted Scnn1b-Tg mice. However, the nonpneumonic LysM(+) MΦ-depleted Scnn1b-Tg mice exhibited increased airway inflammation, the presence of neutrophilic infiltration, and increased levels of inflammatory cytokines in bronchoalveolar lavage fluid compared with Scnn1b-Tg mice. Collectively, these data identify key MΦ-mucus clearance interactions with respect to both infectious and inflammatory components of muco-obstructive lung disease.

  16. Inhalation exposure of rats to asphalt fumes generated at paving temperatures alters pulmonary xenobiotic metabolism pathways without lung injury.

    PubMed Central

    Ma, Jane Y C; Rengasamy, Apavoo; Frazer, Dave; Barger, Mark W; Hubbs, Ann F; Battelli, Lori; Tomblyn, Seith; Stone, Samuel; Castranova, Vince

    2003-01-01

    Asphalt fumes are complex mixtures of various organic compounds, including polycyclic aromatic hydrocarbons (PAHs). PAHs require bioactivation by the cytochrome P-450 monooxygenase system to exert toxic/carcinogenic effects. The present study was carried out to characterize the acute pulmonary inflammatory responses and the alterations of pulmonary xenobiotic pathways in rats exposed to asphalt fumes by inhalation. Rats were exposed at various doses and time periods to air or to asphalt fumes generated at paving temperatures. To assess the acute damage and inflammatory responses, differential cell counts, acellular lactate dehydrogenase (LDH) activity, and protein content of bronchoalveolar lavage fluid were determined. Alveolar macrophage (AM) function was assessed by monitoring generation of chemiluminescence and production of tumor necrosis factor-alpha and interleukin-1. Alteration of pulmonary xenobiotic pathways was determined by monitoring the protein levels and activities of P-450 isozymes (CYP1A1 and CYP2B1), glutathioneS-transferase (GST), and NADPH:quinone oxidoreductase (QR). The results show that acute asphalt fume exposure did not cause neutrophil infiltration, alter LDH activity or protein content, or affect AM function, suggesting that short-term asphalt fume exposure did not induce acute lung damage or inflammation. However, acute asphalt fume exposure significantly increased the activity and protein level of CYP1A1 whereas it markedly reduced the activity and protein level of CYP2B1 in the lung. The induction of CYP1A1 was localized in nonciliated bronchiolar epithelial (Clara) cells, alveolar septa, and endothelial cells by immunofluorescence microscopy. Cytosolic QR activity was significantly elevated after asphalt fume exposure, whereas GST activity was not affected by the exposure. This induction of CYP1A1 and QR with the concomitant down-regulation of CYP2B1 after asphalt fume exposure could alter PAH metabolism and may lead to potential

  17. Acute dietary fat intake initiates alterations in energy metabolism and insulin resistance

    PubMed Central

    Hernández, Elisa Álvarez; Kahl, Sabine; Seelig, Anett; Begovatz, Paul; Kupriyanova, Yuliya; Nowotny, Bettina; Nowotny, Peter; Herder, Christian; Carvalho, Filipa; Neschen, Susanne; Jones, John G.; de Angelis, Martin Hrabě

    2017-01-01

    BACKGROUND. Dietary intake of saturated fat is a likely contributor to nonalcoholic fatty liver disease (NAFLD) and insulin resistance, but the mechanisms that initiate these abnormalities in humans remain unclear. We examined the effects of a single oral saturated fat load on insulin sensitivity, hepatic glucose metabolism, and lipid metabolism in humans. Similarly, initiating mechanisms were examined after an equivalent challenge in mice. METHODS. Fourteen lean, healthy individuals randomly received either palm oil (PO) or vehicle (VCL). Hepatic metabolism was analyzed using in vivo 13C/31P/1H and ex vivo 2H magnetic resonance spectroscopy before and during hyperinsulinemic-euglycemic clamps with isotope dilution. Mice underwent identical clamp procedures and hepatic transcriptome analyses. RESULTS. PO administration decreased whole-body, hepatic, and adipose tissue insulin sensitivity by 25%, 15%, and 34%, respectively. Hepatic triglyceride and ATP content rose by 35% and 16%, respectively. Hepatic gluconeogenesis increased by 70%, and net glycogenolysis declined by 20%. Mouse transcriptomics revealed that PO differentially regulates predicted upstream regulators and pathways, including LPS, members of the TLR and PPAR families, NF-κB, and TNF-related weak inducer of apoptosis (TWEAK). CONCLUSION. Saturated fat ingestion rapidly increases hepatic lipid storage, energy metabolism, and insulin resistance. This is accompanied by regulation of hepatic gene expression and signaling that may contribute to development of NAFLD. REGISTRATION. ClinicalTrials.gov NCT01736202. FUNDING. Germany: Ministry of Innovation, Science, and Research North Rhine–Westfalia, German Federal Ministry of Health, Federal Ministry of Education and Research, German Center for Diabetes Research, German Research Foundation, and German Diabetes Association. Portugal: Portuguese Foundation for Science and Technology, FEDER – European Regional Development Fund, Portuguese Foundation for

  18. Altered pulmonary function in children with asthma associated with highway traffic near residence.

    PubMed

    Margolis, Helene G; Mann, Jennifer K; Lurmann, Frederick W; Mortimer, Kathleen M; Balmes, John R; Hammond, S Katharine; Tager, Ira B

    2009-04-01

    Cross-sectional analyses were conducted to evaluate the effects of exposure to highway traffic on pulmonary function in Fresno, California. Traffic and spirometry data were available for 214 children (enrollment ages six to 11 years). Multiple linear regression was used to evaluate the relations between pulmonary function and traffic parameters. Heavy-duty vehicle count was used as a surrogate measure for diesel-related exposures. Pulmonary function was non-significantly associated with longer distance-to-road and non-significantly associated with higher traffic intensity. Evaluation of effect modification by FEF(25-75)/FVC (a measure of intrinsic airway size) showed that all pulmonary function measures of flow were significantly inversely related to a traffic metric that incorporates traffic intensity and roadway proximity. The results indicate that residence proximity to highway traffic is associated with lower pulmonary function among children with asthma, and smaller airway size is an important modifier of the effect of traffic exposure on pulmonary function and a marker of increased susceptibility.

  19. Monocyte chemotactic protein-1 attenuates and high-fat diet exacerbates bone loss in mice with pulmonary metastasis of Lewis lung carcinoma

    USDA-ARS?s Scientific Manuscript database

    Bone can be adversely affected by obesity and cancer-associated complications including wasting. The objective of this study was to determine whether a high-fat diet and a deficiency in monocyte chemotactic protein-1 (MCP-1) altered bone structural defects found in male C57BL/6 mice with Lewis lung...

  20. Effect of high-fructose and high-fat diets on pulmonary sensitivity, motor activity, and body composition of brown Norway rats exposed to ozone.

    PubMed

    Gordon, C J; Phillips, P M; Johnstone, A F M; Beasley, T E; Ledbetter, A D; Schladweiler, M C; Snow, S J; Kodavanti, U P

    2016-04-01

    Diet-induced obesity has been suggested to lead to increased susceptibility to air pollutants such as ozone (O3); however, there is little experimental evidence. Thirty day old male and female Brown Norway rats were fed a normal, high-fructose or high-fat diet for 12 weeks and then exposed to O3 (acute - air or 0.8 ppm O3 for 5 h, or subacute - air or 0.8 ppm O3 for 5 h/d 1 d/week for 4 weeks). Body composition was measured non-invasively using NMR. Ventilatory parameters and exploratory behavior were measured after the third week of subacute exposure. Bronchoalveolar lavage fluid (BALF) and blood chemistry data were collected 18 h after acute O3 and 18 h after the fourth week of subacute O3. The diets led to increased body fat in male but not female rats. O3-induced changes in ventilatory function were either unaffected or improved with the fructose and fat diets. O3-induced reduction in exploratory behavior was attenuated with fructose and fat diets in males and partially in females. O3 led to a significant decrease in body fat of males fed control diet but not the fructose or fat diet. O3 led to significant increases in BALF eosinophils, increase in albumin, and reductions in macrophages. Female rats appeared to be more affected than males to O3 regardless of diet. Overall, treatment with high-fructose and high-fat diets attenuated some O3 induced effects on pulmonary function, behavior, and metabolism. Exacerbation of toxicity was observed less frequently.

  1. Protein Deficiency Induces Alterations in the Distribution of T-Cell Subsets in Experimental Pulmonary Tuberculosis

    PubMed Central

    Mainali, Elsie S.; McMurray, David N.

    1998-01-01

    Previous research has suggested that dietary protein deficiency alters resistance to experimental pulmonary tuberculosis, in part, by affecting the distribution and trafficking of antigen-reactive T cells. In this study, guinea pigs were maintained on either a protein-deficient (10% ovalbumin) or control (30% ovalbumin) diet and infected 4 to 6 weeks later with a low dose of virulent Mycobacterium tuberculosis H37Rv by the respiratory route. Monoclonal antibodies directed against the CD4 or CD8 markers on guinea pig lymphocytes were used in a flow cytofluorometric assay to determine the proportion of each subset in the peripheral circulation, spleen, and bronchotracheal lymph nodes at 4 weeks after infection. In uninfected guinea pigs, only the spleen exhibited an effect of diet on T-cell distribution, with small but consistent reductions in the proportions of both CD4 and CD8 T lymphocytes. However, following infection, protein deficiency exerted a profound effect on T-cell distribution. Malnourished, tuberculous guinea pigs harbored only 20 and 60% of the T cells (as a proportion of total lymphoid cells) found in the spleen and blood, respectively, of their well-nourished counterparts. Normal relative proportions of CD4 and CD8 cells were observed, however. In striking contrast, the bronchotracheal lymph nodes of protein-deprived guinea pigs with tuberculosis contained more than twice the numbers of T cells of control guinea pigs, and the normal CD4-to-CD8 ratio was reversed. Peripheral T-cell function, as measured by the delayed hypersensitivity skin test to tuberculin, and antigen-induced lymphoproliferation in vitro were markedly suppressed in protein-malnourished animals. Conversely, purified protein derivative-induced (but not concanavalin A-induced) proliferation was significantly enhanced in cultures of lymph node cells from protein-deprived tuberculous animals. Taken together, these results suggest that immunological abnormalities and loss of

  2. Altered Adipogenesis in Zebrafish Larvae Following High Fat Diet and Chemical Exposure Is Visualised by Stimulated Raman Scattering Microscopy.

    PubMed

    den Broeder, Marjo J; Moester, Miriam J B; Kamstra, Jorke H; Cenijn, Peter H; Davidoiu, Valentina; Kamminga, Leonie M; Ariese, Freek; de Boer, Johannes F; Legler, Juliette

    2017-04-24

    Early life stage exposure to environmental chemicals may play a role in obesity by altering adipogenesis; however, robust in vivo methods to quantify these effects are lacking. The goal of this study was to analyze the effects of developmental exposure to chemicals on adipogenesis in the zebrafish (Danio rerio). We used label-free Stimulated Raman Scattering (SRS) microscopy for the first time to image zebrafish adipogenesis at 15 days post fertilization (dpf) and compared standard feed conditions (StF) to a high fat diet (HFD) or high glucose diet (HGD). We also exposed zebrafish embryos to a non-toxic concentration of tributyltin (TBT, 1 nM) or Tris(1,3-dichloroisopropyl)phosphate (TDCiPP, 0.5 µM) from 0-6 dpf and reared larvae to 15 dpf under StF. Potential molecular mechanisms of altered adipogenesis were examined by qPCR. Diet-dependent modulation of adipogenesis was observed, with HFD resulting in a threefold increase in larvae with adipocytes, compared to StF and HGD. Developmental exposure to TBT but not TDCiPP significantly increased adipocyte differentiation. The expression of adipogenic genes such as pparda, lxr and lepa was altered in response to HFD or chemicals. This study shows that SRS microscopy can be successfully applied to zebrafish to visualize and quantify adipogenesis, and is a powerful approach for identifying obesogenic chemicals in vivo.

  3. Coconut water alters maternal high fat diet induced changes in hormones and pup morphometry of Wistar rats.

    PubMed

    Kunle-Alabi, O T; Akindele, O O; Raji, Y

    2015-06-01

    Maternal high fat diet (HFD) during gestation adversely programmes foetal metabolism and cardiovascular function for the development of obesity and its related cardiovascular diseases in adult life. The hypolipidemic actions of coconut water (CW) in the presence of HFD have been reported. This study examined the effects of oral administration of CW on lipid panel, hormone profile, pup and placental morphometry of dams fed HFD during gestation. Twenty-four pregnant Wistar rats were assigned to four groups (n = 6) and treated daily from gestation day (GD) 1 to 21 as follows; Group 1: 1 ml/100g b.wt. distilled water; Group 2: 1ml/100g b.wt. CW; Group 3: HFD (70% standard rat feed plus 30% butter); Group 4: HFD + 1 ml/100g b.wt. CW. Animals were sacrificed on GD 21. Random blood glucose was measured using tail blood. Caesarean section was performed to remove the pups and their placentas which were immediately measured. Oxidative stress status of the placentas; serum lipid and hormone profiles of dams were assessed. HFD+CW resulted in significant (P < 0.05) reductions in pup weight and morphometric indices when compared with pups from HFD. These changes were accompanied by significant improvements in maternal serum lipid profile, alterations in hormone levels and higher placental lipid peroxidation. These results suggest that coconut water is protective against maternal high fat diet-induced changes. Further studies are on-going to determine the actions of coconut water of maternal high fat diet induced foetal programming of adult health.

  4. Prenatal high-fat diet alters the cerebrovasculature and clearance of β-amyloid in adult offspring.

    PubMed

    Hawkes, Cheryl A; Gentleman, Steve M; Nicoll, James Ar; Carare, Roxana O

    2015-03-01

    Alzheimer's disease (AD) is characterized by the accumulation of β-amyloid (Aβ) peptides in the extracellular spaces of the brain as plaques and in the walls of blood vessels as cerebral amyloid angiopathy (CAA). Failure of perivascular drainage of Aβ along cerebrovascular basement membranes contributes to the development of CAA. Mid-life hypercholesterolaemia is a risk factor for the development of AD. Maternal obesity is associated with the development of obesity, hypertension and hypercholesterolaemia in adulthood, suggesting that the risk for AD and CAA may also be influenced by the early-life environment. In the present study, we tested the hypothesis that early-life exposure to a high-fat diet results in changes to the cerebrovasculature and failure of Aβ clearance from the brain. We also assessed whether vascular Aβ deposition is greater in the brains of aged humans with a history of hyperlipidaemia, compared to age-matched controls with normal lipidaemia. Using a mouse model of maternal obesity, we found that exposure to a high-fat diet during gestation and lactation induced changes in multiple components of the neurovascular unit, including a down-regulation in collagen IV, fibronectin and apolipoprotein E, an up-regulation in markers of astrocytes and perivascular macrophages and altered blood vessel morphology in the brains of adult mice. Sustained high-fat diet over the entire lifespan resulted in additional decreases in levels of pericytes and impaired perivascular clearance of Aβ from the brain. In humans, vascular Aβ load was significantly increased in the brains of aged individuals with a history of hypercholesterolaemia. These results support a critical role for early dietary influence on the brain vasculature across the lifespan, with consequences for the development of age-related cerebrovascular and neurodegenerative diseases.

  5. A High-Fat Diet Causes Impairment in Hippocampal Memory and Sex-Dependent Alterations in Peripheral Metabolism

    PubMed Central

    Underwood, Erica L.; Thompson, Lucien T.

    2016-01-01

    While high-fat diets are associated with rising incidence of obesity/type-2 diabetes and can induce metabolic and cognitive deficits, sex-dependent comparisons are rarely systematically made. Effects of exclusive consumption of a high-fat diet (HFD) on systemic metabolism and on behavioral measures of hippocampal-dependent memory were compared in young male and female LE rats. Littermates were fed from weaning either a HFD or a control diet (CD) for 12 wk prior to testing. Sex-different effects of the HFD were observed in classic metabolic signs associated with type-2 diabetes. Males fed the HFD became obese, and had elevated fasted blood glucose levels, elevated corticosterone, and impaired glucose-tolerance, while females on the HFD exhibited only elevated corticosterone. Regardless of peripheral metabolism alteration, rats of both sexes fed the HFD were equally impaired in a spatial object recognition memory task associated with impaired hippocampal function. While the metabolic changes reported here have been characterized previously in males, the set of diet-induced effects observed here in females are novel. Impaired memory can have significant cognitive consequences, over the short-term and over the lifespan. A significant need exists for comparative research into sex-dependent differences underlying obesity and metabolic syndromes relating systemic, cognitive, and neural plasticity mechanisms. PMID:26819773

  6. BMP4-mediated brown fat-like changes in white adipose tissue alter glucose and energy homeostasis.

    PubMed

    Qian, Shu-Wen; Tang, Yan; Li, Xi; Liu, Yuan; Zhang, You-You; Huang, Hai-Yan; Xue, Rui-Dan; Yu, Hao-Yong; Guo, Liang; Gao, Hui-Di; Liu, Yan; Sun, Xia; Li, Yi-Ming; Jia, Wei-Ping; Tang, Qi-Qun

    2013-02-26

    Expression of bone morphogenetic protein 4 (BMP4) in adipocytes of white adipose tissue (WAT) produces "white adipocytes" with characteristics of brown fat and leads to a reduction of adiposity and its metabolic complications. Although BMP4 is known to induce commitment of pluripotent stem cells to the adipocyte lineage by producing cells that possess the characteristics of preadipocytes, its effects on the mature white adipocyte phenotype and function were unknown. Forced expression of a BMP4 transgene in white adipocytes of mice gives rise to reduced WAT mass and white adipocyte size along with an increased number of a white adipocyte cell types with brown adipocyte characteristics comparable to those of beige or brite adipocytes. These changes correlate closely with increased energy expenditure, improved insulin sensitivity, and protection against diet-induced obesity and diabetes. Conversely, BMP4-deficient mice exhibit enlarged white adipocyte morphology and impaired insulin sensitivity. We identify peroxisome proliferator-activated receptor gamma coactivator 1-α (PGC1α) as the target of BMP signaling required for these brown fat-like changes in WAT. This effect of BMP4 on WAT appears to extend to human adipose tissue, because the level of expression of BMP4 in WAT correlates inversely with body mass index. These findings provide a genetic and metabolic basis for BMP4's role in altering insulin sensitivity by affecting WAT development.

  7. Histological alterations in the intestinal epithelium caused by the inclusion of full-fat sunflower kernels in broiler chicken diets.

    PubMed

    Arija, I; Viveros, A; Brenes, A; Canales, R; Pizarro, M; Castaño, M

    2000-09-01

    Changes in small intestinal morphology (jejunum) were examined at 28 d of age in chicks fed with full-fat sunflower kernels (FFSK)-based diets. Jejunal mucosa of chicks (six chicks per treatment) were embedded in Epon-812 for examination by a conventional electron microscope procedure. A portion of the tissues was also sectioned and embedded in paraffin for examination by light microscopy. Brush border, goblet cells, and intraepithelial lymphocytes, on the one hand, and fibroblast and mononuclear cells (lymphocytes, plasma cells, macrophages) were observed in the enterocytes and lamina propria, respectively. The results showed that the birds fed 150 g kg(-1) of FFSK showed a shortening and thickening of the villi, hyperplasia and vacuolar degeneration of enterocytes, and hypertrophy and hyperplasia of goblet cells. Likewise, an increment of intraepithelial lymphoid cells and hypercellularity of the lamina propria was observed. In addition, electron microscopy showed large vacuoles in the enterocytes, which could be dilations of agranular and granular endoplasmic reticulum or Golgi. There were many dark granules within the vacuoles that could be triglyceride-rich lipoproteins (portomicrons). These lesions could have been due to the presence of chlorogenic acid or to the greater concentration of oil in the FFSK diet. Our observations demonstrated that addition of 150 g kg(-1) FFSK to broiler chicken diets caused alterations in jejunal mucosa that could explain the decrease in fat digestibility observed in a previous experiment in which we incorporated FFSK into broiler diets.

  8. Allied industry approaches to alter intramuscular fat content and composition in beef animals.

    PubMed

    Dodson, Michael V; Jiang, Zhihua; Chen, Jie; Hausman, Gary J; Guan, Le Luo; Novakofski, Jan; Thompson, David P; Lorenzen, Carol L; Fernyhough, Melinda E; Mir, Priya S; Reecy, James M

    2010-01-01

    Biochemical and biophysical research tools are used to define the developmental dynamics of numerous cell lineages from a variety of tissues relevant to meat quality. With respect to the adipose cell lineage, much of our present understanding of adipogenesis and lipid metabolism was initially determined through the use of these methods, even though the in vitro or molecular environments are far removed from the tissues of meat animals. This concise review focuses on recent cellular and molecular biology-related research with adipocytes, and how the research might be extended to the endpoint of altering red meat quality. Moreover, economic and policy impacts of such in animal production regimens is discussed. These issues are important, not only with respect to palatability, but also to offer enhanced health benefits to the consumer by altering content of bioactive components in adipocytes.

  9. Physiological and brain alterations produced by high-fat diet in male and female rats can be modulated by increased levels of estradiol during critical periods of development.

    PubMed

    Carrillo, Beatriz; Collado, Paloma; Díaz, Francisca; Chowen, Julie A; Pérez-Izquierdo, Mª Ángeles; Pinos, Helena

    2017-07-11

    Overnutrition due to a high-fat diet (HFD) can increase the vulnerability of the metabolic system to maladjustments. Estradiol has an inhibitory role on food intake and this hormone has demonstrated to be a crucial organizer during brain development. Our aim was to determine whether increased levels of estradiol in the early postnatal period modulate the alterations in metabolism and brain metabolic circuits produced by overnutrition. Twenty-four male and 24 female Wistar rats were submitted to a HFD (34.9% fat) or a control diet (5% fat) from gestational day 6. From postnatal (P) 6 to P13, both control and HFD groups were administered a s.c. injection of vehicle or estradiol benzoate (0.4 mg/kg), resulting in eight experimental groups (n = 6 in each group). Body weight, food intake and subcutaneous, visceral, and brown fat pads were measured. Agouti-related peptide, neuropeptide Y, orexin, and proopiomelanocortin (POMC) were analyzed by quantitative real-time polymerase chain reaction assay and plasma estradiol levels were measured by ELISA. Males fed a HFD showed an increase in body weight and the amount of visceral and subcutaneous fat, which was coincident with an increase in the number of kilocalories ingested. Neonatal estradiol treatment restored the body weight and subcutaneous fat of HFD males to control levels. Hypothalamic POMC mRNA levels in HFD females were increased with respect to control females. This increase was reverted with estradiol treatment during development. HFD and estradiol treatment have different effects on males and females. Overnutrition affects physiological parameters, such as body weight, visceral, and subcutaneous fat content, in males, while females present alterations in hypothalamic POMC mRNA levels. Hence, the increase in estradiol levels during a period that is critical for the programing of the feeding system can modulate some of the alterations produced by the continuous intake of high-fat content food.

  10. Alteration of Loperamide-Induced Prostate Relaxation in High-Fat Diet-Fed Rats

    PubMed Central

    Hsu, Sheng-Lung; Chung, Hsien-Hui; Chen, I-Hung; Tong, Yat-Ching

    2014-01-01

    Objective. To investigate the change of loperamide-induced prostate relaxation in rats fed with high-fat diet (HFD). Materials and Methods. Adult male Wistar rats were divided into 2 groups: (1) control rats fed with normal chow and (2) rats fed with HFD for 6 months. The prostate was removed for histology study. Isolated prostate strips were hung in organ bath and precontracted with 1 μmol/L phenylephrine or 50 mmol/L KCl. The relaxation responses to loperamide 0.1 to 10 μmol/L were recorded. Western blotting analyses were performed for prostate μ-opioid receptors (MOR) and ATP-sensitive potassium (KATP) channel proteins: sulfonylurea receptor (SUR) and inwardly rectifying potassium channel (Kir) 6.2 subunits. Results. Body weight, prostate weight, plasma levels of glucose, insulin, triglyceride, and cholesterol, as well as systolic blood pressure, were significantly increased in the HFD rats. Histology showed prostatic hyperplasia in the HFD rat prostate. Prostatic relaxation induced by loperamide was markedly reduced in HFD when compared to the control. Protein expressions of MOR, SUR, and Kir 6.2 were decreased in HFD-fed rats. Conclusion. Loperamide-induced prostate relaxation is decreased in HFD rats due to reduced MOR and KATP channel expressions. PMID:25506071

  11. Pattern of Pulmonary Involvement and Outcome of Aspiration Pneumonia in Patients with Altered Consciousness Admitted in Dhaka Medical College Hospital.

    PubMed

    Chowdhury, R A; Azad, A K; Sardar, H; Siddiqui, M R; Saad, S; Rahman, S; Sikder, A S

    2016-01-01

    Aspiration is well recognized as a cause of pulmonary disease and is not uncommon in patients with altered consciousness.The mortality rate of aspiration pneumonia is approximately 1% in outpatient setting and upto 25% in those requiring hospitalization. This study was done to see the pattern of pulmonary involvement and outcome of aspiration pneumonia in patients with altered consciousness admitted in medicine department of a tertiary care hospital in our country. This was a prospective observational study conducted among the 52 adult patients of aspiration pneumonia with altered consciousness admitted in the medicine department of Dhaka Medical College Hospital (DMCH), during June 2010 to December 2010. Aspiration pneumonia was confirmed by clinical examination and laboratory investigations. Hematologic measurements (TC of WBC, Hb%, ESR, platelet count), chest X-ray, blood gas analysis, blood urea, creatinine and random blood sugar, sputum for Gram staining, sputum for culture sensitivity and blood culture were done in all patients.Assessment of altered conscious patient was done by application of the Glasgow Coma Scale. Case record forms with appropriate questionnaire were filled for all patients. The mean±SD age was 57.42±13.63 years with ranged from 25 to 90 years. Out of 52 patients, 37(71.15%) patients were male and 15(28.85%) patients were female. Following aspiration 76.92% patients developed pneumonitis, 13.46% patients developed lung abscess and only 9.62% patients developed ARDS. Most (33) of the patients had opacity in right lower zone and 13 patients had opacity in the left lower zone, 6 patients had opacity in right mid zone. Only 10 patients had opacity in both lower zones. In this study overall mortality rate was 23%. If only one lobe was involved radiologically, mortality was 8.33%. If two or more lobes on one or both sides were involved, mortality was in the range of 25-91%.

  12. Type 2 diabetes mellitus is associated with altered CD8(+) T and natural killer cell function in pulmonary tuberculosis.

    PubMed

    Kumar, Nathella P; Sridhar, Rathinam; Nair, Dina; Banurekha, Vaithilingam V; Nutman, Thomas B; Babu, Subash

    2015-04-01

    Type 2 diabetes mellitus (DM) is associated with expanded frequencies of mycobacterial antigen-specific CD4(+) T helper type 1 (Th1) and Th17 cells in individuals with active pulmonary tuberculosis (TB). No data are available on the role of CD8(+) T and natural killer (NK) cells in TB with coincident DM. To identify the role of CD8(+) T and NK cells in pulmonary TB with diabetes, we examined mycobacteria-specific immune responses in the whole blood of individuals with TB and DM (TB-DM) and compared them with those without DM (TB-NDM). We found that TB-DM is characterized by elevated frequencies of mycobacterial antigen-stimulated CD8(+) T cells expressing type 1 [interferon-γ and interleukin-2 (IL-2)] and type 17 (IL-17F) cytokines. We also found that TB-DM is characterized by expanded frequencies of TB antigen-stimulated NK cells expressing type 1 (tumour necrosis factor-α) and type 17 (IL-17A and IL-17F) cytokines. In contrast, CD8(+) T cells were associated with significantly diminished expression of the cytotoxic markers perforin, granzyme B and CD107a both at baseline and following antigen or anti-CD3 stimulation, while NK cells were associated with significantly decreased antigen-stimulated expression of CD107a only. This was not associated with alterations in CD8(+) T-cell or NK cell numbers or subset distribution. Therefore, our data suggest that pulmonary TB complicated with type 2 DM is associated with an altered repertoire of cytokine-producing and cytotoxic molecule-expressing CD8(+) T and NK cells, possibly contributing to increased pathology.

  13. Aging alters bone-fat reciprocity by shifting in vivo mesenchymal precursor cell fate towards an adipogenic lineage.

    PubMed

    Singh, Lakshman; Brennan, Tracy A; Russell, Elizabeth; Kim, Jung-Hoon; Chen, Qijun; Brad Johnson, F; Pignolo, Robert J

    2016-04-01

    Bone marrow derived mesenchymal progenitor cells (MPCs) play an important role in bone homeostasis. Age-related changes occur in bone resulting in a decrease in bone density and a relative increase in adipocity. Although in vitro studies suggest the existence of an age-related lineage switch between osteogenic and adipogenic fates, stem cell and microenvironmental contributions to this process have not been elucidated in vivo. In order to study the effects of MPC and microenvironmental aging on functional engraftment and lineage switching, transplantation studies were performed under non-myeloablative conditions in old recipients, with donor MPCs derived from young and old green fluorescent protein (GFP) transgenic mice. Robust engraftment by young MPCs or their progeny was observed in the marrow, bone-lining region and in the matrix of young recipients; however, significantly lower engraftment was seen at the same sites in old recipients transplanted with old MPCs. Differentiation of transplanted MPCs strongly favored adipogenesis over osteogenesis in old recipients irrespective of MPC donor age, suggesting that microenvironmental alterations that occur with in vivo aging are predominately responsible for MPC lineage switching. These data indicate that aging alters bone-fat reciprocity and differentiation of mesenchymal progenitors towards an adipogenic fate.

  14. Obesity alters immune and metabolic profiles: New insight from obese-resistant mice on high-fat diet.

    PubMed

    Boi, Shannon K; Buchta, Claire M; Pearson, Nicole A; Francis, Meghan B; Meyerholz, David K; Grobe, Justin L; Norian, Lyse A

    2016-10-01

    Diet-induced obesity has been shown to alter immune function in mice, but distinguishing the effects of obesity from changes in diet composition is complicated. It was hypothesized that immunological differences would exist between diet-induced obese (DIO) and obese-resistant (OB-Res) mice fed the same high-fat diet (HFD). BALB/c mice were fed either standard chow or HFD to generate lean or DIO and OB-Res mice, respectively. Resulting mice were analyzed for serum immunologic and metabolic profiles and cellular immune parameters. BALB/c mice on HFD were categorized as DIO or OB-Res, based on body weight versus lean controls. DIO mice were physiologically distinct from OB-Res mice, whose serum insulin, leptin, gastric inhibitory polypeptide, and eotaxin concentrations remained similar to lean controls. DIO mice had increased macrophage(+) crown-like structures in white adipose tissue, although macrophage percentages were unchanged from OB-Res and lean mice. DIO mice also had decreased splenic CD4(+) T cells, elevated serum GM-CSF, and increased splenic CD11c(+) dendritic cells, but impaired dendritic cell stimulatory capacity (P < 0.05 vs. lean controls). These parameters were unaltered in OB-Res mice versus lean controls. Diet-induced obesity results in alterations in immune and metabolic profiles that are distinct from effects caused by HFD alone. © 2016 The Obesity Society.

  15. Neurodegeneration Alters Metabolic Profile and Sirt 1 Signaling in High-Fat-Induced Obese Mice.

    PubMed

    Lima, Leandro Ceotto Freitas; Saliba, Soraya Wilke; Andrade, João Marcus Oliveira; Cunha, Maria Luisa; Cassini-Vieira, Puebla; Feltenberger, John David; Barcelos, Lucíola Silva; Guimarães, André Luiz Sena; de-Paula, Alfredo Mauricio Batista; de Oliveira, Antônio Carlos Pinheiro; Santos, Sérgio Henrique Sousa

    2016-05-16

    Different factors may contribute to the development of neurodegenerative diseases. Among them, metabolic syndrome (MS), which has reached epidemic proportions, has emerged as a potential element that may be involved in neurodegeneration. Furthermore, studies have shown the importance of the sirtuin family in neuronal survival and MS, which opens the possibility of new pharmacological targets. This study investigates the influence of sirtuin metabolic pathways by examining the functional capacities of glucose-induced obesity in an excitotoxic state induced by a quinolinic acid (QA) animal model. Mice were divided into two groups that received different diets for 8 weeks: one group received a regular diet, and the other group received a high-fat diet (HF) to induce MS. The animals were submitted to a stereotaxic surgery and subdivided into four groups: Standard (ST), Standard-QA (ST-QA), HF and HF-QA. The QA groups were given a 250 nL quinolinic acid injection in the right striatum and PBS was injected in the other groups. Obese mice presented with a weight gain of 40 % more than the ST group beyond acquiring an insulin resistance. QA induced motor impairment and neurodegeneration in both ST-QA and HF-QA, although no difference was observed between these groups. The HF-QA group showed a reduction in adiposity when compared with the groups that received PBS. Therefore, the HF-QA group demonstrated a commitment-dependent metabolic pathway. The results suggest that an obesogenic diet does not aggravate the neurodegeneration induced by QA. However, the excitotoxicity induced by QA promotes a sirtuin pathway impairment that contributes to metabolic changes.

  16. Vascular peptide endothelin-1 links fat accumulation with alterations of visceral adipocyte lipolysis.

    PubMed

    van Harmelen, Vanessa; Eriksson, Anna; Aström, Gaby; Wåhlén, Kerstin; Näslund, Erik; Karpe, Fredrik; Frayn, Keith; Olsson, Tommy; Andersson, Jonas; Rydén, Mikel; Arner, Peter

    2008-02-01

    Visceral obesity increases risk of insulin resistance and type 2 diabetes. This may partly be due to a region-specific resistance to insulin's antilipolytic effect in visceral adipocytes. We investigated whether adipose tissue releases the vascular peptide endothelin-1 (ET-1) and whether ET-1 could account for regional differences in lipolysis. One group consisted of eleven obese and eleven nonobese subjects in whom ET-1 levels were compared between abdominal subcutaneous and arterialized blood samples. A second group included subjects undergoing anti-obesity surgery. Abdominal subcutaneous and visceral adipose tissues were obtained to study the effect of ET-1 on differentiated adipocytes regarding lipolysis and gene and protein expression. Adipose tissue had a marked net release of ET-1 in vivo, which was 2.5-fold increased in obesity. In adipocytes treated with ET-1, the antilipolytic effect of insulin was attenuated in visceral but not in subcutaneous adipocytes, which could not be explained by effects of ET-1 on adipocyte differentiation. ET-1 decreased the expression of insulin receptor, insulin receptor substrate-1 and phosphodiesterase-3B and increased the expression of endothelin receptor-B (ET(B)R) in visceral but not in subcutaneous adipocytes. These effects were mediated via ET(B)R with signals through protein kinase C and calmodulin pathways. The effect of ET-1 could be mimicked by knockdown of IRS-1. ET-1 is released from human adipose tissue and links fat accumulation to insulin resistance. It selectively counteracts insulin inhibition of visceral adipocyte lipolysis via ET(B)R signaling pathways, which affect multiple steps in insulin signaling.

  17. Exposure to a high fat diet during the perinatal period alters vagal motoneurone excitability, even in the absence of obesity.

    PubMed

    Bhagat, Ruchi; Fortna, Samuel R; Browning, Kirsteen N

    2015-01-01

    Obesity is recognized as being multifactorial in origin, involving both genetic and environmental factors. The perinatal period is known to be critically important in the development of neural circuits responsible for energy homeostasis and the integration of autonomic reflexes. Diet-induced obesity alters the biophysical, pharmacological and morphological properties of vagal neurocircuits regulating upper gastrointestinal tract functions, including satiety. Less information is available, however, regarding the effects of a high fat diet (HFD) itself on the properties of vagal neurocircuits. The present study was designed to test the hypothesis that exposure to a HFD during the perinatal period alters the electrophysiological, pharmacological and morphological properties of vagal efferent motoneurones innervating the stomach. Our data indicate that perinatal HFD decreases the excitability of gastric-projecting dorsal motor nucleus neurones and dysregulates neurotransmitter release from synaptic inputs and that these alterations occur prior to the development of obesity. These findings represent the first direct evidence that exposure to a HFD modulates the processing of central vagal neurocircuits even in the absence of obesity. The perinatal period is critically important to the development of autonomic neural circuits responsible for energy homeostasis. Vagal neurocircuits are vital to the regulation of upper gastrointestinal functions, including satiety. Diet-induced obesity modulates the excitability and responsiveness of both peripheral vagal afferents and central vagal efferents but less information is available regarding the effects of diet per se on vagal neurocircuit functions. The aims of this study were to investigate whether perinatal exposure to a high fat diet (HFD) dysregulated dorsal motor nucleus of the vagus (DMV) neurones, prior to the development of obesity. Whole cell patch clamp recordings were made from gastric-projecting DMV neurones in thin

  18. High-Fat Diet Alters the Orosensory Sensitivity to Fatty Acids in Obesity-Resistant but not Obesity-Prone Rats

    PubMed Central

    Pittman, David W; Hansen, Dane R; Gilbertson, Timothy A

    2015-01-01

    Gene-environment interactions play a role in the development of obesity but specific effects of diet on the orosensory detection of fatty acids have yet to be clarified. The objective of this study is to characterize the effect of prolonged (5-week) exposure to a high-fat (60%) diet on the behavioral sensitivity to the fatty acid linoleate following a conditioned taste aversion in obesity-prone and obesity-resistant rats. Exposure to the high-fat diet significantly enhanced the sensitivity of obesity-resistant (S5B/Pl) rats to linoleate while producing no effect on the fatty acid sensitivity for obesity-prone rats. Specifically, high-fat diet fed S5B/Pl rats showed stronger initial avoidance of linoleate and slower extinction rates than their normal diet cohorts. Our study suggests that prolonged dietary fat consumption may alter the behavioral sensitivity to fatty acids particularly in obesity-resistant animals. PMID:26097499

  19. Temporal plasma vitamin concentrations are altered by fat-soluble vitamin administration in suckling pigs.

    PubMed

    Jang, Y D; Ma, J Y; Monegue, J S; Monegue, H J; Stuart, R L; Lindemann, M D

    2015-11-01

    Piglets are born with purportedly low plasma vitamin D levels. The objective of this study was to investigate the effect of fat-soluble vitamin administration, primarily vitamin D, by different administration routes on plasma vitamin concentrations in suckling pigs. A total of 45 pigs from 5 litters were allotted at birth to 3 treatments within each litter. Pigs were administered 400 IU of α-tocopherol, 40,000 IU of retinyl palmitate, and 40,000 IU of vitamin D at d 1 of age either orally or by i.m. injection and compared with control pigs with no supplemental vitamin administration. Blood samples were collected at d 0 (initial), 1, 2, 3, 4, 6, 9, 14, and 20 after administration. Plasma 25-hydroxycholecalciferol (25OHD), α-tocopherol, retinyl palmitate, and retinol concentrations were analyzed. Except for retinol, the effects of treatment, day, and day × treatment interaction ( < 0.01) were observed on plasma vitamin concentrations. Plasma concentrations of 25OHD and α-tocopherol increased immediately regardless of administration routes to peak at d 2 and 1 after administration, respectively. Plasma retinyl palmitate concentrations increased only with the injection treatment, with the peak at d 1 after administration. Plasma concentrations of 25OHD in both administration treatments and α-tocopherol in the injection treatment were maintained at greater levels than those in the control treatment until d 20 after administration. With regard to the pharmacokinetic parameters for plasma 25OHD concentrations, the injection treatment had greater elimination half-life ( < 0.01), maximum plasma concentrations ( < 0.05), and all area under the curve parameters ( < 0.01) but a lower elimination rate constant ( < 0.01) than the oral treatment. Relative bioavailability of oral administration compared with injection administration was 55.26%. These results indicate that plasma status of 25OHD,α-tocopherol, and retinyl palmitate are differentially changed between types of

  20. Altered membrane lipid domains limit pulmonary endothelial calcium entry following chronic hypoxia.

    PubMed

    Paffett, Michael L; Naik, Jay S; Riddle, Melissa A; Menicucci, Steven D; Gonzales, Antonio J; Resta, Thomas C; Walker, Benjimen R

    2011-10-01

    Agonist-induced Ca(2+) entry into the pulmonary endothelium depends on activation of both store-operated Ca(2+) (SOC) entry and receptor-operated Ca(2+) (ROC) entry. We previously reported that pulmonary endothelial cell SOC entry and ROC entry are reduced in chronic hypoxia (CH)-induced pulmonary hypertension. We hypothesized that diminished endothelial Ca(2+) entry following CH is due to derangement of caveolin-1 (cav-1) containing cholesterol-enriched membrane domains important in agonist-induced Ca(2+) entry. To test this hypothesis, we measured Ca(2+) influx by fura-2 fluorescence following application of ATP (20 μM) in freshly isolated endothelial cells pretreated with the caveolar-disrupting agent methyl-β-cyclodextrin (mβCD; 10 mM). Cholesterol depletion with mβCD attenuated agonist-induced Ca(2+) entry in control endothelial cells to the level of that from CH rats. Interestingly, endothelial membrane cholesterol was lower in cells isolated from CH rats compared with controls although the density of caveolae did not differ between groups. Cholesterol repletion with a cholesterol:mβCD mixture or the introduction of the cav-1 scaffolding peptide (AP-cav; 10 μM) rescued ATP-induced Ca(2+) entry in endothelia from CH arteries. Agonist-induced Ca(2+) entry assessed by Mn(2+) quenching of fura-2 fluorescence was also significantly elevated by luminal AP-cav in pressurized intrapulmonary arteries from CH rats to levels of controls. Similarly, patch-clamp experiments revealed diminished inward current in response to ATP in cells from CH rats compared with controls that was restored by AP-cav. These data suggest that CH-induced pulmonary hypertension leads to reduced membrane cholesterol that limits the activity of ion channels necessary for agonist-activated Ca(2+) entry.

  1. IN UTERO EXPOSURE TO A MATERNAL HIGH FAT DIET ALTERS THE EPIGENETIC HISTONE CODE IN A MURINE MODEL

    PubMed Central

    Suter, Melissa A.; MA, Jun; Vuguin, Patricia M.; Hartil, Kirsten; Fiallo, Ms. Ariana; Harris, R. Alan; Charron, Maureen J.; Aagaard, Kjersti M.

    2014-01-01

    Objective Data from animal models show that in utero exposure to a maternal high fat diet (HFD) renders susceptibility of these offspring to the adult onset of metabolic syndrome. We and others have previously shown that epigenetic modifications to histones may serve as a molecular memory of the in utero exposure, rendering risk of adult disease. Because mice heterozygous for GLUT4 (insulin sensitive glucose transporter) born to wild-type (WT) mothers demonstrate exacterbated metabolic syndrome when exposed to a high fat diet in utero, we sought to analyze the genome-wide epigenetic changes which occur in the fetal liver in susceptible offspring. Study Design WT and Glut4+/− (G4+/−) offspring of WT mothers exposed either to a control or a HF diet in utero were studied. Immunoblotting was used to measure hepatic histone modifications of fetal and 5 week animals. Chromatin immunoprecipitation (ChIP) followed by hybridization to chip arrays (ChIP on chip) was utilized to detect genome-wide changes of histone modifications with HFD exposure. Results We found that levels of hepatic H3K14ac and H3K9me3 significantly increased with HFD exposure in WT and G4+/− fetal and 5 week offspring. Pathway analysis of our ChIP on chip data reveal differential H3K14ac and H3K9me3 enrichment along pathways which regulate lipid metabolism, specifically in the promoter regions of Pparg, Ppara, Rxra and Rora. Conclusion We conclude that HFD exposure in utero is associated with functional alterations to fetal hepatic histone modifications in both WT and G4+/− offspring, some which persist up to 5 weeks of age. PMID:24793723

  2. Calcium Reduces Liver Injury in Mice on a High-Fat Diet: Alterations in Microbial and Bile Acid Profiles

    PubMed Central

    Nadeem Aslam, Muhammad; Bassis, Christine M.; Zhang, Li; Zaidi, Sameer

    2016-01-01

    A high-fat “Western-style” diet (HFWD) promotes obesity-related conditions including non-alcoholic steatohepatitis (NASH), the histologic manifestation of non-alcoholic fatty liver disease (NAFLD). In addition to high saturated fat and processed carbohydrates, the typical HFWD is deficient in calcium. Calcium-deficiency is an independent risk factor for many conditions associated with the Western-style diet. However, calcium has not been widely evaluated in the context of NAFLD. The goal of the present study was to determine if dietary calcium supplementation could protect mice fed a HFWD from NAFLD, specifically by decreasing non-alcoholic steatohepatitis (NASH) and its down-stream consequences. Male C57BL/6NCrl mice were maintained for 18-months on a HFWD containing dietary calcium at either 0.41 gm/kg feed (unsupplemented) or 5.25 gm/kg feed (supplemented). Although there was no difference in body weight or steatosis, calcium-supplemented mice were protected against downstream consequences of hepatic steatosis, manifested by lower inflammation, less fibrosis, and by lower overall histologic NAFLD activity scores (NAS). Calcium supplementation correlated with distinctly segregating gut fecal and cecal microbial communities as defined by 16S rRNA gene sequence. Further, calcium supplementation also correlated with decreased hepatic concentration of the major conjugated murine primary bile acid, tauro-β-muricholic acid (as well as a decrease in the parent unconjugated bile acid). Thus, calcium was protective against progression of diet-induced hepatic steatosis to NASH and end-stage liver disease, suggesting that calcium supplementation may effectively protect against adverse hepatic consequences of HFWD in cases where overall diet modification cannot be sustained. This protective effect occurred in concert with calcium-mediated gut microbial community shifts and alterations of the hepatic bile acid pool. PMID:27851786

  3. Calcium Reduces Liver Injury in Mice on a High-Fat Diet: Alterations in Microbial and Bile Acid Profiles.

    PubMed

    Nadeem Aslam, Muhammad; Bassis, Christine M; Zhang, Li; Zaidi, Sameer; Varani, James; Bergin, Ingrid L

    2016-01-01

    A high-fat "Western-style" diet (HFWD) promotes obesity-related conditions including non-alcoholic steatohepatitis (NASH), the histologic manifestation of non-alcoholic fatty liver disease (NAFLD). In addition to high saturated fat and processed carbohydrates, the typical HFWD is deficient in calcium. Calcium-deficiency is an independent risk factor for many conditions associated with the Western-style diet. However, calcium has not been widely evaluated in the context of NAFLD. The goal of the present study was to determine if dietary calcium supplementation could protect mice fed a HFWD from NAFLD, specifically by decreasing non-alcoholic steatohepatitis (NASH) and its down-stream consequences. Male C57BL/6NCrl mice were maintained for 18-months on a HFWD containing dietary calcium at either 0.41 gm/kg feed (unsupplemented) or 5.25 gm/kg feed (supplemented). Although there was no difference in body weight or steatosis, calcium-supplemented mice were protected against downstream consequences of hepatic steatosis, manifested by lower inflammation, less fibrosis, and by lower overall histologic NAFLD activity scores (NAS). Calcium supplementation correlated with distinctly segregating gut fecal and cecal microbial communities as defined by 16S rRNA gene sequence. Further, calcium supplementation also correlated with decreased hepatic concentration of the major conjugated murine primary bile acid, tauro-β-muricholic acid (as well as a decrease in the parent unconjugated bile acid). Thus, calcium was protective against progression of diet-induced hepatic steatosis to NASH and end-stage liver disease, suggesting that calcium supplementation may effectively protect against adverse hepatic consequences of HFWD in cases where overall diet modification cannot be sustained. This protective effect occurred in concert with calcium-mediated gut microbial community shifts and alterations of the hepatic bile acid pool.

  4. Metabolic differences between genetically lean and fat chickens are partly attributed to the alteration of insulin signaling in liver.

    PubMed

    Dupont, J; Chen, J; Derouet, M; Simon, J; Leclercq, B; Taouis, M

    1999-11-01

    Insulin signaling [tyrosine phosphorylation of insulin receptor (IR), insulin receptor substrate-1 (IRS-1), Src homology and collagen protein (Shc) and phosphatidyl inositol 3'-kinase activity (PI 3'-kinase)] was studied in the liver and thigh muscles of fat (FL) and lean (LL) chickens. These lines result from a divergent selection on abdominal fat pad size. The divergence is of metabolic origin. Extreme nutritional states were studied (fed, 48-h starved and 30-min refed). Such conditions significantly altered insulin signaling in chicken liver, but surprisingly not in the muscle (except the phosphorylation of Shc in the refed state). No major differences that could account for this divergence were found in muscle. Liver IR number and Shc protein did not differ between genotypes. Liver IRS-1 (protein and messenger) was lower in the fed state and higher in the starved state in FL compared to that in LL chickens. In the fed state, tyrosine phosphorylation of liver IR, IRS-1 and Shc action was higher in FL than in LL chickens that in the absence of insulin resistance rely on higher plasma insulin levels. In the starved state, phosphorylation of liver IR was lower, but the phosphorylation of IR and IRS-1 were higher in LL than in FL chickens, most likely in response to higher plasma glucose and insulin in the lean genotype. In the refed state, the phosphorylation of liver IR and IRS-1 did not differ between genotypes despite significantly lower plasma insulin in FL chickens. Finally, PI 3'-kinase was not affected by the genotype. A significant activation of early steps of insulin signaling in liver of fed FL chickens may at least partly account for their increased liver lipogenesis and ultimately their fattening.

  5. Exercise Prevents Weight Gain and Alters the Gut Microbiota in a Mouse Model of High Fat Diet-Induced Obesity

    PubMed Central

    Evans, Christian C.; LePard, Kathy J.; Kwak, Jeff W.; Stancukas, Mary C.; Laskowski, Samantha; Dougherty, Joseph; Moulton, Laura; Glawe, Adam; Wang, Yunwei; Leone, Vanessa; Antonopoulos, Dionysios A.; Smith, Dan; Chang, Eugene B.; Ciancio, Mae J.

    2014-01-01

    Background Diet-induced obesity (DIO) is a significant health concern which has been linked to structural and functional changes in the gut microbiota. Exercise (Ex) is effective in preventing obesity, but whether Ex alters the gut microbiota during development with high fat (HF) feeding is unknown. Objective Determine the effects of voluntary Ex on the gastrointestinal microbiota in LF-fed mice and in HF-DIO. Methods Male C57BL/6 littermates (5 weeks) were distributed equally into 4 groups: low fat (LF) sedentary (Sed) LF/Sed, LF/Ex, HF/Sed and HF/Ex. Mice were individually housed and LF/Ex and HF/Ex cages were equipped with a wheel and odometer to record Ex. Fecal samples were collected at baseline, 6 weeks and 12 weeks and used for bacterial DNA isolation. DNA was subjected both to quantitative PCR using primers specific to the 16S rRNA encoding genes for Bacteroidetes and Firmicutes and to sequencing for lower taxonomic identification using the Illumina MiSeq platform. Data were analyzed using a one or two-way ANOVA or Pearson correlation. Results HF diet resulted in significantly greater body weight and adiposity as well as decreased glucose tolerance that were prevented by voluntary Ex (p<0.05). Visualization of Unifrac distance data with principal coordinates analysis indicated clustering by both diet and Ex at week 12. Sequencing demonstrated Ex-induced changes in the percentage of major bacterial phyla at 12 weeks. A correlation between total Ex distance and the ΔCt Bacteroidetes: ΔCt Firmicutes ratio from qPCR demonstrated a significant inverse correlation (r2 = 0.35, p = 0.043). Conclusion Ex induces a unique shift in the gut microbiota that is different from dietary effects. Microbiota changes may play a role in Ex prevention of HF-DIO. PMID:24670791

  6. Food Entrainment of Circadian Gene Expression Altered in PPARα−/− Brown Fat and Heart

    PubMed Central

    Goh, Brian C.; Wu, Xiying; Evans, Ann E.; Johnson, Meagan L.; Hill, Molly R.; Gimble, Jeffrey M.

    2008-01-01

    The circadian clock is subject to food entrainment. Since PPARα exhibits a circadian expression profile, we hypothesized that PPARα deficiency would alter the food entrainable response of adipose, cardiac, and liver tissues. Wild type and PPARα null mice were compared under ad libitum or restricted food access for the expression of circadian transcription factor-encoding mRNAs. Temporally restricted food access caused between a mean 5.8 to 11.5 hour phase shift in the expression profiles of the circadian genes Bmal1, Per3, and Rev-erbα in all tissues of control mice. In contrast, these same conditions phase shifted the circadian genes in tissues of PPARα null mice between a mean of 10.8 to 14.2 hr with amplitude attenuation. The food entrained phase shifts in the brown adipose and cardiac tissue circadian transcription factors of the PPARα null mice were prolonged significantly relative to wild type controls. Likewise, PPARα responsive genes in the livers of PPARα null mice exhibited a significantly prolonged phase shift relative to control mice. These findings confirm and extend recent observations in the literature.. PMID:17624301

  7. Omega-6 Fat Supplementation Alters Lipogenic Gene Expression in Bovine Subcutaneous Adipose Tissue

    PubMed Central

    Joseph, Sandeep J.; Pratt, Scott L.; Pavan, Enrique; Rekaya, Romdhane; Duckett., Susan K.

    2010-01-01

    In contrast to rodents, adipose tissue serves as the major site of lipogenesis and storage reservoir for excess dietary energy in cattle. Research in rodents shows that adding corn oil (57% C18:2 n-6) to the diet alters lipogenesis enhancing deposition of omega-6 fatty acids. This study examines changes in lipogenic gene expression of subcutaneous adipose tissue from eighteen steers fed increasing levels of dietary corn oil [0 (NONE), 0.31 kg/d (MED) and 0.62 kg/d (HI)] using two platforms, qPCR and microarray. The results show that MED level of oil supplementation up-regulates gene expression of key lipogenic enzymes but that as oil supplementation reaches HI level mRNA encoding lipogenic enzymes responsible for de novo synthesis and desaturation are down-regulated. Changes in specific lipogenic mRNA levels are correlated with changes in tissue fatty acid composition where de novo and desatured fatty acids were reduced with the highest level of oil supplementation. PMID:21072324

  8. Effect of High-Fat Diet on the Formation of Pulmonary Neutrophil Extracellular Traps during Influenza Pneumonia in BALB/c Mice

    PubMed Central

    Moorthy, Anandi Narayana; Tan, Kong Bing; Wang, Shi; Narasaraju, Teluguakula; Chow, Vincent T.

    2016-01-01

    Obesity is an independent risk factor for severe outcome of influenza infection. Higher dietary fat consumption has been linked to greater morbidity and severe influenza in mouse models. However, the extent of generation of neutrophil extracellular traps (NETs or NETosis) in obese individuals during influenza pneumonia is hitherto unknown. This study investigated pulmonary NETs generation in BALB/c mice fed with high-fat diet (HFD) and low-fat diet (LFD), during the course of influenza pneumonia. Clinical disease progression, histopathology, lung reactive oxygen species, and myeloperoxidase activity were also compared. Consumption of HFD over 18 weeks led to significantly higher body weight, body mass index, and adiposity in BALB/c mice compared with LFD. Lethal challenge of mice (on HFD and LFD) with influenza A/PR/8/34 (H1N1) virus led to similar body weight loss and histopathologic severity. However, NETs were formed at relatively higher levels in mice fed with HFD, despite the absence of significant difference in disease progression between HFD- and LFD-fed mice. PMID:27531997

  9. Histologic and biochemical alterations predict pulmonary mechanical dysfunction in aging mice with chronic lung inflammation.

    PubMed

    Massa, Christopher B; Groves, Angela M; Jaggernauth, Smita U; Laskin, Debra L; Gow, Andrew J

    2017-08-01

    Both aging and chronic inflammation produce complex structural and biochemical alterations to the lung known to impact work of breathing. Mice deficient in surfactant protein D (Sftpd) develop progressive age-related lung pathology characterized by tissue destruction/remodeling, accumulation of foamy macrophages and alteration in surfactant composition. This study proposes to relate changes in tissue structure seen in normal aging and in chronic inflammation to altered lung mechanics using a computational model. Alterations in lung function in aging and Sftpd -/- mice have been inferred from fitting simple mechanical models to respiratory impedance data (Zrs), however interpretation has been confounded by the simultaneous presence of multiple coexisting pathophysiologic processes. In contrast to the inverse modeling approach, this study uses simulation from experimental measurements to recapitulate how aging and inflammation alter Zrs. Histologic and mechanical measurements were made in C57BL6/J mice and congenic Sftpd-/- mice at 8, 27 and 80 weeks of age (n = 8/group). An anatomic computational model based on published airway morphometry was developed and Zrs was simulated between 0.5 and 20 Hz. End expiratory pressure dependent changes in airway caliber and recruitment were estimated from mechanical measurements. Tissue elements were simulated using the constant phase model of viscoelasticity. Baseline elastance distribution was estimated in 8-week-old wild type mice, and stochastically varied for each condition based on experimentally measured alteration in elastic fiber composition, alveolar geometry and surfactant composition. Weighing reduction in model error against increasing model complexity allowed for identification of essential features underlying mechanical pathology and their contribution to Zrs. Using a maximum likelihood approach, alteration in lung recruitment and diminished elastic fiber density were shown predictive of mechanical alteration at

  10. Lingonberries alter the gut microbiota and prevent low-grade inflammation in high-fat diet fed mice

    PubMed Central

    Heyman-Lindén, Lovisa; Kotowska, Dorota; Sand, Elin; Bjursell, Mikael; Plaza, Merichel; Turner, Charlotta; Holm, Cecilia; Fåk, Frida; Berger, Karin

    2016-01-01

    Background The gut microbiota plays an important role in the development of obesity and obesity-associated impairments such as low-grade inflammation. Lingonberries have been shown to prevent diet-induced obesity and low-grade inflammation. However, it is not known whether the effect of lingonberry supplementation is related to modifications of the gut microbiota. The aim of the present study was to describe whether consumption of different batches of lingonberries alters the composition of the gut microbiota, which could be relevant for the protective effect against high fat (HF)-induced metabolic alterations. Methods Three groups of C57BL/6J mice were fed HF diet with or without a supplement of 20% lingonberries from two different batches (Lingon1 and Lingon2) during 11 weeks. The composition and functionality of the cecal microbiota were assessed by 16S rRNA sequencing and PICRUSt. In addition, parameters related to obesity, insulin sensitivity, hepatic steatosis, inflammation and gut barrier function were examined. Results HF-induced obesity was only prevented by the Lingon1 diet, whereas both batches of lingonberries reduced plasma levels of markers of inflammation and endotoxemia (SAA and LBP) as well as modified the composition and functionality of the gut microbiota, compared to the HF control group. The relative abundance of Akkermansia and Faecalibacterium, genera associated with healthy gut mucosa and anti-inflammation, was found to increase in response to lingonberry intake. Conclusions Our results show that supplementation with lingonberries to an HF diet prevents low-grade inflammation and is associated with significant changes of the microbiota composition. Notably, the anti-inflammatory properties of lingonberries seem to be independent of effects on body weight gain. PMID:27125264

  11. Streptomycin treatment alters the intestinal microbiome, pulmonary T cell profile and airway hyperresponsiveness in a cystic fibrosis mouse model

    PubMed Central

    Bazett, Mark; Bergeron, Marie-Eve; Haston, Christina K.

    2016-01-01

    Cystic fibrosis transmembrane conductance regulator deficient mouse models develop phenotypes of relevance to clinical cystic fibrosis (CF) including airway hyperresponsiveness, small intestinal bacterial overgrowth and an altered intestinal microbiome. As dysbiosis of the intestinal microbiota has been recognized as an important contributor to many systemic diseases, herein we investigated whether altering the intestinal microbiome of BALB/c Cftrtm1UNC mice and wild-type littermates, through treatment with the antibiotic streptomycin, affects the CF lung, intestinal and bone disease. We demonstrate that streptomycin treatment reduced the intestinal bacterial overgrowth in Cftrtm1UNC mice and altered the intestinal microbiome similarly in Cftrtm1UNC and wild-type mice, principally by affecting Lactobacillus levels. Airway hyperresponsiveness of Cftrtm1UNC mice was ameliorated with streptomycin, and correlated with Lactobacillus abundance in the intestine. Additionally, streptomycin treated Cftrtm1UNC and wild-type mice displayed an increased percentage of pulmonary and mesenteric lymph node Th17, CD8 + IL-17+ and CD8 + IFNγ+ lymphocytes, while the CF-specific increase in respiratory IL-17 producing γδ T cells was decreased in streptomycin treated Cftrtm1UNC mice. Bone disease and intestinal phenotypes were not affected by streptomycin treatment. The airway hyperresponsiveness and lymphocyte profile of BALB/c Cftrtm1UNC mice were affected by streptomycin treatment, revealing a potential intestinal microbiome influence on lung response in BALB/c Cftrtm1UNC mice. PMID:26754178

  12. Exposure to Deepwater Horizon Crude Oil Burnoff Particulate Matter Induces Pulmonary Inflammation and Alters Adaptive Immune Response.

    PubMed

    Jaligama, Sridhar; Chen, Zaili; Saravia, Jordy; Yadav, Nikki; Lomnicki, Slawomir M; Dugas, Tammy R; Cormier, Stephania A

    2015-07-21

    The ″in situ burning" of trapped crude oil on the surface of Gulf waters during the 2010 Deepwater Horizon (DWH) oil spill released numerous pollutants, including combustion-generated particulate matter (PM). Limited information is available on the respiratory impact of inhaled in situ burned oil sail particulate matter (OSPM). Here we utilized PM collected from in situ burn plumes of the DWH oil spill to study the acute effects of exposure to OSPM on pulmonary health. OSPM caused dose-and time-dependent cytotoxicity and generated reactive oxygen species and superoxide radicals in vitro. Additionally, mice exposed to OSPM exhibited significant decreases in body weight gain, systemic oxidative stress in the form of increased serum 8-isoprostane (8-IP) levels, and airway inflammation in the form of increased macrophages and eosinophils in bronchoalveolar lavage fluid. Further, in a mouse model of allergic asthma, OSPM caused increased T helper 2 cells (Th2), peribronchiolar inflammation, and increased airway mucus production. These findings demonstrate that acute exposure to OSPM results in pulmonary inflammation and alteration of innate/adaptive immune responses in mice and highlight potential respiratory effects associated with cleaning up an oil spill.

  13. 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.

  14. 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.

  15. A chronic high fat diet alters the homologous and heterologous control of appetite regulating peptide receptor expression.

    PubMed

    Kentish, Stephen J; Wittert, Gary A; Blackshaw, L Ashley; Page, Amanda J

    2013-08-01

    Leptin, ghrelin and neuropeptide W (NPW) modulate vagal afferent activity, which may underlie their appetite regulatory actions. High fat diet (HFD)-induced obesity induces changes in the plasma levels of these peptides and alters the expression of receptors on vagal afferents. We investigated homologous and heterologous receptor regulation by leptin, ghrelin and NPW. Mice were fed (12 weeks) a standard laboratory diet (SLD) or HFD. Nodose ganglia were cultured overnight in the presence or absence of each peptide. Leptin (LepR), ghrelin (GHS-R), NPW (GPR7) and cholecystokinin type-1 (CCK1R) receptor mRNA, and the plasma leptin, ghrelin and NPW levels were measured. SLD: leptin reduced LepR, GPR7, increased GHS-R and CCK1R mRNA; ghrelin increased LepR, GPR7, CCK1R, and decreased GHS-R. HFD: leptin decreased GHS-R and GPR7, ghrelin increased GHS-R and GPR7. NPW decreased all receptors except GPR7 which increased with HFD. Plasma leptin was higher and NPW lower in HFD. Thus, HFD-induced obesity disrupts inter-regulation of appetite regulatory receptors in vagal afferents.

  16. Dietary vitamin E and pulmonary biochemical and morphological alterations of rats exposed to 0. 1 ppM ozone

    SciTech Connect

    Chow, C.K.; Plopper, C.G.; Chiu, M.; Dungworth, D.L.

    1981-04-01

    Three groups of 28 1-month-old male Sprague-Dawley rats each were fed a basal vitamin E-deficient diet and supplemented with either 0, 11, or 110 ppM vitamin E for 38 days, and were then exposed to 0 or 0.1 ppM ozone continuously for 7 days. Following ozone exposure, the level of reduced glutathione (GSH) and activities of GSH peroxidase, GSH reductase, glucose-6-phosphate dehydrogenase (G-6-PD), and lactate dehydrogenase (LDH), but not of malic dehydrogenase, were significantly elevated in the lungs of rats fed the vitamin E deficient diet. The level of GSH and activities of GSH peroxidase and G-6-PD were also significantly increased in the lungs of the animal group fed the 11 ppM vitamin E diet, while none of the biochemical measurements made was significantly altered by ozone in the 110-ppM vitamin E diet fed rats. Scanning electron microscope examination revealed that five out of six rats on the vitamin E-deficient diet and four out of six from the 11-ppM vitamin E diet had detectable lesions following ozone exposure, as compared with only one of the six exposed animals from the 110-ppM vitamin E diet. The lesion was restricted to bronchiolar epithelium and alveoli immediately adjacent to the bronchiole-alveolar duct junction. None of the control animals had detectable lesions. The results suggest that exposure to ozone at 0.1-ppM level can produce detectable pulmonary damage, and that dietary vitamin E alters pulmonary susceptibility to ozone exposure.

  17. Quadriceps exercise intolerance in patients with chronic obstructive pulmonary disease: the potential role of altered skeletal muscle mitochondrial respiration

    PubMed Central

    Gifford, Jayson R.; Trinity, Joel D.; Layec, Gwenael; Garten, Ryan S.; Park, Song-Young; Rossman, Matthew J.; Larsen, Steen; Dela, Flemming

    2015-01-01

    This study sought to determine if qualitative alterations in skeletal muscle mitochondrial respiration, associated with decreased mitochondrial efficiency, contribute to exercise intolerance in patients with chronic obstructive pulmonary disease (COPD). Using permeabilized muscle fibers from the vastus lateralis of 13 patients with COPD and 12 healthy controls, complex I (CI) and complex II (CII)-driven State 3 mitochondrial respiration were measured separately (State 3:CI and State 3:CII) and in combination (State 3:CI+CII). State 2 respiration was also measured. Exercise tolerance was assessed by knee extensor exercise (KE) time to fatigue. Per milligram of muscle, State 3:CI+CII and State 3:CI were reduced in COPD (P < 0.05), while State 3:CII and State 2 were not different between groups. To determine if this altered pattern of respiration represented qualitative changes in mitochondrial function, respiration states were examined as percentages of peak respiration (State 3:CI+CII), which revealed altered contributions from State 3:CI (Con 83.7 ± 3.4, COPD 72.1 ± 2.4%Peak, P < 0.05) and State 3:CII (Con 64.9 ± 3.2, COPD 79.5 ± 3.0%Peak, P < 0.05) respiration, but not State 2 respiration in COPD. Importantly, a diminished contribution of CI-driven respiration relative to the metabolically less-efficient CII-driven respiration (CI/CII) was also observed in COPD (Con 1.28 ± 0.09, COPD 0.81 ± 0.05, P < 0.05), which was related to exercise tolerance of the patients (r = 0.64, P < 0.05). Overall, this study indicates that COPD is associated with qualitative alterations in skeletal muscle mitochondria that affect the contribution of CI and CII-driven respiration, which potentially contributes to the exercise intolerance associated with this disease. PMID:26272320

  18. Quadriceps exercise intolerance in patients with chronic obstructive pulmonary disease: the potential role of altered skeletal muscle mitochondrial respiration.

    PubMed

    Gifford, Jayson R; Trinity, Joel D; Layec, Gwenael; Garten, Ryan S; Park, Song-Young; Rossman, Matthew J; Larsen, Steen; Dela, Flemming; Richardson, Russell S

    2015-10-15

    This study sought to determine if qualitative alterations in skeletal muscle mitochondrial respiration, associated with decreased mitochondrial efficiency, contribute to exercise intolerance in patients with chronic obstructive pulmonary disease (COPD). Using permeabilized muscle fibers from the vastus lateralis of 13 patients with COPD and 12 healthy controls, complex I (CI) and complex II (CII)-driven State 3 mitochondrial respiration were measured separately (State 3:CI and State 3:CII) and in combination (State 3:CI+CII). State 2 respiration was also measured. Exercise tolerance was assessed by knee extensor exercise (KE) time to fatigue. Per milligram of muscle, State 3:CI+CII and State 3:CI were reduced in COPD (P < 0.05), while State 3:CII and State 2 were not different between groups. To determine if this altered pattern of respiration represented qualitative changes in mitochondrial function, respiration states were examined as percentages of peak respiration (State 3:CI+CII), which revealed altered contributions from State 3:CI (Con 83.7 ± 3.4, COPD 72.1 ± 2.4%Peak, P < 0.05) and State 3:CII (Con 64.9 ± 3.2, COPD 79.5 ± 3.0%Peak, P < 0.05) respiration, but not State 2 respiration in COPD. Importantly, a diminished contribution of CI-driven respiration relative to the metabolically less-efficient CII-driven respiration (CI/CII) was also observed in COPD (Con 1.28 ± 0.09, COPD 0.81 ± 0.05, P < 0.05), which was related to exercise tolerance of the patients (r = 0.64, P < 0.05). Overall, this study indicates that COPD is associated with qualitative alterations in skeletal muscle mitochondria that affect the contribution of CI and CII-driven respiration, which potentially contributes to the exercise intolerance associated with this disease.

  19. Alteration of serum inflammatory cytokines in active pulmonary tuberculosis following anti-tuberculosis drug therapy.

    PubMed

    Chowdhury, Imran Hussain; Ahmed, Albin Mostaque; Choudhuri, Subhadip; Sen, Aditi; Hazra, Avijit; Pal, Nishith Kumar; Bhattacharya, Basudev; Bahar, Bojlul

    2014-11-01

    Active pulmonary tuberculosis (APTB) is associated with a failure of the host immune system to control the invading Mycobacterium tuberculosis (Mtb). The objective of this study was to quantify and assess the role of serum inflammatory cytokines in active pulmonary tuberculosis patients following anti-tuberculosis drug (ATD) therapy. Blood samples were collected from APTB patients and normal healthy subjects (NHS) (total n=204) at baseline and 2, 4 and 6 months post-therapy and the abundance of serum inflammatory cytokines were measured by cytokine specific ELISA. Compared to NHS, APTB patients at baseline had higher levels of serum pro-inflammatory cytokines IL-12p40 (P<0.001), IFN-γ (P<0.001), TNF-α (P<0.01), IL-1β (P<0.001) and IL-6 (P<0.001) and anti-inflammatory cytokines IL-10 (P<0.001) and TGF-β1 (P<0.001) while there was no change in the level of IL-4. In APTB patients, the serum levels of IFN-γ, TNF-α, IL-6 and TGF-β1 directly relate to the bacterial load while the TNF-α, IL-1β, IL-6 and TGF-β1 relate to radiological severity. At baseline, the IL-6 level in NHS and APTB patients differed most and following ATD therapy, this level rapidly decreased and stabilized by 4-month in APTB patients. It is concluded that a subtle reduction in the serum level of IL-6 of the APTB patients following ATD therapy might play a vital role in immune-protection of the host against Mtb infection and hence the serum IL-6 level can be a useful marker to diagnose the effectiveness of therapy in the patients.

  20. Acute Ozone (O3) Exposure Accelerates Diet-Induced Pulmonary Injury and Metabolic Alterations in a Rat Model of Type II Diabetes

    EPA Science Inventory

    Abstract for Society of Toxicology, March 22-25, 2015, San Diego, CAAcute Ozone (O3) Exposure Accelerates Diet-Induced Pulmonary Injury and Metabolic Alterations in a Rat Model of Type II DiabetesS.J. Snow1,3, D. Miller2, V. Bass2, M. Schladweiler3, A. Ledbetter3, J. Richards3, C...

  1. Acute Ozone (O3) Exposure Accelerates Diet-Induced Pulmonary Injury and Metabolic Alterations in a Rat Model of Type II Diabetes

    EPA Science Inventory

    Abstract for Society of Toxicology, March 22-25, 2015, San Diego, CAAcute Ozone (O3) Exposure Accelerates Diet-Induced Pulmonary Injury and Metabolic Alterations in a Rat Model of Type II DiabetesS.J. Snow1,3, D. Miller2, V. Bass2, M. Schladweiler3, A. Ledbetter3, J. Richards3, C...

  2. High pressure processing alters water distribution enabling the production of reduced-fat and reduced-salt pork sausages.

    PubMed

    Yang, Huijuan; Han, Minyi; Bai, Yun; Han, Yanqing; Xu, Xinglian; Zhou, Guanghong

    2015-04-01

    High pressure processing (HPP) was used to explore novel methods for modifying the textural properties of pork sausages with reduced-salt, reduced-fat and no fat replacement additions. A 2×7 factorial design was set up, incorporating two pressure levels (0.1 or 200 MPa) and seven fat levels (0, 5, 10, 15, 20, 25 and 30%). Sausages treated at 200 MPa exhibited improved tenderness at all fat levels compared with 0.1 MPa treated samples, and the shear force of sausages treated at 200 MPa with 15 or 20% fat content was similar to the 0.1 MPa treated sausages with 30% fat. HPP significantly changed the P₂ peak ratio of the four water components in raw sausages, resulting in improved textural properties of emulsion-type sausages with reduced-fat and reduced-salt. Significant correlations were found between pH, color, shear force and water proportions. The scanning and transmission micrographs revealed the formation of smaller fat globules and an improved network structure in the pressure treated sausages. In conclusion, there is potential to manufacture sausages with reduced-fat and reduced-salt by using HPP to maintain textural qualities. Copyright © 2014. Published by Elsevier Ltd.

  3. High-fat diets rich in soy or fish oil distinctly alter hypothalamic insulin signaling in rats.

    PubMed

    Pimentel, Gustavo D; Dornellas, Ana P S; Rosa, José C; Lira, Fábio S; Cunha, Cláudio A; Boldarine, Valter T; de Souza, Gabriel I H; Hirata, Aparecida E; Nascimento, Cláudia M O; Oyama, Lila M; Watanabe, Regina L H; Ribeiro, Eliane B

    2012-07-01

    Hypothalamic insulin inhibits food intake, preventing obesity. High-fat feeding with polyunsaturated fats may be obesogenic, but their effect on insulin action has not been elucidated. The present study evaluated insulin hypophagia and hypothalamic signaling after central injection in rats fed either control diet (15% energy from fat) or high-fat diets (50% energy from fat) enriched with either soy or fish oil. Soy rats had increased fat pad weight and serum leptin with normal body weight, serum lipid profile and peripheral insulin sensitivity. Fish rats had decreased body and fat pad weight, low leptin and corticosterone levels, and improved serum lipid profile. A 20-mU dose of intracerebroventricular (ICV) insulin inhibited food intake in control and fish groups, but failed to do so in the soy group. Hypothalamic protein levels of IR, IRS-1, IRS-2, Akt, mTOR, p70S6K and AMPK were similar among groups. ICV insulin stimulated IR tyrosine phosphorylation in control (68%), soy (36%) and fish (34%) groups. Tyrosine phosphorylation of the pp185 band was significantly stimulated in control (78%) and soy (53%) rats, but not in fish rats. IRS-1 phosphorylation was stimulated only in control rats (94%). Akt serine phosphorylation was significantly stimulated only in control (90%) and fish (78%) rats. The results showed that, rather than the energy density, the fat type was a relevant aspect of high-fat feeding, since blockade of hypothalamic insulin signal transmission and insulin hypophagia was promoted only by the high-fat soy diet, while they were preserved in the rats fed with the high-fat fish diet. Copyright © 2012 Elsevier Inc. All rights reserved.

  4. Adverse Fetal and Neonatal Outcomes Associated with a Life-Long High Fat Diet: Role of Altered Development of the Placental Vasculature

    PubMed Central

    Petrik, Jim J.; Storozhuk, Yaryna; Paez-Parent, Sabrina; Dai, Qin; Samjoo, Imtiaz A.; Mansell, Margaret; Gruslin, Andree; Holloway, Alison C.; Raha, Sandeep

    2012-01-01

    Maternal obesity results in a number of obstetrical and fetal complications with both immediate and long-term consequences. The increased prevalence of obesity has resulted in increasing numbers of women of reproductive age in this high-risk group. Since many of these obese women have been subjected to hypercaloric diets from early childhood we have developed a rodent model of life-long maternal obesity to more clearly understand the mechanisms that contribute to adverse pregnancy outcomes in obese women. Female Sprague Dawley rats were fed a control diet (CON - 16% of calories from fat) or high fat diet (HF - 45% of calories from fat) from 3 to 19 weeks of age. Prior to pregnancy HF-fed dams exhibited significant increases in body fat, serum leptin and triglycerides. A subset of dams was sacrificed at gestational day 15 to evaluate fetal and placental development. The remaining animals were allowed to deliver normally. HF-fed dams exhibited a more than 3-fold increase in fetal death and decreased neonatal survival. These outcomes were associated with altered vascular development in the placenta, as well as increased hypoxia in the labyrinth. We propose that the altered placental vasculature may result in reduced oxygenation of the fetal tissues contributing to premature demise and poor neonatal survival. PMID:22442686

  5. Diet-induced milk fat depression is associated with alterations in ruminal biohydrogenation pathways and formation of novel fatty acid intermediates in lactating cows.

    PubMed

    Ventto, Laura; Leskinen, Heidi; Kairenius, Piia; Stefański, Tomasz; Bayat, Ali R; Vilkki, Johanna; Shingfield, Kevin J

    2017-02-01

    The biohydrogenation theory of milk fat depression (MFD) attributes decreases in milk fat in cows to the formation of specific fatty acids (FA) in the rumen. Trans-10, cis-12-CLA is the only biohydrogenation intermediate known to inhibit milk fat synthesis, but it is uncertain if increased ruminal synthesis is the sole explanation of MFD. Four lactating cows were used in a 4×4 Latin square with a 2×2 factorial arrangement of treatments and 35-d experimental periods to evaluate the effect of diets formulated to cause differences in ruminal lipid metabolism and milk fat synthesis on the flow of FA and dimethyl acetal at the omasum. Treatments comprised total mixed rations based on grass silage with a forage:concentrate ratio of 35:65 or 65:35 containing 0 or 50 g/kg sunflower oil (SO). Supplementing the high-concentrate diet with SO lowered milk fat synthesis from -20·2 to -31·9 % relative to other treatments. Decreases in milk fat were accompanied by alterations in ruminal biohydrogenation favouring the trans-10 pathway and an increase in the formation of specific intermediates including trans-4 to trans-10-18 : 1, trans-8, trans-10-CLA, trans-9, cis-11-CLA and trans-10, cis-15-18 : 2. Flow of trans-10, cis-12-CLA at the omasum was greater on high- than low-concentrate diets but unaffected by SO. In conclusion, ruminal trans-10, cis-12-CLA formation was not increased on a diet causing MFD suggesting that other biohydrogenation intermediates or additional mechanisms contribute to the regulation of fat synthesis in the bovine mammary gland.

  6. Saturated high-fat feeding independent of obesity alters hypothalamus-pituitary-adrenal axis function but not anxiety-like behaviour.

    PubMed

    Hryhorczuk, Cecile; Décarie-Spain, Léa; Sharma, Sandeep; Daneault, Caroline; Rosiers, Christine Des; Alquier, Thierry; Fulton, Stephanie

    2017-09-01

    Overconsumption of dietary fat can elicit impairments in emotional processes and the response to stress. While excess dietary lipids have been shown to alter hypothalamus-pituitary-adrenal (HPA) axis function and promote anxiety-like behaviour, it is not known if such changes rely on elevated body weight and if these effects are specific to the type of dietary fat. The objective of this study was to investigate the effect of a saturated and a monounsaturated high-fat diet (HFD) on HPA axis function and anxiety-like behaviour in rats. Biochemical, metabolic and behavioural responses were evaluated following eight weeks on one of three diets: (1) a monounsaturated HFD (50%kcal olive oil), (2) a saturated HFD (50%kcal palm oil), or (3) a control low-fat diet. Weight gain was similar across the three diets while visceral fat mass was elevated by the two HFDs. The saturated HFD had specific actions to increase peak plasma levels of corticosterone and tumour-necrosis-factor-alpha and suppress mRNA expression of glucocorticoid and mineralocorticoid receptors, corticotropin-releasing hormone and 11β-hydroxysteroid dehydrogenase-1 in the paraventricular nucleus of the hypothalamus. Both HFDs enhanced the corticosterone-suppressing response to dexamethasone administration without affecting the physiological response to a restraint stress and failed to increase anxiety-like behaviour as measured in the elevated-plus maze and open field tests. These findings demonstrate that prolonged intake of saturated fat, without added weight gain, increases CORT and modulates central HPA feedback processes. That saturated HFD failed to affect anxiety-like behaviour can suggest that the anxiogenic effects of prolonged high-fat feeding may rely on more pronounced metabolic dysfunction. Copyright © 2017 Elsevier Ltd. All rights reserved.

  7. Sex differences in high-fat diet-induced obesity, metabolic alterations and learning, and synaptic plasticity deficits in mice.

    PubMed

    Hwang, Ling-Ling; Wang, Chien-Hua; Li, Tzu-Ling; Chang, Shih-Dar; Lin, Li-Chun; Chen, Ching-Ping; Chen, Chiung-Tong; Liang, Keng-Chen; Ho, Ing-Kang; Yang, Wei-Shiung; Chiou, Lih-Chu

    2010-03-01

    Obesity is a potential risk factor for cognitive deficits in the elder humans. Using a high-fat diet (HFD)-induced obese mouse model, we investigated the impacts of HFD on obesity, metabolic and stress hormones, learning performance, and hippocampal synaptic plasticity. Both male and female C57BL/6J mice fed with HFD (3 weeks to 9-12 months) gained significantly more weights than the sex-specific control groups. Compared with the obese female mice, the obese males had similar energy intake but developed more weight gains. The obese male mice developed hyperglycemia, hyperinsulinemia, hypercholesterolemia, and hyperleptinemia, but not hypertriglyceridemia. The obese females had less hyperinsulinemia and hypercholesterolemia than the obese males, and no hyperglycemia and hypertriglyceridemia. In the contextual fear conditioning and step-down passive avoidance tasks, the obese male, but not female, mice showed poorer learning performance than their normal counterparts. These learning deficits were not due to sensorimotor impairment as verified by the open-field and hot-plate tests. Although, basal synaptic transmission characteristics (input-output transfer and paired-pulse facilitation (PPF) ratio) were not significantly different between normal and HFD groups, the magnitudes of synaptic plasticity (long-term potentiation (LTP) and long-term depression (LTD)) were lower at the Schaffer collateral-CA1 synapses of the hippocampal slices isolated from the obese male, but not female, mice, as compared with their sex-specific controls. Our results suggest that male mice are more vulnerable than the females to the impacts of HFD on weight gains, metabolic alterations and deficits of learning, and hippocampal synaptic plasticity.

  8. Study of retinal alterations in a high fat diet-induced type ii diabetes rodent: Meriones shawi.

    PubMed

    Hammoum, Imane; Mbarek, Sihem; Dellaa, Ahmed; Dubus, Elisabeth; Baccouche, Basma; Azaiz, Rached; Charfeddine, Ridha; Picaud, Serge; Ben Chaouacha-Chekir, Rafika

    2017-01-01

    Diabetic retinopathy is a common complication of type 2 diabetes and the leading cause of blindness in adults of working age. The aim of this work was to study the repercussions of high fat diet (HFD) induced diabetes on the retina of Meriones shawi (M.sh). Two groups of six M.sh each was studied. Group I was a normal control, fed with standard laboratory granules. In Group II, rodents received a HFD of enriched laboratory granules, for a period of 3 months. Body weight and plasma glucose were determined in the two groups. Retinal sections of the two groups were stained with the Hematoxylin-Eosin. Photoreceptors were identified by immunolabeling for rhodopsin (rods) and PNA (cones). Gliosis and microglial activation were identified by immunolabeling for GFAP and Iba-1. Labeling of calretinin and parvalbumin were also carried out to study the AII amacrine cells. Retinal layers thicknesses, gliosis, and specific neural cell populations were quantified by microscopy. The body weight (+77%) and plasma glucose (+108%) were significantly greater in the HFD rodents. Three months of HFD induced a significant loss of 38.77% of cone photoreceptors, as well as gliosis and an increase of 70.67% of microglial cells. Calcium homeostatic enzymes were depleted. This work shows that HFD in Meriones shawi induces a type II diabetes-like condition that causes loss of retinal neurons and photoreceptors, as well as gliosis. Meriones shawi could be a useful experimental animal model for this physiopathology particularly in the study of retinal neuro-glial alterations in Type II diabetes. Copyright © 2016 Elsevier GmbH. All rights reserved.

  9. Prenatal fat-rich diet exposure alters responses of embryonic neurons to the chemokine, CCL2, in the hypothalamus.

    PubMed

    Poon, K; Abramova, D; Ho, H T; Leibowitz, S

    2016-06-02

    Maternal consumption of a high-fat diet (HFD) during pregnancy is found to stimulate the genesis of hypothalamic orexigenic peptide neurons in the offspring, while HFD intake in adult animals produces a systemic low-grade inflammation which increases neuroimmune factors that may affect neurogenesis and neuronal migration. Building on this evidence and our recent study showing that the inflammatory chemokine, CCL2, stimulates the migration of hypothalamic neurons and expression of orexigenic neuropeptides, we tested here the possibility that prenatal exposure to a HFD in rats affects this chemokine system, both CCL2 and its receptors, CCR2 and CCR4, and alters its actions on hypothalamic neurons, specifically those expressing the neuropeptides, enkephalin (ENK) and galanin (GAL). Using primary dissociated hypothalamic neurons extracted from embryos on embryonic day 19, we found that prenatal HFD exposure compared to chow control actually reduces the expression of CCL2 in these hypothalamic neurons, while increasing CCR2 and CCR4 expression, and also reduces the sensitivity of hypothalamic neurons to CCL2. The HFD abolished the dose-dependent, stimulatory effect of CCL2 on the number of migrated neurons and even shifted its normal stimulatory effect on migrational velocity and distance traveled by control neurons to an inhibition of migration. Further, it abolished the dose-dependent, stimulatory effect of CCL2 on neuronal expression of ENK and GAL. These results demonstrate that prenatal HFD exposure greatly disturbs the functioning of the CCL2 chemokine system in embryonic hypothalamic neurons, reducing its endogenous levels and ability to promote the migration of neurons and their expression of orexigenic peptides.

  10. Alteration of sweet taste in high-fat diet induced obese rats after 4 weeks treatment with exenatide.

    PubMed

    Zhang, Xiao-juan; Wang, Yu-qing; Long, Yang; Wang, Lei; Li, Yun; Gao, Fa-bao; Tian, Hao-ming

    2013-09-01

    Exenatide, a glucagon-like peptide-1 (GLP-1) receptor agonist, is effective in inducing weight loss. The exact mechanisms are not fully understood. Reduced appetite and food intake may play important roles. Sweet taste contributes to food palatability, which promotes appetite. Interestingly, GLP-1 and its receptor are expressed in the taste buds of rodents and their interaction has an effect on mediating sweet taste sensitivity. Our aim was to investigate whether sweet taste will be changed after long term treatment with exenatide. The results showed that high-fat diet induced obese rats (HF-C) presented metabolic disorders in food intake, body weight, blood glucose and lipid metabolism compared with long term exenatide treated obese rats (EX) and normal chow fed control rats (NC). Meanwhile, greater preference for sweet taste was observed in HF-C rats but not in EX rats. Compared with NC rats, brain activities induced by sweet taste stimulation were stronger in HF-C rats, however these stronger activities were not found in EX rats. We further found reduced sweet taste receptor T1R3 in circumvallte taste buds of HF-C rats, while GLP-1 was increased. Besides, serum leptin was evaluated in HF-C rats with decreased leptin receptor expressed in taste buds. These changes were not observed in EX rats, which suggest them to be the underlying hormone and molecular mechanisms responsible for alterations in sweet taste of HF-C rats and EX rats. In summary, our results suggest that long term treatment with exenatide could benefit dietary obese rats partially by reversing sweet taste changes.

  11. Caloric restriction induces energy-sparing alterations in skeletal muscle contraction, fiber composition and local thyroid hormone metabolism that persist during catch-up fat upon refeeding

    PubMed Central

    De Andrade, Paula B. M.; Neff, Laurence A.; Strosova, Miriam K.; Arsenijevic, Denis; Patthey-Vuadens, Ophélie; Scapozza, Leonardo; Montani, Jean-Pierre; Ruegg, Urs T.; Dulloo, Abdul G.; Dorchies, Olivier M.

    2015-01-01

    Weight regain after caloric restriction results in accelerated fat storage in adipose tissue. This catch-up fat phenomenon is postulated to result partly from suppressed skeletal muscle thermogenesis, but the underlying mechanisms are elusive. We investigated whether the reduced rate of skeletal muscle contraction-relaxation cycle that occurs after caloric restriction persists during weight recovery and could contribute to catch-up fat. Using a rat model of semistarvation-refeeding, in which fat recovery is driven by suppressed thermogenesis, we show that contraction and relaxation of leg muscles are slower after both semistarvation and refeeding. These effects are associated with (i) higher expression of muscle deiodinase type 3 (DIO3), which inactivates tri-iodothyronine (T3), and lower expression of T3-activating enzyme, deiodinase type 2 (DIO2), (ii) slower net formation of T3 from its T4 precursor in muscles, and (iii) accumulation of slow fibers at the expense of fast fibers. These semistarvation-induced changes persisted during recovery and correlated with impaired expression of transcription factors involved in slow-twitch muscle development. We conclude that diminished muscle thermogenesis following caloric restriction results from reduced muscle T3 levels, alteration in muscle-specific transcription factors, and fast-to-slow fiber shift causing slower contractility. These energy-sparing effects persist during weight recovery and contribute to catch-up fat. PMID:26441673

  12. Histopathological alterations in the prostates of Mongolian gerbils exposed to a high-fat diet and di-n-butyl phthalate individually or in combination.

    PubMed

    de Jesus, Mariana Marcielo; Negrin, Ana Carolina; Taboga, Sebastião Roberto; Pinto-Fochi, Maria Etelvina; Góes, Rejane Maira

    2015-04-01

    Both high-fat diet and exposure to endocrine-disrupting chemicals have been implicated in susceptibility to pathological prostate lesions, but the consequences of combining the two have not yet been examined. We evaluated the effects of gestational and postnatal exposure to a high-fat diet (20% fat) and low doses of di-n-butyl phthalate (DBP; 5mg/kg/day), individually or in combination, on the tissue response and incidence of pathological lesions in the ventral prostate of adult gerbils. Continuous intake of a high-fat diet caused dyslipidemia, hypertrophy, and promoted the development of inflammatory, premalignant and malignant prostate lesions, even in the absence of obesity. Life-time DBP exposure was obesogenic and dyslipidemic and increased the incidence of premalignant prostate lesions. Combined exposure to DBP and a high-fat diet also caused prostate hypertrophy, but the effects were less severe than those of individual treatments; combined exposure neither induced an inflammatory response nor altered serum lipid content. Copyright © 2015 Elsevier Inc. All rights reserved.

  13. Reducing dietary fat from a meal increases the bioavailability of exogenous carbohydrate without altering plasma glucose concentration

    PubMed Central

    Knuth, Nicolas D.; Shrivastava, Cara R.; Horowitz, Jeffrey F.

    2009-01-01

    The primary goal of this study was to determine the acute glycemic and endocrine responses to the reduction of fat content from a meal. On three separate occasions, nine overweight subjects (body mass index = 30 ± 1 kg/m2; 5 men, 4 women) consumed 1) a control meal (∼800 kcal; 100 g of carbohydrate, 31 g of fat, and 30 g of protein), 2) a low-fat meal (∼530 kcal; 100 g of carbohydrate, 1 g of fat, and 30 g of protein), or 3) a low-fat meal plus lipid infusion [same meal as low-fat meal, but the total energy provided was the same as control (800 kcal), with the “missing” fat (∼30 g) provided via an intravenous lipid infusion]. All three meals contained [13C]glucose (3 mg/kg body wt) to assess the bioavailability of ingested glucose. During the 5-h period after each meal, we measured the recovery of [13C]glucose in plasma, plasma glucose, and insulin concentrations. We also measured plasma concentration of the gastrointestinal peptides: glucose-dependent insulinotropic polypeptide (GIP), glucagon-like peptide-1 (GLP-1), and peptide YY3-36 (PYY3-36). The recovery of the ingested [13C]glucose in the hour after ingestion was greater (P < 0.05) after the low-fat than after the control meal [area under the curve (AUC): 1,206 ± 252 and 687 ± 161 μM·h, respectively]. However, removing dietary fat from the meal did not affect the plasma concentration of glucose or insulin. Importantly, [13C]glucose recovery was not different during the low-fat and lipid infusion trials (AUC: 1,206 ± 252 and 1,134 ± 247 μM·h, respectively), indicating that the accelerated delivery of exogenous glucose found after removing fat from the meal is due exclusively to the reduction of fat in the gastrointestinal tract. In parallel with these findings, the reduction in fat calories from the meal reduced plasma concentration of GIP, GLP-1, and PYY3-36. In summary, these data suggest that removing fat from the diet expedited exogenous glucose delivery into the systemic circulation

  14. Pulmonary pathological alterations in sheep exposed to a lethal dose of phosgene

    SciTech Connect

    Assaad, A.; Nold, J.; Petrali, J.; Moore, D.; Mitcheltree, L.; Corcoran, K.; Phillips, K. )

    1991-03-11

    In this study, the authors demonstrated the acute pulmonary cellular changes associated with phosgene exposure, by both light (L.M.) and electron microscopy (E.M.). Adult, unanesthetized sheep were exposed for 10 minutes to either 767 ppm/min of phosgene or room air. Four hours post exposure, all animals were killed, wet lung weight was obtained, and lung tissue was collected for L.M. and E.M. In sheep exposed to phosgene, wet lung weight was significantly higher. Grossly, the lung was congested and edematous. Alveolar and interstitial edema, fibrin and neutrophil exudation in the air spaces, and increased alveolar macrophages, were prominent by L.M. E.M. of Type I pneumocytes showed intracellular swelling, necrosis, and denuding of basement membrane with preservation of the tight junctions. Type II pneumocytes showed loss of lamellar bodies, cytoplasmic swelling, and damage to the endoplasmic reticulum. Endothelial cells showed increased density and vesicular activity, cytoplasmic swelling, and displacement of basement membrane. This study supports the biochemical data the authors previously reported.

  15. Streptomycin treatment alters the intestinal microbiome, pulmonary T cell profile and airway hyperresponsiveness in a cystic fibrosis mouse model.

    PubMed

    Bazett, Mark; Bergeron, Marie-Eve; Haston, Christina K

    2016-01-12

    Cystic fibrosis transmembrane conductance regulator deficient mouse models develop phenotypes of relevance to clinical cystic fibrosis (CF) including airway hyperresponsiveness, small intestinal bacterial overgrowth and an altered intestinal microbiome. As dysbiosis of the intestinal microbiota has been recognized as an important contributor to many systemic diseases, herein we investigated whether altering the intestinal microbiome of BALB/c Cftr(tm1UNC) mice and wild-type littermates, through treatment with the antibiotic streptomycin, affects the CF lung, intestinal and bone disease. We demonstrate that streptomycin treatment reduced the intestinal bacterial overgrowth in Cftr(tm1UNC) mice and altered the intestinal microbiome similarly in Cftr(tm1UNC) and wild-type mice, principally by affecting Lactobacillus levels. Airway hyperresponsiveness of Cftr(tm1UNC) mice was ameliorated with streptomycin, and correlated with Lactobacillus abundance in the intestine. Additionally, streptomycin treated Cftr(tm1UNC) and wild-type mice displayed an increased percentage of pulmonary and mesenteric lymph node Th17, CD8 + IL-17+ and CD8 + IFNγ+ lymphocytes, while the CF-specific increase in respiratory IL-17 producing γδ T cells was decreased in streptomycin treated Cftr(tm1UNC) mice. Bone disease and intestinal phenotypes were not affected by streptomycin treatment. The airway hyperresponsiveness and lymphocyte profile of BALB/c Cftr(tm1UNC) mice were affected by streptomycin treatment, revealing a potential intestinal microbiome influence on lung response in BALB/c Cftr(tm1UNC) mice.

  16. High Fat Diet Alters Gut Microbiota and the Expression of Paneth Cell-Antimicrobial Peptides Preceding Changes of Circulating Inflammatory Cytokines

    PubMed Central

    Li, Jinchao; Tang, Renyong; Zhang, Guodong; Zeng, Huawei; Wood, Richard J.

    2017-01-01

    Obesity is an established risk factor for many diseases including intestinal cancer. One of the responsible mechanisms is the chronic inflammation driven by obesity. However, it remains to be defined whether diet-induced obesity exacerbates the intestinal inflammatory status by cytokines produced in adipose tissue or the high fat diet first alters the gut microbiota and then drives intestinal inflammation. To address this question, we fed C57BL/6 mice with a high fat diet (HF, 60%) and sacrificed them sequentially after 8, 12, and 16 weeks, and then compositions of gut microbiota and expressions of antimicrobial peptides were determined. The compositions of gut microbiota were altered at 8 wk HF feeding, followed with reduced Paneth antimicrobial peptides lysozyme and Reg IIIγ after 12 and 16 wk HF feeding (p < 0.05), whereas elevations of circulating inflammatory cytokines IFNγ and TNF-α were observed until feeding a HF diet for 16 weeks (p < 0.05). These results indicated that high fat diet may stimulate intestinal inflammation via altering gut microbiota, and it occurs prior to the potential influence by circulating inflammatory cytokines. These findings emphasized the importance of microbiota, in addition to adipose tissue per se, in driving intestinal inflammation, which may thereafter promote intestinal tumorigenesis. PMID:28316379

  17. High Fat Diet Alters Gut Microbiota and the Expression of Paneth Cell-Antimicrobial Peptides Preceding Changes of Circulating Inflammatory Cytokines.

    PubMed

    Guo, Xiulan; Li, Jinchao; Tang, Renyong; Zhang, Guodong; Zeng, Huawei; Wood, Richard J; Liu, Zhenhua

    2017-01-01

    Obesity is an established risk factor for many diseases including intestinal cancer. One of the responsible mechanisms is the chronic inflammation driven by obesity. However, it remains to be defined whether diet-induced obesity exacerbates the intestinal inflammatory status by cytokines produced in adipose tissue or the high fat diet first alters the gut microbiota and then drives intestinal inflammation. To address this question, we fed C57BL/6 mice with a high fat diet (HF, 60%) and sacrificed them sequentially after 8, 12, and 16 weeks, and then compositions of gut microbiota and expressions of antimicrobial peptides were determined. The compositions of gut microbiota were altered at 8 wk HF feeding, followed with reduced Paneth antimicrobial peptides lysozyme and Reg IIIγ after 12 and 16 wk HF feeding (p < 0.05), whereas elevations of circulating inflammatory cytokines IFNγ and TNF-α were observed until feeding a HF diet for 16 weeks (p < 0.05). These results indicated that high fat diet may stimulate intestinal inflammation via altering gut microbiota, and it occurs prior to the potential influence by circulating inflammatory cytokines. These findings emphasized the importance of microbiota, in addition to adipose tissue per se, in driving intestinal inflammation, which may thereafter promote intestinal tumorigenesis.

  18. The dose–response association of urinary metals with altered pulmonary function and risks of restrictive and obstructive lung diseases: a population-based study in China

    PubMed Central

    Feng, Wei; Huang, Xiji; Zhang, Ce; Liu, Chuanyao; Cui, Xiuqing; Zhou, Yun; Sun, Huizhen; Qiu, Gaokun; Guo, Huan; He, Meian; Zhang, Xiaomin; Yuan, Jing; Chen, Weihong; Wu, Tangchun

    2015-01-01

    Objective Reduced pulmonary function is an important predictor of environment-related pulmonary diseases; however, evidence of an association between exposures to various metals from all possible routes and altered pulmonary function is limited. We aimed to investigate the association of various metals in urine with pulmonary function, restrictive lung disease (RLD) and obstructive lung disease (OLD) risks in the general Chinese population. Design A cross-sectional investigation in the Wuhan cohort population. Setting A heavily polluted Chinese city. Participants A total of 2460 community-living Chinese adults from the Wuhan cohort were included in our analysis. Main outcome measures Spirometric parameters (FVC, forced vital capacity; FEV1, forced expiratory volumes in 1 s; FEV1/FVC ratio), RLD and OLD. Results The dose–response associations of pulmonary function, and RLD and OLD, with 23 urinary metals were assessed using regression analysis after adjusting for potential confounders. The false discovery rate (FDR) method was used to correct for multiple hypothesis tests. Our results indicated that there were positive dose–response associations of urinary iron with FEV1 and FEV1/FVC ratio, vanadium with FEV1, and copper and selenium with FEV1/FVC ratio, while a negative dose–response association was observed between urinary lead and FEV1/FVC ratio (all p<0.05). After additional adjusting for multiple comparisons, only iron was dose dependently related to FEV1/FVC ratio (FDR adjusted p<0.05). The dose–response association of iron and lead, with decreased and increased chronic obstructive pulmonary disease risk, respectively, was also observed (both p<0.05). Additionally, we found significant association of urinary zinc with RLD and interaction effects of smoking status with lead on FEV1/FVC, and with cadmium on FVC and FEV1. Conclusions These results suggest that multiple urinary metals are associated with altered pulmonary function, and RLD and OLD

  19. Altered stability of pulmonary surfactant in SP-C-deficient mice

    PubMed Central

    Glasser, Stephan W.; Burhans, Michael S.; Korfhagen, Thomas R.; Na, Cheng-Lun; Sly, Peter D.; Ross, Gary F.; Ikegami, Machiko; Whitsett, Jeffrey A.

    2001-01-01

    The surfactant protein C (SP-C) gene encodes an extremely hydrophobic, 4-kDa peptide produced by alveolar epithelial cells in the lung. To discern the role of SP-C in lung function, SP-C-deficient (−/−) mice were produced. The SP-C (−/−) mice were viable at birth and grew normally to adulthood without apparent pulmonary abnormalities. SP-C mRNA was not detected in the lungs of SP-C (−/−) mice, nor was mature SP-C protein detected by Western blot of alveolar lavage from SP-C (−/−) mice. The levels of the other surfactant proteins (A, B, D) in alveolar lavage were comparable to those in wild-type mice. Surfactant pool sizes, surfactant synthesis, and lung morphology were similar in SP-C (−/−) and SP-C (+/+) mice. Lamellar bodies were present in SP-C (−/−) type II cells, and tubular myelin was present in the alveolar lumen. Lung mechanics studies demonstrated abnormalities in lung hysteresivity (a term used to reflect the mechanical coupling between energy dissipative forces and tissue-elastic properties) at low, positive-end, expiratory pressures. The stability of captive bubbles with surfactant from the SP-C (−/−) mice was decreased significantly, indicating that SP-C plays a role in the stabilization of surfactant at low lung volumes, a condition that may accompany respiratory distress syndrome in infants and adults. PMID:11344267

  20. Cardiac and pulmonary alterations in symptomatic and asymptomatic dogs infected naturally with Leishmania (Leishmania) chagasi.

    PubMed

    Alves, G B B; Pinho, F A; Silva, S M M S; Cruz, M S P; Costa, F A L

    2010-03-01

    Fifteen symptomatic and seven asymptomatic dogs infected naturally with Leishmania chagasi were examined in order to identify the presence of parasites and changes in heart and lung. Histopathological, cytological, and immunohistochemical analyses were performed on samples of heart and lung tissues. An inflammatory reaction characterized by inflammatory mononuclear, perivascular and intermuscular infiltrates was observed in both symptomatic and asymptomatic animals on histopathological analysis of the heart. In the lung, there was thickening of the alveolar septa due to congestion, edema, inflammatory infiltrate, and fibroblast proliferation. A focal reaction was observed although a diffuse reaction was present in both groups. On cytological examination, heart and lung imprints revealed amastigotes in two symptomatic animals and heart imprints were found in 1 asymptomatic dog. Immunoperoxidase staining showed amastigotes in the lung and heart of only 1 of 6 symptomatic animals examined. Within the ethical principles and limits of this research, it can be inferred that the study of heart and lung alterations in canine visceral leishmaniasis is increasingly important for understanding the problem related to humans. Dogs with visceral leishmaniasis were a good experimental model, since infection was caused by the same agent and the animals developed clinical, pathological and immunological alterations similar to those observed in humans.

  1. A supplement containing trans-10, cis-12 conjugated linoleic acid reduces milk fat yield but does not alter organ weight or body fat deposition in lactating ewes.

    PubMed

    Sinclair, Liam A; Weerasinghe, Weerasinghe M P B; Wilkinson, Robert G; de Veth, Michael J; Bauman, Dale E

    2010-11-01

    Conjugated linoleic acids (CLA) have been demonstrated to be a potent inhibitor of milk fat synthesis in ruminants, but effects on carcass composition and organ weight are unknown. Our objectives in this experiment were to determine the dose response of ruminally protected CLA on the performance, organ weight, and fatty acid (FA) composition of early lactation dairy ewes. Twenty-four multiparous dairy ewes were fed a basal diet for 10 wk that was supplemented with a lipid-encapsulated CLA at 1 of 3 levels: no CLA (control, CON), low CLA (L-CLA), or high CLA (H-CLA) to supply 0, 1.5, or 3.8 g/d, respectively, of both trans-10, cis-12 and cis-9, trans-11 CLA. Dry matter intake was not affected (P > 0.05) by dietary treatment. Ewes fed H-CLA had a 13% higher milk yield compared with those receiving either CON or L-CLA. Compared with CON, milk fat yield (g/d) was 14 and 24% lower in ewes fed L-CLA or H-CLA, respectively. Supplementing ewes with CLA did not affect carcass or organ weights, carcass composition, or organ FA content. Compared with ewes receiving the CON diet, CLA supplementation had little effect on the FA composition of the Longissimus dorsi, although cis-9, trans-11 and trans-10, cis-12 CLA were increased in ewes receiving H-CLA. The current findings are consistent with the view that the energy spared by the CLA reduction in milk fat content was mainly partitioned to milk yield and there was no evidence of organ hypertrophy or liver steatosis.

  2. Isomalto-oligosaccharides, a prebiotic, functionally augment green tea effects against high fat diet-induced metabolic alterations via preventing gut dysbacteriosis in mice.

    PubMed

    Singh, Dhirendra Pratap; Singh, Jagdeep; Boparai, Ravneet Kaur; Zhu, JianHua; Mantri, Shrikant; Khare, Pragyanshu; Khardori, Romesh; Kondepudi, Kanthi Kiran; Chopra, Kanwaljit; Bishnoi, Mahendra

    2017-09-01

    High fat diet (HFD)-induced alterations in gut microbiota and resultant 'leaky gut' phenomenon promotes metabolic endotoxemia, ectopic fat deposition, and low-grade systemic inflammation. Here we evaluated the effects of a combination of green tea extract (GTE) with isomalto-oligosaccharide (IMOs) on HFD-induced alterations in mice. Male Swiss albino mice were fed with HFD (58% fat kcal) for 12 weeks. Systemic adiposity, gut derangement parameters and V3-V4 region based 16S rRNA metagenomic sequencing, ectopic fat deposition, liver metabolome analysis, systemic and tissue inflammation, and energy homeostasis markers along with gene expression analysis in multiple tissues were done in mice supplemented with GTE, IMOs or their combination. The combination of GTE and IMOs effectively prevented HFD-induced adiposity and lipid accumulation in liver and muscle while normalizing fasting blood glucose, insulin, glucagon, and leptin levels. Co-administration of GTE with IMOs effectively modulated liver metabolome associated with lipid metabolism. It also prevented leaky gut phenotype and HFD-induced increase in circulating lipopolysaccharides and pro-inflammatory cytokines (e.g. resistin, TNF-α, and IL-1β) and reduction in anti-inflammatory cytokines (e.g. adiponectin and IL-6). Gene expression analysis across multiple tissues further supported these functional outcomes. Most importantly, this combination improved beneficial gut microbiota (Lactobacillus sp., Bifidobacteria, Akkermansia muciniphila, Roseburia spp.) abundances, restored Firmicutes/Bacteriodetes and improved Prevotella/Bacteroides proportions. In particular, a combination of these two agents has shown improved beneficial effects on multiple parameters studied. Data presented herein suggests that strategically chosen food components might be highly effective in the prevention of HFD-induced alterations and may further be developed as functional foods. Copyright © 2017 Elsevier Ltd. All rights reserved.

  3. Inhibition of alveolarization and altered pulmonary mechanics in mice expressing GATA-6.

    PubMed

    Liu, Cong; Ikegami, Machiko; Stahlman, Mildred T; Dey, Chitta R; Whitsett, Jeffrey A

    2003-12-01

    GATA-6, a member of a family of zinc finger transcription factors, is expressed in epithelial cells of the developing lung. To further assess the role of GATA-6 in lung morphogenesis, GATA-6 was expressed in respiratory epithelial cells of the developing mouse lung under control of the surfactant protein C promoter (hSP-CGATA-6 mice). Although GATA-6 did not alter lung morphology at embryonic day 18.5, defects in alveolar septation were observed early in the neonatal period, and air space enlargement persisted to adulthood. Airway resistance, airway elastance, tissue damping, and tissue elastance were significantly decreased, and lung volumes were significantly increased at 12 wk of age. Normal postnatal morphogenesis of the lung depends upon precise temporal-spatial regulation of GATA-6.

  4. Exposure to a high-fat diet during development alters leptin and ghrelin sensitivity and elevates renal sympathetic nerve activity and arterial pressure in rabbits.

    PubMed

    Prior, Larissa J; Davern, Pamela J; Burke, Sandra L; Lim, Kyungjoon; Armitage, James A; Head, Geoffrey A

    2014-02-01

    Exposure to maternal obesity or a maternal diet rich in fat during development may have adverse outcomes in offspring, such as the development of obesity and hypertension. The present study examined the effect of a maternal high-fat diet (m-HFD) on offspring blood pressure and renal sympathetic nerve activity, responses to stress, and sensitivity to central administration of leptin and ghrelin. Offspring of New Zealand white rabbits fed a 13% HFD were slightly heavier than offspring from mothers fed a 4% maternal normal fat diet (P<0.05) but had 64% greater fat pad mass (P=0.015). Mean arterial pressure, heart rate, and renal sympathetic nerve activity at 4 months of age were 7%, 7%, and 24% greater, respectively (P<0.001), in m-HFD compared with maternal normal fat diet rabbits, and the renal sympathetic nerve activity response to airjet stress was enhanced in the m-HFD group. m-HFD offspring had markedly elevated pressor and renal sympathetic nerve activity responses to intracerebroventricular leptin (5-100 µg) and enhanced sympathetic responses to intracerebroventricular ghrelin (1-5 nmol). In contrast, there was resistance to the anorexic effects of intracerebroventricular leptin and less neuronal activation as detected by Fos immunohistochemistry in the arcuate (-57%; P<0.001) and paraventricular (-37%; P<0.05) nuclei of the hypothalamus in m-HFD offspring compared with maternal normal fat diet rabbits. We conclude that offspring from mothers consuming an HFD exhibit an adverse cardiovascular profile in adulthood because of altered central hypothalamic sensitivity to leptin and ghrelin.

  5. Alterations in Serum Polyunsaturated Fatty Acids and Eicosanoids in Patients with Mild to Moderate Chronic Obstructive Pulmonary Disease (COPD)

    PubMed Central

    Titz, Bjoern; Luettich, Karsta; Leroy, Patrice; Boue, Stephanie; Vuillaume, Gregory; Vihervaara, Terhi; Ekroos, Kim; Martin, Florian; Peitsch, Manuel C.; Hoeng, Julia

    2016-01-01

    Smoking is a major risk factor for several diseases including chronic obstructive pulmonary disease (COPD). To better understand the systemic effects of cigarette smoke exposure and mild to moderate COPD—and to support future biomarker development—we profiled the serum lipidomes of healthy smokers, smokers with mild to moderate COPD (GOLD stages 1 and 2), former smokers, and never-smokers (n = 40 per group) (ClinicalTrials.gov registration: NCT01780298). Serum lipidome profiling was conducted with untargeted and targeted mass spectrometry-based lipidomics. Guided by weighted lipid co-expression network analysis, we identified three main trends comparing smokers, especially those with COPD, with non-smokers: a general increase in glycero(phospho)lipids, including triglycerols; changes in fatty acid desaturation (decrease in ω-3 polyunsaturated fatty acids, and an increase in monounsaturated fatty acids); and an imbalance in eicosanoids (increase in 11,12- and 14,15-DHETs (dihydroxyeicosatrienoic acids), and a decrease in 9- and 13-HODEs (hydroxyoctadecadienoic acids)). The lipidome profiles supported classification of study subjects as smokers or non-smokers, but were not sufficient to distinguish between smokers with and without COPD. Overall, our study yielded further insights into the complex interplay between smoke exposure, lung disease, and systemic alterations in serum lipid profiles. PMID:27657052

  6. Adipose-specific ablation of Nrf2 transiently delayed high-fat diet-induced obesity by altering glucose, lipid and energy metabolism of male mice.

    PubMed

    Zhang, Le; Dasuri, Kalavathi; Fernandez-Kim, Sun-Ok; Bruce-Keller, Annadora J; Keller, Jeffrey N

    2016-01-01

    Nuclear factor E2-related factor 2 (NRF2) is a well-known master controller of the cellular adaptive antioxidant and detoxification response. Recent studies demonstrated altered glucose, lipid and energy metabolism in mice with a global Nrf2 knockout. In the present study, we aim to determine the effects of an adipose-specific ablation of Nrf2 (ASAN) on diet-induced obesity (DIO) in male mice. The 6-week-old adipose-specific Nrf2 knockout (NK) and its Nrf2 control (NC) mice were fed with either control diet (CD) or high-fat diet (HFD) for 14 weeks. NK mice exhibited transiently delayed body weight (BW) growth from week 5 to week 11 of HFD feeding, higher daily physical activity levels and preferential use of fat over carbohydrates as a source of energy at week 8 of the CD-feeding period. After 14 weeks of feeding, NK mice showed comparable results with NC mice with respect to the overall BW and body fat content, but exhibited reduced blood glucose, reduced number but increased size of adipocytes, accompanied with elevated expression of many genes and proteins in the visceral fat related to glucose, lipid and energy metabolism (e.g. Fgf21, Pgc1a). These results indicated that NRF2 is an important mediator for glucose, lipid and energy metabolism in adipose tissue, and ASAN could have beneficial effect for prevention of DIO during the early development of mice.

  7. Adipose-specific ablation of Nrf2 transiently delayed high-fat diet-induced obesity by altering glucose, lipid and energy metabolism of male mice

    PubMed Central

    Zhang, Le; Dasuri, Kalavathi; Fernandez-Kim, Sun-Ok; Bruce-Keller, Annadora J; Keller, Jeffrey N

    2016-01-01

    Nuclear factor E2-related factor 2 (NRF2) is a well-known master controller of the cellular adaptive antioxidant and detoxification response. Recent studies demonstrated altered glucose, lipid and energy metabolism in mice with a global Nrf2 knockout. In the present study, we aim to determine the effects of an adipose-specific ablation of Nrf2 (ASAN) on diet-induced obesity (DIO) in male mice. The 6-week-old adipose-specific Nrf2 knockout (NK) and its Nrf2 control (NC) mice were fed with either control diet (CD) or high-fat diet (HFD) for 14 weeks. NK mice exhibited transiently delayed body weight (BW) growth from week 5 to week 11 of HFD feeding, higher daily physical activity levels and preferential use of fat over carbohydrates as a source of energy at week 8 of the CD-feeding period. After 14 weeks of feeding, NK mice showed comparable results with NC mice with respect to the overall BW and body fat content, but exhibited reduced blood glucose, reduced number but increased size of adipocytes, accompanied with elevated expression of many genes and proteins in the visceral fat related to glucose, lipid and energy metabolism (e.g. Fgf21, Pgc1a). These results indicated that NRF2 is an important mediator for glucose, lipid and energy metabolism in adipose tissue, and ASAN could have beneficial effect for prevention of DIO during the early development of mice. PMID:28078004

  8. Beef Fat Enriched with Polyunsaturated Fatty Acid Biohydrogenation Products Improves Insulin Sensitivity Without Altering Dyslipidemia in Insulin Resistant JCR:LA-cp Rats.

    PubMed

    Diane, Abdoulaye; Borthwick, Faye; Mapiye, Cletos; Vahmani, Payam; David, Rolland C; Vine, Donna F; Dugan, Michael E R; Proctor, Spencer D

    2016-07-01

    The main dietary sources of trans fatty acids are partially hydrogenated vegetable oils (PHVO), and products derived from polyunsaturated fatty acid biohydrogenation (PUFA-BHP) in ruminants. Trans fatty acid intake has historically been associated with negative effects on health, generating an anti-trans fat campaign to reduce their consumption. The profiles and effects on health of PHVO and PUFA-BHP can, however, be quite different. Dairy products naturally enriched with vaccenic and rumenic acids have many purported health benefits, but the putative benefits of beef fat naturally enriched with PUFA-BHP have not been investigated. The objective of the present experiment was to determine the effects of beef peri-renal fat (PRF) with differing enrichments of PUFA-BHP on lipid and insulin metabolism in a rodent model of dyslipidemia and insulin resistance (JCR:LA-cp rat). The results showed that 6 weeks of diet supplementation with beef PRF naturally enriched due to flaxseed (FS-PRF) or sunflower-seed (SS-PRF) feeding to cattle significantly improved plasma fasting insulin levels and insulin sensitivity, postprandial insulin levels (only in the FS-PRF) without altering dyslipidemia. Moreover, FS-PRF but not SS-PRF attenuated adipose tissue accumulation. Therefore, enhancing levels of PUFA-BHP in beef PRF with FS feeding may be a useful approach to maximize the health-conferring value of beef-derived fats.

  9. Pulmonary biochemical and histological alterations after repeated low-level blast overpressure exposures.

    PubMed

    Elsayed, Nabil M; Gorbunov, Nikolai V

    2007-01-01

    Blast overpressure (BOP), also known as high energy impulse noise, is a damaging outcome of explosive detonations and firing of weapons. Exposure to BOP shock waves alone results in injury predominantly to the hollow organ systems such as auditory, respiratory, and gastrointestinal systems. In recent years, the hazards of BOP that once were confined to military and professional settings have become a global societal problem as terrorist bombings and armed conflicts involving both military and civilian populations increased significantly. We have previously investigated the effects of single BOP exposures at different peak pressures. In this study, we examined the effects of repeated exposure to a low-level BOP and whether the number of exposures or time after exposure would alter the injury outcome. We exposed deeply anesthetized rats to simulated BOP at 62 +/- 2 kPa peak pressure. The lungs were examined immediately after one exposure (1 + 0), or 1 h after one (1 + 1), two (2 + 1), or three (3 + 1) consecutive exposures at 3-min interval. In one group of animals, we examined the effects of repeated exposure on lung weight, methemoglobin, transferrin, antioxidants, and lipid peroxidation. In a second group, the lungs were fixed inflated at 25 cm water, sectioned, and examined histologically after one to three repeated exposures, or after one exposure at 1, 6, and 24 h. We found that single BOP exposure causes notable changes after 1 h, and that repeating BOP exposure did not add markedly to the effect of the first one. However, the effects increased significantly with time from 1 to 24 h. These observations have biological and occupational implications, and emphasize the need for protection from low-level BOP, and for prompt treatment within the first hour following BOP exposure.

  10. Inhibition of the αvβ6 integrin leads to limited alteration of TGF-α-induced pulmonary fibrosis

    PubMed Central

    Madala, Satish K.; Korfhagen, Thomas R.; Schmidt, Stephanie; Davidson, Cynthia; Edukulla, Ramakrishna; Ikegami, Machiko; Violette, Shelia M.; Weinreb, Paul H.; Sheppard, Dean

    2014-01-01

    A number of growth factors and signaling pathways regulate matrix deposition and fibroblast proliferation in the lung. The epidermal growth factor receptor (EGFR) family of receptors and the transforming growth factor-β (TGF-β) family are active in diverse biological processes and are central mediators in the initiation and maintenance of fibrosis in many diseases. Transforming growth factor-α (TGF-α) is a ligand for the EGFR, and doxycycline (Dox)-inducible transgenic mice conditionally expressing TGF-α specifically in the lung epithelium develop progressive fibrosis accompanied with cachexia, changes in lung mechanics, and marked pleural thickening. Although recent studies demonstrate that EGFR activation modulates the fibroproliferative effects involved in the pathogenesis of TGF-β induced pulmonary fibrosis, in converse, the direct role of EGFR induction of the TGF-β pathway in the lung is unknown. The αvβ6 integrin is an important in vivo activator of TGF-β activation in the lung. Immunohistochemical analysis of αvβ6 protein expression and bronchoalveolar analysis of TGF-β pathway signaling indicates activation of the αvβ6/TGF-β pathway only at later time points after lung fibrosis was already established in the TGF-α model. To determine the contribution of the αvβ6/TGF-β pathway on the progression of established fibrotic disease, TGF-α transgenic mice were administered Dox for 4 wk, which leads to extensive fibrosis; these mice were then treated with a function-blocking anti-αvβ6 antibody with continued administration of Dox for an additional 4 wk. Compared with TGF-α transgenic mice treated with control antibody, αvβ6 inhibition significantly attenuated pleural thickening and altered the decline in lung mechanics. To test the effects of genetic loss of the β6 integrin, TGF-α transgenic mice were mated with β6-null mice and the degree of fibrosis was compared in adult mice following 8 wk of Dox administration. Genetic ablation of

  11. Alterations of Ultrastructural and Fission/Fusion Markers in Hepatocyte Mitochondria From Mice Following Calorie Restriction With Different Dietary Fats

    PubMed Central

    2013-01-01

    We analyzed ultrastructural changes and markers of fission/fusion in hepatocyte mitochondria from mice submitted to 40% calorie restriction (CR) for 6 months versus ad-libitum-fed controls. To study the effects of dietary fat under CR, animals were separated into three CR groups with soybean oil (also in controls), fish oil, and lard. CR induced differential changes in hepatocyte and mitochondrial size, in the volume fraction occupied by mitochondria, and in the number of mitochondria per hepatocyte. The number of cristae per mitochondrion was significantly higher in all CR groups compared with controls. Proteins related to mitochondrial fission (Fis1 and Drp1) increased with CR, but no changes were detected in proteins involved in mitochondrial fusion (Mfn1, Mfn2, and OPA1). Although many of these changes could be attributed to CR regardless of dietary fat, changing membrane lipid composition by different fat sources did modulate the effects of CR on hepatocyte mitochondria. PMID:23403066

  12. Neonatal Exposure to Parathion Alters Lipid Metabolism in Adulthood: Interactions with Dietary Fat Intake and Implications for Neurodevelopmental Deficits

    PubMed Central

    Lassiter, T. Leon; Ryde, Ian T.; Levin, Edward D.; Seidler, Frederic J.; Slotkin, Theodore A.

    2009-01-01

    Organophosphates are developmental neurotoxicants but recent evidence also points to metabolic dysfunction. We determined whether neonatal parathion exposure in rats has long-term effects on regulation of adipokines and lipid peroxidation. We also assessed the interaction of these effects with increased fat intake. Rats were given parathion on postnatal days 1–4 using doses (0.1 or 0.2 mg/kg/day) that straddle the threshold for barely detectable cholinesterase inhibition and the first signs of systemic toxicity. In adulthood, animals were either maintained on standard chow or switched to a high-fat diet for seven weeks. We assessed serum leptin and adiponectin, tumor necrosis factor-α (TNFα) in adipose tissues, and thiobarbituric acid reactive species (TBARS) in peripheral tissues and brain regions. Neonatal parathion exposure uncoupled serum leptin levels from their dependence on body weight, suppressed adiponectin and elevated TNFα in white adipose tissue. Some of the effects were offset by a high-fat diet. Parathion reduced TBARS in the adipose tissues, skeletal muscle and temporal/occipital cortex but not in heart, liver, kidney or frontal/parietal cortex; it elevated TBARS in the cerebellum; the high-fat diet again reversed many of the effects. Neonatal parathion exposure disrupts the regulation of adipokines that communicate metabolic status between adipose tissues and the brain, while also evoking an inflammatory adipose response. Our results are consistent with impaired fat utilization and prediabetes, as well as exposing a potential relationship between effects on fat metabolism and on synaptic function in the brain. PMID:19615431

  13. Partial Inhibition of Adipose Tissue Lipolysis Improves Glucose Metabolism and Insulin Sensitivity Without Alteration of Fat Mass

    PubMed Central

    Girousse, Amandine; Tavernier, Geneviève; Valle, Carine; Moro, Cedric; Mejhert, Niklas; Dinel, Anne-Laure; Houssier, Marianne; Roussel, Balbine; Besse-Patin, Aurèle; Combes, Marion; Mir, Lucile; Monbrun, Laurent; Bézaire, Véronic; Prunet-Marcassus, Bénédicte; Waget, Aurélie; Vila, Isabelle; Caspar-Bauguil, Sylvie; Louche, Katie; Marques, Marie-Adeline; Mairal, Aline; Renoud, Marie-Laure; Galitzky, Jean; Holm, Cecilia; Mouisel, Etienne; Thalamas, Claire; Viguerie, Nathalie; Sulpice, Thierry; Burcelin, Rémy; Arner, Peter; Langin, Dominique

    2013-01-01

    When energy is needed, white adipose tissue (WAT) provides fatty acids (FAs) for use in peripheral tissues via stimulation of fat cell lipolysis. FAs have been postulated to play a critical role in the development of obesity-induced insulin resistance, a major risk factor for diabetes and cardiovascular disease. However, whether and how chronic inhibition of fat mobilization from WAT modulates insulin sensitivity remains elusive. Hormone-sensitive lipase (HSL) participates in the breakdown of WAT triacylglycerol into FAs. HSL haploinsufficiency and treatment with a HSL inhibitor resulted in improvement of insulin tolerance without impact on body weight, fat mass, and WAT inflammation in high-fat-diet–fed mice. In vivo palmitate turnover analysis revealed that blunted lipolytic capacity is associated with diminution in FA uptake and storage in peripheral tissues of obese HSL haploinsufficient mice. The reduction in FA turnover was accompanied by an improvement of glucose metabolism with a shift in respiratory quotient, increase of glucose uptake in WAT and skeletal muscle, and enhancement of de novo lipogenesis and insulin signalling in liver. In human adipocytes, HSL gene silencing led to improved insulin-stimulated glucose uptake, resulting in increased de novo lipogenesis and activation of cognate gene expression. In clinical studies, WAT lipolytic rate was positively and negatively correlated with indexes of insulin resistance and WAT de novo lipogenesis gene expression, respectively. In obese individuals, chronic inhibition of lipolysis resulted in induction of WAT de novo lipogenesis gene expression. Thus, reduction in WAT lipolysis reshapes FA fluxes without increase of fat mass and improves glucose metabolism through cell-autonomous induction of fat cell de novo lipogenesis, which contributes to improved insulin sensitivity. PMID:23431266

  14. Partial inhibition of adipose tissue lipolysis improves glucose metabolism and insulin sensitivity without alteration of fat mass.

    PubMed

    Girousse, Amandine; Tavernier, Geneviève; Valle, Carine; Moro, Cedric; Mejhert, Niklas; Dinel, Anne-Laure; Houssier, Marianne; Roussel, Balbine; Besse-Patin, Aurèle; Combes, Marion; Mir, Lucile; Monbrun, Laurent; Bézaire, Véronic; Prunet-Marcassus, Bénédicte; Waget, Aurélie; Vila, Isabelle; Caspar-Bauguil, Sylvie; Louche, Katie; Marques, Marie-Adeline; Mairal, Aline; Renoud, Marie-Laure; Galitzky, Jean; Holm, Cecilia; Mouisel, Etienne; Thalamas, Claire; Viguerie, Nathalie; Sulpice, Thierry; Burcelin, Rémy; Arner, Peter; Langin, Dominique

    2013-01-01

    When energy is needed, white adipose tissue (WAT) provides fatty acids (FAs) for use in peripheral tissues via stimulation of fat cell lipolysis. FAs have been postulated to play a critical role in the development of obesity-induced insulin resistance, a major risk factor for diabetes and cardiovascular disease. However, whether and how chronic inhibition of fat mobilization from WAT modulates insulin sensitivity remains elusive. Hormone-sensitive lipase (HSL) participates in the breakdown of WAT triacylglycerol into FAs. HSL haploinsufficiency and treatment with a HSL inhibitor resulted in improvement of insulin tolerance without impact on body weight, fat mass, and WAT inflammation in high-fat-diet-fed mice. In vivo palmitate turnover analysis revealed that blunted lipolytic capacity is associated with diminution in FA uptake and storage in peripheral tissues of obese HSL haploinsufficient mice. The reduction in FA turnover was accompanied by an improvement of glucose metabolism with a shift in respiratory quotient, increase of glucose uptake in WAT and skeletal muscle, and enhancement of de novo lipogenesis and insulin signalling in liver. In human adipocytes, HSL gene silencing led to improved insulin-stimulated glucose uptake, resulting in increased de novo lipogenesis and activation of cognate gene expression. In clinical studies, WAT lipolytic rate was positively and negatively correlated with indexes of insulin resistance and WAT de novo lipogenesis gene expression, respectively. In obese individuals, chronic inhibition of lipolysis resulted in induction of WAT de novo lipogenesis gene expression. Thus, reduction in WAT lipolysis reshapes FA fluxes without increase of fat mass and improves glucose metabolism through cell-autonomous induction of fat cell de novo lipogenesis, which contributes to improved insulin sensitivity.

  15. Regular tart cherry intake alters abdominal adiposity, adipose gene transcription, and inflammation in obesity-prone rats fed a high fat diet.

    PubMed

    Seymour, E M; Lewis, Sarah K; Urcuyo-Llanes, Daniel E; Tanone, Ignasia I; Kirakosyan, Ara; Kaufman, Peter B; Bolling, Steven F

    2009-10-01

    Obesity, systemic inflammation, and hyperlipidemia are among the components of metabolic syndrome, a spectrum of phenotypes that can precede the development of type 2 diabetes and cardiovascular disease. Animal studies show that intake of anthocyanin-rich extracts can affect these phenotypes. Anthocyanins can alter the activity of tissue peroxisome proliferator-activated receptors (PPARs), which affect energy substrate metabolism and inflammation. However, it is unknown if physiologically relevant, anthocyanin-containing whole foods confer similar effects to concentrated, anthocyanin extracts. The effect of anthocyanin-rich tart cherries was tested in the Zucker fatty rat model of obesity and metabolic syndrome. For 90 days, rats were pair-fed a higher fat diet supplemented with either 1% (wt/wt) freeze-dried, whole tart cherry powder or with a calorie- and macronutrient-matched control diet. Tart cherry intake was associated with reduced hyperlipidemia, percentage fat mass, abdominal fat (retroperitoneal) weight, retroperitoneal interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-alpha) expression, and plasma IL-6 and TNF-alpha. Tart cherry diet also increased retroperitoneal fat PPAR-alpha and PPAR-gamma mRNA (P = .12), decreased IL-6 and TNF-alpha mRNA, and decreased nuclear factor kappaB activity. In conclusion, in at-risk obese rats fed a high fat diet, physiologically relevant tart cherry consumption reduced several phenotypes of metabolic syndrome and reduced both systemic and local inflammation. Tart cherries may reduce the degree or trajectory of metabolic syndrome, thereby reducing risk for the development of type 2 diabetes and heart disease.

  16. Intake of specific fatty acids and fat alters growth, health, and titers following vaccination in dairy calves.

    PubMed

    Esselburn, K M; O'Diam, K M; Hill, T M; Bateman, H G; Aldrich, J M; Schlotterbeck, R L; Daniels, K M

    2013-09-01

    Typical fatty acid profiles of milk and milk replacer (MR) differ. Calf MR in the United States are made from animal fat, which are low in short- and medium-chain fatty acids and linolenic acid. Two 56-d trials compared a control MR containing 27% crude protein and formulated with 3 fat and fatty acid compositions. The 3 MR treatments were (1) only animal fat totaling 17% fat (CON), (2) animal fat supplemented with butyrate, medium-chain fatty acids, and linolenic acid using a commercial product (1.25% NeoTec4 MR; Provimi North America, Brookville, OH) totaling 17% fat (fatty acid-supplemented; FA-S), and (3) milk fat totaling 33% fat (MF). The MR were fed at 660 g of dry matter from d 0 to 42 and weaned. Starter (20% crude protein) and water were fed ad libitum for 56 d. Trial 1 utilized Holstein calves (24 female, 24 male) during summer months and trial 2 utilized Holstein calves (48 male) during fall months. Calves (41±1 kg of initial body weight; 2 to 3d of age) were sourced from a single farm and housed in a naturally ventilated nursery without added heat. Calves were in individual pens with straw bedding. Calf was the experimental unit. Data for each trial were analyzed as a completely randomized design with a 3 (MR treatment) × 2 (sex) factorial arrangement of treatments in trial 1 with repeated measures and as a completely randomized design with 3 MR treatments in trial 2 with repeated measures. Preplanned contrast statements of treatments CON versus FA-S and CON versus MF were used to separate means. We found no interactions of MR treatment by sex. Calf average daily gain, hip width change, and feed efficiency differed (CONFA-S). Titers to bovine respiratory parainfluenza-3 and bovine virus diarrhea type 1 (vaccinations to these pathogens were on d 7 and 28) in serum samples taken on d 49 and 56 differed (CON

  17. Nutritional status is related to fat-free mass, exercise capacity and inspiratory strength in severe chronic obstructive pulmonary disease patients.

    PubMed

    Sabino, Pollyane Galinari; Silva, Bruno Moreira; Brunetto, Antonio Fernando

    2010-06-01

    Being overweight or obese is associated with a higher rate of survival in patients with advanced chronic obstructive pulmonary disease (COPD). This paradoxical relationship indicates that the influence of nutritional status on functional parameters should be further investigated. To investigate the impact of nutritional status on body composition, exercise capacity and respiratory muscle strength in severe chronic obstructive pulmonary disease patients. Thirty-two patients (nine women) were divided into three groups according to their body mass indices (BMI): overweight/obese (25 < or = BMI < or = 34.9 kg/m(2), n=8), normal weight (18.5 < or = BMI < or = 24.9 kg/m(2), n=17) and underweight (BMI <18.5 kg/m(2), n=7). Spirometry, bioelectrical impedance, a six-minute walking distance test and maximal inspiratory and expiratory pressures were assessed. Airway obstruction was similar among the groups (p=0.30); however, overweight/obese patients had a higher fat-free mass (FFM) index [FFMI=FFM/body weight(2) (mean+/-SEM: 17+/-0.3 vs. 15+/-0.3 vs. 14+/-0.5 m/kg(2), p<0.01)], exercise capacity (90+/-8 vs. 79+/-6 vs. 57+/-8 m, p=0.02) and maximal inspiratory pressure (63+/-7 vs. 57+/-5 vs. 35+/-8 % predicted, p=0.03) in comparison to normal weight and underweight patients, respectively. In addition, on backward multiple regression analysis, FFMI was the unique independent predictor of exercise capacity (partial r=0.52, p<0.01). Severe chronic obstructive pulmonary disease (COPD) patients who were overweight or obese had a greater FFM, exercise capacity and inspiratory muscle strength than patients with the same degree of airflow obstruction who were of normal weight or underweight, and higher FFM was independently associated with higher exercise capacity. These characteristics of overweight or obese patients might counteract the drawbacks of excess weight and lead to an improved prognosis in COPD.

  18. Eicosapentaenoic acid reduces high-fat diet-induced insulin resistance by altering adipose tissue glycolytic and inflammatory function

    USDA-ARS?s Scientific Manuscript database

    We previously reported Eicosapentaenoic Acid (EPA)'s ability to prevent high-fat (HF) diet-induced obesity, insulin resistance, and inflammation. In this study, we dissected mechanisms mediating anti-inflammatory and anti-lipogenic actions of EPA, using histology/ immunohistochemistry, transcriptomi...

  19. Can alternating lower body negative and positive pressure during exercise alter regional body fat distribution or skin appearance?

    PubMed

    Löberbauer-Purer, Elisabeth; Meyer, Nanna L; Ring-Dimitriou, Susanne; Haudum, Judith; Kässmann, Helmut; Müller, Erich

    2012-05-01

    The purpose of this study was to determine whether physical activity, with and without lower body pressure, leads to increased regional fat loss in the lower extremities of overweight females. Eighty-six obese women with a female phenotype were randomly assigned into four groups: control group (C), diet only (D), diet plus exercise (DE) or diet, exercise and lower body pressure intervention (DEP). The three treatment groups followed the same diet, the two exercise groups (DE and DEP) additionally followed an endurance training program of 30 min of cycling at 50%VO(2)max three times per week with or without lower body pressure. Body composition and fat distribution were assessed by DXA. Body size circumference measurements were recorded as well as subjective ratings of cellulite and skin appearance. As expected, all test groups (D, DE, DEP) showed a significant decrease (p < 0.05) in total body mass and fat mass. DXA revealed significant differences between the experimental groups and C. The DEP group also lost significantly more body mass and fat mass when compared with D, while no significant difference was observed between the other groups. A similar pattern was seen for circumference measurement data. A significant perceived improvement was made by the DEP group when compared with C, D and DE groups for skin condition and also between the DEP versus C and D groups for cellulite. The combination of diet and exercise is successful for weight reduction. The additional application of lower body pressure especially affects skin appearance.

  20. Enzyme-treated wheat bran alters gut microbiota and liver metabolome in mice fed a high fat diet

    USDA-ARS?s Scientific Manuscript database

    Enzyme-treated wheat bran (ETWB) is a fermentable dietary fiber that has been shown to decrease body fat and modify the gut microbiome. However, it is not clear how these microbiome changes impact peripheral tissue metabolism. We hypothesized that supplementation with ETWB would change gut-derived...

  1. A Diet High in Saturated Fat and Sucrose Alters Glucoregulation and Induces Aortic Fatty Streaks in New Zealand White Rabbits

    PubMed Central

    Yuan, Zhonghua; Wang, Zongbao; Yang, Baotang; Yang, Yongzong

    2002-01-01

    A new and convenient animal model for studying peripheral vascular and coronary artery disease in diabetes was established in this study. Male New Zealand White rabbits weighing approximately 2 kg were divided into 2 groups: a normal control group fed standard laboratory chow and a diabetogenic diet–fed group received a high-fat/high-sucrose diet. The high-fat/high-sucrose diet (contained 10% lard and 37% sucrose) feeding was maintained for 6 months. Plasma total cholesterol, high-density lipoprotein (HDL) cholesterol, triglyceride, superoxide dismutase, nitric oxide, nitric oxide synthase, insulin, and glucose were quantitated at monthly or bimonthly intervals. The aortic fatty streak lesions were quantified following lipid staining with Sudan IV. The aortic samples were observed by electron microscopy. High plasma triglyceride and glucose concentrations were induced. At the end of 6 months, the aortic fatty streak lesions were present in the animals' vascular specimens. As far as we know, this is the first report that demonstrates that New Zealand White rabbits can develop obvious aortic fatty streaks by feeding a high-fat/high-sucrose diet. Our results suggest that NewZealand White rabbits fed a high-fat/high-sucrose diet would provide a convenient model for studying peripheral vascular and coronary artery disease in diabetes. PMID:12458659

  2. Genetic inhibition of hepatic acetyl-CoA carboxylase activity increases liver fat and alters global protein acetylationa

    PubMed Central

    Chow, Jenny D.Y.; Lawrence, Robert T.; Healy, Marin E.; Dominy, John E.; Liao, Jason A.; Breen, David S.; Byrne, Frances L.; Kenwood, Brandon M.; Lackner, Carolin; Okutsu, Saeko; Mas, Valeria R.; Caldwell, Stephen H.; Tomsig, Jose L.; Cooney, Gregory J.; Puigserver, Pere B.; Turner, Nigel; James, David E.; Villén, Judit; Hoehn, Kyle L.

    2014-01-01

    Lipid deposition in the liver is associated with metabolic disorders including fatty liver disease, type II diabetes, and hepatocellular cancer. The enzymes acetyl-CoA carboxylase 1 (ACC1) and ACC2 are powerful regulators of hepatic fat storage; therefore, their inhibition is expected to prevent the development of fatty liver. In this study we generated liver-specific ACC1 and ACC2 double knockout (LDKO) mice to determine how the loss of ACC activity affects liver fat metabolism and whole-body physiology. Characterization of LDKO mice revealed unexpected phenotypes of increased hepatic triglyceride and decreased fat oxidation. We also observed that chronic ACC inhibition led to hyper-acetylation of proteins in the extra-mitochondrial space. In sum, these data reveal the existence of a compensatory pathway that protects hepatic fat stores when ACC enzymes are inhibited. Furthermore, we identified an important role for ACC enzymes in the regulation of protein acetylation in the extra-mitochondrial space. PMID:24944901

  3. Apc deficiency alters pulmonary epithelial cell fate and inhibits Nkx2.1 via triggering TGF-beta signaling.

    PubMed

    Li, Changgong; Li, Aimin; Xing, Yiming; Li, Min; Chan, Belinda; Ouyang, Ruoyun; Taketo, Makoto Mark; Kucherlapati, Raju; Borok, Zea; Minoo, Parviz

    2013-06-01

    Wnt signaling is critical for cell fate specification and cell differentiation in many organs, but its function in pulmonary neuroendocrine cell (PNEC) differentiation has not been fully addressed. In this study, we examined the role of canonical Wnt signaling by targeting the gene for Adenomatous Polyposis Coli (Apc), which controls Wnt signaling activity via mediating phosphorylation of beta-catenin (Ctnnb). Targeting the Apc gene in lung epithelial progenitors by Nkx2.1-cre stabilized Ctnnb and activated canonical Wnt signaling. Apc deficiency altered lung epithelial cell fate by inhibiting Clara and ciliated cell differentiation and activating Uchl1, a marker of neuroendocrine cells. Similar to PNEC in normal lung, Uchl1(positive) cells were innervated. In mice with targeted inactivation of Ctnnb by Nkx2.1-cre, PNEC differentiation was not interrupted. These indicate that, after lung primordium formation, Wnt signaling is not essential for PNEC differentiation; however, its over-activation promotes PNEC features. Interestingly, Nkx2.1 was extinguished in Apc deficient epithelial progenitors before activation of Uchl1. Examination of Nkx2.1 null lungs suggested that early deletion of Nkx2.1 inhibits PNEC differentiation, while late repression does not. Nkx2.1 was specifically inhibited in Apc deficient lungs but not in Ctnnb gain-of-function lungs indicating a functional difference between Apc deletion and Ctnnb stabilization, both of which activate Wnt signaling. Further analysis revealed that Apc deficiency led to increased TGF-beta signaling, which inhibited Nkx2.1 in cultured lung endodermal explants. In contrast, TGF-beta activity was not increased in Ctnnb gain-of-function lungs. Therefore, our studies revealed an important mechanism involving Apc and TGF-beta signaling in regulating the key transcriptional factor, Nkx2.1, for lung epithelial progenitor cell fate determination.

  4. Idiopathic pulmonary fibrosis fibroblasts become resistant to Fas ligand-dependent apoptosis via the alteration of decoy receptor 3.

    PubMed

    Im, Jintaek; Kim, Kyutae; Hergert, Polla; Nho, Richard Seonghun

    2016-09-01

    Idiopathic pulmonary fibrosis (IPF) is an irreversible lethal lung disease with an unknown etiology. IPF patients' lung fibroblasts express inappropriately high Akt activity, protecting them in response to an apoptosis-inducing type I collagen matrix. FasL, a ligand for Fas, is known to be increased in the lung tissues of patients with IPF, implicated with the progression of IPF. Expression of Decoy Receptor3 (DcR3), which binds to FasL, thereby subsequently suppressing the FasL-Fas-dependent apoptotic pathway, is frequently altered in various human disease. However, the role of DcR3 in IPF fibroblasts in regulating their viability has not been examined. We found that enhanced DcR3 expression exists in the majority of IPF fibroblasts on collagen matrices, resulting in the protection of IPF fibroblasts from FasL-induced apoptosis. Abnormally high Akt activity suppresses GSK-3β function, thereby accumulating the nuclear factor of activated T-cells cytoplasmic 1 (NFATc1) in the nucleus, increasing DcR3 expression in IPF fibroblasts. This alteration protects IPF cells from FasL-induced apoptosis on collagen. However, the inhibition of Akt or NFATc1 decreases DcR3 mRNA and protein levels, which sensitizes IPF fibroblasts to FasL-mediated apoptosis. Furthermore, enhanced DcR3 and NFATc1 expression is mainly present in myofibroblasts in the fibroblastic foci of lung tissues derived from IPF patients. Our results showed that when IPF cells interact with collagen matrix, aberrantly activated Akt increases DcR3 expression via GSK-3β-NFATc1 and protects IPF cells from the FasL-dependent apoptotic pathway. These findings suggest that the inhibition of DcR3 function may be an effective approach for sensitizing IPF fibroblasts in response to FasL, limiting the progression of lung fibrosis. Copyright © 2016 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

  5. The effects of short-term fish oil supplementation on pulmonary function and airway inflammation following a high-fat meal.

    PubMed

    Ade, Carl J; Rosenkranz, S K; Harms, C A

    2014-04-01

    Many environmental and dietary influences can cause immune cells to produce biological mediators that increase airway inflammation. A high-fat meal (HFM) is one stimulus that increases airway inflammation in healthy individuals. Supplementation with omega-3 fatty acids can reduce inflammation systemically and may be beneficial to the airways. To determine if omega-3 fatty acid supplementation via fish oil would mitigate the airway inflammatory response induced by a single HFM. Seventeen non-asthmatic men (22 ± 2 years.) were supplemented with 3,000 mg × day(-1) fish oil or a placebo for 3 weeks. Fractional exhaled nitric oxide (FENO; a marker of airway inflammation), impulse oscillometry (a measure of respiratory impedance), pulmonary function, and triglycerides were measured prior to and 2 h following a HFM. Following a HFM, triglycerides increased in both fish oil and placebo groups compared to pre-HFM (~59 and ~49 %, respectively, p < 0.05). The percent increase in FENO was greater in the placebo group compared to the fish oil group (25.7 ± 16.7 vs. -1.99 ± 10.5 %, respectively, p < 0.05). A significant correlation was observed between blood triglycerides and FENO in the placebo group (r = 0.61; p < 0.05), but not the fish oil group (p = 0.21). A single HFM increases airway inflammation and omega-3 fatty acid supplementation via fish oil protects against HFM associated changes in airway health.

  6. Pulmonary hypertension

    MedlinePlus

    Pulmonary arterial hypertension; Sporadic primary pulmonary hypertension; Familial primary pulmonary hypertension; Idiopathic pulmonary arterial hypertension; Primary pulmonary hypertension; PPH; Secondary pulmonary ...

  7. Alteration of Leukocyte Count Correlates With Increased Pulmonary Vascular Permeability and Decreased PaO2:FiO2 Ratio Early After Major Burns.

    PubMed

    Johansson, Joakim; Steinvall, Ingrid; Herwald, Heiko; Lindbom, Lennart; Sjöberg, Folke

    2015-01-01

    Leukocytes are activated systemically and their numbers increase soon after a burn followed by a rapid decline to low normal or subnormal levels, possibly by increased extravasation. Experimental data support that an important target for such extravasation is the lungs and that leukocytes when they adhere to endothelial cells cause an increase in vascular permeability. The authors investigated a possible relation between early increased pulmonary vascular permeability or a decreased PaO2:FiO2 ratio and the dynamic change in concentration of blood leukocytes after a burn. This is a prospective, exploratory, single-center study. The authors measured the dynamic changes of leukocytes in blood starting early after the burn, pulmonary vascular permeability index by thermodilution, and PaO2:FiO2-ratios in 20 patients during the first 21 days after a major burn (>20% TBSA%). Median TBSA was 40% interquartile range (IQR, 25-52) and full thickness burn 28% (IQR, 2-39). There was a correlation between the early (<24 hours) alteration in white blood cell count and both early increased pulmonary vascular permeability (r = .63, P = .004) and the decreased oxygenation index defined as PaO2:FiO2 < 27 kPa (P = .004). The authors have documented a correlation between dynamic change of blood leukocytes and pulmonary failure early after burns.

  8. Weight cycling promotes fat gain and altered clock gene expression in adipose tissue in C57BL/6J mice.

    PubMed

    Dankel, S N; Degerud, E M; Borkowski, K; Fjære, E; Midtbø, L K; Haugen, C; Solsvik, M H; Lavigne, A M; Liaset, B; Sagen, J V; Kristiansen, K; Mellgren, G; Madsen, L

    2014-01-15

    Repeated attempts to lose weight by temporary dieting may result in weight cycling, eventually further gain of body fat, and possible metabolic adaptation. We tested this with a controlled experiment in C57BL/6J mice subjected to four weight cycles (WC), continuous hypercaloric feeding (HF), or low-fat feeding (LF). To search for genes involved in an adaptive mechanism to former weight cycling and avoid acute effects of the last cycle, the last hypercaloric feeding period was prolonged by an additional 2 wk before euthanization. Total energy intake was identical in WC and HF. However, compared with HF, the WC mice gained significantly more total body mass and fat mass and showed increased levels of circulating leptin and lipids in liver. Both the HF and WC groups showed increased adipocyte size and insulin resistance. Despite these effects, we also observed an interesting maintenance of circulating adiponectin and free fatty acid levels after WC, whereas changes in these parameters were observed in HF mice. Global gene expression was analyzed by microarrays. Weight-cycled mice were characterized by a downregulation of several clock genes (Dbp, Tef, Per1, Per2, Per3, and Nr1d2) in adipose tissues, which was confirmed by quantitative PCR. In 3T3-L1 cells, we found reduced expression of Dbp and Tef early in adipogenic differentiation, which was mediated via cAMP-dependent signaling. Our data suggest that clock genes in adipose tissue may play a role in metabolic adaptation to weight cycling.

  9. Effect of mahanimbine, an alkaloid from curry leaves, on high-fat diet-induced adiposity, insulin resistance, and inflammatory alterations.

    PubMed

    Jagtap, Sneha; Khare, Pragyanshu; Mangal, Priyanka; Kondepudi, Kanthi Kiran; Bishnoi, Mahendra; Bhutani, Kamlesh Kumar

    2017-03-01

    Spices and condiments, small but an integral part of the daily diet, are known to affect physiological functions. This study evaluated the effects of mahanimbine, a major carbazole alkaloid from Murraya koenigii (curry leaves), against progression of high-fat diet (HFD)-induced metabolic complications in mice (male and female). Mahanimbine at 2 mg/kg (HFD + LD) and 4 mg/kg (HFD + HD) of body weight was administered daily along with HFD feeding for 12 weeks. At the end of the study, male HFD + LD and HFD + HD groups showed 51.70 ± 3.59% and 47.37 ± 3.73% weight gain, respectively, as compared with 71.02 ± 6.04% in HFD fed mice whereas female HFD + LD and HFD + HD groups showed 24.31 ± 1.68% and 25.10 ± 2.61% weight gain as compared with HFD group with 36.69 ± 3.60% of weight gain. Mahanimbine prevented HFD-induced hyperlipidemia and fat accumulation in adipose tissue and liver along with the restricted progression of systemic inflammation and oxidative stress. Moreover, mahanimbine treatment improved glucose clearance and upregulated the expression of insulin responsive genes in liver and adipose tissue. Male and female mice showed different traits in development of HFD-induced metabolic disturbances; however, mahanimbine treatment exerted similar effects in both the sexes. In addition, mahanimbine lowered the absorption of dietary fat resulting in dietary fat excretion. In conclusion, daily consumption of mahanimbine and thereby curry leaves may alleviate development of HFD-induced metabolic alterations. © 2016 BioFactors, 43(2):220-231, 2017. © 2016 International Union of Biochemistry and Molecular Biology.

  10. Impact of Dietary Fat Type Within the Context of Altered Cholesterol Homeostasis on Cholesterol and Lipoprotein Metabolism in the F1B Hamster

    PubMed Central

    Lecker, Jaime L.; Matthan, Nirupa R.; Billheimer, Jeffrey T.; Rader, Daniel J.; Lichtenstein, Alice H.

    2010-01-01

    Cholesterol status and dietary fat alter several metabolic pathways reflected in lipoprotein profiles. To assess plasma lipoprotein response and mechanisms by which cholesterol and dietary fat type regulate expression of genes involved in lipoprotein metabolism we developed an experimental model system using F1B hamsters fed diets (12 weeks) enriched in 10% (w/w) coconut, olive or safflower oil with either high cholesterol (0.1%; cholesterol-supplemented) or low cholesterol coupled with cholesterol lowering drugs 10-days prior to killing (0.01% cholesterol, 0.15% lovastatin, 2% cholestyramine; cholesterol-depleted). Irrespective of dietary fat, cholesterol-depletion, relative to supplementation, resulted in lower plasma non-high density lipoprotein (HDL) and HDL cholesterol, and triglyceride concentrations (all P<0.05). In the liver, these differences were associated with higher sterol regulatory element binding protein (SREBP)-2, low density lipoprotein (LDL) receptor, 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase and 7-α hydroxylase mRNA levels; higher scavenger receptor B1 and apolipoprotein (apo) A-I mRNA and protein levels; and lower apo E protein levels and in intestine modestly lower sterol transporters ATP binding cassette (ABC) A1, ABCG5 and ABCG8 mRNA levels. Irrespective of cholesterol status, coconut oil, relative to olive and safflower oils, resulted in higher non-HDL cholesterol and triglyceride concentrations (both P<0.05) and modestly higher SREBP-2 mRNA levels. These data suggest that in F1B hamsters, differences in plasma lipoprotein profiles in response to cholesterol depletion are associated with changes in the expression of genes involved in cholesterol metabolism, whereas the effect of dietary fat type on gene expression was modest which limits the usefulness of the experimental animal model. PMID:20197195

  11. Altered expression of nuclear and cytoplasmic histone H1 in pulmonary artery and pulmonary artery smooth muscle cells in patients with IPAH

    PubMed Central

    Talati, Megha; Seeley, Erin; Ihida-Stansbury, Kaori; Delisser, Horace; McDonald, Hayes; Ye, Fei; Zhang, Xueqiong; Shyr, Yu; Caprioli, Richard; Meyrick, Barbara

    2012-01-01

    The pathogenesis of idiopathic pulmonary hypertension is poorly understood. This paper utilized histology-based Matrix-Assisted Laser Desorption Ionization Mass Spectrometry (MALDI MS) to identify as-yet unknown proteins that may be associated with the structural changes in the pulmonary arterial walls of patients with IPAH. The technology identified significant increases in two fragments of histone H1 in the IPAH cases compared to controls. This finding was further examined using immunofluorescence techniques applied to sections from IPAH and control pulmonary arteries. In addition, cultured pulmonary artery smooth muscle cells (PASMCs) were utilized for Western analysis of histone H1 and importin β and importin 7, immunoprecipitation and assessment of nucleosomal repeat length (NRL). Immunofluorescence techniques revealed that nuclear expression of histone H1 was decreased and the chromatin was less compact in the IPAH cases than in the controls; furthermore, some cases showed a marked increase in cytoplasmic histone H1 expression. Using nuclear and cytoplasmic fractions of cultured PASMCs, we confirmed the reduction in histone H1 in the nucleus and an increase in the cytoplasm in IPAH cells compared to controls. Immunoprecipitation demonstrated a decreased association of histone H1 with importin β while importin 7 was unchanged in the IPAH cells compared to controls. The assessment of NRL revealed that the distance between nucleosomes was increased by ~20 bp in IPAH compared to controls. We conclude that at least two factors contribute to the reduction in nuclear histone H1—fragmentation of the protein and decreased import of histone H1 into the nucleus by importins. We further suggest that the decreased nuclear H1 contributes the less compact nucleosomal pattern in IPAH and this, in turn, contributes to the increase in NRL. PMID:23130102

  12. Alterations in Plasma Triglyceride Concentrations following Two Oral Meals with Different Fat Content in Patients with Type 2 Diabetes Mellitus.

    PubMed

    Gavra, Paraskevi; Mellidonis, Andreas; Iraklianou, Stella; Mihas, Constantinos; Kolovou, Vana; Mavrogeni, Sophie; Dimitriadis, George; Rallidis, Loukianos; Vasaramva, Kaliopi; Boutati, Eleni; Katsiki, Niki; Kolovou, Genovefa

    2017-05-28

    Enhanced postprandial lipaemia has been reported in patients with obesity, hypertension, metabolic syndrome and type 2 diabetes mellitus (T2DM). We compared 2 oral fat meal tests (LIPOLD: 149g of fat, 56g of carbohydrates and 11.7g of proteins administrated per 2m2 of body surface) and LIPOTEST: 75g of fat, 25g of carbohydrates and 10g of protein with the addition of 15g common sugar) with regard to changes in triglycerides (TGs) as well as other cardiometabolic parameters between baseline and 4 h after the meals METHODS: We studied 21 men [median age (interquartile range; IQR) = 65 (16) years] with well-controlled T2DM [median glycated haemoglobin (HbA1c) (IQR) = 6.6 (0.9) %]. All participants performed the meals with 1 week interval between the 2 meals. Median (IQR) TG differences in mg/dl were 86 (100) and 46 (60) for LIPOLD and LIPOTEST meals, respectively, whereas the % differences in TGs were 105 (105) and 48 (55), respectively. The differences (in mg/dl and %) between TGs before ingesting the test meal and after 4h were significant for both LIPOLD and LIPOTEST meals (p = 0.003 for mg/dl differences and p = 0.005 for % differences). Patients who had a positive response to the LIPOLD meal (i.e. TGs > 220 mg/dl at 4 h) also had increased postprandial TGs with LIPOTEST. The Homeostasis Model Assessment of Insulin Resistance (HOMA-IR) correlated with TG differences (in mg/dl) following the LIPOLD meal consumption (Spearman's rho = (+) 0.527, p = 0.02). C-peptide correlated with TG differences (in mg/dl) following the LIPOTEST meal consumption (Spearman's rho = (+) 0.538, p = 0.032). There were no differences in TGs and glucose response postprandially in both testing meals according to body mass index (except for TGs between tertile 21.3-24.5 and 25-26.8 kg/m2, p=0.046, in LPOTEST group) and body surface area. An oral fat tolerance test (OFTT), which contains 75g fat, and represents the everyday habits of Western societies, could provide additional information

  13. Adipose tissue NAPE-PLD controls fat mass development by altering the browning process and gut microbiota.

    PubMed

    Geurts, Lucie; Everard, Amandine; Van Hul, Matthias; Essaghir, Ahmed; Duparc, Thibaut; Matamoros, Sébastien; Plovier, Hubert; Castel, Julien; Denis, Raphael G P; Bergiers, Marie; Druart, Céline; Alhouayek, Mireille; Delzenne, Nathalie M; Muccioli, Giulio G; Demoulin, Jean-Baptiste; Luquet, Serge; Cani, Patrice D

    2015-03-11

    Obesity is a pandemic disease associated with many metabolic alterations and involves several organs and systems. The endocannabinoid system (ECS) appears to be a key regulator of energy homeostasis and metabolism. Here we show that specific deletion of the ECS synthesizing enzyme, NAPE-PLD, in adipocytes induces obesity, glucose intolerance, adipose tissue inflammation and altered lipid metabolism. We report that Napepld-deleted mice present an altered browning programme and are less responsive to cold-induced browning, highlighting the essential role of NAPE-PLD in regulating energy homeostasis and metabolism in the physiological state. Our results indicate that these alterations are mediated by a shift in gut microbiota composition that can partially transfer the phenotype to germ-free mice. Together, our findings uncover a role of adipose tissue NAPE-PLD on whole-body metabolism and provide support for targeting NAPE-PLD-derived bioactive lipids to treat obesity and related metabolic disorders.

  14. Adipose tissue NAPE-PLD controls fat mass development by altering the browning process and gut microbiota

    PubMed Central

    Geurts, Lucie; Everard, Amandine; Van Hul, Matthias; Essaghir, Ahmed; Duparc, Thibaut; Matamoros, Sébastien; Plovier, Hubert; Castel, Julien; Denis, Raphael G. P.; Bergiers, Marie; Druart, Céline; Alhouayek, Mireille; Delzenne, Nathalie M.; Muccioli, Giulio G.; Demoulin, Jean-Baptiste; Luquet, Serge; Cani, Patrice D.

    2015-01-01

    Obesity is a pandemic disease associated with many metabolic alterations and involves several organs and systems. The endocannabinoid system (ECS) appears to be a key regulator of energy homeostasis and metabolism. Here we show that specific deletion of the ECS synthesizing enzyme, NAPE-PLD, in adipocytes induces obesity, glucose intolerance, adipose tissue inflammation and altered lipid metabolism. We report that Napepld-deleted mice present an altered browning programme and are less responsive to cold-induced browning, highlighting the essential role of NAPE-PLD in regulating energy homeostasis and metabolism in the physiological state. Our results indicate that these alterations are mediated by a shift in gut microbiota composition that can partially transfer the phenotype to germ-free mice. Together, our findings uncover a role of adipose tissue NAPE-PLD on whole-body metabolism and provide support for targeting NAPE-PLD-derived bioactive lipids to treat obesity and related metabolic disorders. PMID:25757720

  15. Alteration of Endothelin 1, MCP-1 and Chromogranin A in patients with atrial fibrillation undergoing pulmonary vein isolation.

    PubMed

    Lackermair, K; Clauss, S; Voigt, T; Klier, I; Summo, C; Hildebrand, B; Nickel, T; Estner, H L; Kääb, S; Wakili, R; Wilbert-Lampen, U

    2017-01-01

    The relation between arrhythmias and stress is known. The aim of our current study was to elucidate whether plasma levels of previously described stress parameters are altered in highly symptomatic patients with atrial fibrillation (AF) per se and in patients undergoing ablation therapy by pulmonary vein isolation (PVI). 96 patients with AF undergoing PVI were recruited. Plasma levels of Endothelin-1 (ET-1), MCP-1 and Chromogranin-A (CGA) were measured before and three months after ablation completed with clinical follow-up with respect to AF recurrence. Additionally, we examined 40 healthy age- and sex-matched volunteers as a reference. Symptomatic AF patients showed increased levels of ET-1 compared to healthy controls (2.62pg/ml vs. 1.57pg/ml; p<0.01). Baseline levels of ET-1 were higher in patients presenting with AF after PVI (2.96pg/ml vs. 2.57pg/ml;p = 0.02). The temporal comparison revealed decreased ET-1 levels in patients without (2.57pg/ml vs. 2.33pg/ml; p<0.01) and unchanged ET-1 levels in patients with AF after PVI. Baseline MCP-1 was increased in AF patients vs. controls (268pg/ml vs. 227 pg/ml; p = 0.03). Both groups, with and without AF after PVI, showed an increase of MCP-1 compared to baseline (268pg/ml vs. 349pg/ml;p<0.01; 281pg/ml vs. 355pg/ml;p = 0.03). CGA was lower in AF patients compared to healthy controls (13.8ng/ml vs. 25.6ng/ml;p<0.01). Over time patients without AF after PVI showed an increase of CGA (14.2ng/ml vs. 20.7ng/ml;p<0.01). No change was observed in patients with AF after PVI. Our study demonstrated dysregulated levels of ET-1, MCP-1 and CGA in symptomatic AF patients. We could demonstrate an association between ET-1 to presence or absence of AF. Furthermore, we could show that a decrease of ET-1 as well as an increase of CGA after PVI, representing a trend towards control cohort levels, were both associated with restoration of sinus rhythm. These results provide new insights into the role of stress-related biomarkers in AF

  16. High Fat Diet Administration during Specific Periods of Pregnancy Alters Maternal Fatty Acid Profiles in the Near-Term Rat

    PubMed Central

    Cerf, Marlon E.; Herrera, Emilio

    2016-01-01

    Excessive fat intake is a global health concern as women of childbearing age increasingly ingest high fat diets (HFDs). We therefore determined the maternal fatty acid (FA) profiles in metabolic organs after HFD administration during specific periods of gestation. Rats were fed a HFD for the first (HF1), second (HF2), or third (HF3) week, or for all three weeks (HFG) of gestation. Total maternal plasma non-esterified fatty acid (NEFA) concentrations were monitored throughout pregnancy. At day 20 of gestation, maternal plasma, liver, adipose tissue, and placenta FA profiles were determined. In HF3 mothers, plasma myristic and stearic acid concentrations were elevated, whereas docosahexaenoic acid (DHA) was reduced in both HF3 and HFG mothers. In HF3 and HFG mothers, hepatic stearic and oleic acid proportions were elevated; conversely, DHA and linoleic acid (LA) proportions were reduced. In adipose tissue, myristic acid was elevated, whereas DHA and LA proportions were reduced in all mothers. Further, adipose tissue stearic acid proportions were elevated in HF2, HF3, and HFG mothers; with oleic acid increased in HF1 and HFG mothers. In HF3 and HFG mothers, placental neutral myristic acid proportions were elevated, whereas DHA was reduced. Further, placental phospholipid DHA proportions were reduced in HF3 and HFG mothers. Maintenance on a diet, high in saturated fat, but low in DHA and LA proportions, during late or throughout gestation, perpetuated reduced DHA across metabolic organs that adapt during pregnancy. Therefore a diet, with normal DHA proportions during gestation, may be important for balancing maternal FA status. PMID:26742067

  17. High-fat diet alters serum fatty acid profiles in obesity prone rats: implications for in-vitro studies

    PubMed Central

    Liu, Tzu-Wen; Heden, Timothy D.; Morris, E. Matthew; Fritsche, Kevin L.; Vieira-Potter, Victoria J.; Thyfault, John P.

    2015-01-01

    High-fat diets (HFD) are commonly used in rodents to induce obesity, increase serum fatty acids, and induce lipotoxicity in various organs. In-vitro studies commonly utilize individual free fatty acids (FFA) to study lipid exposure in an effort to model what is occurring in-vivo, however, these approaches are not physiological as tissues are exposed to multiple fatty acids in-vivo. Here we characterize circulating lipids in obese-prone rats fed a HFD in both fasted and fed states with the goal of developing physiologically relevant fatty acid mixtures for subsequent in-vitro studies. Rats were fed a HFD (60% kcal fat) or a control diet (10% kcal fat) for 3 weeks; liver tissue, and both portal and systemic blood was collected. Fatty acid profiles and absolute concentrations of triglycerides (TAG) and FFA in the serum and TAG, diacylglycerol (DAG), and phospholipids (PL) in the liver were measured. Surprisingly, both systemic and portal serum TAG were ~40% lower in HFD-fed compared to controls. Overall, compared to the control diet, HFD feeding consistently induced an increase in the proportion of circulating polyunsaturated fatty acids (PUFA) with a concomitant decline in monounsaturated fatty acids (MUFA), and saturated fatty acids (SFA) in both serum TAG and FFA. The elevations of PUFA were mostly attributed to increases in n-6 PUFA, linoleic acid and arachidonic acid. In conclusion, fatty acid mixtures enriched with linoleic and arachidonic acid in addition to SFA and MUFA should be utilized for in-vitro studies attempting to model lipid exposures that occur during in-vivo HFD condition. PMID:26318121

  18. High Fat Diet Administration during Specific Periods of Pregnancy Alters Maternal Fatty Acid Profiles in the Near-Term Rat.

    PubMed

    Cerf, Marlon E; Herrera, Emilio

    2016-01-04

    Excessive fat intake is a global health concern as women of childbearing age increasingly ingest high fat diets (HFDs). We therefore determined the maternal fatty acid (FA) profiles in metabolic organs after HFD administration during specific periods of gestation. Rats were fed a HFD for the first (HF1), second (HF2), or third (HF3) week, or for all three weeks (HFG) of gestation. Total maternal plasma non-esterified fatty acid (NEFA) concentrations were monitored throughout pregnancy. At day 20 of gestation, maternal plasma, liver, adipose tissue, and placenta FA profiles were determined. In HF3 mothers, plasma myristic and stearic acid concentrations were elevated, whereas docosahexaenoic acid (DHA) was reduced in both HF3 and HFG mothers. In HF3 and HFG mothers, hepatic stearic and oleic acid proportions were elevated; conversely, DHA and linoleic acid (LA) proportions were reduced. In adipose tissue, myristic acid was elevated, whereas DHA and LA proportions were reduced in all mothers. Further, adipose tissue stearic acid proportions were elevated in HF2, HF3, and HFG mothers; with oleic acid increased in HF1 and HFG mothers. In HF3 and HFG mothers, placental neutral myristic acid proportions were elevated, whereas DHA was reduced. Further, placental phospholipid DHA proportions were reduced in HF3 and HFG mothers. Maintenance on a diet, high in saturated fat, but low in DHA and LA proportions, during late or throughout gestation, perpetuated reduced DHA across metabolic organs that adapt during pregnancy. Therefore a diet, with normal DHA proportions during gestation, may be important for balancing maternal FA status.

  19. Timing of fat and liquid sugar intake alters substrate oxidation and food efficiency in male Wistar rats.

    PubMed

    Oosterman, Johanneke E; Foppen, Ewout; van der Spek, Rianne; Fliers, Eric; Kalsbeek, Andries; la Fleur, Susanne E

    2015-03-01

    In addition to the amount of ingested calories, both timing of food intake and meal composition are determinants of body weight gain. However, at present, it is unknown if the inappropriate timing of diet components is responsible for body weight gain. In the present study, we therefore studied a time-dependent effect of the diet composition on energy homeostasis. Male Wistar rats were subjected to chow ad libitum (chow group) or a choice diet with saturated fat, a 30% sugar solution, chow and tap water. The choice diet was provided either with all components ad libitum (AL), with ad libitum access to chow, tap water and a 30% sugar solution, but with access to saturated fat only during the light period (LF), or with ad libitum access to chow, tap water and saturated fat, but access to a 30% sugar solution only during the light period (LS). Caloric intake and body weight gain were monitored during 31 days. Energy expenditure was measured in the third week in calorimetric cages. All rats on a choice diet showed hyperphagia and gained more body weight compared to the chow group. Within the choice diet groups, rats on the LS diet were most food efficient (i.e. gained most body weight per ingested calorie) and showed a lower respiratory exchange ratio (RER) with an anti-phasic pattern, whereas no differences in locomotor activity or heat production were found. Collectively these data indicate that the timing of the diet composition affects food efficiency, most likely due to a shifted oxidation pattern, which can predispose for obesity. Further studies are underway to assess putative mechanisms involved in this dysregulation.

  20. Low-carbohydrate, high-protein, high-fat diet alters small peripheral artery reactivity in metabolic syndrome patients.

    PubMed

    Merino, Jordi; Kones, Richard; Ferré, Raimon; Plana, Núria; Girona, Josefa; Aragonés, Gemma; Ibarretxe, Daiana; Heras, Mercedes; Masana, Luis

    2014-01-01

    Low carbohydrate diets have become increasingly popular for weight loss. Although they may improve some metabolic markers, particularly in type 2 diabetes mellitus (T2D) or metabolic syndrome (MS), their net effect on vascular function remains unclear. Evaluate the relation between dietary macronutrient composition and the small artery reactive hyperaemia index (saRHI), a marker of small artery vascular function, in a cohort of MS patients. This cross-sectional study included 160 MS patients. Diet was evaluated by a 3-day food-intake register and reduced to a novel low-carbohydrate diet score (LCDS). Physical examination, demographic, biochemical and anthropometry parameters were recorded, and saRHI was measured in each patient. Individuals in the lowest LCDS quartile (Q1; 45% carbohydrate, 19% protein, 31% fat) had higher saRHI values than those in the top quartile (Q4; 30% carbohydrate, 25% protein, 43% fat) (1.84±0.42 vs. 1.55±0.25, P=.012). These results were similar in T2D patients (Q1=1.779±0.311 vs. Q4=1.618±0.352, P=.011) and also in all of the MS components, except for low HDLc. Multivariate analysis demonstrated that individuals in the highest LCDS quartile, that is, consuming less carbohydrates, had a significantly negative coefficient of saRHI which was independent of confounders (HR: -0.747; 95%CI: 0.201, 0.882; P=.029). These data suggest that a dietary pattern characterized by a low amount of carbohydrate, but reciprocally higher amounts of fat and protein, is associated with poorer vascular reactivity in patients with MS and T2D. Copyright © 2013 Sociedad Española de Arteriosclerosis. Published by Elsevier España. All rights reserved.

  1. Dietary fish oil supplements depress milk fat yield and alter milk fatty acid composition in lactating cows fed grass silage-based diets.

    PubMed

    Kairenius, P; Ärölä, A; Leskinen, H; Toivonen, V; Ahvenjärvi, S; Vanhatalo, A; Huhtanen, P; Hurme, T; Griinari, J M; Shingfield, K J

    2015-08-01

    The potential of dietary fish oil (FO) supplements to increase milk 20:5n-3 and 22:6n-3 concentrations and the associated effects on milk fatty acid (FA) composition, intake, and milk production were examined. Four multiparous lactating cows offered a grass silage-based diet (forage:concentrate ratio 58:42, on a dry matter basis) supplemented with 0, 75, 150, or 300g of FO/d (FO0, FO75, FO150, and FO300, respectively) were used in a 4×4 Latin square with 28-d experimental periods. Milk FA composition was analyzed by complementary silver-ion thin-layer chromatography, gas chromatography-mass spectrometry, and silver-ion HPLC. Supplements of FO decreased linearly dry matter intake, yields of energy-corrected milk, milk fat and protein, and milk fat content. Compared with FO0, milk fat content and yield were decreased by 30.1 and 40.6%, respectively, on the FO300 treatment. Supplements of FO linearly increased milk 20:5n-3 and 22:6n-3 concentrations from 0.07 to 0.18 and 0.03 to 0.10g/100g of FA, respectively. Enrichment of 20:5n-3 and 22:6n-3 was accompanied by decreases in 4- to 18-carbon saturated FA and increases in total conjugated linoleic acid (CLA), trans FA, and polyunsaturated FA concentrations. Fish oil elevated milk fat cis-9,trans-11 CLA content in a quadratic manner, reaching a maximum on FO150 (from 0.61 to 2.15g/100g of FA), whereas further amounts of FO increased trans-10 18:1 with no change in trans-11 18:1 concentration. Supplements of FO also resulted in a dose-dependent appearance of 37 unique 20- and 22-carbon intermediates in milk fat. Concentrations of 16-, 18-, 20-, and 22-carbon trans FA were all increased by FO, with enrichment of trans 18:1 and trans 18:2 being quantitatively the most important. Decreases in milk fat yield to FO were not related to changes in milk trans-10,cis-12 CLA concentration or estimated milk fat melting point. Partial least square regression analysis indicated that FO-induced milk fat depression was associated with

  2. Short-term high-fat-and-fructose feeding produces insulin signaling alterations accompanied by neurite and synaptic reduction and astroglial activation in the rat hippocampus

    PubMed Central

    Calvo-Ochoa, Erika; Hernández-Ortega, Karina; Ferrera, Patricia; Morimoto, Sumiko; Arias, Clorinda

    2014-01-01

    Chronic consumption of high-fat-and-fructose diets (HFFD) is associated with the development of insulin resistance (InsRes) and obesity. Systemic insulin resistance resulting from long-term HFFD feeding has detrimental consequences on cognitive performance, neurogenesis, and long-term potentiation establishment, accompanied by neuronal alterations in the hippocampus. However, diet-induced hippocampal InsRes has not been reported. Therefore, we investigated whether short-term HFFD feeding produced hippocampal insulin signaling alterations associated with neuronal changes in the hippocampus. Rats were fed with a control diet or an HFFD consisting of 10% lard supplemented chow and 20% high-fructose syrup in the drinking water. Our results show that 7 days of HFFD feeding induce obesity and InsRes, associated with the following alterations in the hippocampus: (1) a decreased insulin signaling; (2) a decreased hippocampal weight; (3) a reduction in dendritic arborization in CA1 and microtubule-associated protein 2 (MAP-2) levels; (4) a decreased dendritic spine number in CA1 and synaptophysin content, along with an increase in tau phosphorylation; and finally, (5) an increase in reactive astrocyte associated with microglial changes. To our knowledge, this is the first report addressing hippocampal insulin signaling, as well as morphologic, structural, and functional modifications due to short-term HFFD feeding in the rat. PMID:24667917

  3. Alterations in the plasma metabolite profile associated with improved hepatic function and glycemia in mice fed lingonberry supplemented high-fat diets.

    PubMed

    Al Hamimi, Said; Heyman-Lindén, Lovisa; Plaza, Merichel; Turner, Charlotta; Berger, Karin; Spégel, Peter

    2017-03-01

    Lingonberries have been shown to reduce the detrimental effects of high-fat diet (HFD) on weight gain, plasma glucose, and inflammation. However, the extent of effects was recently shown to vary between different batches of berries. Here, we examine the metabolic response to two independent batches of lingonberries. Alterations in the phenotype and circulating metabolome elicited by three matched HFDs, two of which containing lingonberries (L1D and L2D) from different sources, were investigated. Glycemia was improved only in mice fed L1D, whereas liver function was improved and inflammation reduced in mice fed both L1D and L2D, compared to mice fed HFD. The unique improvement in glycemia elicited by L1D was associated with a 21% increase in circulating levels of fatty acids. Increased levels of phosphatidylcholines (62%) and lysophosphatidylcholines (28%) and decreased levels of serine (-13%) and sphingomyelins (-26%) were observed in mice fed L1D and L2D, as compared to HFD. The unique improvement in glycemia in mice fed L1D was associated with a normal metabolic control with an altered set point. Moreover, the batch-independent reduction in liver steatosis and inflammation, was associated with an altered sphingomyelin metabolism. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  4. Mice Long-Term High-Fat Diet Feeding Recapitulates Human Cardiovascular Alterations: An Animal Model to Study the Early Phases of Diabetic Cardiomyopathy

    PubMed Central

    Calligaris, Sebastián D.; Lecanda, Manuel; Solis, Felipe; Ezquer, Marcelo; Gutiérrez, Jaime; Brandan, Enrique; Leiva, Andrea; Sobrevia, Luis; Conget, Paulette

    2013-01-01

    Background/Aim Hypercaloric diet ingestion and sedentary lifestyle result in obesity. Metabolic syndrome is a cluster of clinical features secondary to obesity, considered as a pre-diabetic condition and recognized as an independent risk factor for cardiovascular diseases. To better understand the relationship between obesity, metabolic syndrome and cardiovascular disease as well as for the development of novel therapeutic strategies, animal models that reproduce the etiology, course and outcomes of these pathologies are required. The aim of this work was to characterize the long-term effects of high-fat diet-induced obesity on the mice cardiovascular system, in order to make available a new animal model for diabetic cardiomyopathy. Methods/Results Male C57BL/6 mice were fed with a standardized high-fat diet (obese) or regular diet (normal) for 16 months. Metabolic syndrome was evaluated testing plasma glucose, triglycerides, cholesterol, insulin, and glucose tolerance. Arterial pressure was measured using a sphygmomanometer (non invasive method) and by hemodynamic parameters (invasive method). Cardiac anatomy was described based on echocardiography and histological studies. Cardiac function was assessed by cardiac catheterization under a stress test. Cardiac remodelling and metabolic biomarkers were assessed by RT-qPCR and immunoblotting. As of month eight, the obese mice were overweight, hyperglycaemic, insulin resistant, hyperinsulinemic and hypercholesterolemic. At month 16, they also presented normal arterial pressure but altered vascular reactivity (vasoconstriction), and cardiac contractility reserve reduction, heart mass increase, cardiomyocyte hypertrophy, cardiac fibrosis, and heart metabolic compensations. By contrast, the normal mice remained healthy throughout the study. Conclusions Mice fed with a high-fat diet for prolonged time recapitulates the etiology, course and outcomes of the early phases of human diabetic cardiomyopathy. PMID:23593350

  5. Obesity Alters Gene Expression for GH/IGF-I Axis in Mouse Mammary Fat Pads: Differential Role of Cortistatin and Somatostatin

    PubMed Central

    Córdoba-Chacón, José; de Lecea, Luis; Pozo-Salas, Ana I.; Delgado-Lista, Francisco Javier; Álvarez-Benito, Marina; López-Miranda, José; Luque, Raúl M.; Castaño, Justo P.

    2015-01-01

    Locally produced growth hormone (GH) and IGF-I are key factors in the regulation of mammary gland (MG) development and may be important in breast cancer development/progression. Somatostatin (SST) and cortistatin (CORT) regulate GH/IGF-I axis at various levels, but their role in regulating GH/IGF-I in MGs remains unknown. Since obesity alters the expression of these systems in different tissues and is associated to MG (patho) physiology, we sought to investigate the role of SST/CORT in regulating GH/IGF-I system in the MGs of lean and obese mice. Therefore, we analyzed GH/IGF-I as well as SST/CORT and ghrelin systems expression in the mammary fat pads (MFPs) of SST- or CORT-knockout (KO) mice and their respective littermate-controls fed a low-fat (LF) or a high-fat (HF) diet for 16wks. Our results demonstrate that the majority of the components of GH/IGF-I, SST/CORT and ghrelin systems are locally expressed in mouse MFP. Expression of elements of the GH/IGF-I axis was significantly increased in MFPs of HF-fed control mice while lack of endogenous SST partially suppressed, and lack of CORT completely blunted, the up-regulation observed in obese WT-controls. Since SST/CORT are known to exert an inhibitory role on the GH/IGFI axis, the increase in SST/CORT-receptor sst2 expression in MFPs of HF-fed CORT- and SST-KOs together with an elevation on circulating SST in CORT-KOs could explain the differences observed. These results offer new information on the factors (GH/IGF-I axis) involved in the endocrine/metabolic dysregulation of MFPs in obesity, and suggest that CORT is not a mere SST sibling in regulating MG physiology. PMID:25806796

  6. Re-esterified palm oils, compared to native palm oil, do not alter fat absorption, postprandial lipemia or growth performance in broiler chicks.

    PubMed

    Vilarrasa, E; Tres, A; Bayés-García, L; Parella, T; Esteve-Garcia, E; Barroeta, A C

    2014-08-01

    Re-esterified palm oils are obtained from the chemical esterification of palm acid oils (rich in free fatty acids) with glycerol, both economically interesting by-products from oil refining and biodiesel industries, respectively. Thus, re-esterified palm oils could be an economically interesting alternative to native palm oil in broiler chick diets. However, because they may have different physicochemical properties than have their corresponding native oil, we assessed the effect of fatty acid (FA) positional distribution within acylglycerol molecules and the effect of acylglycerol composition on FA apparent absorption, and their possible consequences on the evolution of postprandial lipemia and growth performance in broiler chicks. Seventy-two 1-day-old female broiler chicks were randomly distributed into 18 cages. The three treatments used were the result of a basal diet supplemented with 6 wt% of native palm oil (N-TAG), re-esterified palm oil (E-TAG), or re-esterified palm oil high in mono- and diacylglycerols (E-MDAG). Chemical esterification raised the fraction of palmitic acid at the sn-2 position from 9.63 mol% in N-TAG oil to 17.9 mol% in E-TAG oil. Furthermore, E-MDAG oil presented a high proportion of mono- (23.1 wt%) and diacylglycerols (51.2 wt%), with FA mainly located at the sn-1,3 positions, which resulted in a lower gross-energy content and an increased solid-fat index at the chicken's body temperature. However, re-esterified palm oils did not alter fat absorption, postprandial lipemia, or growth performance, compared to native palm oil, so they can be used as alternative fat sources in broiler chick diets.

  7. Genome-wide blood DNA methylation alterations at regulatory elements and heterochromatic regions in monozygotic twins discordant for obesity and liver fat.

    PubMed

    Ollikainen, Miina; Ismail, Khadeeja; Gervin, Kristina; Kyllönen, Anjuska; Hakkarainen, Antti; Lundbom, Jesper; Järvinen, Elina A; Harris, Jennifer R; Lundbom, Nina; Rissanen, Aila; Lyle, Robert; Pietiläinen, Kirsi H; Kaprio, Jaakko

    2015-01-01

    The current epidemic of obesity and associated diseases calls for swift actions to better understand the mechanisms by which genetics and environmental factors affect metabolic health in humans. Monozygotic (MZ) twin pairs showing discordance for obesity suggest that epigenetic influences represent one such mechanism. We studied genome-wide leukocyte DNA methylation variation in 30 clinically healthy young adult MZ twin pairs discordant for body mass index (BMI; average within-pair BMI difference: 5.4 ± 2.0 kg/m(2)). There were no differentially methylated cytosine-guanine (CpG) sites between the co-twins discordant for BMI. However, stratification of the twin pairs based on the level of liver fat accumulation revealed two epigenetically highly different groups. Significant DNA methylation differences (n = 1,236 CpG sites (CpGs)) between the co-twins were only observed if the heavier co-twins had excessive liver fat (n = 13 twin pairs). This unhealthy pattern of obesity was coupled with insulin resistance and low-grade inflammation. The differentially methylated CpGs included 23 genes known to be associated with obesity, liver fat, type 2 diabetes mellitus (T2DM) and metabolic syndrome, and potential novel metabolic genes. Differentially methylated CpG sites were overrepresented at promoters, insulators, and heterochromatic and repressed regions. Based on predictions by overlapping histone marks, repressed and weakly transcribed sites were significantly more often hypomethylated, whereas sites with strong enhancers and active promoters were hypermethylated. Further, significant clustering of differentially methylated genes in vitamin, amino acid, fatty acid, sulfur, and renin-angiotensin metabolism pathways was observed. The methylome in leukocytes is altered in obesity associated with metabolic disturbances, and our findings indicate several novel candidate genes and pathways in obesity and obesity-related complications.

  8. Obesity alters gene expression for GH/IGF-I axis in mouse mammary fat pads: differential role of cortistatin and somatostatin.

    PubMed

    Villa-Osaba, Alicia; Gahete, Manuel D; Córdoba-Chacón, José; de Lecea, Luis; Pozo-Salas, Ana I; Delgado-Lista, Francisco Javier; Álvarez-Benito, Marina; López-Miranda, José; Luque, Raúl M; Castaño, Justo P

    2015-01-01

    Locally produced growth hormone (GH) and IGF-I are key factors in the regulation of mammary gland (MG) development and may be important in breast cancer development/progression. Somatostatin (SST) and cortistatin (CORT) regulate GH/IGF-I axis at various levels, but their role in regulating GH/IGF-I in MGs remains unknown. Since obesity alters the expression of these systems in different tissues and is associated to MG (patho) physiology, we sought to investigate the role of SST/CORT in regulating GH/IGF-I system in the MGs of lean and obese mice. Therefore, we analyzed GH/IGF-I as well as SST/CORT and ghrelin systems expression in the mammary fat pads (MFPs) of SST- or CORT-knockout (KO) mice and their respective littermate-controls fed a low-fat (LF) or a high-fat (HF) diet for 16 wks. Our results demonstrate that the majority of the components of GH/IGF-I, SST/CORT and ghrelin systems are locally expressed in mouse MFP. Expression of elements of the GH/IGF-I axis was significantly increased in MFPs of HF-fed control mice while lack of endogenous SST partially suppressed, and lack of CORT completely blunted, the up-regulation observed in obese WT-controls. Since SST/CORT are known to exert an inhibitory role on the GH/IGFI axis, the increase in SST/CORT-receptor sst2 expression in MFPs of HF-fed CORT- and SST-KOs together with an elevation on circulating SST in CORT-KOs could explain the differences observed. These results offer new information on the factors (GH/IGF-I axis) involved in the endocrine/metabolic dysregulation of MFPs in obesity, and suggest that CORT is not a mere SST sibling in regulating MG physiology.

  9. The circulatory and renal sympathoinhibitory effects of gastric leptin are altered by a high fat diet and obesity.

    PubMed

    How, Jackie M Y; Pumpa, Talia J; Sartor, Daniela M

    2013-10-01

    Gastric leptin elicits its cardiovascular and splanchnic sympathoinhibitory responses via a vagal afferent mechanism, however the latter are blunted/abolished in animals fed a medium high fat diet (MHFD). In a diet-induced obesity model we sought to determine whether the renal sympathetic nerve discharge (RSND) and regional vasodilator responses to gastric leptin are also affected by diet and/or obesity. The diet induced obesity model was used in 2 separate studies. After 13 weeks on a MHFD the animals were classified as either obesity prone (OP) or obesity resistant (OR) depending on their weight gain. Control animals were fed a low fat diet for an equivalent period. Arterial pressure (AP) and heart rate (HR) were monitored in isoflurane-anaesthetised, artificially ventilated animals and RSND or regional vascular responses to leptin (15 μg/kg) administered close to the coeliac artery were evaluated. OP rats had higher baseline AP compared to control/OR rats (P<0.05). Close arterial leptin inhibited RSND in control animals but this response was abolished in OR and OP animals (P<0.01 for both). Leptin administration increased renal vascular conductance in control animals but this response was significantly attenuated only in OP animals (P<0.05). The vasodilator response in the superior mesenteric artery was not significantly different in any of the groups (P>0.05). Together these results suggest that, while the renal sympathoinhibitory responses to gastric leptin are affected by diet, the vasodilator responses to leptin in the renal vascular bed are only affected in OP animals. These changes may impact on cardiovascular homeostatic mechanisms in obesity.

  10. Paradoxical resistance to high-fat diet-induced obesity and altered macrophage polarization in mineralocorticoid receptor-overexpressing mice.

    PubMed

    Kuhn, Emmanuelle; Bourgeois, Christine; Keo, Vixra; Viengchareun, Say; Muscat, Adeline; Meduri, Geri; Le Menuet, Damien; Fève, Bruno; Lombès, Marc

    2014-01-01

    The mineralocorticoid receptor (MR) exerts proadipogenic and antithermogenic effects in vitro, yet its in vivo metabolic impact remains elusive. Wild type (WT) and transgenic (Tg) mice overexpressing human MR were subjected to standard chow (SC) or high-fat diet (HFD) for 16 wk. Tg mice had a lower body weight gain than WT animals and exhibited a relative resistance to HFD-induced obesity. This was associated with a decrease in fat mass, an increased population of smaller adipocytes, and an improved glucose tolerance compared with WT animals. Quantitative RT-PCR studies revealed decreased expression of PPARγ2, a master adipogenic gene, and of glucocorticoid receptor and 11β-hydroxysteroid dehydrogenase type 1, consistent with an impaired local glucocorticoid signaling in adipose tissues (AT). This paradoxical resistance to HFD-induced obesity was not related to an adipogenesis defect since differentiation capacity of Tg preadipocytes isolated from stroma-vascular fractions was unaltered, suggesting that other nonadipocyte factors might compromise AT development. Although AT macrophage infiltration was not different between genotypes, Tg mice exhibited a distinct macrophage polarization, as revealed by FACS analysis and CD11c/CD206 expression studies. We further demonstrated that Tg macrophage-conditioned medium partially impaired preadipocyte differentiation. Therefore, we propose that modification of M1/M2 polarization of hMR-overexpressing macrophages could account in part for the metabolic phenotype of Tg mice. Collectively, our results provide evidence that MR exerts a pivotal immunometabolic role by controlling adipocyte differentiation processes directly but also indirectly through macrophage polarization regulation. Our findings should be taken into account for the pharmacological treatment of metabolic disorders.

  11. Genetic and hypoxic alterations of the microRNA-210-ISCU1/2 axis promote iron–sulfur deficiency and pulmonary hypertension

    PubMed Central

    White, Kevin; Lu, Yu; Annis, Sofia; Hale, Andrew E; Chau, B Nelson; Dahlman, James E; Hemann, Craig; Opotowsky, Alexander R; Vargas, Sara O; Rosas, Ivan; Perrella, Mark A; Osorio, Juan C; Haley, Kathleen J; Graham, Brian B; Kumar, Rahul; Saggar, Rajan; Saggar, Rajeev; Wallace, W Dean; Ross, David J; Khan, Omar F; Bader, Andrew; Gochuico, Bernadette R; Matar, Majed; Polach, Kevin; Johannessen, Nicolai M; Prosser, Haydn M; Anderson, Daniel G; Langer, Robert; Zweier, Jay L; Bindoff, Laurence A; Systrom, David; Waxman, Aaron B; Jin, Richard C; Chan, Stephen Y

    2015-01-01

    Iron–sulfur (Fe-S) clusters are essential for mitochondrial metabolism, but their regulation in pulmonary hypertension (PH) remains enigmatic. We demonstrate that alterations of the miR-210-ISCU1/2 axis cause Fe-S deficiencies in vivo and promote PH. In pulmonary vascular cells and particularly endothelium, hypoxic induction of miR-210 and repression of the miR-210 targets ISCU1/2 down-regulated Fe-S levels. In mouse and human vascular and endothelial tissue affected by PH, miR-210 was elevated accompanied by decreased ISCU1/2 and Fe-S integrity. In mice, miR-210 repressed ISCU1/2 and promoted PH. Mice deficient in miR-210, via genetic/pharmacologic means or via an endothelial-specific manner, displayed increased ISCU1/2 and were resistant to Fe-S-dependent pathophenotypes and PH. Similar to hypoxia or miR-210 overexpression, ISCU1/2 knockdown also promoted PH. Finally, cardiopulmonary exercise testing of a woman with homozygous ISCU mutations revealed exercise-induced pulmonary vascular dysfunction. Thus, driven by acquired (hypoxia) or genetic causes, the miR-210-ISCU1/2 regulatory axis is a pathogenic lynchpin causing Fe-S deficiency and PH. These findings carry broad translational implications for defining the metabolic origins of PH and potentially other metabolic diseases sharing similar underpinnings. PMID:25825391

  12. Trigonelline attenuates hepatic complications and molecular alterations in high-fat high-fructose diet-induced insulin resistance in rats.

    PubMed

    Afifi, Nehal A; Ramadan, Amer; Erian, Emad Y; Saleh, Dalia O; Sedik, Ahmed A; Badawi, Manal; El Hotaby, Walid

    2017-04-01

    The present study aimed to evaluate the effect of trigonelline (TRG) on the hepatic complications associated with high-fat high-fructose (HFHF) diet-induced insulin resistance (IR) in rats. IR was induced by giving a saturated fat diet and 10% fructose in drinking water to rats for 8 weeks. Insulin-resistant rats were orally treated with TRG (50 and 100 mg/kg), sitagliptin (SIT; 5 mg/kg), or a combination of TRG (50 mg/kg) and SIT (5 mg/kg) for 14 days. Liver homogenates were used for assessment of hepatic lipids, oxidative stress biomarkers, and inflammatory cytokines. Histopathological and DNA cytometry examinations were carried out for hepatic and pancreatic tissues. Hepatic tissues were examined using Fourier-transform infrared spectroscopy for assessment of any molecular changes. Results of the present study revealed that oral treatment of insulin-resistant rats with TRG or TRG in combination with SIT significantly decreased homeostatic model assessment of IR, hepatic lipids, oxidative stress biomarkers, and the inflammatory cytokines. TRG or TRG in combination with SIT ameliorated the histopathological, DNA cytometry, and molecular alterations induced by a HFHF diet. Finally, it can be concluded that TRG has beneficial effects on the hepatic complications associated with IR due to its hypoglycemic effect and antioxidant potential.

  13. Long-term dietary supplementation with low-dose nobiletin ameliorates hepatic steatosis, insulin resistance, and inflammation without altering fat mass in diet-induced obesity.

    PubMed

    Kim, Young-Je; Choi, Myung-Sook; Woo, Je Tae; Jeong, Mi Ji; Kim, Sang Ryong; Jung, Un Ju

    2017-08-01

    We evaluated the long-term effect of low-dose nobiletin (NOB), a polymethoxylated flavone, on diet-induced obesity and related metabolic disturbances. C57BL/6J mice were fed a high-fat diet (HFD, 45 kcal% fat) with or without NOB (0.02%, w/w) for 16 weeks. NOB did not alter food intake or body weight. Despite increases in fatty acid oxidation-related genes expression and enzymes activity in adipose tissue, NOB did not affect adipose tissue weight due to simultaneous increases in lipogenic genes expression and fatty acid synthase activity. However, NOB significantly decreased not only pro-inflammatory genes expression in adipose tissue but also proinflammatory cytokine levels in plasma. NOB-supplemented mice also showed improved glucose tolerance and insulin resistance, along with decreased levels of plasma insulin, free fatty acids, total cholesterol, non-HDL-cholesterol, and apolipoprotein B. In addition, NOB caused significant decreases in hepatic lipid droplet accumulation and triglyceride content by activating hepatic fatty acid oxidation-related enzymes. Hepatic proinflammatory TNF-α mRNA expression, collagen accumulation, and plasma levels of aminotransferases, liver damage indicators, were also significantly lower in NOB-supplemented mice. These findings suggest that long-term supplementation with low-dose NOB can protect against HFD-induced inflammation, insulin resistance, dyslipidemia, and nonalcoholic fatty liver disease, without ameliorating adiposity. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  14. Altered endocannabinoid signalling after a high-fat diet in Apoe(-/-) mice: relevance to adipose tissue inflammation, hepatic steatosis and insulin resistance.

    PubMed

    Bartelt, A; Orlando, P; Mele, C; Ligresti, A; Toedter, K; Scheja, L; Heeren, J; Di Marzo, V

    2011-11-01

    Apolipoprotein E (ApoE) deficiency is associated with reduced fat accumulation in white adipose tissue (WAT) and high liver triacylglycerol content. Elevated levels of endocannabinoids and cannabinoid receptor type 1 (CB(1)) receptors in the liver and in epididymal vs subcutaneous WAT are associated with fatty liver, visceral adipose tissue, inflammatory markers and insulin resistance. We investigated, in Apoe (-/-) and wild-type (WT) mice, the effect of a high-fat diet (HFD) on: (1) subcutaneous and epididymal WAT accumulation, liver triacylglycerols, phospholipid-esterified fatty acids, inflammatory markers in WAT and liver, and insulin resistance; and (2) endocannabinoid levels, and the gene expression levels of the Cb ( 1 ) receptor and endocannabinoid metabolic enzymes in liver and WAT. After a 16 week HFD, Apoe (-/-) mice exhibited lower body weight, WAT accumulation and fasting leptin, glucose and insulin levels, and higher hepatic steatosis, than WT mice. Glucose clearance and insulin-mediated glucose disposal following the HFD were slower in WT than Apoe (-/-) mice, which exhibited higher levels of mRNA encoding inflammatory markers (tumour necrosis factor-α [TNF-α], monocyte chemoattractant protein-1 [MCP-1], cluster of differentiation 68 [CD68] and EGF-like module-containing mucin-like hormone receptor-like 1 [EMR1]) in the liver, but lower levels in epididymal WAT. HFD-induced elevation of endocannabinoid levels in the liver or epididymal WAT was higher or lower, respectively, in Apoe (-/-) mice, whereas HFD-induced decrease of subcutaneous WAT endocannabinoid and CB(1) receptor levels was significantly less marked. Alterations in endocannabinoid levels reflected changes in endocannabinoid catabolic enzymes in WAT, or the availability of phospholipid precursors in the liver. Liver and adipose tissue endocannabinoid tone following an HFD is altered on Apoe deletion and strongly associated with inflammation, insulin resistance and hepatic steatosis, or

  15. Neurochemical and electrophysiological deficits in the ventral hippocampus and selective behavioral alterations caused by high-fat diet in female C57BL/6 mice.

    PubMed

    Krishna, S; Keralapurath, M M; Lin, Z; Wagner, J J; de La Serre, C B; Harn, D A; Filipov, N M

    2015-06-25

    Mounting experimental evidence, predominantly from male rodents, demonstrates that high-fat diet (HFD) consumption and ensuing obesity are detrimental to the brain. To shed additional light on the neurological consequences of HFD consumption in female rodents and to determine the relatively early impact of HFD in the likely continuum of neurological dysfunction in the context of chronic HFD intake, this study investigated effects of HFD feeding for up to 12weeks on selected behavioral, neurochemical, and electrophysiological parameters in adult female C57BL/6 mice; particular focus was placed on the ventral hippocampus (vHIP). Selected locomotor, emotional and cognitive functions were evaluated using behavioral tests after 5weeks on HFD or control (low-fat diet) diets. One week later, mice were sacrificed and brain regional neurochemical (monoamine) analysis was performed. Behaviorally naïve mice were maintained on their respective diets for an additional 5-6weeks at which time synaptic plasticity was determined in ex vivo slices from the vHIP. HFD-fed female mice exhibited increased: (i) locomotor activity in the open field testing, (ii) mean turn time on the pole test, (iii) swimming time in the forced swim test, and (iv) number of marbles buried in the marble burying test. In contrast, the novel object recognition memory was unaffected. Mice on HFD also had decreased norepinephrine and dopamine turnover, respectively, in the prefrontal cortex and the vHIP. HFD consumption for a total of 11-12weeks altered vHIP synaptic plasticity, evidenced by significant reductions in the paired-pulse ratio and long-term potentiation (LTP) magnitude. In summary, in female mice, HFD intake for several weeks induced multiple behavioral alterations of mainly anxiety-like nature and impaired monoamine pathways in a brain region-specific manner, suggesting that in the female, certain behavioral domains (anxiety) and associated brain regions, i.e., the vHIP, are preferentially

  16. Maternal dietary fat alters amniotic fluid and fetal intestinal membrane essential n-6 and n-3 fatty acids in the rat.

    PubMed

    Friesen, Russell; Innis, Sheila M

    2006-03-01

    We investigated whether maternal fat intake alters amniotic fluid and fetal intestine phospholipid n-6 and n-3 fatty acids. Female rats were fed a 20% by weight diet from fat with 20% linoleic acid (LA; 18:2n-6) and 8% alpha-linolenic acid (ALA; 18:3n-3) (control diet, n = 8) or 72% LA and 0.2% ALA (n-3 deficient diet, n = 7) from 2 wk before and then throughout gestation. Amniotic fluid and fetal intestine phospholipid fatty acids were analyzed at day 19 gestation using HPLC and gas-liquid chromotography. Amniotic fluid had significantly lower docosahexaenoic acid (DHA; 22:6n-3) and higher docosapentaenoic acid (DPA; 22:5n-6) levels in the n-3-deficient group than in the control group (DHA: 1.29 +/- 0.10 and 6.29 +/- 0.33 g/100 g fatty acid; DPA: 4.01 +/- 0.35 and 0.73 +/- 0.15 g/100 g fatty acid, respectively); these differences in DHA and DPA were present in amniotic fluid cholesterol esters and phosphatidylcholine (PC). Fetal intestines in the n-3-deficient group had significantly higher LA, arachidonic acid (20:4n-6), and DPA levels; lower eicosapentaenoic acid (EPA; 20:5n-3) and DHA levels in PC; and significantly higher DPA and lower EPA and DHA levels in phosphatidylethanolamine (PE) than in the control group; the n-6-to-n-3 fatty acid ratio was 4.9 +/- 0.2 and 32.2 +/- 2.1 in PC and 2.4 +/- 0.03 and 17.1 +/- 0.21 in PE in n-3-deficient and control group intestines, respectively. We demonstrate that maternal dietary fat influences amniotic fluid and fetal intestinal membrane structural lipid essential fatty acids. Maternal dietary fat can influence tissue composition by manipulation of amniotic fluid that is swallowed by the fetus or by transport across the placenta.

  17. Garlic attenuates chrysotile-mediated pulmonary toxicity in rats by altering the phase I and phase II drug metabolizing enzyme system.

    PubMed

    Ameen, Mohamed; Musthapa, M Syed; Abidi, Parveen; Ahmad, Iqbal; Rahman, Qamar

    2003-01-01

    Asbestos and its carcinogenic properties have been extensively documented. Asbestos exposure induces diverse cellular events associated with lung injury. Previously, we have shown that treatment with chrysotile shows significant alteration in phase I and phase II drug metabolizing enzyme system. In this study we have examined some potential mechanisms by which garlic treatment attenuates chrysotile-mediated pulmonary toxicity in rat. Female Wistar rats received an intratracheal instillation of 5 mg chrysotile (0.5 mL saline) as well as intragastric garlic treatment (1% body weight (v/w); 6 days per week). Effect of garlic treatment was evaluated after 1, 15, 30, 90, and 180 days by assaying aryl hydrocarbon hydroxylase (AHH), glutathione (GSH), glutathione S-transferase (GST), and production of thiobarbituric acid reactive substances (TBARS) in rat lung microsome. The results showed that AHH and TBARS formation were significantly reduced at day 90 and day 180 in chrysotile treated garlic cofed rats; GSH recovered 15 days later to the near normal level and GST elevated significantly after treatment of garlic as compared to chrysotile alone treated rat lung microsome. The data obtained shows that inhibition of AHH activity and induction of GST activity could be contributing factor in chrysotile-mediated pulmonary toxicity in garlic cofed rats. However, recovery of GSH and inhibition of TBARS formation by garlic and its constituent(s) showed that garlic may give protection by altering the drug metabolizing enzyme system.

  18. High-fat diet causes bone loss in young mice by promoting osteoclastogenesis through alteration of the bone marrow environment.

    PubMed

    Shu, Lei; Beier, Eric; Sheu, Tzong; Zhang, Hengwei; Zuscik, Michael J; Puzas, Edward J; Boyce, Brendan F; Mooney, Robert A; Xing, Lianping

    2015-04-01

    Obesity is a severe health problem in children, afflicting several organ systems including bone. However, the role of obesity on bone homeostasis and bone cell function in children has not been studied in detail. Here we used young mice fed a high-fat diet (HFD) to model childhood obesity and investigate the effect of HFD on the phenotype of cells within the bone marrow environment. Five-week-old male mice were fed a HFD for 3, 6, and 12 weeks. Decreased bone volume was detected after 3 weeks of HFD treatment. After 6 and 12 weeks, HFD-exposed mice had less bone mass and increased osteoclast numbers. Bone marrow cells, but not spleen cells, from HFD-fed mice had increased osteoclast precursor frequency, elevated osteoclast formation, and bone resorption activity, as well as increased expression of osteoclastogenic regulators including RANKL, TNF, and PPAR-gamma. Bone formation rate and osteoblast and adipocyte numbers were also increased in HFD-fed mice. Isolated bone marrow cells also had a corresponding elevation in the expression of positive regulators of osteoblast and adipocyte differentiation. Our findings indicate that in juvenile mice, HFD-induced bone loss is mainly due to increased osteoclast bone resorption by affecting the bone marrow microenvironment. Thus, targeting osteoclast formation may present a new therapeutic approach for bone complications in obese children.

  19. Effects of n-3 polyunsaturated fatty acids in the fetal pulmonary circulation.

    PubMed

    Houeijeh, Ali; Aubry, Estelle; Coridon, Hélène; Montaigne, Karine; Sfeir, Rony; Deruelle, Philippe; Storme, Laurent

    2011-06-01

    Although evidence exists that n-3 polyunsaturated fatty acids may improve the outcome in patients with severe respiratory failure, little is known regarding their pulmonary circulatory effects. This question is clinically relevant in respiratory failure associated with pulmonary hypertension, in particular in newborn infants with persistent pulmonary hypertension. The objective of this study was to investigate the effects of n-3 polyunsaturated fatty acids on the fetal pulmonary circulation. Randomized, placebo-controlled comparative laboratory investigation. University research facility. Fifty-two chronically prepared lamb fetuses. Catheters and ultrasonic flow transducer were placed through a left thoracotomy in the lamb fetus to determine aortic, pulmonary, and left atrial pressures and left pulmonary artery blood flow. We compared the pulmonary vascular responses to 120 mins of Omegaven (lipid emulsions enriched in n-3 polyunsaturated fatty acids) or Intralipide (lipid emulsions enriched in n-6 polyunsaturated fatty acids) infusion. Then we investigated the effects of Omegaven on the pulmonary circulation after nitric oxide synthase inhibition by L-nitro-arginine, potassium channel blockade by tetraethylammonium, and cytochrome P450 epoxygenase inhibition by (methylsulfonyl)-2-(2-propynyloxy)-benzenehexanamide. Pulmonary artery and aortic pressures as well as blood gases and plasma lactate concentrations did not change during either fat emulsion infusion. Left pulmonary blood flow increased by 30% and pulmonary vascular resistance decreased by 28% during Omegaven infusion, whereas left pulmonary blood flow and pulmonary vascular resistance did not change during Intralipide infusion. This pulmonary vascular response to Omegaven was not altered by l-nitro-arginine. At the opposite, Omegaven induced pulmonary vasodilatation was abolished by tetraethylammonium and markedly attenuated by (methylsulfonyl)-2-(2-propynyloxy)-benzenehexanamide. Lipid emulsion containing

  20. Fat embolism syndrome

    PubMed Central

    Richards, Robin R.

    1997-01-01

    Fat embolism syndrome, an important contributor to the development of acute respiratory distress syndrome, has been associated with both traumatic and nontraumatic disorders. Fat embolization after long bone trauma is probably common as a subclinical event. Fat emboli can deform and pass through the lungs, resulting in systemic embolization, most commonly to the brain and kidneys. The diagnosis of fat embolism syndrome is based on the patient’s history, supported by clinical signs of pulmonary, cerebral and cutaneous dysfunction and confirmed by the demonstration of arterial hypoxemia in the absence of other disorders. Treatment of fat embolism syndrome consists of general supportive measures, including splinting, maintenance of fluid and electrolyte balance and the administration of oxygen. Endotracheal intubation and mechanical ventilatory assistance can be indicated. The role of corticosteroids remains controversial. Early stabilization of long bone fractures has been shown to decrease the incidence of pulmonary complications. Clinical and experimental studies suggest that the exact method of fracture fixation plays a minor role in the development of pulmonary dysfunction. As more is learned about the specifics of the various triggers for the development of fat embolism syndrome, it is hoped that the prospect of more specific therapy for the prevention and treatment of this disorder will become a reality. PMID:9336522

  1. Maternal obesity induced by a high fat diet causes altered cellular development in fetal brains suggestive of a predisposition of offspring to neurological disorders in later life.

    PubMed

    Stachowiak, Ewa K; Srinivasan, Malathi; Stachowiak, Michal K; Patel, Mulchand S

    2013-12-01

    Fetal development in an obese maternal intrauterine environment has been shown to predispose the offspring for a number of metabolic disorders in later life. The observation that a large percentage of women of child-bearing age in the US are overweight/obese during pregnancy is therefore a source of concern. A high fat (HF) diet-induced obesity in female rats has been used as a model for maternal obesity. The objective of this study was to determine cellular development in brains of term fetuses of obese rats fed a HF diet from the time of weaning. Fetal brains were dissected out on gestational day 21 and processed for immunohistochemical analysis in the hypothalamic as well as extra-hypothalamic regions. The major observation of this study is that fetal development in the obese HF female rat induced several alterations in the HF fetal brain. Marked increases were observed in orexigenic signaling and a significant decrease was observed for anorexigenic signaling in the vicinity of the 3rd ventricle in HF brains. Additionally, our results indicated diminished migration and maturation of stem-like cells in the 3rd ventricular region as well as in the brain cortex. The results from the present study indicate developmental alterations in the hypothalamic and extra-hypothalamic regions in the HF fetal brain suggestive of a predisposition for the development of obesity and possibly neurodevelopmental abnormalities in the offspring.

  2. Unsuppressed lipolysis in adipocytes is linked with enhanced gluconeogenesis and altered bile acid physiology in Insr(P1195L/+) mice fed high-fat-diet.

    PubMed

    Lee, Eun Young; Sakurai, Kenichi; Zhang, Xilin; Toda, Chitoku; Tanaka, Tomoaki; Jiang, Meizi; Shirasawa, Takuji; Tachibana, Kaori; Yokote, Koutaro; Vidal-Puig, Antonio; Minokoshi, Yasuhiko; Miki, Takashi

    2015-11-30

    High-fat diet (HFD) triggers insulin resistance and diabetes mellitus, but their link remains unclear. Characterization of overt hyperglycemia in insulin receptor mutant (Insr(P1195L/+)) mice exposed to HFD (Insr(P1195L/+)/HFD mice) revealed increased glucose-6-phosphatase (G6pc) expression in liver and increased gluconeogenesis from glycerol. Lipolysis in white adipose tissues (WAT) and lipolysis-induced blood glucose rise were increased in Insr(P1195L/+)/HFD mice, while wild-type WAT transplantation ameliorated the hyperglycemia and the increased G6pc expression. We found that the expressions of genes involved in bile acid (BA) metabolism were altered in Insr(P1195L/+)/HFD liver. Among these, the expression of Cyp7a1, a BA synthesis enzyme, was insulin-dependent and was markedly decreased in Insr(P1195L/+)/HFD liver. Reduced Cyp7a1 expression in Insr(P1195L/+)/HFD liver was rescued by WAT transplantation, and the expression of Cyp7a1 was suppressed by glycerol administration in wild-type liver. These findings suggest that unsuppressed lipolysis in adipocytes elicited by HFD feeding is linked with enhanced gluconeogenesis from glycerol and with alterations in BA physiology in Insr(P1195L/+)/HFD liver.

  3. Ameliorating effect of Semecarpus anacardium Linn. nut milk extract on altered glucose metabolism in high fat diet STZ induced type 2 diabetic rats.

    PubMed

    Khan, Haseena Banu Hedayathullah; Vinayagam, Kaladevi Siddhi; Palanivelu, Shanthi; Panchanadham, Sachdanandam

    2012-12-01

    To explore the protective effect of the drug Semecarpus anacardium (S. anacardium)on altered glucose metabolism in diabetic rats. Type 2 diabetes mellitus was induced by feeding rats with high fat diet followed by single intraperitoneal injection of streptozotocin (STZ) (35 mg/kg b.w.). Seven days after STZ induction, diabetic rats received nut milk extract of S. anacardium Linn. nut milk extract orally at a dosage of 200 mg/kg daily for 4 weeks. The effect of nut milk extract of S. anacardium on blood glucose, plasma insulin, glucose metabolising enzymes and GSK were studied. Treatment with SA extract showed a significant reduction in blood glucose levels and increase in plasma insulin levels and also increase in HOMA - β and decrease in HOMA -IR. The drug significantly increased the activity of glycolytic enzymes and glucose-6-phosphate dehydrogenase activity and increased the glycogen content in liver of diabetic rats while reducing the activities of gluconeogenic enzymes. The drug also effectively ameliorated the alterations in GSK-3 mRNA expression. Overall, the present study demonstrates the possible mechanism of glucose regulation of S. anacardium suggestive of its therapeutic potential for the management of diabetes mellitus. Copyright © 2012 Hainan Medical College. Published by Elsevier B.V. All rights reserved.

  4. Unsuppressed lipolysis in adipocytes is linked with enhanced gluconeogenesis and altered bile acid physiology in InsrP1195L/+ mice fed high-fat-diet

    PubMed Central

    Lee, Eun Young; Sakurai, Kenichi; Zhang, Xilin; Toda, Chitoku; Tanaka, Tomoaki; Jiang, Meizi; Shirasawa, Takuji; Tachibana, Kaori; Yokote, Koutaro; Vidal-Puig, Antonio; Minokoshi, Yasuhiko; Miki, Takashi

    2015-01-01

    High-fat diet (HFD) triggers insulin resistance and diabetes mellitus, but their link remains unclear. Characterization of overt hyperglycemia in insulin receptor mutant (InsrP1195L/+) mice exposed to HFD (InsrP1195L/+/HFD mice) revealed increased glucose-6-phosphatase (G6pc) expression in liver and increased gluconeogenesis from glycerol. Lipolysis in white adipose tissues (WAT) and lipolysis-induced blood glucose rise were increased in InsrP1195L/+/HFD mice, while wild-type WAT transplantation ameliorated the hyperglycemia and the increased G6pc expression. We found that the expressions of genes involved in bile acid (BA) metabolism were altered in InsrP1195L/+/HFD liver. Among these, the expression of Cyp7a1, a BA synthesis enzyme, was insulin-dependent and was markedly decreased in InsrP1195L/+/HFD liver. Reduced Cyp7a1 expression in InsrP1195L/+/HFD liver was rescued by WAT transplantation, and the expression of Cyp7a1 was suppressed by glycerol administration in wild-type liver. These findings suggest that unsuppressed lipolysis in adipocytes elicited by HFD feeding is linked with enhanced gluconeogenesis from glycerol and with alterations in BA physiology in InsrP1195L/+/HFD liver. PMID:26615883

  5. Altered Body Weight Regulation in CK1ε Null and tau Mutant Mice on Regular Chow and High Fat Diets

    PubMed Central

    Zhou, Lili; Summa, Keith C.; Olker, Christopher; Vitaterna, Martha H.; Turek, Fred W.

    2016-01-01

    Disruption of circadian rhythms results in metabolic dysfunction. Casein kinase 1 epsilon (CK1ε) is a canonical circadian clock gene. Null and tau mutations in CK1ε show distinct effects on circadian period. To investigate the role of CK1ε in body weight regulation under both regular chow (RC) and high fat (HF) diet conditions, we examined body weight on both RC and HF diets in CK1ε−/− and CK1εtau/tau mice on a standard 24 hr light-dark (LD) cycle. Given the abnormal entrainment of CK1εtau/tau mice on a 24 hr LD cycle, a separate set of CK1εtau/tau mice were tested under both diet conditions on a 20 hr LD cycle, which more closely matches their endogenous period length. On the RC diet, both CK1ε−/− and CK1εtau/tau mutants on a 24 hr LD cycle and CK1εtau/tau mice on a 20 hr LD cycle exhibited significantly lower body weights, despite similar overall food intake and activity levels. On the HF diet, CK1εtau/tau mice on a 20 hr LD cycle were protected against the development of HF diet-induced excess weight gain. These results provide additional evidence supporting a link between circadian rhythms and energy regulation at the genetic level, particularly highlighting CK1ε involved in the integration of circadian biology and metabolic physiology. PMID:27144030

  6. Resistant starch intake partly restores metabolic and inflammatory alterations in the liver of high-fat-diet-fed rats.

    PubMed

    Polakof, Sergio; Díaz-Rubio, María Elena; Dardevet, Dominique; Martin, Jean-François; Pujos-Guillot, Estelle; Scalbert, Augustin; Sebedio, Jean-Louis; Mazur, Andrzej; Comte, Blandine

    2013-11-01

    Insulin resistance (IR) constitutes the most important feature of the metabolic syndrome, whose prevalence is highly associated to the consumption of Western diets. Resistant starch (RS) consumption has been shown to have beneficial metabolic effects, including improved insulin sensitivity, and glucose and lipid homeostasis. However, the mechanisms (especially at the molecular level) by which this takes place are still not completely known. In the present study, we aimed to evaluate the role of the liver in the ameliorated high-fat (HF)-induced IR status by RS. Thus, three groups of rats were fed either a control diet, or an HF diet containing or not RS. After 9 weeks of feeding, we evaluated the whole-body insulin sensitivity, and the hepatic glucose and lipid metabolism at the biochemical and molecular levels and the metabolome of the cecum content. We demonstrated for the first time that at least part of the beneficial effects of RS consumption in the context of an HF feeding can be driven by changes elicited at the hepatic level. The ability of the RS to correct the HF-induced dyslipidemia and the associated IR resulted from the return to the basal expression levels of transcription factors involved in lipogenesis (SREBP-1c), cholesterol metabolism (SREBP-2, LXRs) and fatty acid oxidation (PPARα). Moreover, the RS feeding was able to correct the HF-induced reduction in hepatic glucose phosphorylation and muscle glucose transport, improving glucose tolerance. Finally, as a whole, the improved hepatic metabolism seemed to be the result of an ameliorated inflammatory status.

  7. Prenatal Food Restriction with Postweaning High-fat Diet Alters Glucose Metabolic Function in Adult Rat Offspring.

    PubMed

    Xiao, Di; Kou, Hao; Zhang, Li; Guo, Yu; Wang, Hui

    2017-01-01

    The present study was designed to investigate the effects of prenatal food restriction (PFR) with postweaning high-fat diet (HFD) on glucose metabolic function in adult offspring. Pregnant Wistar rats were given PFR treatment from gestational day 11 to spontaneous delivery. All pups were fed by HFD after weaning. Oral glucose tolerance test (OGTT) was conducted at postnatal week (PW) 20. Rats were decapitated in PW24 to collect liver and pancreas, and expression of hepatic insulin signaling genes were then quantified. Body weight from PW4 to PW24 in PFR males was lower than those in control males, whereas there was no distinct difference between females. However, body weight gain rates were higher from PW16 to PW24 in PFR males and females. Fasting serum glucose presented no changes, whereas fasting serum insulin decreased in PW20 in PFR pups. Moreover, glucose intolerance only appeared in PFR males, whereas no changes were shown in PFR females in relative values. Serum insulin increased in both PFR groups after OGTT. Remarkable pathological changes were also found in islets from PFR rats. There was an increase in the hepatic mRNA expression of IR in PFR females and of Glut2 in PFR males. PFR with postweaning HFD induced a catch-up growth in body weight, especially in PFR females. Serum insulin decreased in both PFR groups in fasting status. Insulin resistance after OGTT only existed in PFR males, whereas PFR females showed no obvious changes in glucose metabolism. Copyright © 2017 IMSS. Published by Elsevier Inc. All rights reserved.

  8. Exposure to a high fat diet during the perinatal period alters vagal motoneurone excitability, even in the absence of obesity

    PubMed Central

    Bhagat, Ruchi; Fortna, Samuel R; Browning, Kirsteen N

    2015-01-01

    The perinatal period is critically important to the development of autonomic neural circuits responsible for energy homeostasis. Vagal neurocircuits are vital to the regulation of upper gastrointestinal functions, including satiety. Diet-induced obesity modulates the excitability and responsiveness of both peripheral vagal afferents and central vagal efferents but less information is available regarding the effects of diet per se on vagal neurocircuit functions. The aims of this study were to investigate whether perinatal exposure to a high fat diet (HFD) dysregulated dorsal motor nucleus of the vagus (DMV) neurones, prior to the development of obesity. Whole cell patch clamp recordings were made from gastric-projecting DMV neurones in thin brainstem slices from rats that were exposed to either a control diet or HFD from pregnancy day 13. Our data demonstrate that following perinatal HFD: (i) DMV neurones had decreased excitability and input resistance with a reduced ability to fire action potentials; (ii) the proportion of DMV neurones excited by cholecystokinin (CCK) was unaltered but the proportion of neurones in which CCK increased excitatory glutamatergic synaptic inputs was reduced; (iii) the tonic activation of presynaptic group II metabotropic glutamate receptors on inhibitory nerve terminals was attenuated, allowing modulation of GABAergic synaptic transmission; and (iv) the size and dendritic arborization of gastric-projecting DMV neurones was increased. These results suggest that perinatal HFD exposure compromises the excitability and responsiveness of gastric-projecting DMV neurones, even in the absence of obesity, suggesting that attenuation of vago-vagal reflex signalling may precede the development of obesity. PMID:25556801

  9. Caloric stress alters fat characteristics and Hsp70 expression in milk somatic cells of lactating beef cows.

    PubMed

    Eitam, Harel; Brosh, Arieh; Orlov, Alla; Izhaki, Ido; Shabtay, Ariel

    2009-03-01

    Selection for higher production rate in cattle inhabiting challenging habitats may be considered disadvantageous because of possible deleterious effects on immunity and reproduction and, consequently, on calf crop percentage. In Israel, free-grazing high productive beef cows experience reduction in nutritional quality of forage during up to 8 months of the year. As milk production by dams dictates calf performance, dam's nutritional needs and rebreeding rates, the aim of the present study was to test how lactating beef cows deal with combined caloric and protein stress both at the productive and self protective levels. For this purpose, we studied the effect of long-term caloric stress on milk characteristics and gene expression of stress and milk components producing proteins. Lactating dams responded to caloric stress by decreased body weight, milk, and milk protein production. To compensate for total energy loses in milk, they produced milk of higher fat concentration and shifted the proportions of its fatty acids towards long and unsaturated ones. This was reflected by increased mRNA transcription of the fatty acid binding protein. Prolonged low-energy diet promoted cell-specific heat shock protein (Hsp) response; whereas significant increase of Hsp90 but unchanged levels of Hsp70 proteins were observed in white blood cells, the expression of Hsp70 in milk somatic cells was markedly attenuated, in parallel with a marked increase of alpha(s1)-casein expression. At the mammary gland level, these results may indicate a decrease in turnover of proteins and a shift to an exclusive expression of milk components producing factors. Similar responses to caloric stress were revealed also in ketotic dairy cows. Ketosis promoted a shift towards long and unsaturated fatty acids and an increased expression of alpha(s1)-casein in milk somatic cells. These findings may reflect an evolutionary-preserved mechanism in lactating cows for coping with caloric restriction. Overall

  10. Atelectrauma disrupts pulmonary epithelial barrier integrity and alters the distribution of tight junction proteins ZO-1 and claudin 4

    PubMed Central

    Jacob, Anne-Marie

    2012-01-01

    Mechanical ventilation inevitably exposes the delicate tissues of the airways and alveoli to abnormal mechanical stresses that can induce pulmonary edema and exacerbate conditions such as acute respiratory distress syndrome. The goal of our research is to characterize the cellular trauma caused by the transient abnormal fluid mechanical stresses that arise when air is forced into a liquid-occluded airway (i.e., atelectrauma). Using a fluid-filled, parallel-plate flow chamber to model the “airway reopening” process, our in vitro study examined consequent increases in pulmonary epithelial plasma membrane rupture, paracellular permeability, and disruption of the tight junction (TJ) proteins zonula occludens-1 and claudin-4. Computational analysis predicts the normal and tangential surface stresses that develop between the basolateral epithelial membrane and underlying substrate due to the interfacial stresses acting on the apical cell membrane. These simulations demonstrate that decreasing the velocity of reopening causes a significant increase in basolateral surface stresses, particularly in the region between neighboring cells where TJs concentrate. Likewise, pulmonary epithelial wounding, paracellular permeability, and TJ protein disruption were significantly greater following slower reopening. This study thus demonstrates that maintaining a higher velocity of reopening, which reduces the damaging fluid stresses acting on the airway wall, decreases the mechanical stresses on the basolateral cell surface while protecting cells from plasma membrane rupture and promoting barrier integrity. PMID:22898551

  11. Preventive effect of Caralluma fimbriata vs. Metformin against high-fat diet-induced alterations in lipid metabolism in Wistar rats.

    PubMed

    Gujjala, Sudhakara; Putakala, Mallaiah; Ramaswamy, Rajendran; Desireddy, Saralakumari

    2016-12-01

    The objective of the present study was to investigate the preventive effects of hydro-alcoholic extract of Caralluma fimbriata (CFE) and Metformin (Met) against high-fat diet (HF-diet) induced alterations in lipid metabolism in Wistar rats. The experimental animals were divided into five groups, two of which were fed with chow diet and the other three with HF- (60%) diet. CFE (200mg/kg body weight/day) was administered through oral route to each group of chow-fed rats, HF-fed rats and Met (20mg/kg body weight/day) to one of the HF-diet fed groups. At the end of 90days of experimental period, hypercholestermia, hypertriglycerdemia, with decreased HDL-cholesterol and increased LDL, VLDL-cholesterol and atherogenic index and elevated levels of serum and hepatic transaminases and hepatic lipids (p<0.05) and alterations in the activities of enzymes of lipid metabolism, and the liver showed mild to severe distortion of the normal architecture as well as prominence and widening of the liver sinusoids as observed in HF-fed rats, were prevented by CFE/Met treatment. The results showed that CFE/Met supplementation ameliorated significantly the disturbance in serum and hepatic transaminases, plasma and hepatic lipid profile and lipid metabolism under HF-fed conditions. It can be concluded from these results that CFE might be valuable in reducing the alterations related to lipid metabolism under high calorie diet consumption. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

  12. Caloric stress alters fat characteristics and Hsp70 expression in milk somatic cells of lactating beef cows

    PubMed Central

    Eitam, Harel; Brosh, Arieh; Orlov, Alla; Izhaki, Ido

    2008-01-01

    Selection for higher production rate in cattle inhabiting challenging habitats may be considered disadvantageous because of possible deleterious effects on immunity and reproduction and, consequently, on calf crop percentage. In Israel, free-grazing high productive beef cows experience reduction in nutritional quality of forage during up to 8 months of the year. As milk production by dams dictates calf performance, dam’s nutritional needs and rebreeding rates, the aim of the present study was to test how lactating beef cows deal with combined caloric and protein stress both at the productive and self protective levels. For this purpose, we studied the effect of long-term caloric stress on milk characteristics and gene expression of stress and milk components producing proteins. Lactating dams responded to caloric stress by decreased body weight, milk, and milk protein production. To compensate for total energy loses in milk, they produced milk of higher fat concentration and shifted the proportions of its fatty acids towards long and unsaturated ones. This was reflected by increased mRNA transcription of the fatty acid binding protein. Prolonged low-energy diet promoted cell-specific heat shock protein (Hsp) response; whereas significant increase of Hsp90 but unchanged levels of Hsp70 proteins were observed in white blood cells, the expression of Hsp70 in milk somatic cells was markedly attenuated, in parallel with a marked increase of αs1-casein expression. At the mammary gland level, these results may indicate a decrease in turnover of proteins and a shift to an exclusive expression of milk components producing factors. Similar responses to caloric stress were revealed also in ketotic dairy cows. Ketosis promoted a shift towards long and unsaturated fatty acids and an increased expression of αs1-casein in milk somatic cells. These findings may reflect an evolutionary-preserved mechanism in lactating cows for coping with caloric restriction. Overall, our

  13. Background diet and fat type alters plasma lipoprotein response but not aortic cholesterol accumulation in F1B Golden Syrian hamsters.

    PubMed

    Dillard, Alice; Matthan, Nirupa R; Spartano, Nicole L; Butkowski, Ann E; Lichtenstein, Alice H

    2013-12-01

    Dietary modification alters plasma lipoprotein profiles and atherosclerotic lesion progression in humans and some animal models. Variability in response to diet induced atherosclerosis has been reported in hamsters. Assessed was the interaction between background diet composition and dietary fat type on aortic cholesterol accumulation, lipoprotein profiles, hepatic lipids and selected genes. F1B Golden Syrian hamsters (20/group) were fed (12 weeks) semi-purified or non-purified diets containing either 10 % (w/w) coconut oil or safflower oil and 0.15 % (w/w) cholesterol. The non-purified diets relative to semi-purified diets resulted in significantly higher TC (72 % [percent difference] and 38 %, coconut oil and safflower oil, respectively) and nHDL-C (84 and 61 %, coconut oil and safflower oil, respectively), and lower HDL-C (-47 and -45 %, coconut oil and safflower oil, respectively) concentrations. Plasma triacylglycerol concentrations in the hamsters fed the non-purified coconut oil-supplemented diets were three- to fourfold higher than non-purified safflower oil-supplemented, and both semi-purified diets. With the exception of HDL-C, a significant effect of fat type was observed in TC, nHDL-C and triacylglycerol (all P < 0.05) concentrations. Regardless of diet induced differences in lipoprotein profiles, there was no significant effect on aortic cholesterol accumulation. There was an inverse relationship between plasma nHDL-C and triacylglycerol, and hepatic cholesteryl ester content (P < 0.001). Diet induced differences in hepatic gene transcription (LDL receptor, apoB-100, microsomal transfer protein) were not reflected in protein concentrations. Although hamsters fed non-purified and/or saturated fatty acid-supplemented diets had more atherogenic lipoprotein profiles compared to hamsters fed semi-purified and/or polyunsaturated fatty acid-supplemented diets these differences were not reflected in aortic cholesterol accumulation.

  14. Both food restriction and high-fat diet during gestation induce low birth weight and altered physical activity in adult rat offspring: the "Similarities in the Inequalities" model.

    PubMed

    Cunha, Fábio da Silva; Dalle Molle, Roberta; Portella, André Krumel; Benetti, Carla da Silva; Noschang, Cristie; Goldani, Marcelo Zubaran; Silveira, Patrícia Pelufo

    2015-01-01

    We have previously described a theoretical model in humans, called "Similarities in the Inequalities", in which extremely unequal social backgrounds coexist in a complex scenario promoting similar health outcomes in adulthood. Based on the potential applicability of and to further explore the "similarities in the inequalities" phenomenon, this study used a rat model to investigate the effect of different nutritional backgrounds during gestation on the willingness of offspring to engage in physical activity in adulthood. Sprague-Dawley rats were time mated and randomly allocated to one of three dietary groups: Control (Adlib), receiving standard laboratory chow ad libitum; 50% food restricted (FR), receiving 50% of the ad libitum-fed dam's habitual intake; or high-fat diet (HF), receiving a diet containing 23% fat. The diets were provided from day 10 of pregnancy until weaning. Within 24 hours of birth, pups were cross-fostered to other dams, forming the following groups: Adlib_Adlib, FR_Adlib, and HF_Adlib. Maternal chow consumption and weight gain, and offspring birth weight, growth, physical activity (one week of free exercise in running wheels), abdominal adiposity and biochemical data were evaluated. Western blot was performed to assess D2 receptors in the dorsal striatum. The "similarities in the inequalities" effect was observed on birth weight (both FR and HF groups were smaller than the Adlib group at birth) and physical activity (both FR_Adlib and HF_Adlib groups were different from the Adlib_Adlib group, with less active males and more active females). Our findings contribute to the view that health inequalities in fetal life may program the health outcomes manifested in offspring adult life (such as altered physical activity and metabolic parameters), probably through different biological mechanisms.

  15. Maternal Plane of Nutrition during Late Gestation and Weaning Age Alter Angus × Simmental Offspring Longissimus Muscle Transcriptome and Intramuscular Fat

    PubMed Central

    Moisá, Sonia J.; Shike, Daniel W.; Shoup, Lindsay; Rodriguez-Zas, Sandra L.; Loor, Juan J.

    2015-01-01

    In model organisms both the nutrition of the mother and the young offspring could induce long-lasting transcriptional changes in tissues. In livestock, such changes could have important roles in determining nutrient use and meat quality. The main objective was to evaluate if plane of maternal nutrition during late-gestation and weaning age alter the offspring’s Longissimus muscle (LM) transcriptome, animal performance, and metabolic hormones. Whole-transcriptome microarray analysis was performed on LM samples of early (EW) and normal weaned (NW) Angus × Simmental calves born to grazing cows receiving no supplement [low plane of nutrition (LPN)] or 2.3 kg high-grain mix/day [medium plane of nutrition (MPN)] during the last 105 days of gestation. Biopsies of LM were harvested at 78 (EW), 187 (NW) and 354 (before slaughter) days of age. Despite greater feed intake in MPN offspring, blood insulin was greater in LPN offspring. Carcass intramuscular fat content was greater in EW offspring. Bioinformatics analysis of the transcriptome highlighted a modest overall response to maternal plane of nutrition, resulting in only 35 differentially expressed genes (DEG). However, weaning age and a high-grain diet (EW) strongly impacted the transcriptome (DEG = 167), especially causing a lipogenic program activation. In addition, between 78 and 187 days of age, EW steers had an activation of the innate immune system due presumably to macrophage infiltration of intramuscular fat. Between 187 and 354 days of age (the “finishing” phase), NW steers had an activation of the lipogenic transcriptome machinery, while EW steers had a clear inhibition through the epigenetic control of histone acetylases. Results underscored the need to conduct further studies to understand better the functional outcome of transcriptome changes induced in the offspring by pre- and post-natal nutrition. Additional knowledge on molecular and functional outcomes would help produce more efficient beef

  16. Long term treatment with olanzapine mixed with the food in male rats induces body fat deposition with no increase in body weight and no thermogenic alteration.

    PubMed

    Minet-Ringuet, Julie; Even, Patrick C; Goubern, Marc; Tomé, Daniel; de Beaurepaire, Renaud

    2006-05-01

    Body weight gain is a worrying side effect of many new antipsychotic drugs. The mechanisms by which antipsychotic drugs increase weight in humans are not known. Attempts to model the metabolic effects of antipsychotic drugs in the animal have not been successful. Female rats appear to be sensitive to the effects of antipsychotics, but male rats less, and this does not match the clinical situation in humans. In previous rodent studies, antipsychotics were always given by daily gavage or injections. Antipsychotics have different pharmacokinetics in rodents and humans, and in the present study, we tested the hypothesis that the insensitivity of male rats to the effects of antipsychotics could be related to their mode of administration. Thus, we administered antipsychotic drugs mixed with the food. Animals were treated during 6 weeks with haloperidol (1mg/kg), olanzapine (1mg/kg), ziprasidone (10mg/kg), or a control solution. Animals were allowed to self-select food among three macronutrients (carbohydrates, lipids and proteins). Food selection was measured throughout the study. At the end of the study, body composition was measured by dissection and weighing of the rat's main organs and tissues. Mitochondrial thermogenesis was measured in brown adipose tissue in olanzapine-treated animals. Circulating leptin, insulin, glucose, triglycerides, cholesterol, high-density lipoprotein (HDL) were also assayed at the end of the study. The results show that none of the antipsychotic treatments modified caloric intake, food selection or body weight. Olanzapine did not alter mitochondrial thermogenesis. However, haloperidol and olanzapine induced a significant increase in adiposity and circulating leptin. Ziprasidone produced a moderate fat accumulation. It is concluded that mixing antipsychotic treatments with the food provides a reliable animal model of antipsychotic-induced fat accumulation.

  17. High-fat diet feeding alters metabolic response to fasting/non fasting conditions. Effect on caveolin expression and insulin signalling.

    PubMed

    Gómez-Ruiz, Ana; Milagro, Fermín I; Campión, Javier; Martínez, J Alfredo; de Miguel, Carlos

    2011-04-13

    The effect of food intake on caveolin expression in relation to insulin signalling was studied in skeletal muscle and adipocytes from retroperitoneal (RP) and subcutaneous (SC) adipose tissue, comparing fasted (F) to not fasted (NF) rats that had been fed a control or high-fat (HF) diet for 72 days. Serum glucose was analysed enzymatically and insulin and leptin by ELISA. Caveolins and insulin signalling intermediaries (IR, IRS-1 and 2 and GLUT4) were determined by RT-PCR and western blotting. Caveolin and IR phosphorylation was measured by immunoprecipitation. Data were analysed with Mann-Whitney U test. High-fat fed animals showed metabolic alterations and developed obesity and insulin resistance. In skeletal muscle, food intake (NF) induced activation of IR and increased expression of IRS-2 in control animals with normal metabolic response. HF animals became overweight, hyperglycaemic, hyperinsulinemic, hyperleptinemic and showed insulin resistance. In skeletal muscle of these animals, food intake (NF) also induced IRS-2 expression together with IR, although this was not active. Caveolin 3 expression in this tissue was increased by food intake (NF) in animals fed either diet. In RP adipocytes of control animals, food intake (NF) decreased IR and IRS-2 expression but increased that of GLUT4. A similar but less intense response was found in SC adipocytes. Food intake (NF) did not change caveolin expression in RP adipocytes with either diet, but in SC adipocytes of HF animals a reduction was observed. Food intake (NF) decreased caveolin-1 phosphorylation in RP but increased it in SC adipocytes of control animals, whereas it increased caveolin-2 phosphorylation in both types of adipocytes independently of the diet. Animals fed a control-diet show a normal response to food intake (NF), with activation of the insulin signalling pathway but without appreciable changes in caveolin expression, except a small increase of caveolin-3 in muscle. Animals fed a high-fat diet

  18. Calcitriol concomitantly enhances insulin sensitivity and alters myocellular lipid partitioning in high fat-treated skeletal muscle cells.

    PubMed

    Jefferson, Grace E; Schnell, David M; Thomas, D Travis; Bollinger, Lance M

    2017-10-04

    Vitamin D reduces myocellular insulin resistance, but the effects of vitamin D on intramyocellular lipid (IMCL) partitioning are unknown. The purpose of this study was to understand how calcitriol, the active vitamin D metabolite, affects insulin sensitivity and lipid partitioning in skeletal muscle cells. C2C12 myotubes were treated with calcitriol (100 nM) or vehicle control for 96 h. Insulin-stimulated Akt phosphorylation (Thr 308) was determined by western blot. Intramyocellular triacylglycerol (IMTG), diacylglycerol (DAG), and ceramide content were measured by LC/MS. IMTG partitioning and lipid droplet accumulation were assessed by oil red O. Expression of genes involved in lipid droplet packaging and lipolysis were measured by RT-PCR. Compared to vehicle-treated myotubes, calcitriol augmented insulin-stimulated pAkt. Calcitriol increased total ceramides and DAG in a subspecies-specific manner. Specifically, calcitriol preferentially increased ceramide 24:1 (1.78 fold) and di-18:0 DAG (46.89 fold). Calcitriol increased total IMTG area as assessed by oil red O, but decreased the proportion of lipid within myotubes. Calcitriol increased mRNA content of genes involved in lipid droplet packaging (perilipin 2; PLIN 2, 2.07 fold) and lipolysis (comparative gene identification-58; CGI-58 and adipose triglyceride lipase; ATGL, ~ 1.80 fold). Calcitriol alters myocellular lipid partitioning and lipid droplet packaging which may favor lipid turnover and partially explain improvements in insulin sensitivity.

  19. Altered protein kinase C regulation of pulmonary endothelial store- and receptor-operated Ca2+ entry after chronic hypoxia.

    PubMed

    Paffett, Michael L; Riddle, Melissa A; Kanagy, Nancy L; Resta, Thomas C; Walker, Benjimen R

    2010-09-01

    Chronic hypoxia (CH)-induced pulmonary hypertension is associated with decreased basal pulmonary artery endothelial cell (EC) Ca(2+), which correlates with reduced store-operated Ca(2+) (SOC) entry. Protein kinase C (PKC) attenuates SOC entry in ECs. Therefore, we hypothesized that PKC has a greater inhibitory effect on EC SOC and receptor-operated Ca(2+) entry after CH. To test this hypothesis, we assessed SOC in the presence or absence of the nonselective PKC inhibitor GF109203X [2-[1-(3-dimethylaminopropyl)-1H-indol-3-yl]-3-(1H-indol-3-yl)maleimide] in freshly isolated, Fura-2-loaded ECs obtained from intrapulmonary arteries of control and CH rats (4 weeks at 0.5 atm). We found that SOC entry and 1-oleoyl-2-acetyl-sn-glycerol (OAG)- and ATP-induced Ca(2+) influx were attenuated in ECs from CH rats versus controls, and GF109203X restored SOC and OAG responses to the level of controls. In contrast, nonselective PKC inhibition with GF109203X or the selective PKC(epsilon) inhibitor myristoylated V1-2 attenuated ATP-induced Ca(2+) entry in ECs from control but not CH pulmonary arteries. ATP-induced Ca(2+) entry was also attenuated by the T-type voltage-gated Ca(2+) channel (VGCC) inhibitor mibefradil in control cells. Consistent with the presence of endothelial T-type VGCC, we observed depolarization-induced Ca(2+) influx in control cells that was inhibited by mibefradil. This response was largely absent in ECs from CH arteries. We conclude that CH enhances PKC-dependent inhibition of SOC- and OAG-induced Ca(2+) entry. Furthermore, these data suggest that CH may reduce the ATP-dependent Ca(2+) entry that is mediated, in part, by PKCepsilon and mibefradil-sensitive Ca(2+) channels in control cells.

  20. Fecal fat

    MedlinePlus

    Quantitative stool fat determination; Fat absorption ... This test evaluates fat absorption to tell how well the liver, gallbladder, pancreas, and intestines are working. Fat malabsorption can cause a change in your ...

  1. TNFα drives pulmonary arterial hypertension by suppressing the BMP type-II receptor and altering NOTCH signalling

    PubMed Central

    Hurst, Liam A.; Dunmore, Benjamin J.; Long, Lu; Crosby, Alexi; Al-Lamki, Rafia; Deighton, John; Southwood, Mark; Yang, Xudong; Nikolic, Marko Z.; Herrera, Blanca; Inman, Gareth J.; Bradley, John R.; Rana, Amer A.; Upton, Paul D.; Morrell, Nicholas W.

    2017-01-01

    Heterozygous germ-line mutations in the bone morphogenetic protein type-II receptor (BMPR-II) gene underlie heritable pulmonary arterial hypertension (HPAH). Although inflammation promotes PAH, the mechanisms by which inflammation and BMPR-II dysfunction conspire to cause disease remain unknown. Here we identify that tumour necrosis factor-α (TNFα) selectively reduces BMPR-II transcription and mediates post-translational BMPR-II cleavage via the sheddases, ADAM10 and ADAM17 in pulmonary artery smooth muscle cells (PASMCs). TNFα-mediated suppression of BMPR-II subverts BMP signalling, leading to BMP6-mediated PASMC proliferation via preferential activation of an ALK2/ACTR-IIA signalling axis. Furthermore, TNFα, via SRC family kinases, increases pro-proliferative NOTCH2 signalling in HPAH PASMCs with reduced BMPR-II expression. We confirm this signalling switch in rodent models of PAH and demonstrate that anti-TNFα immunotherapy reverses disease progression, restoring normal BMP/NOTCH signalling. Collectively, these findings identify mechanisms by which BMP and TNFα signalling contribute to disease, and suggest a tractable approach for therapeutic intervention in PAH. PMID:28084316

  2. TNFα drives pulmonary arterial hypertension by suppressing the BMP type-II receptor and altering NOTCH signalling.

    PubMed

    Hurst, Liam A; Dunmore, Benjamin J; Long, Lu; Crosby, Alexi; Al-Lamki, Rafia; Deighton, John; Southwood, Mark; Yang, Xudong; Nikolic, Marko Z; Herrera, Blanca; Inman, Gareth J; Bradley, John R; Rana, Amer A; Upton, Paul D; Morrell, Nicholas W

    2017-01-13

    Heterozygous germ-line mutations in the bone morphogenetic protein type-II receptor (BMPR-II) gene underlie heritable pulmonary arterial hypertension (HPAH). Although inflammation promotes PAH, the mechanisms by which inflammation and BMPR-II dysfunction conspire to cause disease remain unknown. Here we identify that tumour necrosis factor-α (TNFα) selectively reduces BMPR-II transcription and mediates post-translational BMPR-II cleavage via the sheddases, ADAM10 and ADAM17 in pulmonary artery smooth muscle cells (PASMCs). TNFα-mediated suppression of BMPR-II subverts BMP signalling, leading to BMP6-mediated PASMC proliferation via preferential activation of an ALK2/ACTR-IIA signalling axis. Furthermore, TNFα, via SRC family kinases, increases pro-proliferative NOTCH2 signalling in HPAH PASMCs with reduced BMPR-II expression. We confirm this signalling switch in rodent models of PAH and demonstrate that anti-TNFα immunotherapy reverses disease progression, restoring normal BMP/NOTCH signalling. Collectively, these findings identify mechanisms by which BMP and TNFα signalling contribute to disease, and suggest a tractable approach for therapeutic intervention in PAH.

  3. Genetic manipulation of cardiac Hsp72 levels does not alter substrate metabolism but reveals insights into high-fat feeding-induced cardiac insulin resistance.

    PubMed

    Henstridge, Darren C; Estevez, E; Allen, T L; Heywood, S E; Gardner, T; Yang, C; Mellett, N A; Kingwell, B A; Meikle, P J; Febbraio, M A

    2015-05-01

    Heat shock protein 72 (Hsp72) protects cells against a variety of stressors, and multiple studies have suggested that Hsp72 plays a cardioprotective role. As skeletal muscle Hsp72 overexpression can protect against high-fat diet (HFD)-induced insulin resistance, alterations in substrate metabolism may be a mechanism by which Hsp72 is cardioprotective. We investigated the impact of transgenically overexpressing (Hsp72 Tg) or deleting Hsp72 (Hsp72 KO) on various aspects of cardiac metabolism. Mice were fed a normal chow (NC) or HFD for 12 weeks from 8 weeks of age to examine the impact of diet-induced obesity on metabolic parameters in the heart. The HFD resulted in an increase in cardiac fatty acid oxidation and a decrease in cardiac glucose oxidation and insulin-stimulated cardiac glucose clearance; however, there was no difference in Hsp72 Tg or Hsp72 KO mice in these rates compared with their respective wild-type control mice. Although HFD-induced cardiac insulin resistance was not rescued in the Hsp72 Tg mice, it was preserved in the skeletal muscle, suggesting tissue-specific effects of Hsp72 overexpression on substrate metabolism. Comparison of two different strains of mice (BALB/c vs. C57BL/6J) also identified strain-specific differences in regard to HFD-induced cardiac lipid accumulation and insulin resistance. These strain differences suggest that cardiac lipid accumulation can be dissociated from cardiac insulin resistance. Our study finds that genetic manipulation of Hsp72 does not lead to alterations in metabolic processes in cardiac tissue under resting conditions, but identifies mouse strain-specific differences in cardiac lipid accumulation and insulin-stimulated glucose clearance.

  4. The relationship between circulating neutrophil gelatinase-associated lipocalin and early alteration of metabolic parameters is associated with dietary saturated fat intake in non-diabetic Korean women.

    PubMed

    Na, Ga Yoon; Yoon, So Ra; An, Juhyun; Yeo, Rimkyo; Song, Juhyun; Jo, Mi-Na; Han, Seongho; Kim, Oh Yoen

    2016-12-30

    Circulating neutrophil gelatinase-associated lipocalin (NGAL) is associated with obesity-related metabolic disorders. This study investigated the relationship between serum NGAL and early alteration of metabolic parameters in non-diabetic Korean women, particularly with respect to saturated fat (SFA) intake. Anthropometric parameters, fasting glycemic status, and levels of lipids, oxidative stress/inflammatory markers, and NGAL were measured in 82 non-diabetic Korean women [Super-healthy group (n=57) with 0 metabolic syndrome risk factor (MetS RF) and MetS-risk group (n=25) with MetS RF≥1]. Age, weight, waist circumference, blood pressure, fasting glucose, HbA1C, triglyceride, LDL and total-cholesterol, and NGAL levels were higher, and HDL-cholesterol was lower in the MetS-risk group than in the Super-healthy group. Age-adjusted serum NGAL levels were higher in the MetS-risk group than in the Super-healthy group. NGAL increased proportionally with increase in MetS RFs (p=0.038) and correlated positively with BMI, triglycerides, LDL- and total-cholesterol, interleukin-6, white blood cell count, and neutrophil%, and negatively with HDL-cholesterol and superoxide dismutase activity. Serum NGAL levels positively correlated with SFA intake before and after adjustment (age and BMI). Serum NGAL levels were higher in high-SFA consumers [≥7g/day, ≥7% of total calorie intake (TCI)] than in low-SFA consumers (<7g/day, <7% of TCI). Serum NGAL levels were highest in the MetS-risk group consuming higher SFA and lowest in the Super-healthy group consuming lower SFA. However, serum NGAL did not significantly differ between the low-SFA consuming MetS-risk and Super-healthy groups. The relationship between circulating NGAL and early alteration of metabolic parameters is associated with dietary SFA intake in non-diabetic Korean women.

  5. Hemodilution during venous gas embolization improves gas exchange, without altering V(A)/Q or pulmonary blood flow distributions.

    PubMed

    Deem, S; McKinney, S; Polissar, N L; Hedges, R G; Swenson, E R

    1999-12-01

    Isovolemic anemia results in improved gas exchange in rabbits with normal lungs but in relatively poorer gas exchange in rabbits with whole-lung atelectasis. In the current study, the authors characterized the effects of hemodilution on gas exchange in a distinct model of diffuse lung injury: venous gas embolization. Twelve anesthetized rabbits were mechanically ventilated at a fixed rate and volume. Gas embolization was induced by continuous infusion of nitrogen via an internal jugular venous catheter. Serial hemodilution was performed in six rabbits by simultaneous withdrawal of blood and infusion of an equal volume of 6% hetastarch; six rabbits were followed as controls over time. Measurements included hemodynamic parameters and blood gases, ventilation-perfusion (V(A)/Q) distribution (multiple inert gas elimination technique), pulmonary blood flow distribution (fluorescent microspheres), and expired nitric oxide (NO; chemoluminescence). Venous gas embolization resulted in a decrease in partial pressure of arterial oxygen (PaO2) and an increase in partial pressure of arterial carbon dioxide (PaCO2), with markedly abnormal overall V(A)/Q distribution and a predominance of high V(A)/Q areas. Pulmonary blood flow distribution was markedly left-skewed, with low-flow areas predominating. Hematocrit decreased from 30+/-1% to 11+/-1% (mean +/- SE) with hemodilution. The alveolar-arterial PO2 (A-aPO2) difference decreased from 375+/-61 mmHg at 30% hematocrit to 218+/-12.8 mmHg at 15% hematocrit, but increased again (301+/-33 mmHg) at 11% hematocrit. In contrast, the A-aPO2 difference increased over time in the control group (P < 0.05 between groups over time). Changes in PaO2 in both groups could be explained in large part by variations in intrapulmonary shunt and mixed venous oxygen saturation (SvO2); however, the improvement in gas exchange with hemodilution was not fully explained by significant changes in V(A)/Q or pulmonary blood flow distributions, as quantitated

  6. Mice exposed in situ to urban air pollution exhibit pulmonary alterations in gene expression in the lipid droplet synthesis pathways.

    PubMed

    Rowan-Carroll, Andrea; Halappanavar, Sabina; Williams, Andrew; Somers, Christophers M; Yauk, Carole L

    2013-05-01

    It is clear that particulate air pollution poses a serious risk to human health; however, the underlying mechanisms are not completely understood. We investigated pulmonary transcriptional responses in mice following in-situ exposure to ambient air in a heavily industrialized urban environment. Mature C57BL/CBA male mice were caged in sheds near two working steel mills and a major highway in Hamilton, Ontario, Canada in the spring/summer of 2004. Control mice were housed in the same environment, but received only high-efficiency particle filtered air (HEPA). Whole lung tissues were collected from mice exposed for 3, 10, or for 10 weeks followed by 6 weeks recovery in the laboratory (16 weeks). DNA microarrays were used to profile changes in pulmonary gene expression. Transcriptional profiling revealed changes in the expression of genes implicated in the lipid droplet synthesis (Plin I, Dgat2, Lpl, S3-12, and Agpat2), and antioxidant defense (Ucp1) pathways in mice breathing unfiltered air. We postulate that exposure to urban air, containing an abundance of particulate matter adsorbed with polycyclic aromatic hydrocarbons, triggers lipid droplet (holding depots for lipids and malformed/excess proteins tagged for degradation) synthesis in the lungs, which may act to sequester particulates. Increased lipid droplet synthesis could lead to endogenous/stressor-induced production of reactive oxygen species and activation of antioxidant mechanisms. Further investigation into the stimulation of lipid droplet synthesis in the lung in response to air pollution and the resulting health implications is warranted. Copyright © 2013 Wiley Periodicals, Inc.

  7. Deletion of TLR3 alters the pulmonary immune environment and mucus production during respiratory syncytial virus infection.

    PubMed

    Rudd, Brian D; Smit, Jetse J; Flavell, Richard A; Alexopoulou, Lena; Schaller, Matthew A; Gruber, Achim; Berlin, Aaron A; Lukacs, Nicholas W

    2006-02-01

    The detection of a viral infection by pattern recognition receptors (PAMPs) is an integral part of antiviral immunity. In these studies we have investigated the role of TLR3, which recognizes dsRNA, in Respiratory Syncytial virus (RSV) infection using B6 background mice with a TLR3 deletion. Although we observed no changes in viral growth, we did find that TLR3-/- mice demonstrated significant increases in mucus production in the airways of RSV-infected mice. The qualitative assessment was observed by examining differentially stained lungs, followed by immunohistochemical staining for gob5, a mucus-associated protein. The histopathologic observations were verified using quantitative gene expression analyses examining gob5 gene expression. Changes in pulmonary mucus production were accompanied by an increase in pulmonary IL-13 as well as IL-5 expression and eosinophils in the airways of TLR3-/- mice. Examining leukocytes in the airway indicated an accumulation of eosinophils in TLR3-/- mice, but not wild-type mice, after RSV infection. Isolated lung draining lymph node cells from TLR3-/- mice produced significant increases in Th2-type cytokines, IL-5, and IL-13, compared with wild-type TLR3+/+ mice only after RSV infection. To demonstrate a causative link, we depleted TLR3-/- mice of IL-13 during RSV infection and found that mucus and gob5 expression in the lungs was attenuated. Together, these studies highlight that although TLR3 may not be required for viral clearance, it is necessary to maintain the proper immune environment in the lung to avoid developing pathologic symptoms of disease.

  8. LIPGENE food-exchange model for alteration of dietary fat quantity and quality in free-living participants from eight European countries.

    PubMed

    Shaw, Danielle I; Tierney, Audrey C; McCarthy, Sinead; Upritchard, Jane; Vermunt, Susan; Gulseth, Hanne L; Drevon, Christian A; Blaak, Ellen E; Saris, Wim H M; Karlström, Brita; Helal, Olfa; Defoort, Catherine; Gallego, Raquel; López-Miranda, José; Siedlecka, Dominika; Malczewska-Malec, Małgorzata; Roche, Helen M; Lovegrove, Julie A

    2009-03-01

    Controlled human intervention trials are required to confirm the hypothesis that dietary fat quality may influence insulin action. The aim was to develop a food-exchange model, suitable for use in free-living volunteers, to investigate the effects of four experimental diets distinct in fat quantity and quality: high SFA (HSFA); high MUFA (HMUFA) and two low-fat (LF) diets, one supplemented with 1.24 g EPA and DHA/d (LFn-3). A theoretical food-exchange model was developed. The average quantity of exchangeable fat was calculated as the sum of fat provided by added fats (spreads and oils), milk, cheese, biscuits, cakes, buns and pastries using data from the National Diet and Nutrition Survey of UK adults. Most of the exchangeable fat was replaced by specifically designed study foods. Also critical to the model was the use of carbohydrate exchanges to ensure the diets were isoenergetic. Volunteers from eight centres across Europe completed the dietary intervention. Results indicated that compositional targets were largely achieved with significant differences in fat quantity between the high-fat diets (39.9 (sem 0.6) and 38.9 (sem 0.51) percentage energy (%E) from fat for the HSFA and HMUFA diets respectively) and the low-fat diets (29.6 (sem 0.6) and 29.1 (sem 0.5) %E from fat for the LF and LFn-3 diets respectively) and fat quality (17.5 (sem 0.3) and 10.4 (sem 0.2) %E from SFA and 12.7 (sem 0.3) and 18.7 (sem 0.4) %E MUFA for the HSFA and HMUFA diets respectively). In conclusion, a robust, flexible food-exchange model was developed and implemented successfully in the LIPGENE dietary intervention trial.

  9. Transgenic Mice Enriched in Omega-3 Fatty Acids Are More Susceptible to Pulmonary Tuberculosis: Impaired Resistance to Tuberculosis in fat-1 Mice

    PubMed Central

    Bonilla, Diana L.; Fan, Yang-Yi; Chapkin, Robert S.; McMurray, David N.

    2015-01-01

    Background Besides their health benefits, dietary omega-3 fatty acids (n-3 PUFAs) can impair host resistance to intracellular pathogens. Previously, we and others have showed that n-3 PUFA–treated macrophages poorly control Mycobacterium tuberculosis infection in vitro. Methods Wild-type and fat-1 transgenic mice were infected with virulent H37Rv M. tuberculosis via the aerosol route. We evaluated bacteriological and histopathological changes in lungs, as well as differences in activation and antimycobacterial capacity in primary macrophages ex vivo. Results fat-1 mice were more susceptible to tuberculosis, as demonstrated by higher bacterial loads and less robust inflammatory responses in lungs. Macrophages obtained from fat-1 mice were more readily infected with M. tuberculosis in vitro, compared with wild-type macrophages. This impaired bacterial control in cells from fat-1 mice correlated with reduced proinflammatory cytokine secretion, impaired oxidative metabolism, and diminished M. tuberculosis–lysotracker colocalization within phagosomes. Conclusions We showed that endogenous production of n-3 PUFAs in fat-1 mice increases their susceptibility to tuberculosis, which could be explained in part by diminished activation and antimycobacterial responses in cells from fat-1 mice. These data suggest that n-3 PUFA–supplemented diets might have a detrimental effect on immunity to M. tuberculosis and raise concerns regarding the safety of omega-3 dietary supplementation in humans. PMID:20053136

  10. Lung Fibroblasts Share Mesenchymal Stem Cell Features Which Are Altered in Chronic Obstructive Pulmonary Disease via the Overactivation of the Hedgehog Signaling Pathway

    PubMed Central

    Mahrouf-Yorgov, Meriem; Le Gouvello, Sabine; Trébeau, Céline; Sayed, Angeliqua; Stern, Jean-Baptiste; Validire, Pierre; Dubois-Randé, Jean-Luc; Boczkowski, Jorge; Mus-Veteau, Isabelle; Rodriguez, Anne-Marie

    2015-01-01

    Background Alteration of functional regenerative properties of parenchymal lung fibroblasts is widely proposed as a pathogenic mechanism for chronic obstructive pulmonary disease (COPD). However, what these functions are and how they are impaired in COPD remain poorly understood. Apart from the role of fibroblasts in producing extracellular matrix, recent studies in organs different from the lung suggest that such cells might contribute to repair processes by acting like mesenchymal stem cells. In addition, several reports sustain that the Hedgehog pathway is altered in COPD patients thus aggravating the disease. Nevertheless, whether this pathway is dysregulated in COPD fibroblasts remains unknown. Objectives and Methods We investigated the stem cell features and the expression of Hedgehog components in human lung fibroblasts isolated from histologically-normal parenchymal tissue from 25 patients—8 non-smokers/non-COPD, 8 smokers-non COPD and 9 smokers with COPD—who were undergoing surgery for lung tumor resection. Results We found that lung fibroblasts resemble mesenchymal stem cells in terms of cell surface marker expression, differentiation ability and immunosuppressive potential and that these properties were altered in lung fibroblasts from smokers and even more in COPD patients. Furthermore, we showed that some of these phenotypic changes can be explained by an over activation of the Hedgehog signaling in smoker and COPD fibroblasts. Conclusions Our study reveals that lung fibroblasts possess mesenchymal stem cell-features which are impaired in COPD via the contribution of an abnormal Hedgehog signaling. These processes should constitute a novel pathomechanism accounting for disease occurrence and progression. PMID:25815884

  11. 4D cardiovascular magnetic resonance velocity mapping of alterations of right heart flow patterns and main pulmonary artery hemodynamics in tetralogy of Fallot

    PubMed Central

    2012-01-01

    Background To assess changes in right heart flow and pulmonary artery hemodynamics in patients with repaired Tetralogy of Fallot (rTOF) we used whole heart, four dimensional (4D) velocity mapping (VM) cardiovascular magnetic resonance (CMR). Methods CMR studies were performed in 11 subjects with rTOF (5M/6F; 20.1 ± 12.4 years) and 10 normal volunteers (6M/4F; 34.2 ± 13.4 years) on clinical 1.5T and 3.0T MR scanners. 4D VM-CMR was performed using PC VIPR (Phase Contrast Vastly undersampled Isotropic Projection Reconstruction). Interactive streamline and particle trace visualizations of the superior and inferior vena cava (IVC and SVC, respectively), right atrium (RA), right ventricle (RV), and pulmonary artery (PA) were generated and reviewed by three experienced readers. Main PA net flow, retrograde flow, peak flow, time-to-peak flow, peak acceleration, resistance index and mean wall shear stress were quantified. Differences in flow patterns between the two groups were tested using Fisher's exact test. Differences in quantitative parameters were analyzed with the Kruskal-Wallis rank sum test. Results 4D VM-CMR was successfully performed in all volunteers and subjects with TOF. Right heart flow patterns in rTOF subjects were characterized by (a) greater SVC/IVC flow during diastole than systole, (b) increased vortical flow patterns in the RA and in the RV during diastole, and (c) increased helical or vortical flow features in the PA's. Differences in main PA retrograde flow, resistance index, peak flow, time-to-peak flow, peak acceleration and mean wall shear stress were statistically significant. Conclusions Whole heart 4D VM-CMR with PC VIPR enables detection of both normal and abnormal right heart flow patterns, which may allow for comprehensive studies to evaluate interdependencies of post-surgically altered geometries and hemodynamics. PMID:22313680

  12. Altered Right Ventricular Kinetic Energy Work Density and Viscous Energy Dissipation in Patients with Pulmonary Arterial Hypertension: A Pilot Study Using 4D Flow MRI.

    PubMed

    Han, Q Joyce; Witschey, Walter R T; Fang-Yen, Christopher M; Arkles, Jeffrey S; Barker, Alex J; Forfia, Paul R; Han, Yuchi

    2015-01-01

    Right ventricular (RV) function has increasingly being recognized as an important predictor for morbidity and mortality in patients with pulmonary arterial hypertension (PAH). The increased RV after-load increase RV work in PAH. We used time-resolved 3D phase contrast MRI (4D flow MRI) to derive RV kinetic energy (KE) work density and energy loss in the pulmonary artery (PA) to better characterize RV work in PAH patients. 4D flow and standard cardiac cine images were obtained in ten functional class I/II patients with PAH and nine healthy subjects. For each individual, we calculated the RV KE work density and the amount of viscous dissipation in the PA. PAH patients had alterations in flow patterns in both the RV and the PA compared to healthy subjects. PAH subjects had significantly higher RV KE work density than healthy subjects (94.7±33.7 mJ/mL vs. 61.7±14.8 mJ/mL, p = 0.007) as well as a much greater percent PA energy loss (21.1±6.4% vs. 2.2±1.3%, p = 0.0001) throughout the cardiac cycle. RV KE work density and percent PA energy loss had mild and moderate correlations with RV ejection fraction. This study has quantified two kinetic energy metrics to assess RV function using 4D flow. RV KE work density and PA viscous energy loss not only distinguished healthy subjects from patients, but also provided distinction amongst PAH patients. These metrics hold promise as imaging markers for RV function.

  13. Altered Right Ventricular Kinetic Energy Work Density and Viscous Energy Dissipation in Patients with Pulmonary Arterial Hypertension: A Pilot Study Using 4D Flow MRI

    PubMed Central

    Han, Q. Joyce; Witschey, Walter R. T.; Fang-Yen, Christopher M.; Arkles, Jeffrey S.; Barker, Alex J.; Forfia, Paul R.; Han, Yuchi

    2015-01-01

    Introduction Right ventricular (RV) function has increasingly being recognized as an important predictor for morbidity and mortality in patients with pulmonary arterial hypertension (PAH). The increased RV after-load increase RV work in PAH. We used time-resolved 3D phase contrast MRI (4D flow MRI) to derive RV kinetic energy (KE) work density and energy loss in the pulmonary artery (PA) to better characterize RV work in PAH patients. Methods 4D flow and standard cardiac cine images were obtained in ten functional class I/II patients with PAH and nine healthy subjects. For each individual, we calculated the RV KE work density and the amount of viscous dissipation in the PA. Results PAH patients had alterations in flow patterns in both the RV and the PA compared to healthy subjects. PAH subjects had significantly higher RV KE work density than healthy subjects (94.7±33.7 mJ/mL vs. 61.7±14.8 mJ/mL, p = 0.007) as well as a much greater percent PA energy loss (21.1±6.4% vs. 2.2±1.3%, p = 0.0001) throughout the cardiac cycle. RV KE work density and percent PA energy loss had mild and moderate correlations with RV ejection fraction. Conclusion This study has quantified two kinetic energy metrics to assess RV function using 4D flow. RV KE work density and PA viscous energy loss not only distinguished healthy subjects from patients, but also provided distinction amongst PAH patients. These metrics hold promise as imaging markers for RV function. PMID:26418553

  14. Inhaled nitric oxide alters the distribution of blood flow in the healthy human lung, suggesting active hypoxic pulmonary vasoconstriction in normoxia.

    PubMed

    Asadi, Amran K; Sá, Rui Carlos; Kim, Nick H; Theilmann, Rebecca J; Hopkins, Susan R; Buxton, Richard B; Prisk, G Kim

    2015-02-01

    Hypoxic pulmonary vasoconstriction (HPV) is thought to actively regulate ventilation-perfusion (V̇a/Q̇) matching, reducing perfusion in regions of alveolar hypoxia. We assessed the extent of HPV in the healthy human lung using inhaled nitric oxide (iNO) under inspired oxygen fractions (FiO2 ) of 0.125, 0.21, and 0.30 (a hyperoxic stimulus designed to abolish HPV without the development of atelectasis). Dynamic measures of blood flow were made in a single sagittal slice of the right lung of five healthy male subjects using an arterial spin labeling (ASL) MRI sequence, following a block stimulus pattern (3 × 60 breaths) with 40 ppm iNO administered in the central block. The overall spatial heterogeneity, spatiotemporal variability, and regional pattern of pulmonary blood flow was quantified as a function of condition (FiO2 × iNO state). While spatial heterogeneity did not change significantly with iNO administration or FiO2 , there were statistically significant increases in Global Fluctuation Dispersion, (a marker of spatiotemporal flow variability) when iNO was administered during hypoxia (5.4 percentage point increase, P = 0.003). iNO had an effect on regional blood flow that was FiO2 dependent (P = 0.02), with regional changes in the pattern of blood flow occurring in hypoxia (P = 0.007) and normoxia (P = 0.008) tending to increase flow to dependent lung at the expense of nondependent lung. These findings indicate that inhaled nitric oxide significantly alters the distribution of blood flow in both hypoxic and normoxic healthy subjects, and suggests that some baseline HPV may indeed be present in the normoxic lung. Copyright © 2015 the American Physiological Society.

  15. Rapid loss of adiponectin-stimulated fatty acid oxidation in skeletal muscle of rats fed a high fat diet is not due to altered muscle redox state.

    PubMed

    Ritchie, Ian R W; Dyck, David J

    2012-01-01

    A high fat (HF) diet rapidly impairs the ability of adiponectin (Ad) to stimulate fatty acid (FA) oxidation in oxidative soleus muscle, but the underlying mechanism remains elusive. Mere days of HF feeding also increase the muscle's production and accumulation of reactive oxygen species (ROS) and shift cellular redox to a more oxidized state. It seems plausible that this shift towards a more oxidized state might act as negative feedback to suppress the ability of Ad to stimulate FA oxidation and generate more ROS. Therefore, we sought to determine whether i) a shift towards a more oxidized redox state (reduction in GSH/2GSSG) coincided with impaired Ad-stimulated palmitate oxidation in oxidative and glycolytic rodent muscle after 5 days of HF feeding (60% kCal), and ii) if supplementation with the antioxidant, N-acetylcysteine (NAC) could prevent the HF-diet induced impairment in Ad-response. Globular Ad (gAd) increased palmitate oxidation in isolated soleus and EDL muscles by 42% and 34%, respectively (p<0.05) but this was attenuated with HF feeding in both muscles. HF feeding decreased total GSH (-26%, p<0.05) and GSH/2GSSG (-49%, p<0.05) in soleus, but not EDL. Supplementation with NAC prevented the HF diet-induced reductions in GSH and GSH/2GSSG in soleus, but did not prevent the loss of Ad response in either muscle. Furthermore, direct incubations with H(2)O(2) did not impair Ad-stimulated FA oxidation in either muscle. In conclusion, our data indicates that skeletal muscle Ad resistance is rapidly induced in both oxidative and glycolytic muscle, independently of altered cellular redox state.

  16. Therapy with mesenchymal stromal cells or conditioned medium reverse cardiac alterations in a high-fat diet-induced obesity model.

    PubMed

    Daltro, P S; Barreto, B C; Silva, P G; Neto, P Chenaud; Sousa Filho, P H F; Santana Neta, D; Carvalho, G B; Silva, D N; Paredes, B D; de Alcantara, A C; Freitas, L A R; Couto, R D; Santos, R R; Souza, B S F; Soares, M B P; Macambira, S G

    2017-10-01

    Obesity is associated with numerous cardiac complications, including arrhythmias, cardiac fibrosis, remodeling and heart failure. Here we evaluated the therapeutic potential of mesenchymal stromal cells (MSCs) and their conditioned medium (CM) to treat cardiac complications in a mouse model of high-fat diet (HFD)-induced obesity. After obesity induction and HFD withdrawal, obese mice were treated with MSCs, CM or vehicle. Cardiac function was assessed using electrocardiography, echocardiography and treadmill test. Body weight and biochemical parameters were evaluated. Cardiac tissue was used for real time (RT)-polymerase chain reaction (PCR) and histopathologic analysis. Characterization of CM by protein array showed the presence of different cytokines and growth factors, including chemokines, osteopontin, cystatin C, Serpin E1 and Gas 6. HFD-fed mice presented cardiac arrhythmias, altered cardiac gene expression and fibrosis reflected in physical exercise incapacity associated with obesity and diabetes. Administration of MSCs or CM improved arrhythmias and exercise capacity. This functional improvement correlated with normalization of GATA4 gene expression in the hearts of MSC- or CM-treated mice. The gene expression of connexin 43, troponin I, adiponectin, transforming growth factor (TGF) β, peroxisome proliferator activated receptor gamma (PPARγ), insulin-like growth factor 1 (IGF-1), matrix metalloproteinase-9 (MMP9) and tissue inhibitor of metalloproteinases 1 (TIMP1) were significantly reduced in MSCs, but not in CM-treated mice. Moreover, MSC or CM administration reduced the intensity of cardiac fibrosis. Our results suggest that MSCs and CM have a recovery effect on cardiac disturbances due to obesity and corroborate to the paracrine action of MSCs in heart disease models. Copyright © 2017 International Society for Cellular Therapy. Published by Elsevier Inc. All rights reserved.

  17. Adult Neurogenesis in the Female Mouse Hypothalamus: Estradiol and High-Fat Diet Alter the Generation of Newborn Neurons Expressing Estrogen Receptor α

    PubMed Central

    Yang, Jane; Nettles, Sabin A.; Byrnes, Elizabeth M.

    2016-01-01

    Estrogens and leptins act in the hypothalamus to maintain reproduction and energy homeostasis. Neurogenesis in the adult mammalian hypothalamus has been implicated in the regulation of energy homeostasis. Recently, high-fat diet (HFD) and estradiol (E2) have been shown to alter cell proliferation and the number of newborn leptin-responsive neurons in the hypothalamus of adult female mice. The current study tested the hypothesis that new cells expressing estrogen receptor α (ERα) are generated in the arcuate nucleus (ARC) and the ventromedial nucleus of the hypothalamus (VMH) of the adult female mouse, hypothalamic regions that are critical in energy homeostasis. Adult mice were ovariectomized and implanted with capsules containing E2 or oil. Within each hormone group, mice were fed an HFD or standard chow for 6 weeks and treated with BrdU to label new cells. Newborn cells that respond to estrogens were identified in the ARC and VMH, of which a subpopulation was leptin sensitive, indicating that the subpopulation consists of neurons. Moreover, there was an interaction between diet and hormone with an effect on the number of these newborn ERα-expressing neurons that respond to leptin. Regardless of hormone treatment, HFD increased the number of ERα-expressing cells in the ARC and VMH. E2 decreased hypothalamic fibroblast growth factor 10 (Fgf10) gene expression in HFD mice, suggesting a role for Fgf10 in E2 effects on neurogenesis. These findings of newly created estrogen-responsive neurons in the adult brain provide a novel mechanism by which estrogens can act in the hypothalamus to regulate energy homeostasis in females. PMID:27679811

  18. Restricted access to standard or high fat chow alters sensitivity of rats to the 5-HT2A/2C receptor agonist 1-(2,5-dimethoxy-4-methylphenyl)-2-aminopropane (DOM)

    PubMed Central

    Serafine, Katherine M.; France, Charles P.

    2017-01-01

    Feeding conditions can impact sensitivity to drugs acting on dopamine receptors; less is known about the impact of feeding conditions on the effects of drugs acting on serotonin (5-HT) receptors. This study examined the effects of feeding condition on sensitivity to the direct-acting 5-HT2A/2C receptor agonist 1-(2,5-dimethoxy-4-methylphenyl)-2-aminopropane (DOM; 0.1–3.2 mg/kg) and the direct-acting dopamineD3/D2 receptor agonist quinpirole (0.0032–0.32 mg/kg). Male Sprague-Dawley rats had free access (11 weeks) followed by restricted access (6 weeks) to high (34.3%, n = 8) fat or standard (5.7% fat; n = 7) chow. Rats eating high fat chow became insulin resistant and gained more weight than rats eating standard chow. Free access to high fat chow did not alter sensitivity to DOM-induced head twitch but increased sensitivity to quinpirole-induced yawning. Restricting access to high fat or standard chow shifted the DOM-induced head twitch dose-response curve to the right and shifted the quinpirole-induced yawning dose-response curve downward in both groups of rats. Some drugs of abuse and many therapeutic drugs act on 5-HT and dopamine systems; these results demonstrate that feeding condition impacts sensitivity to drugs acting on these systems, thereby possibly impacting vulnerability to abuse as well as therapeutic effectiveness of drugs. PMID:24346289

  19. Factors determining altered perfusion after acute pulmonary embolism assessed by quantified single-photon emission computed tomography-perfusion scan

    PubMed Central

    Meysman, Marc; Everaert, Hendrik; Vincken, Walter

    2017-01-01

    AIM OF THE STUDY: The aim of the study was to analyze the evolution of perfusion (Q)-defects in patients treated for acute pulmonary embolism (PE), correlation with baseline parameters and evaluation of recurrence risk. METHODS: This is a single-center prospective observational cohort study in symptomatic normotensive PE. Comparison of the ventilation/perfusion single-photon emission computed tomography (V/Q-SPECT) acquired at baseline with a quantified SPECT (Q-SPECT) repeated at 1 week and 6 months. The Q-defect extent (percentage of total lung volume affected) was measured semiquantitatively. Data collected at baseline were age, gender, body mass index (BMI), history of previous venous thromboembolism (HVTE), Charlson's Comorbidity Score (CcS), plasma troponin-T and D-dimer levels, PE Severity Index, and tricuspid regurgitation jet (TRJ) velocity. RESULTS: Forty-six patients (22 men/24 women, mean age 61.7 years (± standard deviation 16.3)) completed the study. At 1 week, 13/46 (28.3 %) and at 6 months 22/46 (47.8%) patients had completely normalized Q-SPECT. Persistence of Q-defects was more frequent in female patients in univariate and multivariate analysis. We found no correlation between the persistence of Q-defects on Q-SPECT and HVTE, BMI, plasma troponin-T, and CcS. However, lower TRJ and younger age were statistically significantly linked to normalization of Q-scans after 6 months of treatment only in univariate analysis. There is no difference in the frequency of recurrent PE in relation to the persistence of Q-defects. CONCLUSION: Acute PE patients of female, older age, and higher TRJ in univariate analysis and patients of female in multivariate analysis seem to have a higher risk of persistent Q-defects after 6 months treatment. The presence of residual Q-abnormalities at 6 months was not associated with an increased risk for recurrent PE. PMID:28197219

  20. Oncoprotein mdig contributes to silica-induced pulmonary fibrosis by altering balance between Th17 and Treg T cells

    PubMed Central

    Sun, Jiaying; Zhang, Yadong; Lu, Yongju; Battelli, Lori; Porter, Dale W.; Chen, Fei

    2015-01-01

    Mineral dust-induced gene (mdig, also named Mina53) was first identified from alveolar macrophages of the coal miners with chronic lung inflammation or fibrosis, but how this gene is involved in lung diseases is poorly understood. Here we show that heterozygotic knockout of mdig (mdig+/−) ameliorates silica-induced lung fibrosis by altering the balance between Th17 cells and Treg cells. Relative to the wild type (WT) mice, infiltration of the macrophages and Th17 cells was reduced in lungs from silica-exposed mdig+/− mice. In contrast, an increased infiltration of the T regulatory (Treg) cells to the lung intestitium was observed in the mdig+/− mice treated with silica. Both the number of Th17 cells in the lung lymph nodes and the level of IL-17 in the bronchoalveolar lavage fluids were decreased in the mdig+/− mice in response to silica. Thus, these results suggest that mdig may contribute to silica-induced lung fibrosis by altering the balance between Th17 and Treg cells. Genetic deficiency of mdig impairs Th17 cell infiltration and function, but favors infiltration of the Treg cells, the immune suppressive T cells that are able to limit the inflammatory responses by repressing the Th17 cells and macrophages. PMID:25669985

  1. The ability of genetically lean or fat slow-growing chickens to synthesize and store lipids is not altered by the dietary energy source.

    PubMed

    Baéza, E; Gondret, F; Chartrin, P; Le Bihan-Duval, E; Berri, C; Gabriel, I; Narcy, A; Lessire, M; Métayer-Coustard, S; Collin, A; Jégou, M; Lagarrigue, S; Duclos, M J

    2015-10-01

    The increasing use of unconventional feedstuffs in chicken's diets results in the substitution of starch by lipids as the main dietary energy source. To evaluate the responses of genetically fat or lean chickens to these diets, males of two experimental lines divergently selected for abdominal fat content were fed isocaloric, isonitrogenous diets with either high lipid (80 g/kg), high fiber (64 g/kg) contents (HL), or low lipid (20 g/kg), low fiber (21 g/kg) contents (LL) from 22 to 63 days of age. The diet had no effect on growth performance and did not affect body composition evaluated at 63 days of age. Glycolytic and oxidative energy metabolisms in the liver and glycogen storage in liver and Sartorius muscle at 63 days of age were greater in chicken fed LL diet compared with chicken fed HL diet. In Pectoralis major (PM) muscle, energy metabolisms and glycogen content were not different between diets. There were no dietary-associated differences in lipid contents of the liver, muscles and abdominal fat. However, the percentages of saturated (SFA) and monounsaturated fatty acids (MUFA) in tissue lipids were generally higher, whereas percentages of polyunsaturated fatty acids (PUFA) were lower for diet LL than for diet HL. The fat line had a greater feed intake and average daily gain, but gain to feed ratio was lower in that line compared with the lean line. Fat chickens were heavier than lean chickens at 63 days of age. Their carcass fatness was higher and their muscle yield was lower than those of lean chickens. The oxidative enzyme activities in the liver were lower in the fat line than in the lean line, but line did not affect energy metabolism in muscles. The hepatic glycogen content was not different between lines, whereas glycogen content and glycolytic potential were higher in the PM muscle of fat chickens compared with lean chickens. Lipid contents in the liver, muscles and abdominal fat did not differ between lines, but fat chickens stored less MUFA and

  2. Effect of High Fructose and High Fat Diets on Pulmonary Sensitivity, Motor Activity, and Body Composition of Brown Norway Rats Exposed to Ozone

    EPA Science Inventory

    Diet-induced obesity has been suggested to lead to increased susceptibility to air pollutants such as ozone (03); however, there is little experimental evidence. Thirty day old male and female Brown Norway rats were fed a normal, high-fructose or high-fat diet for 12 weeks and th...

  3. Effect of High Fructose and High Fat Diets on Pulmonary Sensitivity, Motor Activity, and Body Composition of Brown Norway Rats Exposed to Ozone

    EPA Science Inventory

    Diet-induced obesity has been suggested to lead to increased susceptibility to air pollutants such as ozone (03); however, there is little experimental evidence. Thirty day old male and female Brown Norway rats were fed a normal, high-fructose or high-fat diet for 12 weeks and th...

  4. Formation of LID vector complexes in water alters physicochemical properties and enhances pulmonary gene expression in vivo.

    PubMed

    Jenkins, R G; Meng, Q-H; Hodges, R J; Lee, L K; Bottoms, S E W; Laurent, G J; Willis, D; Ayazi Shamlou, P; McAnulty, R J; Hart, S L

    2003-06-01

    There is currently an urgent need to develop efficient gene-delivery systems for the lung that are free of inflammatory effects. The LID vector is a synthetic gene delivery system, comprised of lipofectin (L), an integrin-targeting peptide (I) and DNA (D) that has previously been shown to have high transfection efficiency in the lung. We have assessed the effect of alternative methods of complex preparation on structural features of the complex, levels and duration of reporter gene expression and the host response to the LID vector. We have demonstrated that making the complex in water affects the structure of the LID complexes making them smaller and more stable with a more cationic surface charge than complexes prepared in phosphate-buffered saline (PBS). When the LID vector was constituted in water and instilled intratracheally into the lungs of mice there was a 10-fold increase in luciferase activity compared with preparation in PBS. Furthermore, luciferase activity was still evident 1 week following vector instillation. This enhancement may be because of altered complex structure, although effects of the hypotonic vector solution on the lung cannot be excluded. The inflammatory effects of instilling the LID vector in water were minimal, even after three administrations of the LID vector, with only mild alterations in cytokine and broncho-alveolar lavage fluid (BALF) cell profiles. These results demonstrate that the LID vector can generate high, and prolonged, levels of gene expression in the lung from small quantities of DNA and that careful attention to synthetic polyplex structure may be important to optimize efficiency of gene expression in vivo.

  5. Diabetic mice exhibited a peculiar alteration in body composition with exaggerated ectopic fat deposition after muscle injury due to anomalous cell differentiation.

    PubMed

    Mogi, Masaki; Kohara, Katsuhiko; Nakaoka, Hirotomo; Kan-No, Harumi; Tsukuda, Kana; Wang, Xiao-Li; Chisaka, Toshiyuki; Bai, Hui-Yu; Shan, Bao-Shuai; Kukida, Masayoshi; Iwanami, Jun; Miki, Tetsuro; Horiuchi, Masatsugu

    2016-05-01

    Sarcopenic obesity, age-related muscle loss, which is compensated by an increase in fat mass, impairs quality of life in elderly people. Although the increase in intramuscular fat is associated with decreased insulin sensitivity and increased metabolic risk factors, the origin of diabetes-associated intramuscular fat has not been elucidated. Here, we investigated intramuscular fat deposition using a muscle injury model in type 2 diabetic mice. Male 8-week-old C57BL/6 and 8-week-old and 26-week-old KKAy underwent intramuscular injection of cardiotoxin (Ctx) (100 μL/10 μM) into the tibialis anterior (TA) muscles. After 2 weeks, the muscles were removed and evaluated. KKAy exhibited impaired muscle regeneration and ectopic fat deposition. Such impairment was more marked in older KKAy. These changes were also observed in another diabetic mouse model, db/db and diet-induced obese mice but not in streptozocin-induced diabetic mice. Deposited fat was platelet-derived growth factor (PDGF) receptor alpha positive and its cytoskeleton was stained with Masson's trichrome, indicating it to be of fibro-adipocyte progenitor cell origin. Expression of a myogenic marker, myoD, was lower and that of PDGF receptor alpha and CCAAT/enhancer binding protein (CEBP) alpha was higher in Ctx-injured TA of KKAy compared with that of C57BL/6. Peroxisome proliferator-activated receptor γ (PPARγ) was highly expressed in fat-forming lesions in older KKAy. Treatment with all-trans retinoic acid prevented the formation of intramuscular fat; however, treatment with GW9662, a PPARγ antagonist, increased the fibrotic change in muscle. Diabetic mice showed impaired muscle regeneration with fat deposition, suggesting that diabetes may enhance sarcopenic obesity through a mechanism involving anomalous fibro-adipocyte progenitor cell differentiation.

  6. Dietary saturated fat and docosahexaenoic acid differentially effect cardiac mitochondrial phospholipid fatty acyl composition and Ca(2+) uptake, without altering permeability transition or left ventricular function.

    PubMed

    O'Connell, Kelly A; Dabkowski, Erinne R; de Fatima Galvao, Tatiana; Xu, Wenhong; Daneault, Caroline; de Rosiers, Christine; Stanley, William C

    2013-06-01

    High saturated fat diets improve cardiac function and survival in rodent models of heart failure, which may be mediated by changes in mitochondrial function. Dietary supplementation with the n3-polyunsaturated fatty acid docosahexaenoic acid (DHA, 22:6n3) is also beneficial in heart failure and can affect mitochondrial function. Saturated fatty acids and DHA likely have opposing effects on mitochondrial phospholipid fatty acyl side chain composition and mitochondrial membrane function, though a direct comparison has not been previously reported. We fed healthy adult rats a standard low-fat diet (11% of energy intake from fat), a low-fat diet supplemented with DHA (2.3% of energy intake) or a high-fat diet comprised of long chain saturated fatty acids (45% fat) for 6 weeks. There were no differences among the three diets in cardiac mass or function, mitochondrial respiration, or Ca(2+)-induced mitochondrial permeability transition. On the other hand, there were dramatic differences in mitochondrial phospholipid fatty acyl side chains. Dietary supplementation with DHA increased DHA from 7% to ∼25% of total phospholipid fatty acids in mitochondrial membranes, and caused a proportional depletion of arachidonic acid (20:4n6). The saturated fat diet increased saturated fat and DHA in mitochondria and decreased linoleate (18:2n6), which corresponded to a decrease in Ca(2+) uptake by isolated mitochondria compared to the other diet groups. In conclusion, despite dramatic changes in mitochondrial phospholipid fatty acyl side chain composition by both the DHA and high saturated fat diets, there were no effects on mitochondrial respiration, permeability transition, or cardiac function.

  7. Dietary saturated fat and docosahexaenoic acid differentially effect cardiac mitochondrial phospholipid fatty acyl composition and Ca2+ uptake, without altering permeability transition or left ventricular function

    PubMed Central

    O'Connell, Kelly A; Dabkowski, Erinne R; de Fatima Galvao, Tatiana; Xu, Wenhong; Daneault, Caroline; de Rosiers, Christine; Stanley, William C

    2013-01-01

    High saturated fat diets improve cardiac function and survival in rodent models of heart failure, which may be mediated by changes in mitochondrial function. Dietary supplementation with the n3-polyunsaturated fatty acid docosahexaenoic acid (DHA, 22:6n3) is also beneficial in heart failure and can affect mitochondrial function. Saturated fatty acids and DHA likely have opposing effects on mitochondrial phospholipid fatty acyl side chain composition and mitochondrial membrane function, though a direct comparison has not been previously reported. We fed healthy adult rats a standard low-fat diet (11% of energy intake from fat), a low-fat diet supplemented with DHA (2.3% of energy intake) or a high-fat diet comprised of long chain saturated fatty acids (45% fat) for 6 weeks. There were no differences among the three diets in cardiac mass or function, mitochondrial respiration, or Ca2+-induced mitochondrial permeability transition. On the other hand, there were dramatic differences in mitochondrial phospholipid fatty acyl side chains. Dietary supplementation with DHA increased DHA from 7% to ∼25% of total phospholipid fatty acids in mitochondrial membranes, and caused a proportional depletion of arachidonic acid (20:4n6). The saturated fat diet increased saturated fat and DHA in mitochondria and decreased linoleate (18:2n6), which corresponded to a decrease in Ca2+ uptake by isolated mitochondria compared to the other diet groups. In conclusion, despite dramatic changes in mitochondrial phospholipid fatty acyl side chain composition by both the DHA and high saturated fat diets, there were no effects on mitochondrial respiration, permeability transition, or cardiac function. PMID:24303101

  8. [Nonthrombotic pulmonary embolisms].

    PubMed

    Bach, A G; Schramm, D; Surov, A

    2017-03-01

    The term nonthrombotic pulmonary embolism (NTPE) is defined as embolization of pulmonary arteries caused by foreign bodies (e. g. detached catheter fragments), biological substances (e. g. septic thrombus) or exogenous substances (e. g. gas). The frequency of NTPE is underestimated. Symptoms can cover the spectrum from undetectable to sudden death. In addition to mechanical obstruction of the pulmonary arteries, some NTPEs trigger an inflammatory cascade that causes deterioration of vascular, pulmonary and cardiac function. Radiological imaging in combination with the medical history of patients is sufficient to identify most NTPEs with certainty. The aim of this article is to make readers aware of the symptoms, frequency, relevance, classification, pathophysiology, laboratory findings and radiological findings of the most frequent forms of NTPE. The spectrum of forms presented here includes pulmonary embolisms due to foreign bodies (intravascular, intracorporeal and extracorporeal), amniotic fluid, endogenous tissue, fat, tumors, septic thrombi, hydatids, cement, metallic mercury, gas, silicone and particles.

  9. Altered expression of small proteoglycans, collagen, and transforming growth factor-beta 1 in developing bleomycin-induced pulmonary fibrosis in rats.

    PubMed Central

    Westergren-Thorsson, G; Hernnäs, J; Särnstrand, B; Oldberg, A; Heinegård, D; Malmström, A

    1993-01-01

    The development of bleomycin-induced pulmonary fibrosis in rats was studied over a period of 21 d after an intratracheal instillation of bleomycin. The expression of three small proteoglycans (biglycan, decorin, and fibromodulin), collagen III and TGF-beta 1 was studied by RNA-transfer blot analysis. The proteoglycans were also studied by SDS-polyacrylamide gel electrophoresis and Western blots. TGF-beta 1 mRNA increased threefold already on day 3 and remained elevated until day 10. After the increase of TGF-beta 1 mRNA the messages for biglycan and collagen III steadily increased to reach a maximum 10 d after bleomycin instillation. The mRNA for biglycan increased maximally fourfold and that of collagen III 2.5-fold. Decorin mRNA, in contrast to biglycan decreased and reached 20% of control on day 10. The message for fibromodulin remained constant throughout the study period. The amounts of biglycan and decorin in the tissue changed in accordance with the mRNA levels. The results corroborate and extend previous in vitro studies concerning the effect of TGF-beta 1 on the metabolism of small proteoglycans and show that these macromolecules are regulated differently also in vivo. The marked alterations of biglycan and decorin during the development of fibrosis suggests that these proteoglycans have a regulating role in this process. Images PMID:7688761

  10. Speckle-tracking-derived strain and strain-rate analysis: a technique for the evaluation of early alterations in right ventricle systolic function in patients with systemic sclerosis and normal pulmonary artery pressure.

    PubMed

    Matias, Carla; Isla, Leopoldo Pérez de; Vasconcelos, Mariana; Almería, Carlos; Rodrigo, Jose Luis; Serra, Viviana; Zamorano, José

    2009-02-01

    Systemic sclerosis is associated with pulmonary artery hypertension. Speckle-tracking-derived strain and strain rate may be a diagnostic tool to detect early changes in right ventricular function, before pulmonary artery hypertension development. Our aim was to assess whether speckle-tracking-derived strain and strain-rate parameters may detect right ventricular early alterations in patients with systemic sclerosis with normal pulmonary systolic artery pressure (PAP). Seventeen asymptomatic patients with systemic sclerosis and 22 controls were enrolled. A complete two-dimensional echo with speckle-tracking-derived longitudinal strain and strain rate of the basal right ventricular free wall and interventricular septum was performed. Median age was 56 years (43.8-71.5) in the systemic sclerosis group and 48.5 years (32-56.5) in the control group. No differences in conventional left ventricular parameters, tissue Doppler indexes, or in tricuspid annular plane systolic excursion were found. Patients with systemic sclerosis had higher levels of peak tricuspid regurgitation velocity and less respiratory collapse in the inferior vena cava. There were no differences in the speckle-tracking-derived strain and strain-rate parameters measured at the level of the basal interventricular septum and in the strain values measured at the level of the basal lateral right ventricular free wall. Nevertheless, a significant increase of the longitudinal strain rate measured at the basal lateral free wall of the right ventricle was found in patients with systemic sclerosis when compared with controls [-5.5 (-6.4--2.6)/s vs. -1.8 (-3.9--1.4)/s; P = 0.014]. Speckle-tracking-derived longitudinal strain rate is useful to detect early right ventricular function changes in patients with systemic sclerosis with normal pulmonary systolic artery pressure levels. This alteration may preclude pulmonary artery hypertension development and reflect an adaptive response to higher levels of pulmonary

  11. Silica-induced pulmonary inflammation and fibrosis in mice is altered by acute exposure to nitrogen dioxide

    SciTech Connect

    Vetrano, K.M.; Morris, J.B.; Hubbard, A.K. )

    1992-11-01

    The biologic impact of consecutive exposures to two environmental pollutants was examined in mice exposed to silica crystals (SI) by intratracheal (IT) injection followed by an inhalation exposure to nitrogen dioxide (NO2). C57Bl/6 mice received an IT injection of 2 mg SI or sterile saline (SAL) followed by a 2-h inhalation exposure to NO2 at 20 ppm either within 2 h of or 24 h after SI instillation. During acute inflammation (d 3 postsilica), mice exposed to NO2 at either time showed a dramatic and significant reduction in the number of lavaged alveolar neutrophils (PMN) when compared to silica/air-exposed mice. Animals exposed to NO[sub 2] 24 h after silica also evidenced significant decreases in levels of lavage albumin and lactate dehydrogenase (LDH) 3 d after silica, as well as significant decreases in hydroxyproline content of the lung 30 and 60 d postsilica injection when compared to silica/air-exposed animals. NO[sub 2] administration 24 h after silica appeared to shift the appearance of PMN in the lung from d 3 to d 14, but did not otherwise alter chronic cellular inflammation. These data suggest that the marked neutrophil response and collagen deposition induced by SI can be modulated by NO[sub 2] exposure and that the time of oxidant gas exposure after silica administration is critical to this modulation.

  12. Diabetic mice exhibited a peculiar alteration in body composition with exaggerated ectopic fat deposition after muscle injury due to anomalous cell differentiation

    PubMed Central

    Kohara, Katsuhiko; Nakaoka, Hirotomo; Kan‐no, Harumi; Tsukuda, Kana; Wang, Xiao‐Li; Chisaka, Toshiyuki; Bai, Hui‐Yu; Shan, Bao‐Shuai; Kukida, Masayoshi; Iwanami, Jun; Miki, Tetsuro; Horiuchi, Masatsugu

    2015-01-01

    Abstract Background Sarcopenic obesity, age‐related muscle loss, which is compensated by an increase in fat mass, impairs quality of life in elderly people. Although the increase in intramuscular fat is associated with decreased insulin sensitivity and increased metabolic risk factors, the origin of diabetes‐associated intramuscular fat has not been elucidated. Here, we investigated intramuscular fat deposition using a muscle injury model in type 2 diabetic mice. Methods Male 8‐week‐old C57BL/6 and 8‐week‐old and 26‐week‐old KKAy underwent intramuscular injection of cardiotoxin (Ctx) (100 μL/10 μM) into the tibialis anterior (TA) muscles. After 2 weeks, the muscles were removed and evaluated. Results KKAy exhibited impaired muscle regeneration and ectopic fat deposition. Such impairment was more marked in older KKAy. These changes were also observed in another diabetic mouse model, db/db and diet‐induced obese mice but not in streptozocin‐induced diabetic mice. Deposited fat was platelet‐derived growth factor (PDGF) receptor alpha positive and its cytoskeleton was stained with Masson's trichrome, indicating it to be of fibro‐adipocyte progenitor cell origin. Expression of a myogenic marker, myoD, was lower and that of PDGF receptor alpha and CCAAT/enhancer binding protein (CEBP) alpha was higher in Ctx‐injured TA of KKAy compared with that of C57BL/6. Peroxisome proliferator‐activated receptor γ (PPARγ) was highly expressed in fat‐forming lesions in older KKAy. Treatment with all‐trans retinoic acid prevented the formation of intramuscular fat; however, treatment with GW9662, a PPARγ antagonist, increased the fibrotic change in muscle. Conclusions Diabetic mice showed impaired muscle regeneration with fat deposition, suggesting that diabetes may enhance sarcopenic obesity through a mechanism involving anomalous fibro‐adipocyte progenitor cell differentiation. PMID:27493874

  13. Pulmonary function in advanced pulmonary hypertension.

    PubMed Central

    Burke, C M; Glanville, A R; Morris, A J; Rubin, D; Harvey, J A; Theodore, J; Robin, E D

    1987-01-01

    Pulmonary mechanical function and gas exchange were studied in 33 patients with advanced pulmonary vascular disease, resulting from primary pulmonary hypertension in 18 cases and from Eisenmenger physiology in 15 cases. Evidence of airway obstruction was found in most patients. In addition, mean total lung capacity (TLC) was only 81.5% of predicted and 27% of our subjects had values of TLC less than one standard deviation below the mean predicted value. The mean value for transfer factor (TLCO) was 71.8% of predicted and appreciable arterial hypoxaemia was present, which was disproportionate to the mild derangements in pulmonary mechanics. Patients with Eisenmenger physiology had significantly lower values of arterial oxygen tension (PaO2) (p less than 0.05) and of maximum mid expiratory flow (p less than 0.05) and significantly higher pulmonary arterial pressure (p less than 0.05) than those with primary pulmonary hypertension, but no other variables were significantly different between the two subpopulations. It is concluded that advanced pulmonary vascular disease in patients with primary pulmonary hypertension and Eisenmenger physiology is associated not only with severe hypoxaemia but also with altered pulmonary mechanical function. PMID:3433237

  14. Maternal fat intake in rats alters 20:4n-6 and 22:6n-3 status and the epigenetic regulation of Fads2 in offspring liver.

    PubMed

    Hoile, Samuel P; Irvine, Nicola A; Kelsall, Christopher J; Sibbons, Charlene; Feunteun, Aurélie; Collister, Alex; Torrens, Christopher; Calder, Philip C; Hanson, Mark A; Lillycrop, Karen A; Burdge, Graham C

    2013-07-01

    Poor prenatal nutrition, acting through epigenetic processes, induces persistent changes in offspring phenotype. We investigated the effect of maternal fat intake on polyunsaturated fatty acid (PUFA) status and on the epigenetic regulation of Fads2, encoding Δ6 desaturase (rate limiting in PUFA synthesis), in the adult offspring. Rats (n=6 per dietary group) were fed either 3.5% (w/w), 7% (w/w) or 21% (w/w) butter or fish oil (FO) from 14 days preconception until weaning. Offspring (n=6 males and females per dietary group) were fed 4% (w/w) soybean oil until postnatal day 77. 20:4n-6 and 22:6n-3 levels were lower in liver phosphatidylcholine (PC) and phosphatidylethanolamine and plasma PC (all P<.0001) in offspring of dams fed 21% than 3.5% or 7% fat regardless of type. Hepatic Fads2 expression related inversely to maternal dietary fat. Fads2 messenger RNA expression correlated negatively with methylation of CpGs at -623, -394, -84 and -76 bases relative to the transcription start site (all P<.005). Methylation of these CpGs was higher in offspring of dams fed 21% than 3.5% or 7% fat; FO higher than butter. Feeding adult female rats 7% fat reduced 20:4n-6 status in liver PC and Fads2 expression and increased methylation of CpGs -623, -394, -84 and -76 that reversed in animals switched from 7% to 4% fat diets. These findings suggest that fat exposure during development induces persistent changes, while adults exhibit a transient response, in hepatic PUFA status in offspring through epigenetic regulation of Fads2. Thus, epigenetic regulation of Fads2 may contribute to short- and long-term regulation of PUFA synthesis. Copyright © 2013 Elsevier Inc. All rights reserved.

  15. Single injection of the β2-adrenergic receptor agonist, clenbuterol, into newly hatched chicks alters abdominal fat pad mass in growing birds.

    PubMed

    Ishimaru, Yoshitaka; Ijiri, Daichi; Shimamoto, Saki; Ishitani, Kanae; Nojima, Tsutomu; Ohtsuka, Akira

    2015-01-15

    Excessive energy is stored in white adipose tissue as triacylglycerols in birds as well as in mammals. Although β2-adrenergic receptor agonists reduce adipose tissue mass in birds, the underlying mechanism remains unclear. The aim of the current study was to examine the effects of a single intraperitoneal injection of the β2-adrenergic receptor agonist, clenbuterol, on the abdominal fat pad tissue development. Thirty-three chicks at 1-day-old were given a single intraperitoneal injection of clenbuterol (0.1mg/kg body weight) or phosphate-buffered saline. At 2 weeks post-dose, the weight of the abdominal fat tissue was decreased in the clenbuterol-injected chicks, and small adipocyte-like cells were observed in the abdominal fat pad tissue of the clenbuterol-injected chicks. Then, the expression of mRNAs encoding genes related to avian adipogenesis was examined in the abdominal fat pat tissue. The expression of mRNAs encoding Krüppel-like zinc finger transcription factor 5 (KLF-5), KLF-15, and zinc finger protein 423 in the abdominal fat pad tissue of the clenbuterol-injected chicks was significantly lower (P<0.05) than that of the control chicks, while the expression of mRNA encoding peroxisome proliferator-activated receptor-gamma was not affected. In addition, both mRNA expression (P<0.05) and enzymatic activity (P<0.05) of fatty acid synthase (FAS) were decreased in the abdominal fat pad tissue of the clenbuterol-injected chicks, while clenbuterol injection did not affect FAS activity in liver. These results suggested that a single injection with clenbuterol into newly hatched chicks reduces their abdominal fat pad mass possibly via disrupting adipocyte development during later growth stages. Copyright © 2014 Elsevier Inc. All rights reserved.

  16. Short-term high-fat diet alters postprandial glucose metabolism and circulating vascular cell adhesion molecule-1 in healthy males.

    PubMed

    Numao, Shigeharu; Kawano, Hiroshi; Endo, Naoya; Yamada, Yuka; Takahashi, Masaki; Konishi, Masayuki; Sakamoto, Shizuo

    2016-08-01

    Short-term intake of a high-fat diet aggravates postprandial glucose metabolism; however, the dose-response relationship has not been investigated. We hypothesized that short-term intake of a eucaloric low-carbohydrate/high-fat diet (LCHF) would aggravate postprandial glucose metabolism and circulating adhesion molecules in healthy males. Seven healthy young males (mean ± SE; age: 26 ± 1 years) consumed either a eucaloric control diet (C, approximately 25% fats), a eucaloric intermediate-carbohydrate/intermediate-fat diet (ICIF, approximately 50% fats), or an LCHF (approximately 70% fats) for 3 days. An oral meal tolerance test (MTT) was performed after the 3-day dietary intervention. The concentrations of plasma glucose, insulin, glucagon-like peptide-1 (GLP-1), intercellular adhesion molecule-1, and vascular cell adhesion molecule-1 (VCAM-1) were determined at rest and during MTT. The incremental area under the curve (iAUC) of plasma glucose concentration during MTT was significantly higher in LCHF than in C (P = 0.009). The first-phase insulin secretion indexes were significantly lower in LCHF than in C (P = 0.04). Moreover, the iAUC of GLP-1 and VCAM-1 concentrations was significantly higher in LCHF than in C (P = 0.014 and P = 0.04, respectively). The metabolites from ICIF and C were not significantly different. In conclusion, short-term intake of eucaloric diet containing a high percentage of fats in healthy males excessively increased postprandial glucose and VCAM-1 concentrations and attenuated first-phase insulin release.

  17. Dietary fish oil increases fat absorption and fecal bile acid content without altering bile acid synthesis in 20-d-old weanling rats following massive ileocecal resection.

    PubMed

    Yang, Qing; Lan, Tian; Chen, Yuegang; Dawson, Paul A

    2012-07-01

    Dietary fish oil (FO) was reported to lower fecal fat excretion in a weanling rat model of short bowel syndrome (SBS) after ileocecal resection (ICR), and to induce changes in secretion and synthesis of bile acid (BA) in adults. We hypothesized that dietary FO, as compared with corn oil (CO), increases intestinal fat absorption in weanling SBS rats in part due to increased hepatic BA synthesis and luminal BA concentrations. After undergoing ICR, 20-d-old rats were fed ad lib for 7 d with a CO or FO diet containing 5% sucrose polybehenate (SPB), a marker for dietary fat absorption. Fecal fatty acid, fecal and intestine luminal BA, liver mRNA expressions of cholesterol 7α-hydroxylase (Cyp7α1) and sterol-12α-hydroxylase (Cyp8β1), and serum 7α-hydroxy-4-cholesten-3-1 (7αC4) levels were determined. As compared with CO-ICR rats, FO-ICR rats had higher intestinal absorption of total fat and most individual fatty acids. Although the BA content per gram of dry stool was increased in FO-ICR rats, there were no differences between groups for the BA content in remnant jejunum, liver mRNA expression of BA biosynthetic enzymes, Cyp7α1 and Cyp8β1, or serum 7αC4, a marker for BA synthesis. Dietary FO increases dietary fat absorption without increasing hepatic BA synthesis in weanling SBS rats.

  18. Role of Plasma Lipoproteins in Cortisone-Induced Fat Embolism

    PubMed Central

    Mahley, Robert W.; Gray, Mary E.; LeQuire, Virgil S.

    1972-01-01

    The clinical syndrome of fat embolism can be a complication in patients who have suffered long-bone fracture, and has been associated with a number of conditions in which bone fracture is not a factor. The origin of embolic fat (bone marrow or depot fat versus plasma lipoproteins) has been debated. To test the hypothesis that alterations in the composition of plasma very-low-density lipoproteins (VLDL) could lead to their coalescence and subsequent impaction in pulmonary vasculature, New Zealand white rabbits were injected intramuscularly with 25 mg of cortisone twice a day for 2, 4, 6, 11 and 12 days. Blood samples were obtained from unanesthetized animals prior to the cortisone treatment and at sacrifice. Pulmonary fat embolism that was similar histologically to that found in the human patient with the clinical syndrome was produced in all rabbits treated for 4-12 days. After the fourth day, all animals were hyperlipidemic. There was a tenfold increase in plasma VLDL concentration and the mean particle diameter of the VLDL was increased from 620 Å to 1016 Å. The proportion of triglyceride (TG) was increased, protein (PR) and phospholipid (PL) were decreased and total cholesterol (TC) was unaltered (untreated controls: PR, 16.4%; TG, 58.5%; PL, 19.2%; TC, 6.7% and cortisone-treated: PR, 8.4%; TG, 75.1%; PL, 11%; TC, 6.4%). The lipid composition of pulmonary embolic fat from rabbits treated with cortisone for 6 or 11 days was TG, 81%; PL, 13% and TC, 6%. VLDL from similarly treated rabbits had a lipid composition of TG, 79%; PL, 14.5% and TC, 6.6%. The TC concentration of bone marrow and depot fat from animals treated with cortisone for 11 days was <1%, and the PL concentration was <2%. These data support the hypothesis that plasma lipoproteins, primarily the VLDL, when altered in size and composition can coalesce into globules of sufficient size to occlude peripheral capillaries. ImagesFig 1Fig 2 PMID:5009252

  19. CARDIOVASCULAR AND BLOOD COAGULATION EFFECTS OF PULMONARY ZINC EXPOSURE

    EPA Science Inventory

    Cardiovascular damage induced by pulmonary exposure to environmental chemicals can result from direct action or, secondarily, from pulmonary injury. We have developed a rat model of pulmonary exposure to zinc to demonstrate cardiac, coagulative, and fibrinolytic alterations. Mal...

  20. CARDIOVASCULAR AND BLOOD COAGULATION EFFECTS OF PULMONARY ZINC EXPOSURE

    EPA Science Inventory

    Cardiovascular damage induced by pulmonary exposure to environmental chemicals can result from direct action or, secondarily, from pulmonary injury. We have developed a rat model of pulmonary exposure to zinc to demonstrate cardiac, coagulative, and fibrinolytic alterations. Mal...

  1. PULMONARY CIRCULATION AT EXERCISE

    PubMed Central

    NAEIJE, R; CHESLER, N

    2012-01-01

    The pulmonary circulation is a high flow and low pressure circuit, with an average resistance of 1 mmHg.min.L−1 in young adults, increasing to 2.5 mmHg.min.L−1 over 4–6 decades of life. Pulmonary vascular mechanics at exercise are best described by distensible models. Exercise does not appear to affect the time constant of the pulmonary circulation or the longitudinal distribution of resistances. Very high flows are associated with high capillary pressures, up to a 20–25 mmHg threshold associated with interstitial lung edema and altered ventilation/perfusion relationships. Pulmonary artery pressures of 40–50 mmHg, which can be achieved at maximal exercise, may correspond to the extreme of tolerable right ventricular afterload. Distension of capillaries that decrease resistance may be of adaptative value during exercise, but this is limited by hypoxemia from altered diffusion/perfusion relationships. Exercise in hypoxia is associated with higher pulmonary vascular pressures and lower maximal cardiac output, with increased likelihood of right ventricular function limitation and altered gas exchange by interstitial lung edema. Pharmacological interventions aimed at the reduction of pulmonary vascular tone have little effect on pulmonary vascular pressure-flow relationships in normoxia, but may decrease resistance in hypoxia, unloading the right ventricle and thereby improving exercise capacity. Exercise in patients with pulmonary hypertension is associated with sharp increases in pulmonary artery pressure and a right ventricular limitation of aerobic capacity. Exercise stress testing to determine multipoint pulmonary vascular pressures-flow relationships may uncover early stage pulmonary vascular disease. PMID:23105961

  2. Pulmonary circulation at exercise.

    PubMed

    Naeije, Robert; Chesler, N

    2012-01-01

    The pulmonary circulation is a high-flow and low-pressure circuit, with an average resistance of 1 mmHg/min/L in young adults, increasing to 2.5 mmHg/min/L over four to six decades of life. Pulmonary vascular mechanics at exercise are best described by distensible models. Exercise does not appear to affect the time constant of the pulmonary circulation or the longitudinal distribution of resistances. Very high flows are associated with high capillary pressures, up to a 20 to 25 mmHg threshold associated with interstitial lung edema and altered ventilation/perfusion relationships. Pulmonary artery pressures of 40 to 50 mmHg, which can be achieved at maximal exercise, may correspond to the extreme of tolerable right ventricular afterload. Distension of capillaries that decrease resistance may be of adaptative value during exercise, but this is limited by hypoxemia from altered diffusion/perfusion relationships. Exercise in hypoxia is associated with higher pulmonary vascular pressures and lower maximal cardiac output, with increased likelihood of right ventricular function limitation and altered gas exchange by interstitial lung edema. Pharmacological interventions aimed at the reduction of pulmonary vascular tone have little effect on pulmonary vascular pressure-flow relationships in normoxia, but may decrease resistance in hypoxia, unloading the right ventricle and thereby improving exercise capacity. Exercise in patients with pulmonary hypertension is associated with sharp increases in pulmonary artery pressure and a right ventricular limitation of aerobic capacity. Exercise stress testing to determine multipoint pulmonary vascular pressures-flow relationships may uncover early stage pulmonary vascular disease.

  3. Molecular adaptations underlying the beneficial effects of hydroxytyrosol in the pathogenic alterations induced by a high-fat diet in mouse liver: PPAR-α and Nrf2 activation, and NF-κB down-regulation.

    PubMed

    Valenzuela, Rodrigo; Illesca, Paola; Echeverría, Francisca; Espinosa, Alejandra; Rincón-Cervera, Miguel Ángel; Ortiz, Macarena; Hernandez-Rodas, María Catalina; Valenzuela, Alfonso; Videla, Luis A

    2017-04-19

    Non-alcoholic fatty liver disease (NAFLD) is a condition characterized by an increment in the liver fat content, with a concomitant reduction in the content of n-3-long chain polyunsaturated fatty acids (n-3 LCPUFAs), downregulation of PPAR-α activity, and upregulation of NF-κB activity, effects that induce pro-lipogenic and pro-inflammatory responses. Hydroxytyrosol (HT), a polyphenol with cytoprotective effects present in extra virgin olive oil, improves the cellular antioxidant capacity for activation of transcription factor Nrf2. The objective of this work is to evaluate the molecular adaptations involved in the anti-lipogenic, anti-inflammatory, and anti-oxidant effects of HT supplementation in high-fat diet (HFD)-fed mice. Male C57BL/6J mice received (i) control diet (10% fat); (ii) control diet + HT (daily doses of 5 mg per kg body weight), (iii) HFD (60% fat); or (iv) HFD + HT for 12 weeks. HFD-fed mice exhibited (i) liver steatosis; (ii) inflammation; (iii) oxidative stress; and (iv) depletion of n-3 LCPUFAs, together with down-regulation of PPAR-α and Nrf2, and up-regulation of NF-κB. HT supplementation attenuated the metabolic alterations produced by HFD, normalizing the activity of Nrf2, reducing the drop in activity of PPAR-α, and attenuating increment of NF-κB activation. Supplementation with HT activating transcription factors PPAR-α and Nrf2, along with the deactivation of NF-κB, may reduce the liver alterations induced in HFD-fed mice.

  4. Green tea, black tea, and epigallocatechin modify body composition, improve glucose tolerance, and differentially alter metabolic gene expression in rats fed a high-fat diet.

    PubMed

    Chen, Nora; Bezzina, Rebecca; Hinch, Edward; Lewandowski, Paul A; Cameron-Smith, David; Mathai, Michael L; Jois, Markandeya; Sinclair, Andrew J; Begg, Denovan P; Wark, John D; Weisinger, Harrison S; Weisinger, Richard S

    2009-11-01

    The mechanisms of how tea and epigallocatechin-3-gallate (EGCG) lower body fat are not completely understood. This study investigated long-term administration of green tea (GT), black tea (BT), or isolated EGCG (1 mg/kg per day) on body composition, glucose tolerance, and gene expression related to energy metabolism and lipid homeostasis; it was hypothesized that all treatments would improve the indicators of metabolic syndrome. Rats were fed a 15% fat diet for 6 months from 4 weeks of age and were supplied GT, BT, EGCG, or water. GT and BT reduced body fat, whereas GT and EGCG increased lean mass. At 16 weeks GT, BT, and EGCG improved glucose tolerance. In the liver, GT and BT increased the expression of genes involved in fatty acid synthesis (SREBP-1c, FAS, MCD, ACC) and oxidation (PPAR-alpha, CPT-1, ACO); however, EGCG had no effect. In perirenal fat, genes that mediate adipocyte differentiation were suppressed by GT (Pref-1, C/EBP-beta, and PPAR-gamma) and BT (C/EBP-beta), while decreasing LPL, HSL, and UCP-2 expression; EGCG increased expression of UCP-2 and PPAR-gamma genes. Liver triacylglycerol content was unchanged. The results suggest that GT and BT suppressed adipocyte differentiation and fatty acid uptake into adipose tissue, while increasing fat synthesis and oxidation by the liver, without inducing hepatic fat accumulation. In contrast, EGCG increased markers of thermogenesis and differentiation in adipose tissue, while having no effect on liver or muscle tissues at this dose. These results show novel and separate mechanisms by which tea and EGCG may improve glucose tolerance and support a role for these compounds in obesity prevention.

  5. Dietary Fat Alters Body Composition, Mammary Development, and Cytochrome P450 Induction after Maternal TCDD Exposure in DBA/2J Mice with Low-Responsive Aryl Hydrocarbon Receptors

    PubMed Central

    La Merrill, Michele; Kuruvilla, Bittu S.; Pomp, Daniel; Birnbaum, Linda S.; Threadgill, David W.

    2009-01-01

    Background Increased fat intake is associated with obesity and may make obese individuals uniquely susceptible to the effects of lipophilic aryl hydrocarbon receptor (AHR) ligands. Objectives We investigated the consequences of high-fat diet (HFD) and AHR ligands on body composition, mammary development, and hepatic P450 expression. Methods Pregnant C57BL/6J (B6) and DBA/2J (D2) dams, respectively expressing high- or low-responsive AHR, were dosed at mid-gestation with TCDD. At parturition, mice were placed on an HFD or a low-fat diet (LFD). Body fat of progeny was measured before dosing with 7,12-dimethylbenz[a]anthracene (DMBA). Fasting blood glucose was measured, and liver and mammary glands were analyzed. Results Maternal TCDD exposure resulted in reduced litter size in D2 mice and, on HFD, reduced postpartum survival in B6 mice. In D2 mice, HFD increased body mass and fat in off-spring, induced precocious mammary gland development, and increased AHR expression compared with mice given an LFD. Maternal TCDD exposure increased hepatic Cyp1a1 and Cyp1b1 expression in offspring on both diets, but DMBA depressed Cyp1b1 expression only in mice fed an HFD. In D2 progeny, TCDD exposure decreased mammary terminal end bud size, and DMBA exposure decreased the number of terminal end buds. Only in D2 progeny fed HFD did perinatal TCDD increase blood glucose and the size of mammary fat pads, while decreasing both branch elongation and the number of terminal end buds. Conclusions We conclude that despite having a low-responsive AHR, D2 progeny fed a diet similar to that consumed by most people are susceptible to TCDD and DMBA exposure effects blood glucose levels, mammary differentiation, and hepatic Cyp1 expression. PMID:19750107

  6. Supplementation of soy protein with branched-chain amino acids alters protein metabolism in healthy elderly and even more in patients with chronic obstructive pulmonary disease.

    PubMed

    Engelen, Mariëlle P K J; Rutten, Erica P A; De Castro, Carmen L N; Wouters, Emiel F M; Schols, Annemie M W J; Deutz, Nicolaas E P

    2007-02-01

    It is often suggested that chronic wasting diseases [eg, chronic obstructive pulmonary disease (COPD)] may benefit from branched-chain amino acid (BCAA) administration via improved protein metabolism. The aim was to examine whether adding BCAAs to a soy protein meal would enhance protein anabolism in COPD patients and in healthy elderly persons. Eight normal-weight COPD patients and 8 healthy control subjects were examined on 2 test days. Simultaneous continuous intravenous infusion of l-[ring-(2)H(5)]phenylalanine (Phe) and l-[ring-(2)H(2)]tyrosine tracers was done postabsorptively and at 2 h of ingestion of a maltodextrin soy or maltodextrin soy + BCAA protein meal (rate of ingestion: 0.02 g protein.kg body weight(-1).20 min(-1)) in a crossover design. Together with the meal, oral ingestion of 1-[(13)C]Phe was performed to measure first-pass Phe splanchnic extraction (SPE(Phe)). The endogenous rate of Phe appearance [reflecting whole-body protein breakdown (WbPB)], whole-body protein synthesis (WbPS), and net WbPS (WbPS - WbPB) were calculated. Arterialized venous blood was sampled for amino acid enrichment and concentration analyses. Soy feeding induced a reduction in WbPB and an increase in WbPS. BCAA supplementation of soy protein resulted in a significantly higher (P < 0.05) increase in WbPS than did soy protein alone in COPD patients but not in the healthy elderly. BCAA supplementation did not significantly alter the change in WbPB or net WbPS. Furthermore, BCAA supplementation decreased (absolute) SPE(Phe) (P < 0.05) but did not change the percentage Phe hydroxylation in the splanchnic area, which indicates a BCAA-related reduction in splanchnic protein synthesis. BCAA supplementation to soy protein enhances WbPS in patients with COPD and alters interorgan protein metabolism in favor of the peripheral (muscle) compartment in healthy elderly and even more in COPD patients.

  7. Patients with Chronic Obstructive Pulmonary Disease Walk with Altered Step Time and Step Width Variability as Compared with Healthy Control Subjects.

    PubMed

    Yentes, Jennifer M; Rennard, Stephen I; Schmid, Kendra K; Blanke, Daniel; Stergiou, Nicholas

    2017-06-01

    Compared with control subjects, patients with chronic obstructive pulmonary disease (COPD) have an increased incidence of falls and demonstrate balance deficits and alterations in mediolateral trunk acceleration while walking. Measures of gait variability have been implicated as indicators of fall risk, fear of falling, and future falls. To investigate whether alterations in gait variability are found in patients with COPD as compared with healthy control subjects. Twenty patients with COPD (16 males; mean age, 63.6 ± 9.7 yr; FEV1/FVC, 0.52 ± 0.12) and 20 control subjects (9 males; mean age, 62.5 ± 8.2 yr) walked for 3 minutes on a treadmill while their gait was recorded. The amount (SD and coefficient of variation) and structure of variability (sample entropy, a measure of regularity) were quantified for step length, time, and width at three walking speeds (self-selected and ±20% of self-selected speed). Generalized linear mixed models were used to compare dependent variables. Patients with COPD demonstrated increased mean and SD step time across all speed conditions as compared with control subjects. They also walked with a narrower step width that increased with increasing speed, whereas the healthy control subjects walked with a wider step width that decreased as speed increased. Further, patients with COPD demonstrated less variability in step width, with decreased SD, compared with control subjects at all three speed conditions. No differences in regularity of gait patterns were found between groups. Patients with COPD walk with increased duration of time between steps, and this timing is more variable than that of control subjects. They also walk with a narrower step width in which the variability of the step widths from step to step is decreased. Changes in these parameters have been related to increased risk of falling in aging research. This provides a mechanism that could explain the increased prevalence of falls in patients with COPD.

  8. Pulmonary Sarcomatoid Carcinomas Commonly Harbor Either Potentially Targetable Genomic Alterations or High Tumor Mutational Burden as Observed by Comprehensive Genomic Profiling.

    PubMed

    Schrock, Alexa B; Li, Shuyu D; Frampton, Garrett M; Suh, James; Braun, Eduardo; Mehra, Ranee; Buck, Steven C; Bufill, Jose A; Peled, Nir; Karim, Nagla Abdel; Hsieh, K Cynthia; Doria, Manuel; Knost, James; Chen, Rong; Ou, Sai-Hong Ignatius; Ross, Jeffrey S; Stephens, Philip J; Fishkin, Paul; Miller, Vincent A; Ali, Siraj M; Halmos, Balazs; Liu, Jane J

    2017-06-01

    Pulmonary sarcomatoid carcinoma (PSC) is a high-grade NSCLC characterized by poor prognosis and resistance to chemotherapy. Development of targeted therapeutic strategies for PSC has been hampered because of limited and inconsistent molecular characterization. Hybrid capture-based comprehensive genomic profiling was performed on DNA from formalin-fixed paraffin-embedded sections of 15,867 NSCLCs, including 125 PSCs (0.8%). Tumor mutational burden (TMB) was calculated from 1.11 megabases (Mb) of sequenced DNA. The median age of the patients with PSC was 67 years (range 32-87), 58% were male, and 78% had stage IV disease. Tumor protein p53 gene (TP53) genomic alterations (GAs) were identified in 74% of cases, which had genomics distinct from TP53 wild-type cases, and 62% featured a GA in KRAS (34%) or one of seven genes currently recommended for testing in the National Comprehensive Cancer Network NSCLC guidelines, including the following: hepatocyte growth factor receptor gene (MET) (13.6%), EGFR (8.8%), BRAF (7.2%), erb-b2 receptor tyrosine kinase 2 gene (HER2) (1.6%), and ret proto-oncogene (RET) (0.8%). MET exon 14 alterations were enriched in PSC (12%) compared with non-PSC NSCLCs (∼3%) (p < 0.0001) and were more prevalent in PSC cases with an adenocarcinoma component. The fraction of PSC with a high TMB (>20 mutations per Mb) was notably higher than in non-PSC NSCLC (20% versus 14%, p = 0.056). Of nine patients with PSC treated with targeted or immunotherapies, three had partial responses and three had stable disease. Potentially targetable GAs in National Comprehensive Cancer Network NSCLC genes (30%) or intermediate or high TMB (43%, >10 mutations per Mb) were identified in most of the PSC cases. Thus, the use of comprehensive genomic profiling in clinical care may provide important treatment options for a historically poorly characterized and difficult to treat disease. Copyright © 2017 International Association for the Study of Lung Cancer. Published

  9. Boron deprivation alters rat behaviour and brain mineral composition differently when fish oil instead of safflower oil is the diet fat source.

    PubMed

    Nielsen, Forrest H; Penland, James G

    2006-01-01

    To determine whether boron deprivation affects rat behaviour and whether behavioural responses to boron deprivation are modified by differing amounts of dietary long-chain omega-3 fatty acids. Female rats were fed diets containing 0.1 mg (9 micromol)/kg boron in a factorial arrangement with dietary variables of supplemental boron at 0 and 3mg (278 micromol)/kg and fat sources of 75 g/kg safflower oil or 65 g/kg fish (menhaden) oil plus 10 g/kg linoleic acid. After 6 weeks, six females per treatment were bred. Dams and pups continued on their respective diets through gestation, lactation and after weaning. Between ages 6 and 20 weeks, behavioural tests were performed on 13-15 male offspring from three dams in each dietary treatment. The rats were euthanized at age 21 weeks for the collection of tissues and blood. At ages 6 and 19 weeks, auditory startle was evaluated with an acoustic startle system and avoidance behaviour was evaluated by using an elevated plus maze. At ages 7 and 20 weeks, spontaneous behaviour activity was evaluated with a photobeam activity system. A brightness discrimination test was performed on the rats between age 15 and 16 weeks. Brain mineral composition was determined by coupled argon plasma atomic emission spectroscopy. Plasma total glutathione was determined by HPLC and total cholesterol and 8-iso-prostaglandin F2alpha (8-iso-PGF2alpha) were determined by using commercially available kits. Boron-deficient rats were less active than boron-adequate rats when fed safflower oil based on reduced number, distance and time of horizontal movements, front entries, margin distance and vertical breaks and jumps in the spontaneous activity evaluation. Feeding fish oil instead of safflower oil attenuated the activity response to boron deprivation. In the plus maze evaluation, the behavioural reactivity of the boron-deficient rats fed fish oil was noticeably different than the other three treatments. They made more entries into both open and closed

  10. Female mice lacking p47phox have altered adipose tissue gene expression and are protected against high fat-induced obesity

    USDA-ARS?s Scientific Manuscript database

    Oxidative stress in the fat and the liver has been linked to the development of obesity and the metabolic syndrome. However, the molecular origin of reactive oxygen species and the role of these in obesity remain areas of active investigation. The NADPH oxidases (NOX) enzymes are a major source of ...

  11. Dietary fat source alters hepatic gene expression profile and determines the type of liver pathology in rats overfed via total enteral nutrition

    USDA-ARS?s Scientific Manuscript database

    This study was designed to determine if the fatty acid composition of the diet affects the development and progression of nonalcoholic fatty liver disease (NAFLD). Male Sprague-Dawley rats (n = 5-6/group) were overfed low (5%) or high (70%) fat diets with different fatty acid sources: olive oil (OO,...

  12. High fat diet alters gut microbiota and the expression of Paneth cell-antimicrobial peptides preceding changes of circulating inflammatory cytokines

    USDA-ARS?s Scientific Manuscript database

    Obesity is established as a critical risk factor for many diseases including intestinal cancer. One of the responsible mechanisms for this relationship is the chronic inflammation driven by obesity. However, it remains to be defined whether high fat diet-induced obesity first exacerbates the intesti...

  13. Substitution of vegetable oil for a partially-hydrogenated fat favorably alters cardiovascular disease risk factors in moderately hypercholesterolemic postmenopausal women

    USDA-ARS?s Scientific Manuscript database

    Partially-hydrogenated fat is associated with increased cardiovascular disease risk. Acceptable alternatives must be adjudicated. The objective was to assess the effect of replacing partially-hydrogenated soybean oil with an alternative currently in use. Using a double-blind cross-over design, 30...

  14. A 3-day high-fat/low-carbohydrate diet does not alter exercise-induced growth hormone response in healthy males.

    PubMed

    Sasaki, Hiroto; Ishibashi, Aya; Tsuchiya, Yoshihumi; Shimura, Nobuhiro; Kurihara, Toshiyuki; Ebi, Kumiko; Goto, Kazushige

    2015-12-01

    The purpose of the present study was to examine the effects of 3 days isoenergetic high-fat/low-carbohydrate diet (HF-LC) relative to low-fat/high-carbohydrate diet (LF-HC) on the exercise-induced growth hormone (GH) response in healthy male subjects. Ten healthy young males participated in this study. Each subject consumed the HF-LC (18±1% protein, 61±2% fat, 21±1% carbohydrate, 2720 kcal per day) for 3 consecutive days after consuming the LF-HC (18±1% protein, 20±1% fat, 62±1% carbohydrate, 2755 kcal per day) for 3 consecutive days. After each dietary intervention period, the hormonal and metabolic responses to an acute exercise (30 min of continuous pedaling at 60% of V˙O2max) were compared. The intramyocellular lipid (IMCL) contents in the vastus lateralis, soleus, and tibialis anterior were evaluated by proton magnetic resonance spectroscopy. Serum GH concentrations increased significantly during the exercise after both the HF-LC and LF-HC periods (P<0.05). However, the exercise-induced GH response was not significantly different between the two periods. Fat utilization and lipolytic responses during the exercise were enhanced significantly after the HF-LC period compared with the LF-HC period. IMCL content did not differ significantly in any portion of muscle after the dietary interventions. We could not show that short-term HF-LC consumption changed significantly exercise-induced GH response or IMCL content in healthy young males. Copyright © 2015 Elsevier Ltd. All rights reserved.

  15. Pulmonary Artery Denervation Reduces Pulmonary Artery Pressure and Induces Histological Changes in an Acute Porcine Model of Pulmonary Hypertension

    PubMed Central

    Arnold, Nadine D.; Chang, William; Watson, Oliver; Swift, Andrew J.; Condliffe, Robin; Elliot, Charlie A.; Kiely, David G.; Suvarna, S. Kim; Gunn, Julian; Lawrie, Allan

    2015-01-01

    Background— Pulmonary arterial hypertension is a devastating disease with high morbidity and mortality and limited treatment options. Recent studies have shown that pulmonary artery denervation improves pulmonary hemodynamics in an experimental model and in an early clinical trial. We aimed to evaluate the nerve distribution around the pulmonary artery, to determine the effect of radiofrequency pulmonary artery denervation on acute pulmonary hypertension induced by vasoconstriction, and to demonstrate denervation of the pulmonary artery at a histological level. Methods and Results— Histological evaluation identified a circumferential distribution of nerves around the proximal pulmonary arteries. Nerves were smaller in diameter, greater in number, and located in closer proximity to the luminal aspect of the pulmonary arterial wall beyond the pulmonary artery bifurcation. To determine the effect of pulmonary arterial denervation acute pulmonary hypertension was induced in 8 pigs by intravenous infusion of thromboxane A2 analogue. Animals were assigned to either pulmonary artery denervation, using a prototype radiofrequency catheter and generator, or a sham procedure. Pulmonary artery denervation resulted in reduced mean pulmonary artery pressure and pulmonary vascular resistance and increased cardiac output. Ablation lesions on the luminal surface of the pulmonary artery were accompanied by histological and biochemical alteration in adventitial nerves and correlated with improved hemodynamic parameters. Conclusions— Pulmonary artery denervation offers the possibility of a new treatment option for patients with pulmonary arterial hypertension. Further work is required to determine the long-term efficacy and safety. PMID:26553697

  16. Fat necrosis.

    PubMed

    Canteli, B; Saez, F; de los Ríos, A; Alvarez, C

    1996-04-01

    We report the MR appearance of a case of subcutaneous fat necrosis, which is a previously unreported etiology for knee mass. The role of MR imaging in differentiating fat necrosis from other causes of soft tissue masses is discussed. We conclude that MR characteristics of subcutaneous fat necrosis are typical and allow its differentiation from other types of soft tissue lesions.

  17. Coconut fats.

    PubMed

    Amarasiri, W A L D; Dissanayake, A S

    2006-06-01

    In many areas of Sri Lanka the coconut tree and its products have for centuries been an integral part of life, and it has come to be called the "Tree of life". However, in the last few decades, the relationship between coconut fats and health has been the subject of much debate and misinformation. Coconut fats account for 80% of the fat intake among Sri Lankans. Around 92% of these fats are saturated fats. This has lead to the belief that coconut fats are 'bad for health', particularly in relation to ischaemic heart disease. Yet most of the saturated fats in coconut are medium chain fatty acids whose properties and metabolism are different to those of animal origin. Medium chain fatty acids do not undergo degradation and re-esterification processes and are directly used in the body to produce energy. They are not as 'bad for health' as saturated fats. There is the need to clarify issues relating to intake of coconut fats and health, more particularly for populations that still depend on coconut fats for much of their fat intake. This paper describes the metabolism of coconut fats and its potential benefits, and attempts to highlight its benefits to remove certain misconceptions regarding its use.

  18. Pulmonary aspects of obesity in critical care.

    PubMed

    Siela, Debra

    2009-09-01

    Critically ill obese patients have many challenging pulmonary problems. The first key is to understand pathophysiology in the pulmonary system related to obesity. Second, it is important to identify the altered physical assessments and diagnostics that occur because of the pulmonary pathophysiology of obesity. Lastly, one should be aware of medical and nursing intervention options that treat symptoms or pulmonary problems of obesity. This article summarizes pulmonary issues related to obesity in critical care.

  19. Carbohydrate/fat ratio in the diet alters histone acetylation on the sucrase-isomaltase gene and its expression in mouse small intestine.

    PubMed

    Honma, Kazue; Mochizuki, Kazuki; Goda, Toshinao

    2007-06-15

    A diet with a high carbohydrate/fat ratio enhances jejunal SI gene expression. Using ChIP assay, we revealed that the acetylation of histone H3 on transcriptional region and H4 on promoter region, respectively, of mouse SI gene are high. The acetylation of histone H3 and H4 as well as binding of HNF-1 and Cdx-2 on SI gene, was enhanced by increase in carbohydrate/fat ratio in the diet. These suggest that induction of SI gene by the diet rich in carbohydrate is associated with acetylation of histone H3 and H4 as well as binding of HNF-1 and Cdx-2 on SI gene.

  20. High-Fat Diet Promotion of Endometriosis in an Immunocompetent Mouse Model is Associated With Altered Peripheral and Ectopic Lesion Redox and Inflammatory Status.

    PubMed

    Heard, Melissa E; Melnyk, Stepan B; Simmen, Frank A; Yang, Yanqing; Pabona, John Mark P; Simmen, Rosalia C M

    2016-07-01

    Endometriosis is a benign gynecological condition that causes considerable morbidity due to associated infertility, debilitating pelvic pain and inflammatory dysfunctions. Diet is a highly modifiable risk factor for many chronic diseases, but its contribution to endometriosis has not been extensively investigated, due partly to the paradoxical inverse association between obesity and disease incidence. Nevertheless, chronic exposure to dietary high-fat intake has been linked to greater systemic inflammation and oxidative stress, both features of women with endometriosis. Here, we evaluated the effects of a high-fat diet (HFD) (45% fat kcal) on endometriosis progression using an immunocompetent mouse model where ectopic lesion incidence was induced in wild-type recipients by ip administration of endometrial fragments from transcription factor Krüppel-like factor 9-null donor mice. We show that HFD significantly increased ectopic lesion numbers in recipient mice with no significant weight gain and modifications in systemic ovarian steroid hormone and insulin levels, relative to control diet-fed (17% fat kcal) mice. HFD promotion of lesion establishment was associated with reductions in stromal estrogen receptor 1 isoform and progesterone receptor expression, increased F4/80-positive macrophage infiltration, higher stromal but not glandular epithelial proliferation, and enhanced expression of proinflammatory and prooxidative stress pathway genes. Lesion-bearing HFD-fed mice also displayed higher peritoneal fluid TNFα and elevated local and systemic redox status than control diet-fed counterparts. Our results suggest that HFD intake exacerbates endometriosis outcome in the absence of ovarian dysfunction and insulin resistance in mice and warrants further consideration with respect to clinical management of endometriosis progression and recurrence in nonobese patients.

  1. Benzyl isothiocyanate suppresses high-fat diet-stimulated mammary tumor progression via the alteration of tumor microenvironments in obesity-resistant BALB/c mice.

    PubMed

    Kim, Minhee; Cho, Han Jin; Kwon, Gyoo Taik; Kang, Young-Hee; Kwon, Seung-Hae; Her, Song; Park, Taesung; Kim, Yongkang; Kee, Yun; Park, Jung Han Yoon

    2015-01-01

    We previously reported that a high-fat diet (HFD) and M2-macrophages induce changes in tumor microenvironments and stimulate tumor growth and metastasis of 4T1 mammary cancer cells in BALB/c mice. In this study, we attempted to determine whether benzyl isothiocyanate (BITC) inhibits HFD-induced changes in tumor progression and in tumor microenvironments. Four groups of female BALB/c mice (4-week-old) were fed on a control diet (CD, 10 kcal% fat) and HFD (60 kcal% fat) containing BITC (0, 25, or 100 mg/kg diet) for 20 weeks. Following 16 weeks of feeding, 4T1 cells (5×10(4) cells) were injected into the mammary fat pads, and animals were killed 30 d after the injection. HFD feeding increased solid tumor growth and the number of tumor nodules in the lung and liver, as compared to the CD group, and these increases were inhibited by BITC supplementation. The number of lipid vacuoles, CD45+ leukocytes and CD206+ M2-macrophages, expression of Ki67, levels of cytokines/chemokines, including macrophage-colony stimulating factor (M-CSF) and monocyte chemoattractant protein-1, and mRNA levels of F4/80, CD86, Ym1, CD163, CCR2, and M-CSF receptor were increased in the tumor tissues of HFD-fed mice, and these increases were inhibited by BITC supplementation. In vitro culture results demonstrated that BITC inhibited macrophage migration as well as lipid droplet accumulation in 3T3-L1 cells. These results suggest that suppression of lipid accumulation and macrophage infiltration in tumor tissues may be one of the mechanisms by which BITC suppresses tumor progression in HFD-fed mice. © 2014 Wiley Periodicals, Inc.

  2. Glucagon-like peptide-1 receptor activation stimulates hepatic lipid oxidation and restores hepatic signalling alteration induced by a high-fat diet in nonalcoholic steatohepatitis.

    PubMed

    Svegliati-Baroni, Gianluca; Saccomanno, Stefania; Rychlicki, Chiara; Agostinelli, Laura; De Minicis, Samuele; Candelaresi, Cinzia; Faraci, Graziella; Pacetti, Deborah; Vivarelli, Marco; Nicolini, Daniele; Garelli, Paolo; Casini, Alessandro; Manco, Melania; Mingrone, Geltrude; Risaliti, Andrea; Frega, Giuseppe N; Benedetti, Antonio; Gastaldelli, Amalia

    2011-10-01

    High-fat dietary intake and low physical activity lead to insulin resistance, nonalcoholic fatty liver disease (NAFLD) and nonalcoholic steatohepatitis (NASH). Recent studies have shown an effect of glucagon-like peptide-1 (GLP-1) on hepatic glucose metabolism, although GLP-1 receptors (GLP-1r) have not been found in human livers. The aim of this study was to investigate the presence of hepatic GLP-1r and the effect of exenatide, a GLP-1 analogue, on hepatic signalling. The expression of GLP-1r was evaluated in human liver biopsies and in the livers of high-fat diet-treated rats. The effect of exenatide (100 nM) was evaluated in hepatic cells of rats fed 3 months with the high-fat diet. GLP-1r is expressed in human hepatocytes, although reduced in patients with NASH. Similarly, in rats with NASH resulted from 3 months of the high-fat diet, we found a decreased expression of GLP-1r and peroxisome proliferator-activated receptor γ (PPARγ), and reduced peroxisome proliferator-activated receptor α (PPARα) activity. Incubation of hepatocytes with exenatide increased PPARγ expression, which also exerted an insulin-sensitizing action by reducing JNK phosphorylation. Moreover, exenatide increased protein kinase A (PKA) activity, Akt and AMPK phosphorylation and determined a PKA-dependent increase of PPARα activity. GLP-1 has a direct effect on hepatocytes, by activating genes involved in fatty acid β-oxidation and insulin sensitivity. GLP-1 analogues could be a promising treatment approach to improve hepatic insulin resistance in patients with NAFLD/NASH. © 2011 John Wiley & Sons A/S.

  3. Altered Left Ventricular Ion Channel Transcriptome in a High-Fat-Fed Rat Model of Obesity: Insight into Obesity-Induced Arrhythmogenesis.

    PubMed

    Ashrafi, Reza; Yon, Marianne; Pickavance, Lucy; Yanni Gerges, Joseph; Davis, Gershan; Wilding, John; Jian, Kun; Zhang, Henggui; Hart, George; Boyett, Mark

    2016-01-01

    Introduction. Obesity is increasingly common and is associated with an increased prevalence of cardiac arrhythmias. The aim of this study was to see whether in obesity there is proarrhythmic gene expression of ventricular ion channels and related molecules. Methods and Results. Rats were fed on a high-fat diet and compared to control rats on a normal diet (n = 8). After 8 weeks, rats on the high-fat diet showed significantly greater weight gain and higher adiposity. Left ventricle samples were removed at 8 weeks and mRNA expression of ion channels and other molecules was measured using qPCR. Obese rats had significant upregulation of Cav1.2, HCN4, Kir2.1, RYR2, NCX1, SERCA2a, and RYR2 mRNA and downregulation of ERG mRNA. In the case of HCN4, it was confirmed that there was a significant increase in protein expression. The potential effects of the mRNA changes on the ventricular action potential and intracellular Ca(2+) transient were predicted using computer modelling. Modelling predicted prolongation of the ventricular action potential and an increase in the intracellular Ca(2+) transient, both of which would be expected to be arrhythmogenic. Conclusion. High-fat diet causing obesity results in arrhythmogenic cardiac gene expression of ion channels and related molecules.

  4. Momordica charantia ameliorates insulin resistance and dyslipidemia with altered hepatic glucose production and fatty acid synthesis and AMPK phosphorylation in high-fat-fed mice.

    PubMed

    Shih, Chun-Ching; Shlau, Min-Tzong; Lin, Cheng-Hsiu; Wu, Jin-Bin

    2014-03-01

    Momordica charantia Linn. (Cucurbitaceae) fruit is commonly known as bitter melon. C57BL/6J mice were firstly divided randomly into two groups: the control (CON) group was fed with a low-fat diet, whereas the experimental group was fed a 45% high-fat (HF) diet for 8 weeks. Afterwards, the CON group was treated with vehicle, whereas the HF group was subdivided into five groups and still on HF diet and was given orally M. charantia extract (MCE) or rosiglitazone (Rosi) or not for 4 weeks. M. charantia decreased the weights of visceral fat and caused glucose lowering. AMP-activated protein kinase (AMPK) is a major cellular regulator of lipid and glucose metabolism. MCE significantly increases the hepatic protein contents of AMPK phosphorylation by 126.2-297.3% and reduces expression of phosphenolpyruvate carboxykinase (PEPCK) and glucose production. Most importantly, MCE decreased expression of hepatic 11beta hydroxysteroid dehydroxygenase (11beta-HSD1) gene, which contributed in attenuating diabetic state. Furthermore, MCE lowered serum triglycerides (TGs) by inhibition of hepatic fatty acid synthesis by dampening sterol response element binding protein 1c and fatty acid synthase mRNA leading to reduction in TGs synthesis. This study demonstrates M. charantia ameliorates diabetic and hyperlipidemic state in HF-fed mice occurred by regulation of hepatic PEPCK, 11beta-HSD1 and AMPK phosphorylation.

  5. Early postnatal alteration of body composition in preterm and small-for-gestational-age infants: implications of catch-up fat.

    PubMed

    Okada, Tomoo; Takahashi, Shigeru; Nagano, Nobuhiko; Yoshikawa, Kayo; Usukura, Yukihiro; Hosono, Shigeharu

    2015-01-01

    The concept of the developmental origins of health and disease is based on studies by Barker et al. They proposed a hypothesis that undernutrition in utero permanently changes the body's structure, function, and metabolism in ways that lead to atherosclerosis and insulin resistance in later life. In addition, profound effects on the extent of body fatness and insulin sensitivity are demonstrated, if there is a "mismatch" between prenatal and postnatal environments. In previous studies, undernutrition in utero has been evaluated simply by birth weight itself or birth weight for gestational age, and the degree of mismatch has been estimated by postnatal rapid weight gain. Recently, we investigated subcutaneous fat accumulation in small-for-gestational-age infants and found that a rapid catch-up in skinfold thickness developed prior to the body weight catch-up. Furthermore, insulin-like growth factor-I and lipoprotein lipase mass concentrations also demonstrate rapid increase during the neonatal period with fat accumulation. Investigating the precise mechanisms of developmental origins of health and disease including mediating metabolic and hormonal factors may provide a new approach to prevent atherosclerosis and insulin resistance. Better management of undernutrition during gestation and neonatal growth during the early postnatal period is an important theme for future health.

  6. Altered Left Ventricular Ion Channel Transcriptome in a High-Fat-Fed Rat Model of Obesity: Insight into Obesity-Induced Arrhythmogenesis

    PubMed Central

    Yon, Marianne; Pickavance, Lucy; Yanni Gerges, Joseph; Davis, Gershan; Wilding, John; Jian, Kun; Hart, George; Boyett, Mark

    2016-01-01

    Introduction. Obesity is increasingly common and is associated with an increased prevalence of cardiac arrhythmias. The aim of this study was to see whether in obesity there is proarrhythmic gene expression of ventricular ion channels and related molecules. Methods and Results. Rats were fed on a high-fat diet and compared to control rats on a normal diet (n = 8). After 8 weeks, rats on the high-fat diet showed significantly greater weight gain and higher adiposity. Left ventricle samples were removed at 8 weeks and mRNA expression of ion channels and other molecules was measured using qPCR. Obese rats had significant upregulation of Cav1.2, HCN4, Kir2.1, RYR2, NCX1, SERCA2a, and RYR2 mRNA and downregulation of ERG mRNA. In the case of HCN4, it was confirmed that there was a significant increase in protein expression. The potential effects of the mRNA changes on the ventricular action potential and intracellular Ca2+ transient were predicted using computer modelling. Modelling predicted prolongation of the ventricular action potential and an increase in the intracellular Ca2+ transient, both of which would be expected to be arrhythmogenic. Conclusion. High-fat diet causing obesity results in arrhythmogenic cardiac gene expression of ion channels and related molecules. PMID:27747100

  7. Thiol-redox antioxidants protect against lung vascular endothelial cytoskeletal alterations caused by pulmonary fibrosis inducer, bleomycin: comparison between classical thiol-protectant, N-acetyl-L-cysteine, and novel thiol antioxidant, N,N'-bis-2-mercaptoethyl isophthalamide.

    PubMed

    Patel, Rishi B; Kotha, Sainath R; Sauers, Lynn A; Malireddy, Smitha; Gurney, Travis O; Gupta, Niladri N; Elton, Terry S; Magalang, Ulysses J; Marsh, Clay B; Haley, Boyd E; Parinandi, Narasimham L

    2012-06-01

    Lung vascular alterations and pulmonary hypertension associated with oxidative stress have been reported to be involved in idiopathic lung fibrosis (ILF). Therefore, here, we hypothesize that the widely used lung fibrosis inducer, bleomycin, would cause cytoskeletal rearrangement through thiol-redox alterations in the cultured lung vascular endothelial cell (EC) monolayers. We exposed the monolayers of primary bovine pulmonary artery ECs to bleomycin (10 µg) and studied the cytotoxicity, cytoskeletal rearrangements, and the macromolecule (fluorescein isothiocyanate-dextran, 70,000 mol. wt.) paracellular transport in the absence and presence of two thiol-redox protectants, the classic water-soluble N-acetyl-L-cysteine (NAC) and the novel hydrophobic N,N'-bis-2-mercaptoethyl isophthalamide (NBMI). Our results revealed that bleomycin induced cytotoxicity (lactate dehydrogenase leak), morphological alterations (rounding of cells and filipodia formation), and cytoskeletal rearrangement (actin stress fiber formation and alterations of tight junction proteins, ZO-1 and occludin) in a dose-dependent fashion. Furthermore, our study demonstrated the formation of reactive oxygen species, loss of thiols (glutathione, GSH), EC barrier dysfunction (decrease of transendothelial electrical resistance), and enhanced paracellular transport (leak) of macromolecules. The observed bleomycin-induced EC alterations were attenuated by both NAC and NBMI, revealing that the novel hydrophobic thiol-protectant, NBMI, was more effective at µM concentrations as compared to the water-soluble NAC that was effective at mM concentrations in offering protection against the bleomycin-induced EC alterations. Overall, the results of the current study suggested the central role of thiol-redox in vascular EC dysfunction associated with ILF.

  8. Thiol-redox antioxidants protect against lung vascular endothelial cytoskeletal alterations caused by pulmonary fibrosis inducer, bleomycin: comparison between classical thiol-protectant, N-acetyl-l-cysteine, and novel thiol antioxidant, N,N′-bis-2-mercaptoethyl isophthalamide

    PubMed Central

    Patel, Rishi B.; Kotha, Sainath R.; Sauers, Lynn A.; Malireddy, Smitha; Gurney, Travis O.; Gupta, Niladri N.; Elton, Terry S.; Magalang, Ulysses J.; Marsh, Clay B.; Haley, Boyd E.; Parinandi, Narasimham L.

    2012-01-01

    Lung vascular alterations and pulmonary hypertension associated with oxidative stress have been reported to be involved in idiopathic lung fibrosis (ILF). Therefore, here, we hypothesize that the widely used lung fibrosis inducer, bleomycin, would cause cytoskeletal rearrangement through thiol-redox alterations in the cultured lung vascular endothelial cell (EC) monolayers. We exposed the monolayers of primary bovine pulmonary artery ECs to bleomycin (10 µg) and studied the cytotoxicity, cytoskeletal rearrangements, and the macromolecule (fluorescein isothiocyanate-dextran, 70,000 mol. wt.) paracellular transport in the absence and presence of two thiol-redox protectants, the classic water-soluble N-acetyl-l-cysteine (NAC) and the novel hydrophobic N,N′-bis-2-mercaptoethyl isophthalamide (NBMI). Our results revealed that bleomycin induced cytotoxicity (lactate dehydrogenase leak), morphological alterations (rounding of cells and filipodia formation), and cytoskeletal rearrangement (actin stress fiber formation and alterations of tight junction proteins, ZO-1 and occludin) in a dose-dependent fashion. Furthermore, our study demonstrated the formation of reactive oxygen species, loss of thiols (glutathione, GSH), EC barrier dysfunction (decrease of transendothelial electrical resistance), and enhanced paracellular transport (leak) of macromolecules. The observed bleomycin-induced EC alterations were attenuated by both NAC and NBMI, revealing that the novel hydrophobic thiol-protectant, NBMI, was more effective at µM concentrations as compared to the water-soluble NAC that was effective at mM concentrations in offering protection against the bleomycin-induced EC alterations. Overall, the results of the current study suggested the central role of thiol-redox in vascular EC dysfunction associated with ILF. PMID:22409285

  9. The pulmonary extracellular lining.

    PubMed Central

    George, G; Hook, G E

    1984-01-01

    The extracellular lining of the lungs is reviewed. The pulmonary extracellular lining is a complex mixture of phospholipids, proteins and carbohydrates which is absolutely essential for the maintenance of normal pulmonary functions such as gas exchange. Without the lining the lungs would collapse. Alterations in the pulmonary extracellular lining may underlie some disease conditions induced by toxic agents, especially those which interfere with the formation of pulmonary surfactant. The extracellular lining could be used to detect and monitor damage and disease caused by agents toxic to the lungs. The lining contains many hydrolytic enzymes which may act to detoxify certain toxic agents such as those which contain ester groups. The pulmonary extracellular lining could play a significant role mediating the toxic action of inhaled agents as well as the removal of those agents from the lungs. Images FIGURE 1. PMID:6376100

  10. Pulmonary angiography

    MedlinePlus

    ... Pulmonary arteriography; Pulmonary angiogram; Angiogram of the lungs Images Pulmonary arteries References Jackson JE, Meaney JFM. Angiography. ... urac.org). URAC's accreditation program is an independent audit to verify that A.D.A.M. follows ...

  11. Pulmonary Rehabilitation

    MedlinePlus

    ... Topics Bronchitis COPD Cystic Fibrosis Idiopathic Pulmonary Fibrosis Sarcoidosis Send a link to NHLBI to someone by ... people who have COPD (chronic obstructive pulmonary disease), sarcoidosis (sar-koy-DOE-sis), idiopathic pulmonary fibrosis , or ...

  12. Alteration in Intrapulmonary Pharmacokinetics of Aerosolized Model Compounds Due to Disruption of the Alveolar Epithelial Barriers Following Bleomycin-Induced Pulmonary Fibrosis in Rats.

    PubMed

    Togami, Kohei; Chono, Sumio; Tada, Hitoshi

    2016-03-01

    Idiopathic pulmonary fibrosis is a lethal lung disease that is characterized by the accumulation of extracellular matrix and a change in lung structure. In this study, intrapulmonary pharmacokinetics of aerosolized model compounds were evaluated using rats with bleomycin-induced pulmonary fibrosis. Aerosol formulations of indocyanine green, 6-carboxyfluorescein (6-CF), and fluorescein isothiocyanate dextrans (FD; 4.4, 10, 70, and 250 kDa) were administered to rat lungs using a MicroSprayer. Indocyanine green fluorescence signals were significantly weaker in fibrotic lungs than in control lungs and 6-CF and FD concentrations in the plasma of pulmonary fibrotic animals were markedly higher than in the plasma of control animals. Moreover, disrupted epithelial tight junctions, including claudins-1, -3, and -5, were observed in pulmonary fibrotic lesions using immunofluorescence microscopy. In addition, destruction of tight junctions on model alveolar epithelial cells (NCI-H441) by transforming growth factor-β1 treatment enhanced the permeability of 6-CF and FDs through NCI-H441 cell monolayers. These results indicate that aerosolized drugs are easily distributed into the plasma after leakage through damaged tight junctions of alveolar epithelium. Therefore, the development of delivery systems for anti-fibrotic agents to improve intrapulmonary pharmacokinetics may be necessary for effective idiopathic pulmonary fibrosis therapy.

  13. Substance P (SP)-neurokinin-1 receptor (NK-1R) alters adipose tissue responses to high-fat diet and insulin action.

    PubMed

    Karagiannides, Iordanes; Stavrakis, Dimitris; Bakirtzi, Kyriaki; Kokkotou, Efi; Pirtskhalava, Tamara; Nayeb-Hashemi, Hamed; Bowe, Collin; Bugni, James M; Nuño, Miriam; Lu, Bao; Gerard, Norma P; Leeman, Susan E; Kirkland, James L; Pothoulakis, Charalabos

    2011-06-01

    Peripheral administration of a specific neurokinin-1 receptor (NK-1R) antagonist to mice leads to reduced weight gain and circulating levels of insulin and leptin after high-fat diet (HFD). Here, we assessed the contribution of substance P (SP) and NK-1R in diet-induced obesity using NK-1R deficient [knockout (KO)] mice and extended our previous findings to show the effects of SP-NK-1R interactions on adipose tissue-associated insulin signaling and glucose metabolic responses. NK-1R KO and wild-type (WT) littermates were fed a HFD for 3 wk, and obesity-associated responses were determined. Compared with WT, NK-1 KO mice show reduced weight gain and circulating levels of leptin and insulin in response to HFD. Adiponectin receptor mRNA levels are higher in mesenteric fat and liver in NK-1 KO animals compared with WT, after HFD. Mesenteric fat from NK-1R KO mice fed with HFD has reduced stress-activated protein kinase/c-Jun N-terminal kinase and protein kinase C activation compared with WT mice. After glucose challenge, NK-1R KO mice remove glucose from the circulation more efficiently than WT and pair-fed controls, suggesting an additional peripheral effect of NK-1R-mediated signaling on glucose metabolism. Glucose uptake experiments in isolated rat adipocytes showed that SP directly inhibits insulin-mediated glucose uptake. Our results further establish a role for SP-NK-1R interactions in adipose tissue responses, specifically as they relate to obesity-associated pathologies such as glucose intolerance and insulin resistance. Our results highlight this pathway as an important therapeutic approach for type 2 diabetes.

  14. Substitution of vegetable oil for a partially-hydrogenated fat favorably alters cardiovascular disease risk factors in moderately hypercholesterolemic postmenopausal womena,b

    PubMed Central

    Vega-López, Sonia; Matthan, Nirupa R.; Ausman, Lynne M.; Ai, Masumi; Otokozawa, Seiko; Schaefer, Ernst J.; Lichtenstein, Alice H.

    2010-01-01

    Objective Compared to vegetable oils in their unmodified state, partially-hydrogenated fat is associated with less favorable effects on cardiovascular disease (CVD) risk factors. Acceptable alternatives must be adjudicated. Our objective was to assess the effect of a recent commercial fat substitution, corn oil for partially-hydrogenated soybean oil. Methods Using a double-blind cross-over design, 30 postmenopausal women ≥50 y with LDL-cholesterol concentrations ≥120 mg/dL were randomly assigned to each of two 35-day phases; all food and beverage was provided to maintain body weight. Corn or partially-hydrogenated soybean oil was incorporated throughout the diet and contributed two-thirds of fat. Primary outcomes included fasting and non-fasting lipid, lipoprotein, apolipoprotein, and fasting high sensitivity C-reactive protein (hsCRP) concentrations; secondary outcomes included fasting small dense LDL (sdLDL)-cholesterol, remnant lipoprotein cholesterol (RemLC), glycated albumin, adiponectin and immunoreactive insulin concentrations, and endogenous cholesteryl ester transfer protein (CETP) and lecithin:cholesterol acyl transferase (LCAT) activities. Results Relative to the partially-hydrogenated soybean oil-enriched diet, the corn oil enriched diet resulted in lower fasting total cholesterol (7%; P<0.0001), LDL-cholesterol (10%; P<0.0001), VLDL-cholesterol (7%; P=0.052), apo B (9%; P<0.0001), Lp(a) (5%; P=0.024), sdLDL-cholesterol (17%; P=0.001), and RemLC (20%; P=0.007) concentrations, and no significant effect on the other outcomes. Changes in postprandial (4-h post-meal) lipid, lipoprotein and apolipoprotein concentrations were similar to the fasting state. Conclusion The replacement of partially-hydrogenated soybean oil with corn oil favorably affects a range of CVD risk factors and is an appropriate option to decrease cardiovascular disease risk factors in moderately hypercholesterolemic individuals. PMID:19423109

  15. Exposure to a high-fat diet alters leptin sensitivity and elevates renal sympathetic nerve activity and arterial pressure in rabbits.

    PubMed

    Prior, Larissa J; Eikelis, Nina; Armitage, James A; Davern, Pamela J; Burke, Sandra L; Montani, Jean-Pierre; Barzel, Benjamin; Head, Geoffrey A

    2010-04-01

    The activation of the sympathetic nervous system through the central actions of the adipokine leptin has been suggested as a major mechanism by which obesity contributes to the development of hypertension. However, direct evidence for elevated sympathetic activity in obesity has been limited to muscle. The present study examined the renal sympathetic nerve activity and cardiovascular effects of a high-fat diet (HFD), as well as the changes in the sensitivity to intracerebroventricular leptin. New Zealand white rabbits fed a 13.5% HFD for 4 weeks showed modest weight gain but a 2- to 3-fold greater accumulation of visceral fat compared with control rabbits. Mean arterial pressure, heart rate, and plasma norepinephrine concentration increased by 8%, 26%, and 87%, respectively (P<0.05), after 3 weeks of HFD. Renal sympathetic nerve activity was 48% higher (P<0.05) in HFD compared with control diet rabbits and was correlated to plasma leptin (r=0.87; P<0.01). Intracerebroventricular leptin administration (5 to 100 microg) increased mean arterial pressure similarly in both groups, but renal sympathetic nerve activity increased more in HFD-fed rabbits. By contrast, intracerebroventricular leptin produced less neurons expressing c-Fos in HFD compared with control rabbits in regions important for appetite and sympathetic actions of leptin (arcuate: -54%, paraventricular: -69%, and dorsomedial hypothalamus: -65%). These results suggest that visceral fat accumulation through consumption of a HFD leads to marked sympathetic activation, which is related to increased responsiveness to central sympathoexcitatory effects of leptin. The paradoxical reduction in hypothalamic neuronal activation by leptin suggests a marked "selective leptin resistance" in these animals.

  16. A Difference in Fatty Acid Composition of Isocaloric High-Fat Diets Alters Metabolic Flexibility in Male C57BL/6JOlaHsd Mice.

    PubMed

    Duivenvoorde, Loes P M; van Schothorst, Evert M; Swarts, Hans M; Kuda, Ondrej; Steenbergh, Esther; Termeulen, Sander; Kopecky, Jan; Keijer, Jaap

    2015-01-01

    Poly-unsaturated fatty acids (PUFAs) are considered to be healthier than saturated fatty acids (SFAs), but others postulate that especially the ratio of omega-6 to omega-3 PUFAs (n6/n3 ratio) determines health. Health can be determined with biomarkers, but functional health status is likely better reflected by challenge tests that assess metabolic flexibility. The aim of this study was to determine the effect of high-fat diets with different fatty acid compositions, but similar n6/n3 ratio, on metabolic flexibility. Therefore, adult male mice received isocaloric high-fat diets with either predominantly PUFAs (HFpu diet) or predominantly SFAs (HFs diet) but similar n6/n3 ratio for six months, during and after which several biomarkers for health were measured. Metabolic flexibility was assessed by the response to an oral glucose tolerance test, a fasting and re-feeding test and an oxygen restriction test (OxR; normobaric hypoxia). The latter two are non-invasive, indirect calorimetry-based tests that measure the adaptive capacity of the body as a whole. We found that the HFs diet, compared to the HFpu diet, increased mean adipocyte size, liver damage, and ectopic lipid storage in liver and muscle; although, we did not find differences in body weight, total adiposity, adipose tissue health, serum adipokines, whole body energy balance, or circadian rhythm between HFs and HFpu mice. HFs mice were, furthermore, less flexible in their response to both fasting- re-feeding and OxR, while glucose tolerance was indistinguishable. To conclude, the HFs versus the HFpu diet increased ectopic fat storage, liver damage, and mean adipocyte size and reduced metabolic flexibility in male mice. This study underscores the physiological relevance of indirect calorimetry-based challenge tests.

  17. Alteration of strain background and a high omega-6 fat diet induces earlier onset of pancreatic neoplasia in EL-Kras transgenic mice.

    PubMed

    Cheon, Eric C; Strouch, Matthew J; Barron, Morgan R; Ding, Yongzeng; Melstrom, Laleh G; Krantz, Seth B; Mullapudi, Bhargava; Adrian, Kevin; Rao, Sambasiva; Adrian, Thomas E; Bentrem, David J; Grippo, Paul J

    2011-06-15

    Diets containing omega-6 (ω-6) fat have been associated with increased tumor development in carcinogen-induced pancreatic cancer models. However, the effects of ω-6 fatty acids and background strain on the development of genetically-induced pancreatic neoplasia is unknown. We assessed the effects of a diet rich in ω-6 fat on the development of pancreatic neoplasia in elastase (EL)-Kras(G12D) (EL-Kras) mice in two different backgrounds. EL-Kras FVB mice were crossed to C57BL/6 (B6) mice to produce EL-Kras FVB6 F1 (or EL-Kras F1) and EL-Kras B6 congenic mice. Age-matched EL-Kras mice from each strain were compared to one another on a standard chow. Two cohorts of EL-Kras FVB and EL-Kras F1 mice were fed a 23% corn oil diet and compared to age-matched mice fed a standard chow. Pancreata were scored for incidence, frequency, and size of neoplastic lesions, and stained for the presence of mast cells to evaluate changes in the inflammatory milieu secondary to a high fat diet. EL-Kras F1 mice had increased incidence, frequency, and size of pancreatic neoplasia compared to EL-Kras FVB mice. The frequency and size of neoplastic lesions and the weight and pancreatic mast cell densities in EL-Kras F1 mice were increased in mice fed a high ω-6 fatty acid diet compared to mice fed a standard chow. We herein introduce the EL-Kras B6 mouse model which presents with increased frequency of pancreatic neoplasia compared to EL-Kras F1 mice. The phenotype in EL-Kras F1 and FVB mice is promoted by a diet rich in ω-6 fatty acid.

  18. Skin-specific deletion of stearoyl-CoA desaturase-1 alters skin lipid composition and protects mice from high fat diet-induced obesity.

    PubMed

    Sampath, Harini; Flowers, Matthew T; Liu, Xueqing; Paton, Chad M; Sullivan, Ruth; Chu, Kiki; Zhao, Minghui; Ntambi, James M

    2009-07-24

    Stearoyl-CoA desaturase-1 (SCD1) catalyzes the synthesis of monounsaturated fatty acids and is an important regulator of whole body energy homeostasis. Severe cutaneous changes in mice globally deficient in SCD1 also indicate a role for SCD1 in maintaining skin lipids. We have generated mice with a skin-specific deletion of SCD1 (SKO) and report here that SKO mice display marked sebaceous gland hypoplasia and depletion of sebaceous lipids. In addition, SKO mice have significantly increased energy expenditure and are protected from high fat diet-induced obesity, thereby recapitulating the hypermetabolic phenotype of global SCD1 deficiency. Genes of fat oxidation, lipolysis, and thermogenesis, including uncoupling proteins and peroxisome proliferator-activated receptor-gamma co-activator-1alpha, are up-regulated in peripheral tissues of SKO mice. However, unlike mice globally deficient in SCD1, SKO mice have an intact hepatic lipogenic response to acute high carbohydrate feeding. Despite increased basal thermogenesis, SKO mice display severe cold intolerance because of rapid depletion of fuel substrates, including hepatic glycogen, to maintain core body temperature. These data collectively indicate that SKO mice have increased cold perception because of loss of insulating factors in the skin. This results in up-regulation of thermogenic processes for temperature maintenance at the expense of fuel economy, illustrating cross-talk between the skin and peripheral tissues in maintaining energy homeostasis.

  19. High-fat diet reduces local myostatin-1 paralog expression and alters skeletal muscle lipid content in rainbow trout, Oncorhynchus mykiss.

    PubMed

    Galt, Nicholas J; Froehlich, Jacob Michael; Meyer, Ben M; Barrows, Frederic T; Biga, Peggy R

    2014-06-01

    Muscle growth is an energetically demanding process that is reliant on intramuscular fatty acid depots in most fishes. The complex mechanisms regulating this growth and lipid metabolism are of great interest for human health and aquaculture applications. It is well established that the skeletal muscle chalone, myostatin, plays a role in lipid metabolism and adipogenesis in mammals; however, this function has not been fully assessed in fishes. We therefore examined the interaction between dietary lipid levels and myostatin expression in rainbow trout (Oncorhynchus mykiss). Five weeks of high-fat diet (HFD; 25 % lipid) intake increased white muscle lipid content and decreased circulating glucose levels and hepatosomatic index when compared to low-fat diet (LFD; 10 % lipid) intake. In addition, HFD intake reduced myostatin-1a and myostatin-1b expression in white muscle and myostatin-1b expression in brain tissue. Characterization of the myostatin-1a, myostatin-1b, and myostatin-2a promoters revealed putative binding sites for a subset of transcription factors associated with lipid metabolism. Taken together, these data suggest that HFD may regulate myostatin expression through cis-regulatory elements sensitive to increased lipid intake. Further, these findings provide a framework for future investigations of mechanisms describing the relationships between myostatin and lipid metabolism in fish.

  20. High-fat diet reduces local myostatin-1 paralog expression and alters skeletal muscle lipid content in rainbow trout, Oncorhynchus mykiss

    PubMed Central

    Galt, Nicholas J.; Froehlich, Jacob Michael; Meyer, Ben M.; Barrows, Frederic T.; Biga, Peggy R.

    2014-01-01

    Muscle growth is an energetically demanding process that is reliant on intramuscular fatty acid depots in most fishes. The complex mechanisms regulating this growth and lipid metabolism are of great interest for human health and aquaculture applications. It is well established that the skeletal muscle chalone, myostatin, plays a role in lipid metabolism and adipogenesis in mammals; however, this function has not been fully assessed in fishes. We therefore examined the interaction between dietary lipid levels and myostatin expression in rainbow trout (Oncorhynchus mykiss). Five-weeks of high-fat (HFD; 25% lipid) dietary intake increased white muscle lipid content, and decreased circulating glucose levels and hepatosomatic index when compared to low-fat diet (LFD; 10% lipid) intake. In addition HFD intake reduced myostatin-1a and -1b expression in white muscle and myostatin-1b expression in brain tissue. Characterization of the myostatin-1a, -1b, and -2a promoters revealed putative binding sites for a subset of transcription factors associated with lipid metabolism. Taken together, these data suggest that HFD may regulate myostatin expression through cis-regulatory elements sensitive to increased lipid intake. Further, these findings provide a framework for future investigations of mechanisms describing the relationships between myostatin and lipid metabolism in fish. PMID:24264425

  1. Perinatal maternal high-fat diet promotes alterations in hepatic lipid metabolism and resistance to the hypolipidemic effect of fish oil in adolescent rat offspring.

    PubMed

    Oliveira, Lorraine S; Souza, Luana L; Souza, Aline F P; Cordeiro, Aline; Kluck, George E G; Atella, Georgia C; Trevenzoli, Isis H; Pazos-Moura, Carmen C

    2016-11-01

    Maternal high-fat diet (HFD) promotes obesity and metabolic disturbances in offspring at weaning and adult life. We investigated metabolic consequences of maternal HFD in adolescent rat offspring and the potential benefic effects of fish oil (FO) (n-3 polyunsaturated fatty acid source). Female rats received isocaloric, standard diet (STD: 9% fat) or HFD (28.6%) before mating, and throughout pregnancy and lactation. After weaning, male offspring received standard diet and, from 25th to 45th day, received oral administration of soybean oil (SO) or FO. HFD offspring showed higher body weight and adiposity, which was not attenuated by FO. In STD offspring, FO reduced serum triglyceride and cholesterol, as expected, but not in HFD offspring. Liver of HFD offspring groups showed increased free cholesterol and FO-treated HFD group showed lower expression of Abcg8, suggesting decreased cholesterol biliary excretion. HFD offspring presented higher hepatic expression of lipogenic markers, Srebf1 mRNA and acetyl CoA carboxylase (ACC). Serum n-3 PUFA were decreased in FO-treated HFD compared to FO-treated STD offspring, which may explain the reduced hypolipidemic FO effect. Maternal HFD impaired the ability of FO to reduce adiposity and serum lipids in adolescent offspring, suggesting a potential predisposition to future development of metabolic disorders. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  2. The lung inflammation and skeletal muscle wasting induced by subchronic cigarette smoke exposure are not altered by a high-fat diet in mice.

    PubMed

    Hansen, Michelle J; Chen, Hui; Jones, Jessica E; Langenbach, Shenna Y; Vlahos, Ross; Gualano, Rosa C; Morris, Margaret J; Anderson, Gary P

    2013-01-01

    Obesity and cigarette smoking independently constitute major preventable causes of morbidity and mortality and obesity is known to worsen lung inflammation in asthma. Paradoxically, higher body mass index (BMI) is associated with reduced mortality in smoking induced COPD whereas low BMI increases mortality risk. To date, no study has investigated the effect of a dietary-induced obesity and cigarette smoke exposure on the lung inflammation and loss of skeletal muscle mass in mice. Male BALB/c mice were exposed to 4 cigarettes/day, 6 days/week for 7 weeks, or sham handled. Mice consumed either standard laboratory chow (3.5 kcal/g, 12% fat) or a high fat diet (HFD, 4.3 kcal/g, 32% fat). Mice exposed to cigarette smoke for 7 weeks had significantly more inflammatory cells in the BALF (P<0.05) and the mRNA expression of pro-inflammatory cytokines and chemokines was significantly increased (P<0.05); HFD had no effect on these parameters. Sham- and smoke-exposed mice consuming the HFD were significantly heavier than chow fed animals (12 and 13%, respectively; P<0.05). Conversely, chow and HFD fed mice exposed to cigarette smoke weighed 16 and 15% less, respectively, compared to sham animals (P<0.05). The skeletal muscles (soleus, tibialis anterior and gastrocnemius) of cigarette smoke-exposed mice weighed significantly less than sham-exposed mice (P<0.05) and the HFD had no protective effect. For the first time we report that cigarette smoke exposure significantly decreased insulin-like growth factor-1 (IGF-1) mRNA expression in the gastrocnemius and tibialis anterior and IGF-1 protein in the gastrocnemius (P<0.05). We have also shown that cigarette smoke exposure reduced circulating IGF-1 levels. IL-6 mRNA expression was significantly elevated in all three skeletal muscles of chow fed smoke-exposed mice (P<0.05). In conclusion, these findings suggest that a down-regulation in local IGF-1 may be responsible for the loss of skeletal muscle mass following cigarette smoke

  3. Facts about monounsaturated fats

    MedlinePlus

    Monounsaturated fatty acid; MUFA; Oleic acid; Cholesterol - monounsaturated fat; Atherosclerosis - monounsaturated fat; Hardening of the arteries - monounsaturated fat; Hyperlipidemia - monounsaturated fat; ...

  4. Facts about polyunsaturated fats

    MedlinePlus

    Polyunsaturated fatty acid; PUFA; Cholesterol - polyunsaturated fat; Atherosclerosis - polyunsaturated fat; Hardening of the arteries - polyunsaturated fat; Hyperlipidemia - polyunsaturated fat; Hypercholesterolemia - polyunsaturated ...

  5. Mice fed a high-fat diet supplemented with resistant starch display marked shifts in the liver metabolome concurrent with altered gut bacteria

    USDA-ARS?s Scientific Manuscript database

    High-amylose maize resistant starch type 2 (HAMRS2) is a fermentable dietary fiber known to alter the gut milieu, including the gut microbiota, which may explain reported effects of resistant starch to ameliorate obesity-associated metabolic dysfunction. Our working hypothesis is that HAMRS2-induced...

  6. Long-term intake of a high prebiotic fiber diet but not high protein reduces metabolic risk after a high fat challenge and uniquely alters gut microbiota and hepatic gene expression.

    PubMed

    Saha, Dolan C; Reimer, Raylene A

    2014-09-01

    A mismatch between early developmental diet and adulthood may increase obesity risk. Our objective was to determine the effects of re-matching rats to their weaning diets high in protein or fiber after transient high-fat/high-sucrose challenge in adulthood. We hypothesize that a long-term high fiber diet will be associated with a gut microbiota and hepatic gene expression reflective of reduced adiposity. Wistar rat pups were fed a control (C), high prebiotic fiber (HF), or high protein (HP) diet from 3-15 weeks of age; a high-fat/high-sucrose diet from 15-21 weeks; their respective C, HF, or HP diets from 21-25 weeks. Gut microbiota of cecal contents and hepatic gene expression were measured when rats were terminated at 25 weeks of age. HF rats had higher total bacteria, bifidobacteria and Bacteroides/Prevotella spp than C and HP at 25 weeks (P < 0.05). Firmicutes, especially Clostridium leptum, decreased in HF compared to C and HP (P < .05). The ratio of Firmicutes:Bacteroidetes was markedly lower in HF versus C and HP at 25 weeks (P < .05). HF decreased hepatic cholesterol content compared to HP and C at 25 weeks. HF and HP increased 3-hydroxy-3-methylglutaryl-CoA reductase mRNA and decreased lecithin-cholesterol acyltransferase mRNA compared to C (P < .05). In conclusion, re-matching rats to a HF but not HP diet attenuated the typical increase in Firmicutes:Bacteroidetes ratio associated with consumption of a high fat diet. Lower hepatic cholesterol with long-term HF diet intake may be related to alterations in gut microbiota and hepatic lipid metabolism. Copyright © 2014 Elsevier Inc. All rights reserved.

  7. The beneficial effects of early short-term exercise in the offspring of obese mothers are accompanied by alterations in the hypothalamic gene expression of appetite regulators and FTO (fat mass and obesity associated) gene.

    PubMed

    Caruso, V; Bahari, H; Morris, M J

    2013-08-01

    Maternal overnutrition is implicated in the development of adult metabolic disease, and has been shown to alter the expression of genes involved in energy homeostasis. In the present study, we aimed to test whether a short period of voluntary exercise, followed by a sedentary period, would regulate hypothalamic markers involved in appetite. Adult female Sprague-Dawley rats were fed either normal chow or high-fat diet (HFD) ad lib. for 5 weeks, mated and continued on their assigned diet during gestation/lactation. At weaning males, were separated into chow or HFD groups; half were exercised (running wheels), whereas the remainder were sedentary. At week 10, wheels were removed and rats remained sedentary for 5 weeks, prior to tissue collection. Maternal obesity increased offspring adiposity at 15 weeks and this was exacerbated by postnatal HFD (P < 0.05). Body weight and fat mass were reduced in offspring of obese mothers if they exercised, and this was maintained even after 5 weeks without exercise. At 15 weeks, fasting plasma insulin, leptin and triglyceride concentrations were significantly reduced by exercise in offspring of lean and obese mothers consuming chow, with little benefit in those consuming HFD. Hypothalamic mRNA expression of pro-opiomelanocortin was increased by exercise but only in offspring of lean mothers. Exercise reduced hypothalamic FTO (fat mass and obesity associated) mRNA in offspring of lean dams regardless of diet. A short period of exercise early in life had lasting beneficial effects on body weight, adiposity and hormone profile of male offspring from obese and lean dams, despite being followed by a period of inactivity. The effects of exercise on hypothalamic appetite regulators were more marked in offspring of lean dams. © 2013 British Society for Neuroendocrinology.

  8. Dietary supplementation with fish oil alters the expression levels of proteins governing mitochondrial dynamics and prevents high-fat diet-induced endothelial dysfunction.

    PubMed

    Sun, Ruifang; Wang, Xiaoming; Liu, Yan; Xia, Min

    2014-07-28

    Diets supplemented with fish oil (FO), which is rich in n-3 PUFA, have been shown to modify several key risk factors for CVD. The purpose of the present study was to determine the effect of FO supplementation on mitochondrial dynamic protein expression in the endothelium and on endothelial cell function. Male apoE-deficient (apoE-/-) mice (8 weeks old, n 12 per group) were fed a high-fat diet containing 45% fat (HFD group) or a HFD with partial replacement of lard with 10% (w/w) FO (FO group) (total EPA and DHA content 64.1 g/kg) for 8 weeks. ApoE-/- mice in the FO group had a greater endothelium-dependent vasorelaxation response to acetylcholine (Ach) than those in the HFD group. The atherosclerotic lesion volume in the aortic sinus of mice in the FO group was 54% lower than that in the HFD group (P< 0.01). In addition, the aortas isolated from mice in the FO group had higher expression levels of Mfn2 and Opa1 but lower expression levels of Fis1 than those from the HFD group. Compared with mice fed the HFD, those fed the FO diet showed significantly lower levels of mitochondrial oxidative stress, cytochrome c release and caspase-3 activity (each P< 0.05). Furthermore, FO-fed mice displayed increased NO release and availability and enhanced endothelial NO synthase activity compared with HFD-fed mice. Taken together, these results reveal a novel mechanism by which FO protects against endothelial cell dysfunction, which may result in improved mitochondrial dynamics.

  9. Agmatine ameliorates type 2 diabetes induced-Alzheimer's disease-like alterations in high-fat diet-fed mice via reactivation of blunted insulin signalling.

    PubMed

    Kang, Somang; Kim, Chul-Hoon; Jung, Hosung; Kim, Eosu; Song, Ho-Taek; Lee, Jong Eun

    2017-02-01

    The risk of Alzheimer's disease (AD) is higher in patients with type 2 diabetes mellitus (T2DM). Previous studies in high-fat diet-induced AD animal models have shown that brain insulin resistance in these animals leads to the accumulation of amyloid beta (Aβ) and the reduction in GSK-3β phosphorylation, which promotes tau phosphorylation to cause AD. No therapeutic treatments that target AD in T2DM patients have yet been discovered. Agmatine, a primary amine derived from l-arginine, has exhibited anti-diabetic effects in diabetic animals. The aim of this study was to investigate the ability of agmatine to treat AD induced by brain insulin resistance. ICR mice were fed a 60% high-fat diet for 12 weeks and received one injection of streptozotocin (100 mg/kg/ip) 4 weeks into the diet. After the 12-week diet, the mice were treated with agmatine (100 mg/kg/ip) for 2 weeks. Behaviour tests were conducted prior to sacrifice. Brain expression levels of the insulin signal molecules p-IRS-1, p-Akt, and p-GSK-3β and the accumulation of Aβ and p-tau were evaluated. Agmatine administration rescued the reduction in insulin signalling, which in turn reduced the accumulation of Aβ and p-tau in the brain. Furthermore, agmatine treatment also reduced cognitive decline. Agmatine attenuated the occurrence of AD in T2DM mice via the activation of the blunted insulin signal. Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.

  10. PPARγ activation alters fatty acid composition in adipose triglyceride, in addition to proliferation of small adipocytes, in insulin resistant high-fat fed rats.

    PubMed

    Sato, Daisuke; Oda, Kanako; Kusunoki, Masataka; Nishina, Atsuyoshi; Takahashi, Kazuaki; Feng, Zhonggang; Tsutsumi, Kazuhiko; Nakamura, Takao

    2016-02-15

    It was reported that adipocyte size is potentially correlated in part to amount of long chain polyunsaturated fatty acids (PUFAs) and insulin resistance because several long chain PUFAs can be ligands of peroxisome proliferator-activated receptors (PPARs). In our previous study, marked reduction of PUFAs was observed in insulin-resistant high-fat fed rats, which may indicate that PUFAs are consumed to improve insulin resistance. Although PPARγ agonist, well known as an insulin sensitizer, proliferates small adipocytes, the effects of PPARγ agonist on FA composition in adipose tissue have not been clarified yet. In the present study, we administered pioglitazone, a PPARγ agonist, to high-fat fed rats, and measured their FA composition of triglyceride fraction in adipose tissue and adipocyte diameters in pioglitazone-treated (PIO) and non-treated (control) rats. Insulin sensitivity was obtained with hyperinsulinemic euglycemic clamp. Average adipocyte diameter in the PIO group were smaller than that in the control one without change in tissue weight. In monounsaturated FAs (MUFAs), 14:1n-5, 16:1n-7, and 18:1n-9 contents in the PIO group were lower than those, respectively, in the control group. In contrast, 22:6n-3, 20:3n-6, 20:4n-6, and 22:4n-6 contents in the PIO group were higher than those, respectively, in the control group. Insulin sensitivity was higher in the PIO group than in the control one. These findings suggest that PPARγ activation lowered MUFAs whereas suppressed most of C20 or C22 PUFAs reduction, and that the change of fatty acid composition may be relevant with increase in small adipocytes. Copyright © 2016 Elsevier B.V. All rights reserved.

  11. Prenatal Metformin Exposure in a Maternal High Fat Diet Mouse Model Alters the Transcriptome and Modifies the Metabolic Responses of the Offspring

    PubMed Central

    Salomäki, Henriikka; Heinäniemi, Merja; Vähätalo, Laura H.; Ailanen, Liisa; Eerola, Kim; Ruohonen, Suvi T.; Pesonen, Ullamari; Koulu, Markku

    2014-01-01

    Aims Despite the wide use of metformin in metabolically challenged pregnancies, the long-term effects on the metabolism of the offspring are not known. We studied the long-term effects of prenatal metformin exposure during metabolically challenged pregnancy in mice. Materials and Methods Female mice were on a high fat diet (HFD) prior to and during the gestation. Metformin was administered during gestation from E0.5 to E17.5. Male and female offspring were weaned to a regular diet (RD) and subjected to HFD at adulthood (10-11 weeks). Body weight and several metabolic parameters (e.g. body composition and glucose tolerance) were measured during the study. Microarray and subsequent pathway analyses on the liver and subcutaneous adipose tissue of the male offspring were performed at postnatal day 4 in a separate experiment. Results Prenatal metformin exposure changed the offspring's response to HFD. Metformin exposed offspring gained less body weight and adipose tissue during the HFD phase. Additionally, prenatal metformin exposure prevented HFD-induced impairment in glucose tolerance. Microarray and annotation analyses revealed metformin-induced changes in several metabolic pathways from which electron transport chain (ETC) was prominently affected both in the neonatal liver and adipose tissue. Conclusion This study shows the beneficial effects of prenatal metformin exposure on the offspring's glucose tolerance and fat mass accumulation during HFD. The transcriptome data obtained at neonatal age indicates major effects on the genes involved in mitochondrial ATP production and adipocyte differentiation suggesting the mechanistic routes to improved metabolic phenotype at adulthood. PMID:25541979

  12. High-fat and fructose intake induces insulin resistance, dyslipidemia, and liver steatosis and alters in vivo macrophage-to-feces reverse cholesterol transport in hamsters.

    PubMed

    Briand, François; Thiéblemont, Quentin; Muzotte, Elodie; Sulpice, Thierry

    2012-04-01

    Reverse cholesterol transport (RCT) promotes the egress of cholesterol from peripheral tissues to the liver for biliary and fecal excretion. Although not demonstrated in vivo, RCT is thought to be impaired in patients with metabolic syndrome, in which liver steatosis prevalence is relatively high. Golden Syrian hamsters were fed a nonpurified (CON) diet and normal drinking water or a high-fat (HF) diet containing 27% fat, 0.5% cholesterol, and 0.25% deoxycholate as well as 10% fructose in drinking water for 4 wk. Compared to CON, the HF diet induced insulin resistance and dyslipidemia, with significantly higher plasma non-HDL-cholesterol concentrations and cholesteryl ester transfer protein activity. The HF diet induced severe liver steatosis, with significantly higher cholesterol and TG levels compared to CON. In vivo RCT was assessed by i.p. injecting ³H-cholesterol labeled macrophages. Compared to CON, HF hamsters had significantly greater ³H-tracer recoveries in plasma, but not HDL. After 72 h, ³H-tracer recovery in HF hamsters was 318% higher in liver and 75% lower in bile (P < 0.01), indicating that the HF diet impaired hepatic cholesterol fluxes. However, macrophage-derived cholesterol fecal excretion was 45% higher in HF hamsters than in CON hamsters. This effect was not related to intestinal cholesterol absorption, which was 89% higher in HF hamsters (P < 0.05), suggesting a possible upregulation of transintestinal cholesterol excretion. Our data indicate a significant increase in macrophage-derived cholesterol fecal excretion in a hamster model of metabolic syndrome, which may not compensate for the diet-induced dyslipidemia and liver steatosis.

  13. Dietary Fats

    MedlinePlus

    ... PHOs to food. Try to replace them with oils such as canola, olive, safflower, sesame, or sunflower. Of course, eating too much fat will put on the pounds. Fat has twice as many calories as proteins or carbohydrates. NIH: National Heart, Lung, and Blood Institute

  14. Signal transduction by the Fat cytoplasmic domain

    PubMed Central

    Pan, Guohui; Feng, Yongqiang; Ambegaonkar, Abhijit A.; Sun, Gongping; Huff, Matthew; Rauskolb, Cordelia; Irvine, Kenneth D.

    2013-01-01

    The large atypical cadherin Fat is a receptor for both Hippo and planar cell polarity (PCP) pathways. Here we investigate the molecular basis for signal transduction downstream of Fat by creating targeted alterations within a genomic construct that contains the entire fat locus, and by monitoring and manipulating the membrane localization of the Fat pathway component Dachs. We establish that the human Fat homolog FAT4 lacks the ability to transduce Hippo signaling in Drosophila, but can transduce Drosophila PCP signaling. Targeted deletion of conserved motifs identifies a four amino acid C-terminal motif that is essential for aspects of Fat-mediated PCP, and other internal motifs that contribute to Fat-Hippo signaling. Fat-Hippo signaling requires the Drosophila Casein kinase 1ϵ encoded by discs overgrown (Dco), and we characterize candidate Dco phosphorylation sites in the Fat intracellular domain (ICD), the mutation of which impairs Fat-Hippo signaling. Through characterization of Dachs localization and directed membrane targeting of Dachs, we show that localization of Dachs influences both the Hippo and PCP pathways. Our results identify a conservation of Fat-PCP signaling mechanisms, establish distinct functions for different regions of the Fat ICD, support the correlation of Fat ICD phosphorylation with Fat-Hippo signaling, and confirm the importance of Dachs membrane localization to downstream signaling pathways. PMID:23318637

  15. Nephrocalcinosis and hyperlipidemia in rats fed a cholesterol- and fat-rich diet: association with hyperoxaluria, altered kidney and bone minerals, and renal tissue phospholipid-calcium interaction.

    PubMed

    Schmiedl, A; Schwille, P O; Bonucci, E; Erben, R G; Grayczyk, A; Sharma, V

    2000-12-01

    To determine whether an "atherogenic" diet (excess of cholesterol and neutral fat) induces pathological calcification in various organs, including the kidney, and abnormal oxalate metabolism, 24 male Sprague-Dawley rats were fed either normal lab chow (controls, n = 12) or the cholesterol- and fat-rich experimental diet (CH-F, n = 12) for 111 +/- 3 days. CH-F rats developed dyslipidemia [high blood levels of triglycerides, total, low-density lipoprotein (LDL)-, very low-density lipoprotein (VLDL)-, high-density lipoprotein (HDL)-bound cholesterol, total phospholipids], elevated serum total alkaline phosphatase and lactate dehydrogenase (LDH) levels, in the absence of changes in overall renal function, extracellular mineral homeostasis [serum protein-corrected total calcium, magnesium, parathyroid hormone (PTH), 1,25-dihydroxyvitamin D (1,25(OH)2D)], plasma glycolate and oxalate levels. There was a redistribution of bone calcium and enhanced exchange of this within the extraosseous space, which was accompanied by significant bone calcium loss, but normal bone histomorphometry. Liver oxalate levels, if expressed per unit of defatted (DF) dry liver, were three times higher than in the controls. Urinary glycolate, oxalate, calcium and total protein excretion levels were elevated, the latter showing an excess of proteins > 100 kD and a deficit of proteins > 30-50 kD. Urinary calcium oxalate supersaturation was increased, and calcium phosphate supersaturation was unchanged. There were dramatically increased (by number, circumference, and area) renal calcium phosphate calcifications in the cortico-medullary region, but calcium oxalate deposits were not detectable. Electron microscopy (EM) and elemental analysis revealed intratubular calcium phosphate, apparently needle-like hydroxyapatite. Immunohistochemistry of renal tissue calcifications revealed co-localization of phospholipids and calcium phosphate. It is concluded that rats fed the CH-F diet exhibited: (1) a

  16. Dietary supplementation of conjugated linoleic acid in horses increases plasma conjugated linoleic acid and decreases plasma arachidonic acid but does not alter body fat.

    PubMed

    Headley, S; Coverdale, J A; Jenkins, T C; Klein, C M; Sharp, J L; Vernon, K L

    2012-12-01

    Studies using dietary supplementation of eicosapentaenoic and docosahexaenoic fatty acids (FA) in horses report inconsistent anti-inflammatory results but consistently report an increase in plasma arachidonic acid (C20:4), the major substrate of cyclooxygenase (COX) II inflammatory pathway. Conjugated linoleic acid has shown anti-inflammatory effects in laboratory and food animal species, but effects of CLA supplementation in horses have not been reported. Our objective was to determine the effects of CLA supplementation on plasma CLA and C20:4 and body fat in healthy horses at maintenance. In a crossover study, 12 mature mares were blocked by breed, age, and BCS and separated into 2 treatment groups (n = 6/group). Groups were fed CLA and corn oil (CO; isocaloric control) for two 6-wk feeding periods, separated by a 4-wk period during which treatment was withheld. Corn oil or CLA supplement (55% mixed CLA isomers) was incorporated into diets at 0.01% BW/d. Mares were fed individually and restricted to dry lots to control forage intake. Rump fat thickness (RFT), BW, and BCS were measured before (d 0) and after (d 42) each feeding period. Blood was collected on d 0, 14, 28, and 42 of each 6-wk period for GLC analysis of plasma CLA isomers (cis-9, trans-11; trans-10, cis-12; and trans-9, trans-11) and C20:4. An ANOVA was conducted to compare the response of RFT, BW, and BCS of CLA-treated and control mares. A mixed methods analysis with repeated measures was used to detect differences in plasma FA concentrations. There were no differences in BW, RFT, or BCS between treatment groups. All CLA isomers present in the CLA supplement were greater in plasma of horses fed CLA compared with controls (P < 0.01). Additionally, plasma concentrations of C20:4 were decreased in horses fed CLA (P < 0.05). This decline in C20:4 may impact the COX II pathway and warrants further investigation. These results suggest that in an equine model, dietary CLA increases circulating

  17. [Fat-embolic vascular occlusions in avian lungs. Research of histologically determinable neutral fats in parrotlike birds (Psittaciformes)].

    PubMed

    Brunner, P; Meinl, M

    1976-01-01

    In 50 flying birds (49 parrot-like, one peacock), the content of fat-embolic vascular occlusions was determined. In 22 cases, fat-embolic occlusions of low intensity were found in pulmonary capillaries. There were no occlusions in renal vessels. The fat embolies had no influence on a lethal outcome. There was no statistically significant correlation between the fatty infiltration of the liver, the fat content of the bone marrow, and the frequency of fat-embolic occlusion of blood vessels. In 18 cases, mycoses were the cause of death. These infections did not influence the number of fat-embolic vascular occlusions.

  18. Congenital diaphragmatic hernia-associated pulmonary hypertension.

    PubMed

    Harting, Matthew T

    2017-06-01

    Congenital diaphragmatic hernia (CDH) is a complex entity wherein a diaphragmatic defect allows intrathoracic herniation of intra-abdominal contents and both pulmonary parenchymal and vascular development are stifled. Pulmonary pathology and pathophysiology, including pulmonary hypoplasia and pulmonary hypertension, are hallmarks of CDH and are associated with disease severity. Pulmonary hypertension (PH) is sustained, supranormal pulmonary arterial pressure, and among patients with CDH (CDH-PH), is driven by hypoplastic pulmonary vasculature, including alterations at the molecular, cellular, and tissue levels, along with pathophysiologic pulmonary vasoreactivity. This review addresses the basic mechanisms, altered anatomy, definition, diagnosis, and management of CDH-PH. Further, emerging therapies targeting CDH-PH and PH are explored. Published by Elsevier Inc.

  19. Reperfusion pulmonary edema

    SciTech Connect

    Klausner, J.M.; Paterson, I.S.; Mannick, J.A.; Valeri, C.R.; Shepro, D.; Hechtman, H.B. )

    1989-02-17

    Reperfusion following lower-torso ischemia in humans leads to respiratory failure manifest by pulmonary hypertension, hypoxemia, and noncardiogenic pulmonary edema. The mechanism of injury has been studied in the sheep lung lymph preparation, where it has been demonstrated that the reperfusion resulting in pulmonary edema is due to an increase in microvascular permeability of the lung to protein. This respiratory failure caused by reperfusion appears to be an inflammatory reaction associated with intravascular release of the chemoattractants leukotriene B{sub 4} and thromboxane. Histological studies of the lung in experimental animals revealed significant accumulation of neutrophils but not platelets in alveolar capillaries. The authors conclude that thromboxane generated and released from the ischemic tissue is responsible for the transient pulmonary hypertension. Second, it is likely that the chemoattractants are responsible for leukosequestration, and third, neutrophils, oxygen-derived free radicals, and thromboxane moderate the altered lung permeability.

  20. [Pulmonary thromboembolism in obstetrics].

    PubMed

    Angulo Vázquez, José; Ramírez García, Andrés; Torres Gómez, Luis Guillermo; Vargas González, Alejandro; Cortés Sanabria, Laura

    2004-08-01

    Pulmonary embolism is a serious and sometimes mortal complication of pregnant and puerperal women. Pulmonary embolism diagnosis can be difficult. In Mexico, it causes between 2.5 and 16% of maternal mortality. To estimate the incidence of pulmonary embolism, to identify most frequently risk factors that contribute to the presence of pulmonary embolism as an obstetrical complication and to determine clinical characteristics and specific diagnostic tests in hospitalized patients at the Hospital de Ginecoobstetricia, Centro Medico Nacional de Occidente, Instituto Mexicano del Seguro Social. We conducted a cross-sectional study from January 1st 1997 to December 31st, 2002. We identified 30 patients with pulmonary embolism confirmed by ventilation-perfusion scan. Incidence of 4.7 cases per 10,000 pregnancies was found. Most frequently, risk factors were varicose veins in lower extremities (0.045), previous thromboembolic event (0.030) and pre-eclampsia/eclampsia (0.05). Cesarean section was present in 85% of the cases with pulmonary embolism during puerperium. The most common clinical findings were: dyspnea (100%), chest pain (63%), tachycardia (93%) and tachypnea (93%). Sinus tachycardia (93%) and S1 Q3 T3 were the electrocardiogram findings most commonly observed. 83% of the patients showed abnormalities in chest radiography. 100% presented altered blood values. Mortality rate was of 6.6%. Diagnosis of pulmonary embolism should be based on risk factors and clinical findings. Basic laboratory and scan are essential. Early diagnosis and treatment significantly reduce mortality rates.

  1. Network analysis of adipose tissue gene expression highlights altered metabolic and regulatory transcriptomic activity in high-fat-diet-fed IL-1RI knockout mice.

    PubMed

    Morine, Melissa J; Toomey, Sinead; McGillicuddy, Fiona C; Reynolds, Clare M; Power, Karen A; Browne, John A; Loscher, Christine; Mills, Kingston H G; Roche, Helen M

    2013-05-01

    A subacute inflammatory phenotype is implicated in the pathology of insulin resistance (IR) and type 2 diabetes mellitus. Interleukin (IL)-1α and IL-1β are produced by innate immune cells, including macrophages, and mediate their inflammatory response through the IL-1 type I receptor (IL-IRI). This study sought to understand the transcriptomic signature of adipose tissue in obese IL-1RI(-/-) mice. Following dietary intervention, markers of insulin sensitivity and inflammation in adipose tissue were determined, and gene expression was assessed with microarrays. IL-1RI(-/-) mice fed a high-fat diet (HFD) had significantly lower plasma inflammatory cytokine concentrations than wild-type mice. Metabolic network analysis of transcriptomic effects identified up-regulation and co-expression of genes involved in lipolysis, lipogenesis and tricarboxylic acid (TCA) cycle. Further assessment of gene expression in a network of protein interactions related to innate immunity highlighted Stat3 as a potential transcriptional regulator of IL-1 signalling. The complex, downstream effects of IL-1 signalling through the IL-1RI receptor remain poorly defined. Using network-based analyses of transcriptomic signatures in IL-1RI(-/-) mice, we have identified expression changes in genes involved in lipid cycling and TCA cycle, which may be more broadly indicative of a restoration of mitochondrial function in the context of HFD. Our results also highlight a potential role for Stat3 in linking IL-1 signalling to adipogenesis and IR. Copyright © 2013 Elsevier Inc. All rights reserved.

  2. Nigella sativa Relieves the Altered Insulin Receptor Signaling in Streptozotocin-Induced Diabetic Rats Fed with a High-Fat Diet

    PubMed Central

    El-Zeftawy, Marwa; Taha, Nabil; Mandour, Abdel Wahab

    2016-01-01

    The black cumin (Nigella sativa) “NS” or the black seeds have many pharmacological activities such as antioxidant, anticarcinogenic, antihypertensive, and antidiabetic properties. In this work, streptozotocin-induced diabetic rats fed with a high-fat diet were treated daily with NS oil (NSO) in order to study the effect on the blood glucose, lipid profile, oxidative stress parameters, and the gene expression of some insulin receptor-induced signaling molecules. This treatment was combined also with some drugs (metformin and glimepiride) and the insulin receptor inhibitor I-OMe-AG538. The administration of NSO significantly induced the gene expression of insulin receptor compared to rats that did not receive NSO. Also, it upregulated the expression of insulin-like growth factor-1 and phosphoinositide-3 kinase, whereas the expression of ADAM-17 was downregulated. The expression of ADAM-17 is corroborated by the analysis of TIMP-3 content. In addition, the NSO significantly reduced blood glucose level, components of the lipid profile, oxidative stress parameters, serum insulin/insulin receptor ratio, and the tumor necrosis factor-α, confirming that NSO has an antidiabetic activity. Thus, the daily NSO treatment in our rat model indicates that NSO has a potential in the management of diabetes as well as improvement of insulin-induced signaling. PMID:27579151

  3. Diet-Induced Maternal Obesity Alters Insulin Signalling in Male Mice Offspring Rechallenged with a High-Fat Diet in Adulthood.

    PubMed

    Fante, Thaís de; Simino, Laís Angélica; Reginato, Andressa; Payolla, Tanyara Baliani; Vitoréli, Débora Cristina Gustavo; Souza, Monique de; Torsoni, Márcio Alberto; Milanski, Marciane; Torsoni, Adriana Souza

    2016-01-01

    Modern lifestyle has resulted in an increase in the prevalence of obesity and its comorbidities in pregnant women and the young population. It has been well established that the consumption of a high-fat diet (HFD) has many direct effects on glucose metabolism. However, it is important to assess whether maternal consumption of a HFD during critical periods of development can lead to metabolic changes in the offspring metabolism. This study evaluated the potential effects of metabolic programming on the impairment of insulin signalling in recently weaned offspring from obese dams. Additionally, we investigated if early exposure to an obesogenic environment could exacerbate the impairment of glucose metabolism in adult life in response to a HFD. Swiss female mice were fed with Standard Chow (SC) or a HFD during gestation and lactation and tissues from male offspring were analysed at d28 and d82. Offspring from obese dams had greater weight gain and higher adiposity and food intake than offspring from control dams. Furthermore, they showed impairment in insulin signalling in central and peripheral tissues, which was associated with the activation of inflammatory pathways. Adipose tissue was ultimately the most affected in adult offspring after HFD rechallenge; this may have contributed to the metabolic deregulation observed. Overall, our results suggest that diet-induced maternal obesity leads to increased susceptibility to obesity and impairment of insulin signalling in offspring in early and late life that cannot be reversed by SC consumption, but can be aggravated by HFD re-exposure.

  4. Diet-Induced Maternal Obesity Alters Insulin Signalling in Male Mice Offspring Rechallenged with a High-Fat Diet in Adulthood

    PubMed Central

    de Fante, Thaís; Simino, Laís Angélica; Reginato, Andressa; Payolla, Tanyara Baliani; Vitoréli, Débora Cristina Gustavo; de Souza, Monique; Torsoni, Márcio Alberto; Milanski, Marciane; Torsoni, Adriana Souza

    2016-01-01

    Modern lifestyle has resulted in an increase in the prevalence of obesity and its comorbidities in pregnant women and the young population. It has been well established that the consumption of a high-fat diet (HFD) has many direct effects on glucose metabolism. However, it is important to assess whether maternal consumption of a HFD during critical periods of development can lead to metabolic changes in the offspring metabolism. This study evaluated the potential effects of metabolic programming on the impairment of insulin signalling in recently weaned offspring from obese dams. Additionally, we investigated if early exposure to an obesogenic environment could exacerbate the impairment of glucose metabolism in adult life in response to a HFD. Swiss female mice were fed with Standard Chow (SC) or a HFD during gestation and lactation and tissues from male offspring were analysed at d28 and d82. Offspring from obese dams had greater weight gain and higher adiposity and food intake than offspring from control dams. Furthermore, they showed impairment in insulin signalling in central and peripheral tissues, which was associated with the activation of inflammatory pathways. Adipose tissue was ultimately the most affected in adult offspring after HFD rechallenge; this may have contributed to the metabolic deregulation observed. Overall, our results suggest that diet-induced maternal obesity leads to increased susceptibility to obesity and impairment of insulin signalling in offspring in early and late life that cannot be reversed by SC consumption, but can be aggravated by HFD re-exposure. PMID:27479001

  5. Short-term high fat diet increases the presence of astrocytes in the hypothalamus of C57BL6 mice without altering leptin sensitivity.

    PubMed

    Balland, Eglantine; Cowley, Michael A

    2017-07-12

    Diet-induced obesity is associated with hypothalamic inflammation and this phenomenon has been proposed to explain leptin resistance. In this study we used a short-term high fat diet (HFD) paradigm for 10days and analysed the cellular and physiological responses to leptin administration in C57BL6 mice. In parallel we performed GFAP immuno-staining to measure the presence of astrocytes in the arcuate nucleus of the hypothalamus (ARH) after 10 days and 20 weeks of HFD. Interestingly our results demonstrate that the presence of star-like astrocytes is significantly increased after 10 days of HFD but this is not associated with the absence of cellular and physiological response to leptin administration in mice. All together our study suggest that star-like astrocytes rapidly increase in numbers in the ARH in response to HFD but this phenomenon cannot explain the development of leptin resistance by itself. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

  6. Targeted disruption of G0/G1 switch gene 2 enhances adipose lipolysis, alters hepatic energy balance, and alleviates high-fat diet-induced liver steatosis.

    PubMed

    Zhang, Xiaodong; Xie, Xitao; Heckmann, Bradlee L; Saarinen, Alicia M; Czyzyk, Traci A; Liu, Jun

    2014-03-01

    Recent biochemical and cell-based studies identified G0/G1 switch gene 2 (G0S2) as an inhibitor of adipose triglyceride lipase (ATGL), a key mediator of intracellular triacylglycerol (TG) mobilization. Here, we show that upon fasting, G0S2 protein expression exhibits an increase in liver and a decrease in adipose tissue. Global knockout of G0S2 in mice enhanced adipose lipolysis and attenuated gain of body weight and adiposity. More strikingly, G0S2 knockout mice displayed a drastic decrease in hepatic TG content and were resistant to high-fat diet (HFD)-induced liver steatosis, both of which were reproduced by liver-specific G0S2 knockdown. Mice with hepatic G0S2 knockdown also showed increased ketogenesis, accelerated gluconeogenesis, and decelerated glycogenolysis. Conversely, overexpression of G0S2 inhibited fatty acid oxidation in mouse primary hepatocytes and caused sustained steatosis in liver accompanied by deficient TG clearance during the fasting-refeeding transition. In response to HFD, there was a profound increase in hepatic G0S2 expression in the fed state. Global and hepatic ablation of G0S2 both led to improved insulin sensitivity in HFD-fed mice. Our findings implicate a physiological role for G0S2 in the control of adaptive energy response to fasting and as a contributor to obesity-associated liver steatosis.

  7. Nitric oxide deficiency and endothelial dysfunction in pulmonary arterial hypertension.

    PubMed

    Klinger, James R; Abman, Steven H; Gladwin, Mark T

    2013-09-15

    Nitric oxide (NO) signaling plays a major role in modulating vascular tone and remodeling in the pulmonary circulation, but its role in the pathogenesis of pulmonary vascular diseases is still not completely understood. Numerous abnormalities of NO synthesis and signaling have been identified in animal models of pulmonary vascular disease and in humans with pulmonary hypertension. Many of these abnormalities have become targets of new therapies for the treatment of pulmonary hypertension. However, it is unclear to what extent alterations in NO signaling contribute to pulmonary hypertensive responses or merely reflect abnormalities induced by the underlying disease. This perspective examines the current understanding of altered NO signaling in pulmonary hypertensive diseases and discusses how these alterations may contribute to the pathogenesis of pulmonary hypertension. The efficacy and limitations of presently available therapies for pulmonary hypertension that target NO signaling are reviewed along with an update on investigational therapies that use this pathway to reverse pulmonary hypertensive changes.

  8. High saturated fat diet alters the lipid composition of triacylglycerol and polar lipids in the femur of dam and offspring rats.

    PubMed

    Miotto, Paula M; Castelli, Laura M; Amoye, Foyinsola; Ward, Wendy E; LeBlanc, Paul J

    2015-06-01

    Previous work has shown that dietary lipids alter femur lipid composition. Specifically, we have shown that exposure to high saturated fatty acid (SFA) diets in utero, during suckling, or post-weaning alters femur total lipid composition, resulting in higher percent bone mass in males and females and bone mineral density (BMD) in female offspring with no effect on bone mineral outcomes in dams. Comparatively, high n-3 polyunsaturated fatty acid (PUFA) diets increase femur polar (PL) lipid n-3 content, which has been associated with increased bone mineral content and strength. However, the extent that PL or triacylglycerol (TAG) lipids change with high SFA diets is unknown. The current investigation examined the influence of a high SFA diet (20 % lard by weight) on femur PL and TAG lipid composition in 5-month old female Wistar rats (fed high SFA diet from age 28 days onwards; dams) and their 19-day old offspring (exposed to high SFA in utero and during suckling; pups). High SFA exposure resulted in increased monounsaturates and decreased n-3 and n-6 PUFA in the TAG fraction in both dams and pups, and higher SFA and n-6:n-3 ratio in dams only. The PL fraction showed decreased n-6 PUFA in both dams and pups. The magnitude of the diet-mediated responses, specifically TAG 18:1 and PL n-6 PUFA, may have contributed to the previously reported altered BMD, which was supported with correlation analysis. Future research should investigate the relationship of diet-induced changes in bone lipids on bone structure, as quantified through micro-computed tomography.

  9. Pulmonary hypertension in women

    PubMed Central

    Pugh, Meredith E; Hemnes, Anna R

    2011-01-01

    Female predominance in pulmonary arterial hypertension (PAH) has been known for several decades and recent interest in the effects of sex hormones on the development of disease has substantially increased our understanding of this epidemiologic observation. Basic science data suggest a beneficial effect of estrogens in the pulmonary vasculature both acutely and chronically, which seems to contradict the known predilection in women. Recent human and rodent data have suggested that altered levels of estrogen, differential signaling and altered metabolism of estrogens in PAH may underlie the gender difference in this disease. Studies of the effects of sex hormones on the right ventricle in animal and human disease will further aid in understanding gender differences in PAH. This article focuses on the effects of sex hormones on the pulmonary vasculature and right ventricle on both a basic science and translational level. PMID:21090930

  10. Cerebral Fat Embolism: A diagnostic challenge

    PubMed Central

    Gupta, Babita; Kaur, Manpreet; D’souza, Nita; Dey, Chandan Kumar; Shende, Seema; Kumar, Atin; Gamangatti, Shivanand

    2011-01-01

    Fat embolism syndrome (FES) is a rare but a serious clinical catastrophe occurring after traumatic injury to long bones. Cerebral involvement in the absence of pulmonary or dermatological manifestation on initial presentation may delay the diagnosis of cerebral fat embolism (CFE). We discuss a case series of CFE which posed a challenge in diagnosis. The clinical presentations of these patients did not satisfy the commonly used clinical criteria for aiding the diagnosis of FES. Early MRI brain (DWI and T2 weighted sequences) in patients with neurological symptoms after trauma even in the absence of pulmonary and dermatological findings should be the goal. PMID:21957425

  11. Dietary fish oil inhibits bleomycin-induced pulmonary fibrosis in the rat.

    PubMed

    Kennedy, J I; Chandler, D B; Fulmer, J D; Wert, M B; Grizzle, W E

    1989-03-01

    Intratracheal bleomycin induces pulmonary fibrosis in experimental animals, but the mechanisms involved are poorly understood. Since altered levels of fatty acid metabolites are associated with bleomycin-induced lung injury, we examined the effects of a change in dietary fat on bleomycin-induced fibrosis. Previously we have shown that an essential fatty acid-deficient diet can reduce the severity of bleomycin-induced pulmonary fibrosis. The present study examined the effect of replacement of usual dietary fat with menhaden oil, rich in eicosapentaenoic acid, on the development of pulmonary fibrosis. Weanling rats were raised on a standard laboratory diet or a diet consisting of a fat-free powder to which was added 25% (w/w) of menhaden oil. After 8 weeks of feeding, the animals received either 1.5 units of bleomycin or an equivalent volume of saline intratracheally. In animals receiving the laboratory diet, bleomycin treatment produced a 44% increase in total lung protein content when compared to saline-treated controls (p less than 0.001) and a 77% increase in total lung hydroxyproline content (p less than 0.01). In contrast, bleomycin-treated animals receiving the menhaden oil diet had only small increases, which did not reach statistical significance, in protein and hydroxyproline content in the lung. Bronchoalveolar lavage cellularity did not differ among the treatment groups, but the percentage of lavage macrophages was slightly diminished in bleomycin-treated animals receiving the laboratory diet. Cellular differentials of lavage fluid did not differ significantly between bleomycin- and saline-treated animals receiving the menhaden oil diet. Bleomycin-induced histologic changes, quantitated by morphometric analysis, were significantly reduced with the menhaden oil diet. We conclude that a diet rich in eicosapentaenoic acid can significantly ameliorate bleomycin-induced pulmonary fibrosis, possibly via alterations in eicosanoid metabolism.

  12. Diet and diet combined with chronic aerobic exercise decreases body fat mass and alters plasma and adipose tissue inflammatory markers in obese women.

    PubMed

    Lakhdar, Nadia; Denguezli, Myriam; Zaouali, Monia; Zbidi, Abdelkrim; Tabka, Zouhair; Bouassida, Anissa

    2013-12-01

    The purpose of this study was to investigate the effect of 6 months aerobic exercise and diet alone or in combination on markers of inflammation (MOI) in circulation and in adipose abdominal tissue (AT) in obese women. Thirty obese subjects were randomized into a 24-week intervention: (1) exercise (EX), (2) diet (DI), and (3) exercise and diet (EXD). Blood samples were collected at baseline, after 12 and 24 weeks. AT biopsies were obtained only at baseline and after 24 weeks. In the EXD and DI groups, the fat loss was after 12 weeks was -13.74 and -7.8 % (P < 0.01) and after 24 weeks was -21.82 and -17 % (P < 0.01) with no changes in the EX group. After 12 and 24 weeks, maximal oxygen consumption (VO2max) was increased by 21.81-39.54 % (P < 0.05) in the EXD group and 18.09-40.95 % in the EX group with no changes in the DI group. In the EXD and DI groups, circulating levels of tumor necrosis factor α and interleukin 6 were decreased after 24 weeks for both groups (P < 0.01). No changes in the EX group. Homeostatic model assessment for insulin resistance decreased (P < 0.05) only after 24 weeks in the EXD group. In AT biopsies, subjects in the EXD and DI groups exhibited a significant decrease in MO (P < 0.01 for all). No changes in AT biopsies were found in the EX group. In conclusion, chronic aerobic exercise was found to have no effects on circulating and AT MOI despite an increased VO2max. Rather important body composition modifications were found to have beneficial effects on circulating and AT MOI in these obese women.

  13. Perinatal undernutrition alters intestinal alkaline phosphatase and its main transcription factors KLF4 and Cdx1 in adult offspring fed a high-fat diet.

    PubMed

    Lallès, Jean-Paul; Orozco-Solís, Ricardo; Bolaños-Jiménez, Francisco; de Coppet, Pierre; Le Dréan, Gwénola; Segain, Jean-Pierre

    2012-11-01

    Nutrient restriction during gestation and/or suckling is associated with an increased risk of developing inflammation, obesity and metabolic diseases in adulthood. However, the underlying mechanisms, including the role of the small intestine, are unclear. We hypothesized that intestinal adaptation to the diet in adulthood is modulated by perinatal nutrition. This hypothesis was tested using a split-plot design experiment with 20 controls and 20 intrauterine growth-retarded (IUGR) rats aged 240 days and randomly assigned to be fed a standard chow or a high-fat (HF) diet for 10 days. Jejunal tissue was collected at necropsy and analyzed for anatomy, digestive enzymes, goblet cells and mRNA levels. Cecal contents and blood serum were analyzed for alkaline phosphatase (AP). IUGR rats failed to adapt to HF by increasing AP activity in jejunal tissue and cecal content as observed in controls. mRNA levels of transcription factors KLF4 and Cdx1 were blunted in jejunal epithelial cell of IUGR rats fed HF. mRNA levels of TNF-α were lower in IUGR rats. They also displayed exacerbated aminopeptidase N response and reduced jejunal goblet cell density. Villus and crypt architecture and epithelial cell proliferation increased with HF in both control and IUGR rats. Serum AP tended to be lower, and serum levamisole inhibition-resistant AP fraction was lower, in IUGR than controls with HF. Serum fatty acids and triglycerides were higher in IUGR rats and higher with HF. In conclusion, the adult intestine adapts to an HF diet differentially depending on early nutrition, jejunal AP and transcription factors being blunted in IUGR individuals fed HF. Copyright © 2012 Elsevier Inc. All rights reserved.

  14. Increased intramyocellular lipid/impaired insulin sensitivity is associated with altered lipid metabolic genes in muscle of high responders to a high-fat diet.

    PubMed

    Kakehi, Saori; Tamura, Yoshifumi; Takeno, Kageumi; Sakurai, Yuko; Kawaguchi, Minako; Watanabe, Takahiro; Funayama, Takashi; Sato, Fumihiko; Ikeda, Shin-Ichi; Kanazawa, Akio; Fujitani, Yoshio; Kawamori, Ryuzo; Watada, Hirotaka

    2016-01-01

    The accumulation of intramyocellular lipid (IMCL) is recognized as an important determinant of insulin resistance, and is increased by a high-fat diet (HFD). However, the effects of HFD on IMCL and insulin sensitivity are highly variable. The aim of this study was to identify the genes in muscle that are related to this inter-individual variation. Fifty healthy men were recruited for this study. Before and after HFD for 3 days, IMCL levels in the tibialis anterior were measured by (1)H magnetic resonance spectroscopy, and peripheral insulin sensitivity was evaluated by glucose infusion rate (GIR) during the euglycemic-hyperinsulinemic clamp. Subjects who showed a large increase in IMCL and a large decrease in GIR by HFD were classified as high responders (HRs), and subjects who showed a small increase in IMCL and a small decrease in GIR were classified as low responders (LRs). In five subjects from each group, the gene expression profile of the vastus lateralis muscle was analyzed by DNA microarray analysis. Before HFD, gene expression profiles related to lipid metabolism were comparable between the two groups. Gene Set Enrichment Analysis demonstrated that five gene sets related to lipid metabolism were upregulated by HFD in the HR group but not in the LR group. Changes in gene expression patterns were confirmed by qRT-PCR using more samples (LR, n = 9; HR, n = 11). These results suggest that IMCL accumulation/impaired insulin sensitivity after HFD is closely associated with changes in the expression of genes related to lipid metabolism in muscle. Copyright © 2016 the American Physiological Society.

  15. Exposure to bisphenol-A during pregnancy partially mimics the effects of a high-fat diet altering glucose homeostasis and gene expression in adult male mice.

    PubMed

    García-Arevalo, Marta; Alonso-Magdalena, Paloma; Rebelo Dos Santos, Junia; Quesada, Ivan; Carneiro, Everardo M; Nadal, Angel

    2014-01-01

    Bisphenol-A (BPA) is one of the most widespread EDCs used as a base compound in the manufacture of polycarbonate plastics. The aim of our research has been to study how the exposure to BPA during pregnancy affects weight, glucose homeostasis, pancreatic β-cell function and gene expression in the major peripheral organs that control energy flux: white adipose tissue (WAT), the liver and skeletal muscle, in male offspring 17 and 28 weeks old. Pregnant mice were treated with a subcutaneous injection of 10 µg/kg/day of BPA or a vehicle from day 9 to 16 of pregnancy. One month old offspring were divided into four different groups: vehicle treated mice that ate a normal chow diet (Control group); BPA treated mice that also ate a normal chow diet (BPA); vehicle treated animals that had a high fat diet (HFD) and BPA treated animals that were fed HFD (HFD-BPA). The BPA group started to gain weight at 18 weeks old and caught up to the HFD group before week 28. The BPA group as well as the HFD and HFD-BPA ones presented fasting hyperglycemia, glucose intolerance and high levels of non-esterified fatty acids (NEFA) in plasma compared with the Control one. Glucose stimulated insulin release was disrupted, particularly in the HFD-BPA group. In WAT, the mRNA expression of the genes involved in fatty acid metabolism, Srebpc1, Pparα and Cpt1β was decreased by BPA to the same extent as with the HFD treatment. BPA treatment upregulated Pparγ and Prkaa1 genes in the liver; yet it diminished the expression of Cd36. Hepatic triglyceride levels were increased in all groups compared to control. In conclusion, male offspring from BPA-treated mothers presented symptoms of diabesity. This term refers to a form of diabetes which typically develops in later life and is associated with obesity.

  16. Streptozotocin-Treated High Fat Fed Mice: A New Type 2 Diabetes Model Used to Study Canagliflozin-Induced Alterations in Lipids and Lipoproteins.

    PubMed

    Yu, Tian; Sungelo, Mitchell J; Goldberg, Ira J; Wang, Hong; Eckel, Robert H

    2017-05-01

    The pharmacological effects of type 2 diabetes (T2DM) medications on lipoprotein metabolism are difficult to assess in preclinical models because those created failure to replicate the human condition in which insulin deficiency is superimposed on obesity-related insulin resistance. To create a better model, we fed mice with high fat (HF) diet and treated the animals with low dose streptozotocin (STZ) to mimic T2DM. We used this model to evaluate the effects of canagliflozin (CANA), a drug that reduces plasma glucose by inhibiting the sodium-glucose transporter 2 (SGLT2), which mediates ~90% of renal glucose reabsorption] on lipid and lipoprotein metabolism. After 6 weeks of CANA (30 mg/kg/day) treatment, the increase in total plasma cholesterol in HF-STZ diabetic mice was reversed, but plasma triglycerides were not affected. Lipoprotein fractionation and cholesterol distribution analysis showed that CANA kept HDL-Cholesterol, LDL-Cholesterol, and IDL-Cholesterol levels steady while these lipoprotein species were increased in placebo- and insulin-treated control groups. CANA treatment of HF-STZ mice reduced post-heparin plasma lipoprotein lipase (LPL) activity at 2 (-40%) and 5 (-30%) weeks compared to placebo. Tissue-specific LPL activity following CANA treatment showed similar reduction. In summary, CANA prevented the total cholesterol increase in HF-STZ mice without effects on plasma lipids or lipoproteins, but did decrease LPL, implying a potential role of LPL-dependent lipoprotein metabolism in CANA action. These effects did not recapitulate the effect of SGLT2 inhibitors on lipids and lipoproteins in human, suggesting that a better murine T2DM model (such as the ApoB100 humanized CETP-overexpressing mouse) is needed next. © Georg Thieme Verlag KG Stuttgart · New York.

  17. Exposure to Bisphenol-A during Pregnancy Partially Mimics the Effects of a High-Fat Diet Altering Glucose Homeostasis and Gene Expression in Adult Male Mice

    PubMed Central

    García-Arevalo, Marta; Alonso-Magdalena, Paloma; Rebelo Dos Santos, Junia; Quesada, Ivan; Carneiro, Everardo M.; Nadal, Angel

    2014-01-01

    Bisphenol-A (BPA) is one of the most widespread EDCs used as a base compound in the manufacture of polycarbonate plastics. The aim of our research has been to study how the exposure to BPA during pregnancy affects weight, glucose homeostasis, pancreatic β-cell function and gene expression in the major peripheral organs that control energy flux: white adipose tissue (WAT), the liver and skeletal muscle, in male offspring 17 and 28 weeks old. Pregnant mice were treated with a subcutaneous injection of 10 µg/kg/day of BPA or a vehicle from day 9 to 16 of pregnancy. One month old offspring were divided into four different groups: vehicle treated mice that ate a normal chow diet (Control group); BPA treated mice that also ate a normal chow diet (BPA); vehicle treated animals that had a high fat diet (HFD) and BPA treated animals that were fed HFD (HFD-BPA). The BPA group started to gain weight at 18 weeks old and caught up to the HFD group before week 28. The BPA group as well as the HFD and HFD-BPA ones presented fasting hyperglycemia, glucose intolerance and high levels of non-esterified fatty acids (NEFA) in plasma compared with the Control one. Glucose stimulated insulin release was disrupted, particularly in the HFD-BPA group. In WAT, the mRNA expression of the genes involved in fatty acid metabolism, Srebpc1, Pparα and Cpt1β was decreased by BPA to the same extent as with the HFD treatment. BPA treatment upregulated Pparγ and Prkaa1 genes in the liver; yet it diminished the expression of Cd36. Hepatic triglyceride levels were increased in all groups compared to control. In conclusion, male offspring from BPA-treated mothers presented symptoms of diabesity. This term refers to a form of diabetes which typically develops in later life and is associated with obesity. PMID:24959901

  18. HMBPP-deficient Listeria mutant immunization alters pulmonary/systemic responses, effector functions, and memory polarization of Vγ2Vδ2 T cells

    PubMed Central

    Frencher, James T.; Shen, Hongbo; Yan, Lin; Wilson, Jessica O.; Freitag, Nancy E.; Rizzo, Alicia N.; Chen, Crystal Y.; Chen, Zheng W.

    2014-01-01

    Whereas infection or immunization of humans/primates with microbes coproducing HMBPP/IPP can remarkably activate Vγ2Vδ2 T cells, in vivo studies have not been done to dissect HMBPP- and IPP-driven expansion, pulmonary trafficking, effector functions, and memory polarization of Vγ2Vδ2 T cells. We define these phosphoantigen-host interplays by comparative immunizations of macaques with the HMBPP/IPP-coproducing Listeria ΔactA prfA* and HMBPP-deficient Listeria ΔactAΔgcpE prfA* mutant. The HMBPP-deficient ΔgcpE mutant shows lower ability to expand Vγ2Vδ2 T cells in vitro than the parental HMBPP-producing strain but displays comparably attenuated infectivity or immunogenicity. Respiratory immunization of macaques with the HMBPP-deficient mutant elicits lower pulmonary and systemic responses of Vγ2Vδ2 T cells compared with the HMBPP-producing vaccine strain. Interestingly, HMBPP-deficient mutant reimmunization or boosting elicits enhanced responses of Vγ2Vδ2 T cells, but the magnitude is lower than that by HMBPP-producing listeria. HMBPP-deficient listeria differentiated fewer Vγ2Vδ2 T effector cells capable of coproducing IFN-γ and TNF-α and inhibiting intracellular listeria than HMBPP-producing listeria. Furthermore, HMBPP deficiency in listerial immunization influences memory polarization of Vγ2Vδ2 T cells. Thus, both HMBPP and IPP production in listerial immunization or infection elicit systemic/pulmonary responses and differentiation of Vγ2Vδ2 T cells, but a role for HMBPP is more dominant. Findings may help devise immune intervention. PMID:25114162

  19. Early life stress and post-weaning high fat diet alter tyrosine hydroxylase regulation and AT1 receptor expression in the adrenal gland in a sex dependent manner.

    PubMed

    Bobrovskaya, Larisa; Maniam, Jayanthi; Ong, Lin Kooi; Dunkley, Peter R; Morris, Margaret J

    2013-04-01

    Previous studies have shown that early life stress induced by maternal separation or non-handling can lead to behavioural deficits in rats and that these deficits can be alleviated by providing palatable cafeteria high-fat diet (HFD). In these studies we investigated the effects of maternal separation or non-handling and HFD on tyrosine hydroxylase (TH) protein and TH phosphorylation at Ser40 (pSer40TH) and the expression of angiotensin II receptor type 1 (AT1R) protein in the adrenal gland as markers of sympatho-adrenomedullary activation. After littering, Sprague-Dawley rats were assigned to short maternal separation, S15 (15 min), prolonged maternal separation, S180 (180 min) daily from postnatal days 2-14 or were non-handled (NH) until weaning. Siblings were exposed to HFD or chow from day 21 until 19 weeks when adrenals were harvested. Maternal separation and non-handling had no effects on adrenal TH protein in both sexes. We found an effect of HFD only in the females; HFD significantly increased TH levels in NH rats and pSer40TH in S180 rats (relative to corresponding chow-fed groups), but had no effect on AT1R expression in any group. In contrast, in male rats HFD had no effect on TH protein levels, but significantly increased pSer40TH across all treatment groups. There was no effect of HFD on AT1R expression in male rats; however, maternal separation (for 15 or 180 min) caused significant increases in AT1R expression (relative to NH group regardless of diet). This is the first study to report that early life stress and diet modulate TH protein, pSer40TH and AT1R protein levels in the adrenal gland in a sex dependent manner. These results are interpreted in respect to the potential adverse effects that these changes in the adrenal gland may have in males and females in adult life.

  20. Pulmonary Hypertension and Pulmonary Vasodilators.

    PubMed

    Keller, Roberta L

    2016-03-01

    Pulmonary hypertension in the perinatal period can present acutely (persistent pulmonary hypertension of the newborn) or chronically. Clinical and echocardiographic diagnosis of acute pulmonary hypertension is well accepted but there are no broadly validated criteria for echocardiographic diagnosis of pulmonary hypertension later in the clinical course, although there are significant populations of infants with lung disease at risk for this diagnosis. Contributing cardiovascular comorbidities are common in infants with pulmonary hypertension and lung disease. It is not clear who should be treated without confirmation of pulmonary vascular disease by cardiac catheterization, with concurrent evaluation of any contributing cardiovascular comorbidities.

  1. Pulmonary Fibrosis

    MedlinePlus

    Pulmonary fibrosis is a condition in which the tissue deep in your lungs becomes scarred over time. This tissue ... may not get enough oxygen. Causes of pulmonary fibrosis include environmental pollutants, some medicines, some connective tissue ...

  2. Pulmonary Rehabilitation

    MedlinePlus

    Pulmonary Rehabilitation If you have shortness of breath because of lung problems, you may have asked yourself: • Can I ... medications do I really need to take? Pulmonary rehabilitation can help answer these and other questions. Enrolling ...

  3. Both Food Restriction and High-Fat Diet during Gestation Induce Low Birth Weight and Altered Physical Activity in Adult Rat Offspring: The “Similarities in the Inequalities” Model

    PubMed Central

    Portella, André Krumel; Benetti, Carla da Silva; Noschang, Cristie; Goldani, Marcelo Zubaran; Silveira, Patrícia Pelufo

    2015-01-01

    We have previously described a theoretical model in humans, called “Similarities in the Inequalities”, in which extremely unequal social backgrounds coexist in a complex scenario promoting similar health outcomes in adulthood. Based on the potential applicability of and to further explore the “similarities in the inequalities” phenomenon, this study used a rat model to investigate the effect of different nutritional backgrounds during gestation on the willingness of offspring to engage in physical activity in adulthood. Sprague-Dawley rats were time mated and randomly allocated to one of three dietary groups: Control (Adlib), receiving standard laboratory chow ad libitum; 50% food restricted (FR), receiving 50% of the ad libitum-fed dam’s habitual intake; or high-fat diet (HF), receiving a diet containing 23% fat. The diets were provided from day 10 of pregnancy until weaning. Within 24 hours of birth, pups were cross-fostered to other dams, forming the following groups: Adlib_Adlib, FR_Adlib, and HF_Adlib. Maternal chow consumption and weight gain, and offspring birth weight, growth, physical activity (one week of free exercise in running wheels), abdominal adiposity and biochemical data were evaluated. Western blot was performed to assess D2 receptors in the dorsal striatum. The “similarities in the inequalities” effect was observed on birth weight (both FR and HF groups were smaller than the Adlib group at birth) and physical activity (both FR_Adlib and HF_Adlib groups were different from the Adlib_Adlib group, with less active males and more active females). Our findings contribute to the view that health inequalities in fetal life may program the health outcomes manifested in offspring adult life (such as altered physical activity and metabolic parameters), probably through different biological mechanisms. PMID:25738800

  4. Vascular Remodeling in Pulmonary Hypertension

    PubMed Central

    Shimoda, Larissa A; Laurie, Steven S.

    2013-01-01

    Pulmonary hypertension is a complex, progressive condition arising from a variety of genetic and pathogenic causes. Patients present with a spectrum of histologic and pathophysiological features, likely reflecting the diversity in underlying pathogenesis. It is widely recognized that structural alterations in the vascular wall contribute to all forms of pulmonary hypertension. Features characteristic of the remodeled vasculature in patients with pulmonary hypertension include increased stiffening of the elastic proximal pulmonary arteries, thickening of the intimal and/or medial layer of muscular arteries, development of vaso-occlusive lesions and the appearance of cells expressing smooth muscle specific markers in normally non-muscular small diameter vessels, resulting from proliferation and migration of pulmonary arterial smooth muscle cells and cellular trans-differentiation. The development of several animal models of pulmonary hypertension has provided the means to explore the mechanistic underpinnings of pulmonary vascular remodeling, although none of the experimental models currently used entirely replicates the pulmonary arterial hypertension observed in patients. Herein, we provide an overview of the histological abnormalities observed in humans with pulmonary hypertension and in preclinical models and discuss insights gained regarding several key signaling pathways contributing to the remodeling process. In particular, we will focus on the roles of ion homeostasis, endothelin-1, serotonin, bone morphogenetic proteins, Rho kinase and hypoxia-inducible factor 1 in pulmonary arterial smooth muscle and endothelial cells, highlighting areas of cross-talk between these pathways and potentials for therapeutic targeting. PMID:23334338

  5. Incorporating freeze-dried strawberry powder into a high-fat meal does not alter postprandial vascular function or blood markers of cardiovascular disease risk: a randomized controlled trial.

    PubMed

    Richter, Chesney K; Skulas-Ray, Ann C; Gaugler, Trent L; Lambert, Joshua D; Proctor, David N; Kris-Etherton, Penny M

    2017-02-01

    Postprandial dysmetabolism-an exaggerated spike in triglycerides, glucose, and insulin-increases cardiovascular disease risk by inducing oxidative stress, inflammation, and endothelial dysfunction. Polyphenol-rich foods may blunt these effects when they are incorporated into a high-fat, calorie-dense meal. Strawberries are a rich source of polyphenols, but there is little research on their postprandial effects. This study was designed to investigate the effect of adding 40 g freeze-dried strawberry powder (∼1 lb. or 0.45 kg fresh strawberries) to a high-fat (50 g total fat) meal on postprandial vascular function, as well as triglyceride, glucose, and insulin responses. Healthy, overweight or obese [mean ± SEM body mass index (in kg/m(2)): 31 ± 0.5] adults (mean ± SEM age: 28 ± 2 y; 17 men and 13 women) consumed a control meal and a strawberry meal in a randomized crossover design. Testing sessions were separated by ≥1 wk for men and ∼1 mo for women to control for hormonal variations. Blood samples were obtained before the meal and 0.5, 1, 2, and 4 h after the meal. Central blood pressure and arterial stiffness indexes were measured at baseline and 2 and 4 h postmeal with the use of pulse waveform analysis. There were no significant differences between the strawberry and control meals for any outcomes. Consumption of either meal significantly decreased the augmentation index at 2 and 4 h (P < 0.002) and significantly increased triglycerides, insulin, and glucose at all time points (P < 0.001) relative to baseline. The strawberry intervention did not alter vascular function or attenuate postprandial metabolic derangements in triglycerides, glucose, or insulin relative to the control meal. Additional research is needed to clarify whether strawberries or other polyphenol-rich interventions improve postprandial responses, and future studies should take into account the acute meal-induced improvements in measures of vascular function. This trial was registered

  6. Combined therapy with metformin and insulin attenuates systemic and hepatic alterations in a model of high-fat diet-/streptozotocin-induced diabetes.

    PubMed

    Silvares, Raquel Rangel; Pereira, Evelyn Nunes Goulart da Silva; Flores, Edgar Eduardo Ilaquita; Estato, Vanessa; Reis, Patrícia Alves; Silva, Igor José da; Machado, Marcelo Pelajo; Neto, Hugo Caire de Castro Faria; Tibiriça, Eduardo; Daliry, Anissa

    2016-06-01

    In this study we have explored the pathogenesis of the hepatic alterations which occur in diabetes and the modulation of these complications by the combination of metformin adjunct treatment and insulin monotherapy. For this purpose, diabetic rats were treated with insulin (DM + Ins) or metformin plus insulin (DM + Met + Ins). Biochemical and cardiometabolic parameters were analysed by spectrophotometry. Intravital microscopy was used to study the hepatic microcirculation. In the liver tissue, real-time PCR was used to analyse oxidative stress enzymes, inflammatory markers and receptors for advanced glycation end products (AGE) (RAGE) gene expression. Lipid peroxidation was assessed by thiobarbituric acid reactive species (TBARs) analyses. AGE deposition and RAGE protein expression were studied by fluorescence spectrophotometry and Western blot respectively. Body weight, %HbA1c , urea, total proteins and oxidative stress parameters were found to be similarly improved by insulin or Met + Ins treatments. On the other hand, Met + Ins treatment showed a more pronounced effect on fasting blood glucose level than insulin monotherapy. Fructosamine, uric acid, creatinine, albumin and amylase levels and daily insulin dose requirements were found to be only improved by the combined Met + Ins treatment. Liver, renal and pancreatic dysfunction markers were found to be more positively affected by metformin adjunct therapy when compared to insulin treatment. Liver microcirculation damage was found to be completely protected by Met + Ins treatment, while insulin monotherapy showed no effect. Our results suggest that oxidative stress, microcirculatory damage and glycated proteins could be involved in the aetiology of liver disease due to diabetes. Additionally, metformin adjunct treatment improved systemic and liver injury in induced diabetes and showed a more pronounced effect than insulin monotherapy. © 2016 The Authors. International Journal of Experimental

  7. Consequences of a Maternal High-Fat Diet and Late Gestation Diabetes on the Developing Rat Lung

    PubMed Central

    Forred, Benjamin J.; Larsen, Tricia D.; Jensen, Danielle N.; Wachal, Angela L.; Khan, Muhammad Ali; Vitiello, Peter F.

    2016-01-01

    Rationale Infants born to diabetic or obese mothers are at risk of respiratory distress and persistent pulmonary hypertension of the newborn (PPHN), conceivably through fuel-mediated pathogenic mechanisms. Prior research and preventative measures focus on controlling maternal hyperglycemia, but growing evidence suggests a role for additional circulating fuels including lipids. Little is known about the individual or additive effects of a maternal high-fat diet on fetal lung development. Objective The objective of this study was to determine the effects of a maternal high-fat diet, alone and alongside late-gestation diabetes, on lung alveologenesis and vasculogenesis, as well as to ascertain if consequences persist beyond the perinatal period. Methods A rat model was used to study lung development in offspring from control, diabetes-exposed, high-fat diet-exposed and combination-exposed pregnancies via morphometric, histologic (alveolarization and vasculogenesis) and physiologic (echocardiography, pulmonary function) analyses at birth and 3 weeks of age. Outcomes were interrogated for diet, diabetes and interaction effect using ANOVA with significance set at p≤0.05. Findings prompted additional mechanistic inquiry of key molecular pathways. Results Offspring exposed to maternal diabetes or high-fat diet, alone and in combination, had smaller lungs and larger hearts at birth. High-fat diet-exposed, but not diabetes-exposed offspring, had a higher perinatal death rate and echocardiographic evidence of PPHN at birth. Alveolar mean linear intercept, septal thickness, and airspace area (D2) were not significantly different between the groups; however, markers of lung maturity were. Both diabetes-exposed and diet-exposed offspring expressed more T1α protein, a marker of type I cells. Diet-exposed newborn pups expressed less surfactant protein B and had fewer pulmonary vessels enumerated. Mechanistic inquiry revealed alterations in AKT activation, higher endothelin-1

  8. Lung volume quantified by MRI reflects extracellular-matrix deposition and altered pulmonary function in bleomycin models of fibrosis: effects of SOM230.

    PubMed

    Egger, Christine; Gérard, Christelle; Vidotto, Nella; Accart, Nathalie; Cannet, Catherine; Dunbar, Andrew; Tigani, Bruno; Piaia, Alessandro; Jarai, Gabor; Jarman, Elizabeth; Schmid, Herbert A; Beckmann, Nicolau

    2014-06-15

    Idiopathic pulmonary fibrosis is a progressive and lethal disease, characterized by loss of lung elasticity and alveolar surface area, secondary to alveolar epithelial cell injury, reactive inflammation, proliferation of fibroblasts, and deposition of extracellular matrix. The effects of oropharyngeal aspiration of bleomycin in Sprague-Dawley rats and C57BL/6 mice, as well as of intratracheal administration of ovalbumin to actively sensitized Brown Norway rats on total lung volume as assessed noninvasively by magnetic resonance imaging (MRI) were investigated here. Lung injury and volume were quantified by using nongated or respiratory-gated MRI acquisitions [ultrashort echo time (UTE) or gradient-echo techniques]. Lung function of bleomycin-challenged rats was examined additionally using a flexiVent system. Postmortem analyses included histology of collagen and hydroxyproline assays. Bleomycin induced an increase of MRI-assessed total lung volume, lung dry and wet weights, and hydroxyproline content as well as collagen amount. In bleomycin-treated rats, gated MRI showed an increased volume of the lung in the inspiratory and expiratory phases of the respiratory cycle and a temporary decrease of tidal volume. Decreased dynamic lung compliance was found in bleomycin-challenged rats. Bleomycin-induced increase of MRI-detected lung volume was consistent with tissue deposition during fibrotic processes resulting in decreased lung elasticity, whereas influences by edema or emphysema could be excluded. In ovalbumin-challenged rats, total lung volume quantified by MRI remained unchanged. The somatostatin analog, SOM230, was shown to have therapeutic effects on established bleomycin-induced fibrosis in rats. This work suggests MRI-detected total lung volume as readout for tissue-deposition in small rodent bleomycin models of pulmonary fibrosis.

  9. Chest MR imaging in the follow-up of pulmonary alterations in paediatric patients with middle lobe syndrome: comparison with chest X-ray.

    PubMed

    Fraioli, F; Serra, G; Ciarlo, G; Massaccesi, V; Liberali, S; Fiorelli, A; Macrì, F; Catalano, C

    2013-04-01

    The authors evaluated the role of magnetic resonance (MR) imaging of the chest in comparison with chest X-ray in the follow-up of pulmonary abnormalities detected by computed tomography (CT) in paediatric patients with middle lobe syndrome. Seventeen patients with middle lobe syndrome (mean age 6.2 years) underwent chest CT at the time of diagnosis (100 kV, CARE dose with quality reference of 70 mAs; collimation 24×1.2 mm; rotation time 0.33 s; scan time 5 s); at follow-up after a mean of 15.3 months, all patients were evaluated with chest MR imaging with a respiratory-triggered T2-weighted BLADE sequence (TR 2,000; TE 27 ms; FOV 400 mm; flip angle 150°; slice thickness 5 mm) and chest X-ray. Images from each modality were assessed for the presence of pulmonary consolidations, bronchiectases, bronchial wall thickening and mucous plugging. Hilar and mediastinal lymphadenopathies were assessed on CT and MR images. Baseline CT detected consolidations in 100% of patients, bronchiectases in 35%, bronchial wall thickening in 53% and mucous plugging in 35%. MR imaging and chest X-ray identified consolidations in 65% and 35%, bronchiectases in 35% and 29%, bronchial wall thickening in 59% and 6% and mucous plugging in 25% and 0%, respectively. Lymphadenopathy was seen in 64% of patients at CT and in 47% at MR imaging. Patients with middle lobe syndrome show a wide range of parenchymal and bronchial abnormalities at diagnosis. Compared with MR imaging, chest X-ray seems to underestimate these changes. Chest MR imaging might represent a feasible and radiation-free option for an overall assessment of the lung in the follow-up of patients with middle lobe syndrome.

  10. Effect of exercise test on pulmonary function of obese adolescents.

    PubMed

    Faria, Alethéa Guimarães; Ribeiro, Maria Angela G O; Marson, Fernando Augusto Lima; Schivinski, Camila Isabel S; Severino, Silvana Dalge; Ribeiro, José Dirceu; Barros Filho, Antônio A

    2014-01-01

    to investigate the pulmonary response to exercise of non-morbidly obese adolescents, considering the gender. a prospective cross-sectional study was conducted with 92 adolescents (47 obese and 45 eutrophic), divided in four groups according to obesity and gender. Anthropometric parameters, pulmonary function (spirometry and oxygen saturation [SatO2]), heart rate (HR), blood pressure (BP), respiratory rate (RR), and respiratory muscle strength were measured. Pulmonary function parameters were measured before, during, and after the exercise test. BP and HR were higher in obese individuals during the exercise test (p = 0.0001). SatO2 values decreased during exercise in obese adolescents (p = 0.0001). Obese males had higher levels of maximum inspiratory and expiratory pressures (p = 0.0002) when compared to obese and eutrophic females. Obese males showed lower values of maximum voluntary ventilation, forced vital capacity, and forced expiratory volume in the first second when compared to eutrophic males, before and after exercise (p = 0.0005). Obese females had greater inspiratory capacity compared to eutrophic females (p = 0.0001). Expiratory reserve volume was lower in obese subjects when compared to controls (p ≤ 0,05). obese adolescents presented changes in pulmonary function at rest and these changes remained present during exercise. The spirometric and cardiorespiratory values were different in the four study groups. The present data demonstrated that, in spite of differences in lung growth, the model of fat distribution alters pulmonary function differently in obese female and male adolescents. Copyright © 2013 Sociedade Brasileira de Pediatria. Published by Elsevier Editora Ltda. All rights reserved.

  11. Changes in fat contents of US snack foods in response to mandatory trans fat labelling.

    PubMed

    Van Camp, Debra; Hooker, Neal H; Lin, Chung-Tung Jordan

    2012-06-01

    Impact of mandatory trans fat labelling on US snack food introductions is examined. Using label information, lipid ingredients and fat profiles are compared pre- and post-labelling. Key products in the US snack food industry contribute significant amounts of artificial trans fat. Industry efforts to reformulate products to lower trans fat may alter the overall fat profile, in particular saturates. Composition data for more than 5000 chip and cookie products introduced for sale between 2001 (pre-labelling) and 2009 (post-labelling) were analysed. One-way ANOVA was used to test for significant changes in saturated fat content per serving and the ratio of saturated to total fat. The shares of chip and cookie introductions containing partially hydrogenated vegetable oil declined by 45 and 42 percentage points, respectively. In cookies, there was an increase of 0·49 (98 % CI 0·01, 0·98) g in the average saturated fat content per 30 g serving and an increase of 9 (98 % CI 3, 15) % in the average ratio of saturated to total fat. No statistically significant changes in fat content were observed in chips. This research suggests that, holding other factors constant, the policy has resulted in a decreased use of partially hydrogenated vegetable oil in chip products without a corresponding increase in saturated fat content, but led to significantly higher levels of saturated fat and ratio of saturated fat to total fat in cookie products.

  12. Saturated fat (image)

    MedlinePlus

    ... saturated fats. Vegetable sources of saturated fat include coconut and palm oils. When looking at a food ... saturated fats. Vegetable sources of saturated fat include coconut and palm oils. When looking at a food ...

  13. Fat cell turnover in humans.

    PubMed

    Arner, Peter; Spalding, Kirsty L

    2010-05-21

    Obesity is a condition where excess body fat accumulates to such an extent that one's health may be affected. Owing to the cardiovascular and metabolic disorders associated with obesity, and the epidemic of obesity facing most countries today, life expectancy in the developed world may start to decrease for the first time in recent history. Other conditions, such as anorexia nervosa and cachexia, are characterised by subnormal levels of adipose tissue and as with obesity lead to morbidity and mortality. Given the significant personal and economic costs of these conditions and their increasing prevalence in society, understanding the factors that determine the fat mass is therefore of prime interest and may lead to effective treatments and/or interventions for these disorders. Fat mass can be regulated in two ways. The lipid filling of pre-existing fat cells could be altered and the number of fat cells could be changed by the generation of new fat cells or the dying of old ones (i.e. adipocyte turnover). This review summarizes what is known about fat cell turnover in humans and the potential clinical implications. 2010 Elsevier Inc. All rights reserved.

  14. Fat Analysis

    NASA Astrophysics Data System (ADS)

    Min, David B.; Ellefson, Wayne C.

    Lipids, proteins, and carbohydrates constitute the principal structural components of foods. Lipids are a group of substances that, in general, are soluble in ether, chloroform, or other organic solvents but are sparingly soluble in water. However, there exists no clear scientific definition of a lipid, primarily due to the water solubility of certain molecules that fall within one of the variable categories of food lipids (1). Some lipids, such as triacylglycerols, are very hydrophobic. Other lipids, such as di- and monoacylglycerols, have both hydrophobic and hydrophilic moieties in their molecules and are soluble in relatively polar solvents (2). Short-chain fatty acids such as C1-C4 are completely miscible in water and insoluble in nonpolar solvents (1). The most widely accepted definition is based on solubility as previously stated. While most macromolecules are characterized by common structural features, the designation of "lipid" being defined by solubility characteristics is unique to lipids (2). Lipids comprise a broad group of substances that have some common properties and compositional similarities (3). Triacylglycerols are fats and oils that represent the most prevalent category of the group of compounds known as lipids. The terms lipids, fats, and oils are often used interchangeably. The term "lipid" commonly refers to the broad, total collection of food molecules that meet the definition previously stated. Fats generally refer to those lipids that are solid at room temperature and oils generally refer to those lipids that are liquid at room temperature. While there may not be an exact scientific definition, the US Food and Drug Administration (FDA) has established a regulatory definition for nutrition labeling purposes. The FDA has defined total fat as the sum of fatty acids from C4 to C24, calculated as triglycerides. This definition provides a clear path for resolution of any nutrition labeling disputes.

  15. Low levels of the AhR in chronic obstructive pulmonary disease (COPD)-derived lung cells increases COX-2 protein by altering mRNA stability

    PubMed Central

    Zago, Michela; Sheridan, Jared A.; Traboulsi, Hussein; Hecht, Emelia; Zhang, Yelu; Guerrina, Necola; Matthews, Jason; Nair, Parameswaran; Eidelman, David H.; Hamid, Qutayba

    2017-01-01

    Heightened inflammation, including expression of COX-2, is associated with chronic obstructive pulmonary disease (COPD) pathogenesis. The aryl hydrocarbon receptor (AhR) is a ligand-activated transcription factor that is reduced in COPD-derived lung fibroblasts. The AhR also suppresses COX-2 in response to cigarette smoke, the main risk factor for COPD, by destabilizing the Cox-2 transcript by mechanisms that may involve the regulation of microRNA (miRNA). Whether reduced AhR expression is responsible for heightened COX-2 in COPD is not known. Here, we investigated the expression of COX-2 as well as the expression of miR-146a, a miRNA known to regulate COX-2 levels, in primary lung fibroblasts derived from non-smokers (Normal) and smokers (At Risk) with and without COPD. To confirm the involvement of the AhR, AhR knock-down via siRNA in Normal lung fibroblasts and MLE-12 cells was employed as were A549-AhRko cells. Basal expression of COX-2 protein was higher in COPD lung fibroblasts compared to Normal or Smoker fibroblasts but there was no difference in Cox-2 mRNA. Knockdown of AhR in lung structural cells increased COX-2 protein by stabilizing the Cox-2 transcript. There was less induction of miR-146a in COPD-derived lung fibroblasts but this was not due to the AhR. Instead, we found that RelB, an NF-κB protein, was required for transcriptional induction of both Cox-2 and miR-146a. Therefore, we conclude that the AhR controls COX-2 protein via mRNA stability by a mechanism independent of miR-146a. Low levels of the AhR may therefore contribute to the heightened inflammation common in COPD patients. PMID:28749959

  16. Body fat distribution in Parkinson's disease: An MRI-based body fat quantification study.

    PubMed

    Bernhardt, Denise; Müller, Hans-Peter; Ludolph, Albert C; Dupuis, Luc; Kassubek, Jan

    2016-12-01

    There is some evidence that Parkinson's Disease (PD) patients have lower body weight and lower fat mass when compared to healthy subjects and that lower body weight and fat mass influence disease risk and progression. It remains unclear, however, if weight loss of fat mass loss occurs only in a subgroup of patients and whether fat distribution is altered during PD. The aim of this study was to prospectively investigate adipose tissue content and distribution in PD patients. The body fat composition of PD patients (N = 54) was compared with age matched healthy controls (N = 55) using a magnetic resonance imaging (MRI)-based method. A longitudinal MRI scan was acquired in 25 PD patients after a mean follow up period of 12 months. The volume of total body fat as well as of visceral fat showed no difference between PD patients and healthy controls at baseline or at follow up. However, PD patients displayed decreased subcutaneous fat tissue (p = 0.01) and a higher visceral to subcutaneous fat ratio as compared to controls (p = 0.004). After follow up, 16 PD patients did not lose weight, while 9 PD patients lost between 0.5 and 10 kg. Fat distribution is altered in PD patients, with an increased ratio of visceral to subcutaneous fat. Copyright © 2016 Elsevier Ltd. All rights reserved.

  17. Prior Exercise Increases Subsequent Utilization of Dietary Fat.

    ERIC Educational Resources Information Center

    Votruba, Susan B.; Atkinson, Richard L.; Hirvonen, Matt D.; Schoeller, Dale A.

    2002-01-01

    Investigated whether exercise would alter the partitioning of dietary fat between oxidation and storage. Seven women participated in rest, light exercise, and heavy exercise. Researchers calculated stationary cycle exercise sessions and dietary fat oxidation. Prior exercise had a positive effect on oxidation of dietary monosaturated fat but not…

  18. Prior Exercise Increases Subsequent Utilization of Dietary Fat.

    ERIC Educational Resources Information Center

    Votruba, Susan B.; Atkinson, Richard L.; Hirvonen, Matt D.; Schoeller, Dale A.

    2002-01-01

    Investigated whether exercise would alter the partitioning of dietary fat between oxidation and storage. Seven women participated in rest, light exercise, and heavy exercise. Researchers calculated stationary cycle exercise sessions and dietary fat oxidation. Prior exercise had a positive effect on oxidation of dietary monosaturated fat but not…

  19. Monocyte chemotactic protein-1 deficiency attenuates and high-fat diet exacerbates bone loss in mice with Lewis lung carcinoma.

    PubMed

    Yan, Lin; Nielsen, Forrest H; Sundaram, Sneha; Cao, Jay

    2017-04-04

    Bone loss occurs in obesity and cancer-associated complications including wasting. This study determined whether a high-fat diet and a deficiency in monocyte chemotactic protein-1 (MCP-1) altered bone structural defects in male C57BL/6 mice with Lewis lung carcinoma (LLC) metastases in lungs. Compared to non-tumor-bearing mice, LLC reduced bone volume fraction, connectivity density, trabecular number, trabecular thickness and bone mineral density and increased trabecular separation in femurs. Similar changes occurred in vertebrae. The high-fat diet compared to the AIN93G diet exacerbated LLC-induced detrimental structural changes; the exacerbation was greater in femurs than in vertebrae. Mice deficient in MCP-1 compared to wild-type mice exhibited increases in bone volume fraction, connectivity density, trabecular number and decreases in trabecular separation in both femurs and vertebrae, and increases in trabecular thickness and bone mineral density and a decrease in structure model index in vertebrae. Lewis lung carcinoma significantly decreased osteocalcin but increased tartrate-resistant acid phosphatase 5b (TRAP 5b) in plasma. In LLC-bearing mice, the high-fat diet increased and MCP-1 deficiency decreased plasma TRAP 5b; neither the high-fat diet nor MCP-1 deficiency resulted in significant changes in plasma concentration of osteocalcin. In conclusion, pulmonary metastasis of LLC is accompanied by detrimental bone structural changes; MCP-1 deficiency attenuates and high-fat diet exacerbates the metastasis-associated bone wasting.

  20. Pulmonary Embolism

    MedlinePlus

    ... for the Public » Health Topics » Pulmonary Embolism Explore Pulmonary Embolism What Is... Other Names Causes Who Is at Risk Signs & Symptoms Diagnosis Treatments Prevention Living With Clinical Trials Links Related Topics Arrhythmia Deep Vein Thrombosis Lung VQ Scan Overweight and Obesity Send a ...

  1. Pulmonary blastomycosis.

    PubMed

    Bariola, J Ryan; Vyas, Keyur S

    2011-12-01

    Blastomyces dermatitidis is acquired in almost all cases via inhalation, and pulmonary disease is the most frequent clinical manifestation of blastomycosis. Pulmonary disease can range from asymptomatic infection to rapidly severe and fatal disease. Most cases will present as pneumonia, either acute or chronic, or as a lung mass. In rare cases pulmonary blastomycosis is associated with the acute respiratory distress syndrome. Blastomycosis can present as isolated pulmonary disease or along with coexisting extrapulmonary disease that usually will involve the skin, bony structures, genitourinary tract, or central nervous system. Diagnosis is largely based on isolation of the organism via culture or visualization of the organism in clinical specimens. Detection of urinary Blastomyces antigen is a recent addition to diagnostic options. Itraconazole is the drug of choice for most forms of the disease; amphotericin B is reserved for the more severe forms. Newer azoles such as voriconazole and posaconazole have a limited role in the treatment of pulmonary blastomycosis. © Thieme Medical Publishers.

  2. Pulmonary infections in swine induce altered porcine surfactant protein D expression and localization to dendritic cells in bronchial-associated lymphoid tissue

    PubMed Central

    Soerensen, Charlotte M; Holmskov, Uffe; Aalbaek, Bent; Boye, Mette; Heegaard, Peter M; Nielsen, Ole L

    2005-01-01

    Surfactant protein D (SP-D) is a pattern-recognition molecule of the innate immune system that recognizes various microbial surface-specific carbohydrate and lipid patterns. In vitro data has suggested that this binding may lead to increased microbial association with macrophages and dendritic cells. The aim of the present in vivo study was to study the expression of porcine SP-D (pSP-D) in the lung during different pulmonary bacterial infections, and the effect of the routes of infection on this expression was elucidated. Furthermore, the aim was to study the in vivo spatial relationship among pSP-D, pathogens, phagocytic cells and dendritic cells. Lung tissue was collected from experimental and natural bronchopneumonias caused by Actinobacillus pleuropneumoniae or Staphylococcus aureus, and from embolic and diffuse interstitial pneumonia, caused by Staph. aureus or Arcanobacterium pyogenes and Streptococcus suis serotype 2, respectively. By comparing normal and diseased lung tissue from the same lungs, increased diffuse pSP-D immunoreactivity was seen in the surfactant in both acute and chronic bronchopneumonias, while such increased expression of pSP-D was generally not present in the interstitial pneumonias. Co-localization of pSP-D, alveolar macrophages and bacteria was demonstrated, and pSP-D showed a patchy distribution on the membranes of alveolar macrophages. SP-D immunoreactivity was intracellular in dendritic cells. The dendritic cells were identified by their morphology, the absence of macrophage marker immunoreactivity and the presence of dendritic cell marker immunoreactivity. Increased expression of pSP-D in the surfactant coincided with presence of pSP-D-positive dendritic cells in bronchus-associated lymphoid tissue (BALT), indicating a possible transport of pSP-D through the specialized M cells overlying (BALT). In conclusion, we have shown that pSP-D expression in the lung surfactant is induced by bacterial infection by an aerogenous route rather

  3. Pulmonary function in space

    NASA Technical Reports Server (NTRS)

    West, J. B.; Elliott, A. R.; Guy, H. J.; Prisk, G. K.

    1997-01-01

    The lung is exquisitely sensitive to gravity, and so it is of interest to know how its function is altered in the weightlessness of space. Studies on National Aeronautics and Space Administration (NASA) Spacelabs during the last 4 years have provided the first comprehensive data on the extensive changes in pulmonary function that occur in sustained microgravity. Measurements of pulmonary function were made on astronauts during space shuttle flights lasting 9 and 14 days and were compared with extensive ground-based measurements before and after the flights. Compared with preflight measurements, cardiac output increased by 18% during space flight, and stroke volume increased by 46%. Paradoxically, the increase in stroke volume occurred in the face of reductions in central venous pressure and circulating blood volume. Diffusing capacity increased by 28%, and the increase in the diffusing capacity of the alveolar membrane was unexpectedly large based on findings in normal gravity. The change in the alveolar membrane may reflect the effects of u