Fatty Acid Binding Protein FABP4 Mechanistically Links Obesity with Aggressive AML by Enhancing Aberrant DNA Methylation in AML Cells

PubMed Central

Yan, F; Shen, N; Pang, JX; Zhang, YW; Rao, EY; Bode, AM; Al-Kali, A; Zhang, DE; Litzow, MR; Li, B; Liu, SJ

2016-01-01

Obesity is becoming more prevalent worldwide and is a major risk factor for cancer development. Acute myeloid leukemia (AML), the most common acute leukemia in adults, remains a frequently fatal disease. Here, we investigated the molecular mechanisms by which obesity favors AML growth and uncovered the fatty acid binding protein 4 (FABP4) and DNA methyltransferase 1 (DNMT1) regulatory axis that mediates aggressive AML in obesity. We showed that leukemia burden was much higher in high-fat diet-induced obese mice, which had higher levels of FABP4 and IL-6 in sera. Upregulation of environmental and cellular FABP4 accelerated AML cell growth in both a cell-autonomous and cell-non-autonomous manner. Genetic disruption of FABP4 in AML cells or in mice blocked cell proliferation in vitro and induced leukemia regression in vivo. Mechanistic investigations showed that FABP4 upregulation increased IL-6 expression and STAT3 phosphorylation leading to DNMT1 overexpression and further silencing of the p15INK4B tumor suppressor gene in AML cells. Conversely, FABP4 ablation reduced DNMT1-dependent DNA methylation and restored p15INK4B expression, thus conferring substantial protection against AML growth. Our findings reveal the FABP4/DNMT1 axis in the control of AML cell fate in obesity, and suggest that interference with the FABP4/DNMT1 axis might be a new strategy to treat leukemia. PMID:27885273

Fatty acid-binding protein FABP4 mechanistically links obesity with aggressive AML by enhancing aberrant DNA methylation in AML cells.

PubMed

Yan, F; Shen, N; Pang, J X; Zhang, Y W; Rao, E Y; Bode, A M; Al-Kali, A; Zhang, D E; Litzow, M R; Li, B; Liu, S J

2017-06-01

Obesity is becoming more prevalent worldwide and is a major risk factor for cancer development. Acute myeloid leukemia (AML), the most common acute leukemia in adults, remains a frequently fatal disease. Here we investigated the molecular mechanisms by which obesity favors AML growth and uncovered the fatty acid-binding protein 4 (FABP4) and DNA methyltransferase 1 (DNMT1) regulatory axis that mediates aggressive AML in obesity. We showed that leukemia burden was much higher in high-fat diet-induced obese mice, which had higher levels of FABP4 and interleukin (IL)-6 in the sera. Upregulation of environmental and cellular FABP4 accelerated AML cell growth in both a cell-autonomous and cell-non-autonomous manner. Genetic disruption of FABP4 in AML cells or in mice blocked cell proliferation in vitro and induced leukemia regression in vivo. Mechanistic investigations showed that FABP4 upregulation increased IL-6 expression and signal transducer and activator of transcription factor 3 phosphorylation leading to DNMT1 overexpression and further silencing of the p15 INK4B tumor-suppressor gene in AML cells. Conversely, FABP4 ablation reduced DNMT1-dependent DNA methylation and restored p15 INK4B expression, thus conferring substantial protection against AML growth. Our findings reveal the FABP4/DNMT1 axis in the control of AML cell fate in obesity and suggest that interference with the FABP4/DNMT1 axis might be a new strategy to treat leukemia.

Angiopoietin-like protein 3 and 4 in obesity, type 2 diabetes mellitus, and malnutrition: the effect of weight reduction and realimentation.

PubMed

Cinkajzlová, Anna; Mráz, Miloš; Lacinová, Zdeňka; Kloučková, Jana; Kaválková, Petra; Kratochvílová, Helena; Trachta, Pavel; Křížová, Jarmila; Haluzíková, Denisa; Škrha, Jan; Papežová, Hana; Haluzík, Martin

2018-04-25

Angiopoietin-like proteins (ANGPTLs) 3 and 4 are circulating factors that participate in the regulation of lipid and glucose metabolism. We measured serum ANGPTL3 and 4 levels in 23 patients with obesity, 40 patients with obesity and type 2 diabetes mellitus (T2DM), 22 patients with anorexia nervosa (AN), 15 subjects undergoing 72-h fasting, and 12 patients with short bowel syndrome (SBS), and their changes after very-low-calorie diet (VLCD), bariatric surgery, partial realimentation, acute fasting, and parenteral nutrition in order to assess their possible role in metabolic regulations. Serum ANGPTL4 levels were higher in obese subjects without/with T2DM (94.50 ± 9.51 and 134.19 ± 7.69 vs. 50.34 ± 4.22 ng/ml, p < 0.001) and lower in subjects with AN relative to healthy control subjects (38.22 ± 4.48 vs. 65.80 ± 7.98 ng/ml, p = 0.002), while serum ANGPTL3 levels demonstrated inverse tendency. Nutritional status had no effect on ANGPTL3 and 4 mRNA expression in adipose tissue. Fasting decreased ANGPTL3 and increased ANGPTL4 levels, while VLCD reduced only ANGPTL3. Bariatric surgery and realimentation of AN or SBS patients had no effect on either ANGPTL. Multiple regression analysis identified BMI as an independent predictor of ANGPTL3; and BMI and HbA 1c as independent predictors of ANGPTL4, respectively. Taken together, our data suggest that serum ANGPTL3 and 4 levels are influenced by nutritional status and fasting and could be involved in the metabolic disturbances present in obesity and AN.

Prevalence of Canine Obesity, Obesity-Related Metabolic Dysfunction, and Relationship with Owner Obesity in an Obesogenic Region of Spain.

PubMed

Montoya-Alonso, J Alberto; Bautista-Castaño, Inmaculada; Peña, Cristina; Suárez, Lourdes; Juste, M Candelaria; Tvarijonaviciute, Asta

2017-01-01

The main objective of this study was to evaluate the prevalence of canine obesity and obesity-related metabolic dysfunction (ORMD) in the obesogenic area in Spain. The prevalence of overweight/obesity among owners of obese pets was also evaluated. In the sample population studied (93 client-owned dogs), 40.9% of dogs presented obesity (body condition score 7-9/9), 40.9% of dogs presented hypertension, 20.4% of dogs presented fasting hypertriglyceridemia, 20.4% fasting hypercholesterolemia, and 5.4% of dogs presented fasting hyperglycemia. The overall prevalence of ORMD was of 22.6%. Seventy-eight percent of overweight/obese owners had overweight/obese dogs ( P  < 0.001) including all dogs diagnosed with ORMD. In conclusion, in the studied obesogenic region of Spain, the prevalence of canine obesity and ORMD was shown to be elevated and related to the presence of overweight/obesity in owners. All dogs with ORMD were owned by overweight/obese persons. These results provide new inputs for future studies highlighting the relationship between owner and pet obesity and indicating the need of further efforts to control and reduce obesity prevalence in both.

Mitochondrial-related proteomic changes during obesity and fasting in mice are greater in the liver than skeletal muscles.

PubMed

Nesteruk, Monika; Hennig, Ewa E; Mikula, Michal; Karczmarski, Jakub; Dzwonek, Artur; Goryca, Krzysztof; Rubel, Tymon; Paziewska, Agnieszka; Woszczynski, Marek; Ledwon, Joanna; Dabrowska, Michalina; Dadlez, Michal; Ostrowski, Jerzy

2014-03-01

Although mitochondrial dysfunction is implicated in the pathogenesis of obesity, the molecular mechanisms underlying obesity-related metabolic abnormalities are not well established. We performed mitochondrial quantitative proteomic and whole transcriptome analysis followed by functional annotations within liver and skeletal muscles, using fasted and non-fasted 16- and 48-week-old high-fat diet (HFD)-fed and normal diet-fed (control group) wild-type C56BL/6J mice, and hyperphagic ob/ob and db/db obese mice. Our study identified 1,675 and 704 mitochondria-associated proteins with at least two peptides in liver and muscle, respectively. Of these, 221 liver and 44 muscle proteins were differentially expressed (adjusted p values ≤ 0.05) between control and all obese mice, while overnight fasting altered expression of 107 liver and 35 muscle proteins. In the liver, we distinguished a network of 27 proteins exhibiting opposite direction of expression changes in HFD-fed and hyperphagic mice when compared to control. The network centered on cytochromes P450 3a11 (Cyp3a11) and 4a14 (Cyp4a14), and fructose-bisphosphate aldolase B (Aldob) proteins which bridged proteins cluster involved in Metabolism of xenobiotics with proteins engaged in Fatty acid metabolism and PPAR signaling pathways. Functional annotations revealed that most of the hepatic molecular alterations, which characterized both obesity and fasting, related to different aspects of energy metabolism (such as Fatty acid metabolism, Peroxisome, and PPAR signaling); however, only a limited number of functional annotations could be selected from skeletal muscle data sets. Thus, our comprehensive molecular overview revealed that both obesity and fasting states induce more pronounced mitochondrial proteome changes in the liver than in the muscles.

Obesity-related known and candidate SNP markers can significantly change affinity of TATA-binding protein for human gene promoters

PubMed Central

2015-01-01

Background Obesity affects quality of life and life expectancy and is associated with cardiovascular disorders, cancer, diabetes, reproductive disorders in women, prostate diseases in men, and congenital anomalies in children. The use of single nucleotide polymorphism (SNP) markers of diseases and drug responses (i.e., significant differences of personal genomes of patients from the reference human genome) can help physicians to improve treatment. Clinical research can validate SNP markers via genotyping of patients and demonstration that SNP alleles are significantly more frequent in patients than in healthy people. The search for biomedical SNP markers of interest can be accelerated by computer-based analysis of hundreds of millions of SNPs in the 1000 Genomes project because of selection of the most meaningful candidate SNP markers and elimination of neutral SNPs. Results We cross-validated the output of two computer-based methods: DNA sequence analysis using Web service SNP_TATA_Comparator and keyword search for articles on comorbidities of obesity. Near the sites binding to TATA-binding protein (TBP) in human gene promoters, we found 22 obesity-related candidate SNP markers, including rs10895068 (male breast cancer in obesity); rs35036378 (reduced risk of obesity after ovariectomy); rs201739205 (reduced risk of obesity-related cancers due to weight loss by diet/exercise in obese postmenopausal women); rs183433761 (obesity resistance during a high-fat diet); rs367732974 and rs549591993 (both: cardiovascular complications in obese patients with type 2 diabetes mellitus); rs200487063 and rs34104384 (both: obesity-caused hypertension); rs35518301, rs72661131, and rs562962093 (all: obesity); and rs397509430, rs33980857, rs34598529, rs33931746, rs33981098, rs34500389, rs63750953, rs281864525, rs35518301, and rs34166473 (all: chronic inflammation in comorbidities of obesity). Using an electrophoretic mobility shift assay under nonequilibrium conditions, we

Altered fatty acid-binding protein 4 (FABP4) expression and function in human and animal models of hepatocellular carcinoma.

PubMed

Thompson, Kyle J; Austin, Rebecca Garland; Nazari, Shayan S; Gersin, Keith S; Iannitti, David A; McKillop, Iain H

2017-11-24

Hepatocellular carcinoma (HCC) is the third leading cause of cancer-related mortality. Risk factors for developing HCC include viral hepatitis, alcohol and obesity. Fatty acid-binding proteins (FABPs) bind long-chain free fatty acids (FFAs) and are expressed in a tissue-specific pattern; FABP1 being the predominant hepatic form, and FABP4 the predominant adipocyte form. The aims of this study were to investigate the expression and function of FABPs1-9 in human and animal models of obesity-related HCC. FABP1-9 expression was determined in a mouse model of obesity-promoted HCC. Based on these data, expression and function of FABP4 was determined in human HCC cells (HepG2 and HuH7) in vitro. Serum from patients with different underlying hepatic pathologies was analysed for circulating FABP4 levels. Livers from obese mice, independent of tumour status, exhibited increased FABP4 mRNA and protein expression concomitant with elevated serum FABP4. In vitro, FABP4 expression was induced in human HCC cells by FFA treatment, and led to FABP4 release into culture medium. Treatment of HCC cells with exogenous FABP4 significantly increased proliferation and migration of human HCC cells. Patient serum analysis demonstrated significantly increased FABP4 in those with underlying liver disease, particularly non-alcoholic fatty liver disease (NAFLD) and HCC. These data suggest FABP4, an FABP not normally expressed in the liver, can be synthesized and secreted by hepatocytes and HCC cells, and that FABP4 may play a role in regulating tumour progression in the underlying setting of obesity. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Combined Treatment of Mulberry Leaf and Fruit Extract Ameliorates Obesity-Related Inflammation and Oxidative Stress in High Fat Diet-Induced Obese Mice

PubMed Central

Lim, Hyun Hwa; Yang, Soo Jin; Kim, Yuri; Lee, Myoungsook

2013-01-01

Abstract The aim of this study was to investigate whether a combined treatment of mulberry leaf extract (MLE) and mulberry fruit extract (MFE) was effective for improving obesity and obesity-related inflammation and oxidative stress in high fat (HF) diet-induced obese mice. After obesity was induced by HF diet for 9 weeks, the mice were divided into eight groups: (1) lean control, (2) HF diet-induced obese control, (3) 1:1 ratio of MLE and MFE at doses of 200 (L1:1), (4) 500 (M1:1), and (5) 1000 (H1:1) mg/kg per day, and (6) 2:1 ratio of MLE and MFE at doses of 200 (L2:1), (7) 500 (M2:1), and (8) 1000 (H2:1) mg/kg per day. All six combined treatments significantly lowered body weight gain, plasma triglycerides, and lipid peroxidation levels after the 12-week treatment period. Additionally, all combined treatments suppressed hepatic fat accumulation and reduced epididymal adipocyte size. These improvements were accompanied by decreases in protein levels of proinflammatory markers (tumor necrosis factor-alpha, C-reactive protein, interleukin-1, inducible nitric oxide synthase, and phospho-nuclear factor-kappa B inhibitor alpha) and oxidative stress markers (heme oxygenase-1 and manganese superoxide dismutase). M2:1 was the most effective ratio and dose for the improvements in obesity, inflammation, and oxidative stress. These results demonstrate that a combined MLE and MFE treatment ameliorated obesity and obesity-related metabolic stressors and suggest that it can be used as a means to prevent and/or treat obesity. PMID:23957352

Combined treatment of mulberry leaf and fruit extract ameliorates obesity-related inflammation and oxidative stress in high fat diet-induced obese mice.

PubMed

Lim, Hyun Hwa; Yang, Soo Jin; Kim, Yuri; Lee, Myoungsook; Lim, Yunsook

2013-08-01

The aim of this study was to investigate whether a combined treatment of mulberry leaf extract (MLE) and mulberry fruit extract (MFE) was effective for improving obesity and obesity-related inflammation and oxidative stress in high fat (HF) diet-induced obese mice. After obesity was induced by HF diet for 9 weeks, the mice were divided into eight groups: (1) lean control, (2) HF diet-induced obese control, (3) 1:1 ratio of MLE and MFE at doses of 200 (L1:1), (4) 500 (M1:1), and (5) 1000 (H1:1) mg/kg per day, and (6) 2:1 ratio of MLE and MFE at doses of 200 (L2:1), (7) 500 (M2:1), and (8) 1000 (H2:1) mg/kg per day. All six combined treatments significantly lowered body weight gain, plasma triglycerides, and lipid peroxidation levels after the 12-week treatment period. Additionally, all combined treatments suppressed hepatic fat accumulation and reduced epididymal adipocyte size. These improvements were accompanied by decreases in protein levels of proinflammatory markers (tumor necrosis factor-alpha, C-reactive protein, interleukin-1, inducible nitric oxide synthase, and phospho-nuclear factor-kappa B inhibitor alpha) and oxidative stress markers (heme oxygenase-1 and manganese superoxide dismutase). M2:1 was the most effective ratio and dose for the improvements in obesity, inflammation, and oxidative stress. These results demonstrate that a combined MLE and MFE treatment ameliorated obesity and obesity-related metabolic stressors and suggest that it can be used as a means to prevent and/or treat obesity.

Meta-review of protein network regulating obesity between validated obesity candidate genes in the white adipose tissue of high-fat diet-induced obese C57BL/6J mice.

PubMed

Kim, Eunjung; Kim, Eun Jung; Seo, Seung-Won; Hur, Cheol-Goo; McGregor, Robin A; Choi, Myung-Sook

2014-01-01

Worldwide obesity and related comorbidities are increasing, but identifying new therapeutic targets remains a challenge. A plethora of microarray studies in diet-induced obesity models has provided large datasets of obesity associated genes. In this review, we describe an approach to examine the underlying molecular network regulating obesity, and we discuss interactions between obesity candidate genes. We conducted network analysis on functional protein-protein interactions associated with 25 obesity candidate genes identified in a literature-driven approach based on published microarray studies of diet-induced obesity. The obesity candidate genes were closely associated with lipid metabolism and inflammation. Peroxisome proliferator activated receptor gamma (Pparg) appeared to be a core obesity gene, and obesity candidate genes were highly interconnected, suggesting a coordinately regulated molecular network in adipose tissue. In conclusion, the current network analysis approach may help elucidate the underlying molecular network regulating obesity and identify anti-obesity targets for therapeutic intervention.

The PLIN4 Variant rs8887 Modulates Obesity Related Phenotypes in Humans through Creation of a Novel miR-522 Seed Site

PubMed Central

Richardson, Kris; Louie-Gao, Qiong; Arnett, Donna K.; Parnell, Laurence D.; Lai, Chao-Qiang; Davalos, Alberto; Fox, Caroline S.; Demissie, Serkalem; Cupples, L. Adrienne; Fernandez-Hernando, Carlos; Ordovas, Jose M.

2011-01-01

PLIN4 is a member of the PAT family of lipid storage droplet (LSD) proteins. Associations between seven single nucleotide polymorphisms (SNPs) at human PLIN4 with obesity related phenotypes were investigated using meta-analysis followed by a determination if these phenotypes are modulated by interactions between PLIN4 SNPs and dietary PUFA. Samples consisted of subjects from two populations of European ancestry. We demonstrated association of rs8887 with anthropometrics. Meta-analysis demonstrated significant interactions between the rs8887 minor allele with PUFA n3 modulating anthropometrics. rs884164 showed interaction with both n3 and n6 PUFA modulating anthropometric and lipid phenotypes. In silico analysis of the PLIN4 3′UTR sequence surrounding the rs8887 minor A allele predicted a seed site for the human microRNA-522 (miR-522), suggesting a functional mechanism. Our data showed that a PLIN4 3′UTR luciferase reporter carrying the A allele of rs8887 was reduced in response to miR-522 mimics compared to the G allele. These results suggest variation at the PLIN4 locus, and its interaction with PUFA as a modulator of obesity related phenotypes, acts in part through creation of a miR-522 regulatory site. PMID:21533135

Impact of obesity on 7,12-dimethylbenz[a]anthracene-induced altered ovarian connexin gap junction proteins in female mice

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

Ganesan, Shanthi, E-mail: shanthig@iastate.edu; Nteeba, Jackson, E-mail: nteeba@iastate.edu; Keating, Aileen F., E-mail: akeating@iastate.edu

The ovarian gap junction proteins alpha 4 (GJA4 or connexin 37; CX37), alpha 1 (GJA1 or connexin 43; CX43) and gamma 1 (GJC1 or connexin 45; CX45) are involved in cell communication and folliculogenesis. 7,12-dimethylbenz[a]anthracene (DMBA) alters Cx37 and Cx43 expression in cultured neonatal rat ovaries. Additionally, obesity has an additive effect on DMBA-induced ovarian cell death and follicle depletion, thus, we investigated in vivo impacts of obesity and DMBA on CX protein levels. Ovaries were collected from lean and obese mice aged 6, 12, 18, or 24 wks. A subset of 18 wk old mice (lean and obese) weremore » dosed with sesame oil or DMBA (1 mg/kg; ip) for 14 days and ovaries collected 3 days thereafter. Cx43 and Cx45 mRNA and protein levels decreased (P < 0.05) after 18 wks while Cx37 mRNA and protein levels decreased (P < 0.05) after 24 wks in obese ovaries. Cx37 mRNA and antral follicle protein staining intensity were reduced (P < 0.05) by obesity while total CX37 protein was reduced (P < 0.05) in DMBA exposed obese ovaries. Cx43 mRNA and total protein levels were decreased (P < 0.05) by DMBA in both lean and obese ovaries while basal protein staining intensity was reduced (P < 0.05) in obese controls. Cx45 mRNA, total protein and protein staining intensity level were decreased (P < 0.05) by obesity. These data support that obesity temporally alters gap junction protein expression and that DMBA-induced ovotoxicity may involve reduced gap junction protein function. - Highlights: • Ovarian gap junction proteins are affected by ovarian aging and obesity. • DMBA exposure negatively impacts gap junction proteins. • Altered gap junction proteins may contribute to infertility.« less

Influence of Protein Intake, Race, and Age on Responses to a Weight-Reduction Intervention in Obese Women.

PubMed

Bales, Connie W; Porter Starr, Kathryn N; Orenduff, Melissa C; McDonald, Shelley R; Molnar, Karen; Jarman, Aubrey K; Onyenwoke, Ann; Mulder, Hillary; Payne, Martha E; Pieper, Carl F

2017-05-01

Women have higher rates of obesity than men and develop more pronounced functional deficits as a result. Yet, little is known about how obesity reduction affects their functional status, including whether their responses differ when protein intake is enhanced. The aim of this study was to confirm the feasibility of delivery of a higher-protein (balanced at each meal) calorie-restricted diet in obese women and determine its efficacy for influencing function and retention of lean mass. Obese community-dwelling women [ n = 80; body mass index (in kg/m 2 ), in means ± SDs: 37.8 ± 5.9; aged 45-78 y; 58.8% white] were enrolled in a weight-loss (-500 kcal/d) study and randomly assigned to either a Control-Weight-Loss (C-WL; 0.8 g protein/kg body weight) group or a High-Protein-Weight-Loss (HP-WL; 1.2 g protein/kg body weight; 30 g protein 3 times/d) group in a 1:2 allocation. Primary outcomes were function by 6-min walk test (6MWT) and lean mass by using the BodPod (Life Measurement, Inc.) at 0, 4, and 6 mo. Both groups reduced calorie intakes and body weights ( P < 0.001), and the feasibility of the HP-WL intervention was confirmed. The 6MWT results improved ( P < 0.01) at 4 mo in the HP-WL group and at 6 mo in both groups ( P < 0.001). Both groups improved function by several other measures while slightly decreasing ( P < 0.01) lean mass (-1.0 kg, C-WL; -0.6 kg, HP-WL). Weight loss was greater in white than in black women at both 4 mo (6.0 ± 3.6 compared with 3.7 ± 3.4 kg; P < 0.02) and 6 mo (7.2 ± 4.8 compared with 4.0 ± 4.7 kg; P < 0.04) and tended to be positively related to age ( P < 0.06). A clinically important functional benefit of obesity reduction was confirmed in both study groups, with no significant group effect. Our findings of racial differences in response to the intervention and a potential influence of participant age lend support for further studies sufficiently powered to explore the interaction of race and age with functional responses to

Taurine supplementation regulates Iκ-Bα protein expression in adipose tissue and serum IL-4 and TNF-α concentrations in MSG obesity.

PubMed

Caetano, Luiz Carlos; Bonfleur, Maria Lúcia; Ribeiro, Rosane Aparecida; Nardelli, Tarlliza Romanna; Lubaczeuski, Camila; do Nascimento da Silva, Juliana; Carneiro, Everardo Magalhães; Balbo, Sandra Lucinei

2017-03-01

Obesity is usually associated with low-grade inflammation, which impairs insulin action. The amino acid, taurine (TAU), regulates glucose homeostasis and lipid metabolism and presents anti-inflammatory actions. Here, we evaluated whether inflammatory markers are altered in the serum and retroperitoneal adipose tissue of monosodium glutamate (MSG) obese rats, supplemented or not with TAU. Male Wistar rats received subcutaneous injections of MSG (4 mg/kg body weight/day, MSG group) or hypertonic saline (CTL) during the first 5 days of life. From 21 to 120 days of age, half of each of the MSG and CTL groups received 2.5 % TAU in their drinking water (CTAU and MTAU). At 120 days of age, MSG rats were obese and hyperinsulinemic. TAU supplementation reduced fat deposition without affecting insulinemia in MTAU rats. MSG rats presented increased pIκ-Bα/Iκ-Bα protein expression in the retroperitoneal adipose tissue. TAU supplementation decreased the ratio of pIκ-Bα/Iκ-Bα protein, possibly contributing to the increased Iκ-Bα content in MTAU adipose tissue. Furthermore, MSG obesity or supplementation did not alter TNF-α, IL-1β or IL-6 content in adipose tissue. In contrast, MSG rats presented lower serum TNF-α, IL-4 and IL-10 concentrations, and these alterations were prevented by TAU treatment. MSG obesity in rats was not associated with alterations in pro-inflammatory markers in retroperitoneal fat stores; however, reductions in the serum concentrations of anti-inflammatory cytokines and of TNF-α were observed. TAU treatment decreased adiposity, and this effect was associated with the normalization of circulating TNF-α and IL-4 concentrations in MTAU rats.

Links between Dietary Protein Sources, the Gut Microbiota, and Obesity.

PubMed

Madsen, Lise; Myrmel, Lene S; Fjære, Even; Liaset, Bjørn; Kristiansen, Karsten

2017-01-01

The association between the gut microbiota and obesity is well documented in both humans and in animal models. It is also demonstrated that dietary factors can change the gut microbiota composition and obesity development. However, knowledge of how diet, metabolism and gut microbiota mutually interact and modulate energy metabolism and obesity development is still limited. Epidemiological studies indicate an association between intake of certain dietary protein sources and obesity. Animal studies confirm that different protein sources vary in their ability to either prevent or induce obesity. Different sources of protein such as beans, vegetables, dairy, seafood, and meat differ in amino acid composition. Further, the type and level of other factors, such as fatty acids and persistent organic pollutants (POPs) vary between dietary protein sources. All these factors can modulate the composition of the gut microbiota and may thereby influence their obesogenic properties. This review summarizes evidence of how different protein sources affect energy efficiency, obesity development, and the gut microbiota, linking protein-dependent changes in the gut microbiota with obesity.

Links between Dietary Protein Sources, the Gut Microbiota, and Obesity

PubMed Central

Madsen, Lise; Myrmel, Lene S.; Fjære, Even; Liaset, Bjørn; Kristiansen, Karsten

2017-01-01

The association between the gut microbiota and obesity is well documented in both humans and in animal models. It is also demonstrated that dietary factors can change the gut microbiota composition and obesity development. However, knowledge of how diet, metabolism and gut microbiota mutually interact and modulate energy metabolism and obesity development is still limited. Epidemiological studies indicate an association between intake of certain dietary protein sources and obesity. Animal studies confirm that different protein sources vary in their ability to either prevent or induce obesity. Different sources of protein such as beans, vegetables, dairy, seafood, and meat differ in amino acid composition. Further, the type and level of other factors, such as fatty acids and persistent organic pollutants (POPs) vary between dietary protein sources. All these factors can modulate the composition of the gut microbiota and may thereby influence their obesogenic properties. This review summarizes evidence of how different protein sources affect energy efficiency, obesity development, and the gut microbiota, linking protein-dependent changes in the gut microbiota with obesity. PMID:29311977

Green tea polyphenols reduce body weight in rats by modulating obesity-related genes.

PubMed

Lu, Chuanwen; Zhu, Wenbin; Shen, Chwan-Li; Gao, Weimin

2012-01-01

Beneficial effects of green tea polyphenols (GTP) against obesity have been reported, however, the mechanism of this protection is not clear. Therefore, the objective of this study was to identify GTP-targeted genes in obesity using the high-fat-diet-induced obese rat model. A total of three groups (n = 12/group) of Sprague Dawley (SD) female rats were tested, including the control group (rats fed with low-fat diet), the HF group (rats fed with high-fat diet), and the HF+GTP group (rats fed with high-fat diet and GTP in drinking water). The HF group increased body weight as compared to the control group. Supplementation of GTP in the drinking water in the HF+GTP group reduced body weight as compared to the HF group. RNA from liver samples was extracted for gene expression analysis. A total of eighty-four genes related to obesity were analyzed using PCR array. Compared to the rats in the control group, the rats in the HF group had the expression levels of 12 genes with significant changes, including 3 orexigenic genes (Agrp, Ghrl, and Nr3c1); 7 anorectic genes (Apoa4, Cntf, Ghr, IL-1β, Ins1, Lepr, and Sort); and 2 genes that relate to energy expenditure (Adcyap1r1 and Adrb1). Intriguingly, the HF+GTP group restored the expression levels of these genes in the high-fat-induced obese rats. The protein expression levels of IL-1β and IL-6 in the serum samples from the control, HF, and HF+GTP groups confirmed the results of gene expression. Furthermore, the protein expression levels of superoxide dismutase-1 (SOD1) and catechol-O-methyltransferase (COMT) also showed GTP-regulated protective changes in this obese rat model. Collectively, this study revealed the beneficial effects of GTP on body weight via regulating obesity-related genes, anti-inflammation, anti-oxidant capacity, and estrogen-related actions in high-fat-induced obese rats.

Green Tea Polyphenols Reduce Body Weight in Rats by Modulating Obesity-Related Genes

PubMed Central

Lu, Chuanwen; Zhu, Wenbin; Shen, Chwan-Li; Gao, Weimin

2012-01-01

Beneficial effects of green tea polyphenols (GTP) against obesity have been reported, however, the mechanism of this protection is not clear. Therefore, the objective of this study was to identify GTP-targeted genes in obesity using the high-fat-diet-induced obese rat model. A total of three groups (n = 12/group) of Sprague Dawley (SD) female rats were tested, including the control group (rats fed with low-fat diet), the HF group (rats fed with high-fat diet), and the HF+GTP group (rats fed with high-fat diet and GTP in drinking water). The HF group increased body weight as compared to the control group. Supplementation of GTP in the drinking water in the HF+GTP group reduced body weight as compared to the HF group. RNA from liver samples was extracted for gene expression analysis. A total of eighty-four genes related to obesity were analyzed using PCR array. Compared to the rats in the control group, the rats in the HF group had the expression levels of 12 genes with significant changes, including 3 orexigenic genes (Agrp, Ghrl, and Nr3c1); 7 anorectic genes (Apoa4, Cntf, Ghr, IL-1β, Ins1, Lepr, and Sort); and 2 genes that relate to energy expenditure (Adcyap1r1 and Adrb1). Intriguingly, the HF+GTP group restored the expression levels of these genes in the high-fat-induced obese rats. The protein expression levels of IL-1β and IL-6 in the serum samples from the control, HF, and HF+GTP groups confirmed the results of gene expression. Furthermore, the protein expression levels of superoxide dismutase-1 (SOD1) and catechol-O-methyltransferase (COMT) also showed GTP-regulated protective changes in this obese rat model. Collectively, this study revealed the beneficial effects of GTP on body weight via regulating obesity-related genes, anti-inflammation, anti-oxidant capacity, and estrogen-related actions in high-fat-induced obese rats. PMID:22715380

Interaction between the RGS6 gene and psychosocial stress on obesity-related traits.

PubMed

Kim, Hyun-Jin; Min, Jin-Young; Min, Kyoung-Bok

2017-03-31

Obesity is a major risk factor for chronic diseases and arises from the interactions between environmental factors and multiple genes. Psychosocial stress may affect the risk for obesity, modifying food intake and choice. A recent study suggested regulator of G-protein signaling 6 (RGS6) as a novel candidate gene for obesity in terms of reward-related feeding under stress. In this study, we tried to verify the unidentified connection between RGS6 and human obesity with psychosocial stress in a Korean population. A total of 1,462 adult subjects, who participated in the Korean Association Resource cohort project, were included for this analysis. Obesity-related traits including waist circumference, body mass index, and visceral adipose tissue were recorded. A total of 4 intronic SNPs for the RGS6 gene were used for this study. We found that interactions between SNP rs2239219 and psychosocial stress are significantly associated with abdominal obesity (p = 0.007). As risk allele of this SNP increased, prevalence of abdominal obesity under high-stress conditions gradually increased (p = 0.013). However, we found no SNPs-by-stress interaction effect on other adiposity phenotypes. This study suggests that RGS6 is closely linked to stress-induced abdominal obesity in Korean adults.

Intraduodenal Administration of Intact Pea Protein Effectively Reduces Food Intake in Both Lean and Obese Male Subjects

PubMed Central

Geraedts, Maartje C. P.; Troost, Freddy J.; Munsters, Marjet J. M.; Stegen, Jos H. C. H.; de Ridder, Rogier J.; Conchillo, Jose M.; Kruimel, Joanna W.; Masclee, Ad A. M.; Saris, Wim H. M.

2011-01-01

Background Human duodenal mucosa secretes increased levels of satiety signals upon exposure to intact protein. However, after oral protein ingestion, gastric digestion leaves little intact proteins to enter the duodenum. This study investigated whether bypassing the stomach, through intraduodenal administration, affects hormone release and food-intake to a larger extent than orally administered protein in both lean and obese subjects. Methods Ten lean (BMI:23.0±0.7 kg/m2) and ten obese (BMI:33.4±1.4 kg/m2) healthy male subjects were included. All subjects randomly received either pea protein solutions (250 mg/kg bodyweight in 0.4 ml/kg bodyweight of water) or placebo (0.4 ml/kg bodyweight of water), either orally or intraduodenally via a naso-duodenal tube. Appetite-profile, plasma GLP-1, CCK, and PYY concentrations were determined over a 2 h period. After 2 h, subjects received an ad-libitum meal and food-intake was recorded. Results CCK levels were increased at 10(p<0.02) and 20(p<0.01) minutes after intraduodenal protein administration (IPA), in obese subjects, compared to lean subjects, but also compared to oral protein administration (OPA)(p<0.04). GLP-1 levels increased after IPA in obese subjects after 90(p<0.02) to 120(p<0.01) minutes, compared to OPA. Food-intake was reduced after IPA both in lean and obese subjects (-168.9±40 kcal (p<0.01) and −298.2±44 kcal (p<0.01), respectively), compared to placebo. Also, in obese subjects, food-intake was decreased after IPA (−132.6±42 kcal; p<0.01), compared to OPA. Conclusions Prevention of gastric proteolysis through bypassing the stomach effectively reduces food intake, and seems to affect obese subjects to a greater extent than lean subjects. Enteric coating of intact protein supplements may provide an effective dietary strategy in the prevention/treatment of obesity. PMID:21931864

Leucine and protein metabolism in obese zucker rats

USDA-ARS?s Scientific Manuscript database

Branched-chain amino acids (BCAAs) are circulating nutrient signals for protein accretion, however they increase in obesity and appear to prognosticate diabetes onset. To understand the mechanisms whereby obesity affects BCAAs and protein metabolism, we employed metabolomics and measured rates of [1...

Retinol Binding Protein 4 in Relation to Diet, Inflammation, Immunity, and Cardiovascular Diseases12

PubMed Central

Zabetian-Targhi, Fateme; Mahmoudi, Mohammad J; Rezaei, Nima; Mahmoudi, Maryam

2015-01-01

Retinol binding protein 4 (RBP4), previously called retinol binding protein (RBP), is considered a specific carrier of retinol in the blood. It is also an adipokine that has been implicated in the pathophysiology of insulin resistance. RBP4 seems to be correlated with cardiometabolic markers in inflammatory chronic diseases, including obesity, type 2 diabetes, metabolic syndrome, and cardiovascular diseases (CVDs). It has recently been suggested that inflammation produced by RBP4 induces insulin resistance and CVD. The clinical relevance of this hypothesis is discussed in this review. Knowledge concerning the association of RBP4 with inflammation markers, oxidative stress, and CVDs as well as concerning the role of diet and antioxidants in decreasing RBP4 concentrations are discussed. Special attention is given to methodologies used in previously published studies and covariates that should be controlled when planning new studies on this adipokine. PMID:26567199

Effects of energy expenditure gene polymorphisms on obesity-related traits in obese children.

PubMed

Csernus, Katalin; Pauler, Gábor; Erhardt, Éva; Lányi, Éva; Molnár, Dénes

2015-01-01

To assess the frequencies of common polymorphisms of genes associated with energy expenditure among Hungarian obese children and investigate their influences on obesity-related traits and metabolic complications of common childhood obesity. In a total of 528 obese children (age 13.2±2.6 years) an oral glucose tolerance test and determination of fasting serum lipid levels were carried out, blood pressure and resting energy expenditure were measured and the children were genotyped for the following gene polymorphisms: Trp64Arg of β3-adrenoreceptor (ADRB3), -3826 A/G of uncoupling protein (UCP)-1, exon 8 45 bp del/ins and -866 G/A of UCP-2, -55 C/T of UCP-3, and Pro12Ala of peroxisome-proliferator activated receptor gamma-2. Carriers of the ADRB3 Arg64 allele had a significantly higher relative body weight and relative body mass index compared with non-carriers. The UCP-2 exon 8 del/ins polymorphism was associated with higher degree of obesity, insulin resistance, dyslipideamia and lower adjusted metabolic rate. Children with UCP-3 -55 T/T genotype had a significantly lower adjusted metabolic rate than the C allele carriers. We found evidence for associations between common polymorphisms of the ADRB3, the UCP-2 and UCP-3 genes and basic metabolic rate as well as level and metabolic consequences of common obesity among Hungarian school-aged children. Copyright © 2014 Asian Oceanian Association for the Study of Obesity. Published by Elsevier Ltd. All rights reserved.

Obesity-Related Hormones in Low-Income Preschool-Age Children: Implications for School Readiness

ERIC Educational Resources Information Center

Miller, Alison L.; Lumeng, Carey N.; Delproposto, Jennifer; Florek, Brian; Wendorf, Kristin; Lumeng, Julie C.

2013-01-01

Mechanisms underlying socioeconomic disparities in school readiness and health outcomes, particularly obesity, among preschool-aged children are complex and poorly understood. Obesity can induce changes in proteins in the circulation that contribute to the negative impact of obesity on health; such changes may relate to cognitive and emotion…

Association of RBP4 genetic variants with childhood obesity and cardiovascular risk factors.

PubMed

Codoñer-Franch, Pilar; Carrasco-Luna, Joaquín; Allepuz, Paula; Codoñer-Alejos, Alan; Guillem, Vicent

2016-12-01

Recent data suggest that retinol-binding protein 4 (RBP4) gene variants could be associated with a risk of obesity and its co-morbidities, such as metabolic syndrome, which increases the risk of developing type 2 diabetes mellitus and cardiovascular disease. The present study examined the potential association of RBP4 single nucleotide polymorphisms (SNPs) with childhood obesity and its metabolic complications. Four RBP4 SNPs, rs3758538 (3944A>C), rs3758539 (4406G>A), rs12265684 (12177G>C) and rs34571439 (14684T>G), were genotyped in a population of 180 Spanish Caucasian children (97 obese and 83 normal-weight children). Association of RBP4 SNPs with obesity, metabolic risk factors (blood pressure, triglycerides, high-density lipoprotein cholesterol, insulin resistance) and markers of vascular inflammation, such as high-sensitive C-reactive protein (hs-CRP), was tested. We found SNP rs3758538 to be associated with obesity (p = 0.007). Specifically, each copy of the minor allele C was associated with an increased risk of obesity, by more than twofold, in respect of being homozygous for the major allele A (odds ratio = 2.4; 95% confidence interval = 1.2-4.8). The rs3758538 and rs34571439 RBP4 SNPs correlated with plasma RBP4 levels. The SNPs rs12265684 and rs34571439 correlated with plasma triglyceride levels. The rs34571439 was also associated to hs-CRP levels. Marginal association of RBP4 SNPs with plasma high-density lipoprotein levels (rs34571439), blood pressure (rs12265684) and insulin resistance (rs3758539) was also observed. These findings suggest that childhood obesity may be associated with variations in RBP4 gene. The presence of selective SNPs in the RBP4 gene may account for metabolic complications. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Interaction between obesity-related genes, FTO and MC4R, associated to an increase of breast cancer risk.

PubMed

da Cunha, Patrícia Amorim; de Carlos Back, Lia Kubelka; Sereia, Aline Fernanda Rodrigues; Kubelka, Clara; Ribeiro, Maria Cecíia Menks; Fernandes, Bráulio Leal; de Souza, Ilíada Rainha

2013-12-01

Breast cancer (BC) is a complex disease and obesity is a well-known risk factor for its development, especially after menopause. Several studies have shown Single Nucleotide Polymorphisms (SNPs) linked to overweight and obesity, such as: rs1121980 (T/C) and rs9939609 (A/T) in Fat Mass and Obesity Associated gene (FTO) and rs17782313 (T/C) in Melanocortin 4 Receptor gene (MC4R). Thus, we aimed to investigate the association between these obesity-related SNPs and BC risk. One hundred BC patients and 148 healthy women from Santa Catarina, Brazil entered the study. SNPs were genotyped using Taqman assays. For statistical analyses SNPStats and SPSS softwares were used. Association analyses were performed by logistic regression and were adjusted for age and Body mass index (BMI). Multiple SNPs inheritance models (log-additive, dominant, recessive, codominant) were performed to determine odds ratios (ORs), assuming 95 % confidence interval (CI) and P value = 0.05 as the significance limit. When analyzed alone, FTO rs1121980 and rs9939609 did not show significant associations with BC development, however MC4R rs17782313 showed increased risk for BC even after adjustments (P-value = 0.032). Interestingly, the interaction of FTO and MC4R polymorphisms showed a powerful association with BC. We observed a 4.59-fold increased risk for woman who have the allele combination C/T/C (FTO rs1121980/FTO rs9939609/MC4R rs17782313) (P-value = 0.0011, adjusted for age and BMI). We found important and unpublished associations between these obesity-related genes and BC risk. These associations seem to be independent of their effect on BMI, indicating a direct role of the interaction between FTO and MC4R polymorphisms in BC development.

Association of melanocortin-4 receptor gene polymorphisms with obesity-related parameters in Malaysian Malays.

PubMed

Apalasamy, Yamunah Devi; Ming, Moy Foong; Rampal, Sanjay; Bulgiba, Awang; Mohamed, Zahurin

2013-01-01

Melanocortin-4 receptor (MC4R) is an important regulator of body weight and energy intake. Genetic polymorphisms of the MC4R gene have been found to be linked to obesity in many recent studies across the globe. This study aimed to examine the effects of MC4R polymorphisms on obesity parameters, Linkage disequilibrium (LD) pattern and haplotypes in Malaysian Malays. The study subjects were 652 Malaysian Malays. Genomic DNA was extracted from buccal swabs. Genotyping was performed using Sequenom MassARRAY® iPLEX platform. Anthropometric and blood lipid profiles were measured. MC4R rs571312 SNP was associated with logBMI (p = 0.008) and systolic blood pressure (p = 0.005), while MC4R rs2229616 SNP was associated with total cholesterol (TC) levels (p = 0.016). The MC4R rs7227255 SNP did not show any association with obesity parameters. The strength of LD of the MC4R gene region is low and the haplotypes were not associated with obesity in Malaysian Malays.

Carbonylated plasma proteins as potential biomarkers of obesity induced type 2 diabetes mellitus.

PubMed

Bollineni, Ravi Chand; Fedorova, Maria; Blüher, Matthias; Hoffmann, Ralf

2014-11-07

Protein carbonylation is a common nonenzymatic oxidative post-translational modification, which is often considered as biomarker of oxidative stress. Recent evidence links protein carbonylation also to obesity and type 2 diabetes mellitus (T2DM), though the protein targets of carbonylation in human plasma have not been identified. In this study, we profiled carbonylated proteins in plasma samples obtained from lean individuals and obese patients with or without T2DM. The plasma samples were digested with trypsin, carbonyl groups were derivatized with O-(biotinylcarbazoylmethyl)hydroxylamine, enriched by avidin affinity chromatography, and analyzed by RPC-MS/MS. Signals of potentially modified peptides were targeted in a second LC-MS/MS analysis to retrieve the peptide sequence and the modified residues. A total of 158 unique carbonylated proteins were identified, of which 52 were detected in plasma samples of all three groups. Interestingly, 36 carbonylated proteins were detected only in obese patients with T2DM, whereas 18 were detected in both nondiabetic groups. The carbonylated proteins originated mostly from liver, plasma, platelet, and endothelium. Functionally, they were mainly involved in cell adhesion, signaling, angiogenesis, and cytoskeletal remodeling. Among the identified carbonylated proteins were several candidates, such as VEGFR-2, MMP-1, argin, MKK4, and compliment C5, already connected before to diabetes, obesity and metabolic diseases.

The most effective factors to offset sarcopenia and obesity in the older Korean: Physical activity, vitamin D, and protein intake.

PubMed

Oh, Chorong; Jeon, Byeong Hwan; Reid Storm, Shaun Nicholas; Jho, Sunkug; No, Jae-Kyung

2017-01-01

The aim of this study was to evaluate the effects of the types and levels of physical activity in conjunction with protein intake and vitamin D on sarcopenia and obesity status in an elderly population. Study participants (N = 4452) were ages ≥60 y and included 1929 men and 2523 women who completed a body composition analysis with a dual energy x-ray absorptiometry and provided health and dietary data. Higher appendicular skeletal muscle mass/weight was observed in the non-obese group, although obese participants had greater weights. The non-obese sarcopenia subgroup showed health problems related to insulin resistance and metabolic-related factors compared with the nonsarcopenic group. The total metabolic equivalent was significantly different in both obese categories, regardless of sarcopenic status. The prevalence of obesity, sarcopenia, and sarcopenic obesity relatively increased with a diet deficient of protein intake and vitamin D. These data suggest that sarcopenia had a significant association with metabolic-related factors; physical activity, especially vigorous activity; and protein intake and vitamin D levels in a non-obese elderly population. Therefore, maintaining healthy body weight by means of resistance exercise and enhanced protein intake and vitamin D may help offset sarcopenia in this age group. Copyright © 2016 Elsevier Inc. All rights reserved.

Evaluation of Hypocaloric Diet With Protein Supplementation in Middle-Aged Sarcopenic Obese Women: A Pilot Study.

PubMed

Sammarco, Rosa; Marra, Maurizio; Di Guglielmo, Maria Luisa; Naccarato, Marianna; Contaldo, Franco; Poggiogalle, Eleonora; Donini, Lorenzo Maria; Pasanisi, Fabrizio

2017-01-01

The aim of this study was to evaluate the efficacy of a nutritional program, which is characterized by a different modulation of proteins, in adult patients with sarcopenic obesity. We studied 18 obese women aged 41-74 years. Obesity was diagnosed as fat mass > 34.8% and sarcopenia was defined when lean body mass was <90% of the subject's ideal fat free mass. All subjects were randomly assigned to different nutritional interventions: Hypocaloric diet plus placebo (A) and hypocaloric high-protein diet (1.2-1.4 g / kg body weight reference / day) (B). Anthropometric measurements, body composition, resting energy expenditure, handgrip test, Short Physical Performance Battery (SPPB), and SF-36 questionnaire were evaluated at baseline and after 4 months. Weight significantly decreased in both groups. Women with high-protein diet preserved lean body mass compared to low-calorie diet and improved significantly muscle strength; SPPB score did not change in both groups. SF-36 test showed a significant change for general health after 4 months in group B. In our study, sarcopenic obese patients with high-protein diet showed an improvement in muscle strength. Furthermore, dietary protein enrichment may represent a protection from the risk of sarcopenia following a hypocaloric diet. © 2017 The Author(s) Published by S. Karger GmbH, Freiburg.

Evaluation of Hypocaloric Diet With Protein Supplementation in Middle-Aged Sarcopenic Obese Women: A Pilot Study

PubMed Central

Sammarco, Rosa; Marra, Maurizio; Di Guglielmo, Maria Luisa; Naccarato, Marianna; Contaldo, Franco; Poggiogalle, Eleonora; Donini, Lorenzo Maria; Pasanisi, Fabrizio

2017-01-01

Objective The aim of this study was to evaluate the efficacy of a nutritional program, which is characterized by a different modulation of proteins, in adult patients with sarcopenic obesity. Methods We studied 18 obese women aged 41–74 years. Obesity was diagnosed as fat mass > 34.8% and sarcopenia was defined when lean body mass was <90% of the subject's ideal fat free mass. All subjects were randomly assigned to different nutritional interventions: Hypocaloric diet plus placebo (A) and hypocaloric high-protein diet (1.2–1.4 g/kg body weight reference/day) (B). Anthropometric measurements, body composition, resting energy expenditure, handgrip test, Short Physical Performance Battery (SPPB), and SF-36 questionnaire were evaluated at baseline and after 4 months. Results Weight significantly decreased in both groups. Women with high-protein diet preserved lean body mass compared to low-calorie diet and improved significantly muscle strength; SPPB score did not change in both groups. SF-36 test showed a significant change for general health after 4 months in group B. Conclusions In our study, sarcopenic obese patients with high-protein diet showed an improvement in muscle strength. Furthermore, dietary protein enrichment may represent a protection from the risk of sarcopenia following a hypocaloric diet. PMID:28528340

Using molecular functional networks to manifest connections between obesity and obesity-related diseases

PubMed Central

Yang, Jialiang; Qiu, Jing; Wang, Kejing; Zhu, Lijuan; Fan, Jingjing; Zheng, Deyin; Meng, Xiaodi; Yang, Jiasheng; Peng, Lihong; Fu, Yu; Zhang, Dahan; Peng, Shouneng; Huang, Haiyun; Zhang, Yi

2017-01-01

Obesity is a primary risk factor for many diseases such as certain cancers. In this study, we have developed three algorithms including a random-walk based method OBNet, a shortest-path based method OBsp and a direct-overlap method OBoverlap, to reveal obesity-disease connections at protein-interaction subnetworks corresponding to thousands of biological functions and pathways. Through literature mining, we also curated an obesity-associated disease list, by which we compared the methods. As a result, OBNet outperforms other two methods. OBNet can predict whether a disease is obesity-related based on its associated genes. Meanwhile, OBNet identifies extensive connections between obesity genes and genes associated with a few diseases at various functional modules and pathways. Using breast cancer and Type 2 diabetes as two examples, OBNet identifies meaningful genes that may play key roles in connecting obesity and the two diseases. For example, TGFB1 and VEGFA are inferred to be the top two key genes mediating obesity-breast cancer connection in modules associated with brain development. Finally, the top modules identified by OBNet in breast cancer significantly overlap with modules identified from TCGA breast cancer gene expression study, revealing the power of OBNet in identifying biological processes involved in the disease. PMID:29156709

[Generation and phenotype analysis of zebrafish mutations of obesity-related genes lepr and mc4r].

PubMed

Fei, Fei; Sun, Shao-Yang; Yao, Yu-Xiao; Wang, Xu

2017-02-25

Obesity has become a severe public health problem across the world, and seriously affects the health and life quality of human beings. Here we generated lepr and mc4r mutant zebrafish via the CRISPR/Cas9 technique, and performed morphological and functional characterizations of those mutants. We observed that there was no significant phenotypic difference between homozygous mutants and wild-type controls before 2.5 months post-fertilization (mpf). However, the adult lepr -/- and mc4r -/- individuals displayed increased food intake, heavier weight, and higher body fat percentage, the characteristics of obesity phenotypes. Blood glucose test showed that overfeeding induced significantly impaired glucose tolerance in adult lepr -/- and mc4r -/- zebrafish. Furthermore, we analyzed 76 energy metabolism-related transcripts in lepr -/- and mc4r -/- zebrafish livers by using real-time RT-PCR, and compared the results with the published microarray data of Lep ob/ob mouse livers, and found that the changes in the expression of insulin/IGF signaling (IIS) pathway genes in lepr -/- zebrafish and Lep ob/ob mouse were positively correlated, suggesting that the IIS pathway maintains functional conservation between zebrafish and mammals during the evolution of the obesity-regulating molecule network.

Progranulin concentration in relation to bone mineral density among obese individuals.

PubMed

Milajerdi, Alireza; Maghbooli, Zhila; Mohammadi, Farzad; Hosseini, Banafsheh; Mirzaei, Khadijeh

2018-01-01

Adipose tissue, particularly visceral adipose tissue, secretes a variety of cytokines, among which progranulin is a glycoprotein related to the immune system. Along with other secreted proteins, progranulin may be associated with bone mineral density. The aim of this study was to find out whether there are associations between the progranulin and bone mineral density among obese people. This cross-sectional study was conducted on 244 obese participants (aged 22-52). Serum progranulin, high sensitive C-reactive protein, oxidised-low dencity lipoprotein, tumor necrosis factor-α, parathormone, vitamin D, and interleukins of 1 β, 4, 6, 10, 13, and 17 concentrations were measured. Anthropometric measurements, body composition and bone mineral density were also assessed. Serum progranulin was directly associated with interleukin-6 and interleukin-1β, while it had a negative association with interleukin-17 and tumor necrosis factor-α. We also observed a statistically significant direct association between progranulin concentration and visceral fat, abdominal fat, waist, abdominal and hip circumferences, hip T-score, and Z-score and T-score for the lumbar region. A partial correlation test has also shown a significant positive correlation regarding serum progranulin and the hip Z-score. Moreover, progranulin level is inversely associated with ospteopenia (P = 0.04 and CI: 0.17,0.96). Our study revealed that central obesity may be related to increased progranulin concentration. In addition, progranulin concentration was directly related to bone formation parameters, which indicates the protective effects of progranulin on bone density. Further studies are needed to clarify the exact mechanisms underlying these associations.

Soy protein isolate modified metabolic phenotype and hepatic Wnt signaling in obese Zucker rats.

PubMed

Cain, J; Banz, W J; Butteiger, D; Davis, J E

2011-10-01

We have previously shown that soy protein isolate (SPI) with intact phytoestrogen content prevented obesity-related dysfunction. Recent data have suggested that soy ingredients may act as regulators of adipogenic programming in adipose tissue (AT) and liver. Thus, the current study was undertaken to determine whether the beneficial effects of SPI are linked to changes in adipogenic regulators, such as the Wnt signaling cascade. For this, lean (LZR) and obese Zucker (OZR) rats were provided isocaloric and isonitrogenous diets containing SPI, sodium caseinate, or dairy whey protein for 17 weeks. At termination, SPI increased body weight and total adiposity in rodents, which corresponded with an increase in both adipocyte size and number. Furthermore, markers of inflammation, hypercholesterolemia, and hepatic steatosis were all reduced in OZR rats provided SPI. Transcript abundance of several canonical and noncanonical Wnt signaling intermediates in liver, but not AT, was distinctly modified by SPI. Collectively, these data confirm the protective SPI attenuated obesity-related metabolic dysfunction conceivably through regulation of adipogenic programming, as evident by changes in AT morphology and hepatic Wnt signaling. Collectively, this study confirmed the potential utilization of soy protein and its bioactive ingredients for prevention and treatment of obesity-related comorbidities. © Georg Thieme Verlag KG Stuttgart · New York.

Improved Function With Enhanced Protein Intake per Meal: A Pilot Study of Weight Reduction in Frail, Obese Older Adults.

PubMed

Porter Starr, Kathryn N; Pieper, Carl F; Orenduff, Melissa C; McDonald, Shelley R; McClure, Luisa B; Zhou, Run; Payne, Martha E; Bales, Connie W

2016-10-01

Obesity is a significant cause of functional limitations in older adults; yet, concerns that weight reduction could diminish muscle along with fat mass have impeded progress toward an intervention. Meal-based enhancement of protein intake could protect function and/or lean mass but has not been studied during geriatric obesity reduction. In this 6-month randomized controlled trial, 67 obese (body mass index ≥30kg/m(2)) older (≥60 years) adults with a Short Physical Performance Battery score of 4-10 were randomly assigned to a traditional (Control) weight loss regimen or one with higher protein intake (>30g) at each meal (Protein). All participants were prescribed a hypo-caloric diet, and weighed and provided dietary guidance weekly. Physical function (Short Physical Performance Battery) and lean mass (BOD POD), along with secondary measures, were assessed at 0, 3, and 6 months. At the 6-month endpoint, there was significant (p < .001) weight loss in both the Control (-7.5±6.2kg) and Protein (-8.7±7.4kg) groups. Both groups also improved function but the increase in the Protein (+2.4±1.7 units; p < .001) was greater than in the Control (+0.9±1.7 units; p < .01) group (p = .02). Obese, functionally limited older adults undergoing a 6-month weight loss intervention with a meal-based enhancement of protein quantity and quality lost similar amounts of weight but had greater functional improvements relative to the Control group. If confirmed, this dietary approach could have important implications for improving the functional status of this vulnerable population (ClinicalTrials.gov identifier: NCT01715753). © The Author 2016. Published by Oxford University Press on behalf of The Gerontological Society of America.

Improved Function With Enhanced Protein Intake per Meal: A Pilot Study of Weight Reduction in Frail, Obese Older Adults

PubMed Central

Pieper, Carl F.; Orenduff, Melissa C.; McDonald, Shelley R.; McClure, Luisa B.; Zhou, Run; Payne, Martha E.; Bales, Connie W.

2016-01-01

Abstract Background: Obesity is a significant cause of functional limitations in older adults; yet, concerns that weight reduction could diminish muscle along with fat mass have impeded progress toward an intervention. Meal-based enhancement of protein intake could protect function and/or lean mass but has not been studied during geriatric obesity reduction. Methods: In this 6-month randomized controlled trial, 67 obese (body mass index ≥30kg/m2) older (≥60 years) adults with a Short Physical Performance Battery score of 4–10 were randomly assigned to a traditional (Control) weight loss regimen or one with higher protein intake (>30g) at each meal (Protein). All participants were prescribed a hypo-caloric diet, and weighed and provided dietary guidance weekly. Physical function (Short Physical Performance Battery) and lean mass (BOD POD), along with secondary measures, were assessed at 0, 3, and 6 months. Results: At the 6-month endpoint, there was significant (p < .001) weight loss in both the Control (−7.5±6.2kg) and Protein (−8.7±7.4kg) groups. Both groups also improved function but the increase in the Protein (+2.4±1.7 units; p < .001) was greater than in the Control (+0.9±1.7 units; p < .01) group (p = .02). Conclusion: Obese, functionally limited older adults undergoing a 6-month weight loss intervention with a meal-based enhancement of protein quantity and quality lost similar amounts of weight but had greater functional improvements relative to the Control group. If confirmed, this dietary approach could have important implications for improving the functional status of this vulnerable population (ClinicalTrials.gov identifier: NCT01715753). PMID:26786203

Dietary Tuna Dark Muscle Protein Attenuates Hepatic Steatosis and Increases Serum High-Density Lipoprotein Cholesterol in Obese Type-2 Diabetic/Obese KK-Ay Mice.

PubMed

Maeda, Hayato; Hosomi, Ryota; Fukuda, Mari; Ikeda, Yuki; Yoshida, Munehiro; Fukunaga, Kenji

2017-05-01

Tuna muscle consists of light and dark muscle in approximately equal proportions. However, besides for the light muscle of tuna, cod, sardine, and salmon, few researches have assessed the health-promoting functions of fish protein. Therefore, we evaluated the mechanisms underlying the alteration of lipid storage and cholesterol metabolism following the intake of tuna dark muscle protein (TDMP) by obese type-2 diabetic/obese mice. Four-week-old male KK-A y mice were separated into 2 dietary groups, with one group receiving a casein-based diet and the other receiving a diet with the substitution of part of the protein (50%, w/w) by TDMP (TDMP diet) for 4 wk. The TDMP diet significantly increased the content of serum high-density lipoprotein cholesterol, partly due to the reduction of the expression of scavenger receptor class B member 1 in epididymal white adipose tissue. In addition, dietary TDMP decreased the content of hepatic triacylglycerol, which could be due to the enhancement of carnitine palmitoyltransferase-2 activity through the activation of the expression of the peroxisome proliferative activated receptor-α in the liver. These results suggest that TDMP could have the potential to prevent the development of obesity-related diseases by suppressing the storage of hepatic triacylglycerol and cholesterol. © 2017 Institute of Food Technologists®.

Analysis of vascular endothelial dysfunction genes and related pathways in obesity through systematic bioinformatics.

PubMed

Zhang, Hui; Wang, Jing; Sun, Ling; Xu, Qiuqin; Hou, Miao; Ding, Yueyue; Huang, Jie; Chen, Ye; Cao, Lei; Zhang, Jianmin; Qian, Weiguo; Lv, Haitao

2015-01-01

Obesity has become an increasingly serious health problem and popular research topic. It is associated with many diseases, especially cardiovascular disease (CVD)-related endothelial dysfunction. This study analyzed genes related to endothelial dysfunction and obesity and then summarized their most significant signaling pathways. Genes related to vascular endothelial dysfunction and obesity were extracted from a PubMed database, and analyzed by STRING, DAVID, and Gene-Go Meta-Core software. 142 genes associated with obesity were found to play a role in endothelial dysfunction in PubMed. A significant pathway (Angiotensin system maturation in protein folding and maturation) associated with obesity and endothelial dysfunction was explored. The genes and the pathway explored may play an important role in obesity. Further studies about preventing vascular endothelial dysfunction obesity should be conducted through targeting these loci and pathways.

Mapping and annotating obesity-related genes in pig and human genomes.

PubMed

Martelli, Pier Luigi; Fontanesi, Luca; Piovesan, Damiano; Fariselli, Piero; Casadio, Rita

2014-01-01

Background. Obesity is a major health problem in both developed and emerging countries. Obesity is a complex disease whose etiology involves genetic factors in strong interplay with environmental determinants and lifestyle. The discovery of genetic factors and biological pathways underlying human obesity is hampered by the difficulty in controlling the genetic background of human cohorts. Animal models are then necessary to further dissect the genetics of obesity. Pig has emerged as one of the most attractive models, because of the similarity with humans in the mechanisms regulating the fat deposition. Results. We collected the genes related to obesity in humans and to fat deposition traits in pig. We localized them on both human and pig genomes, building a map useful to interpret comparative studies on obesity. We characterized the collected genes structurally and functionally with BAR+ and mapped them on KEGG pathways and on STRING protein interaction network. Conclusions. The collected set consists of 361 obesity related genes in human and pig genomes. All genes were mapped on the human genome, and 54 could not be localized on the pig genome (release 2012). Only for 3 human genes there is no counterpart in pig, confirming that this animal is a good model for human obesity studies. Obesity related genes are mostly involved in regulation and signaling processes/pathways and relevant connection emerges between obesity-related genes and diseases such as cancer and infectious diseases.

Reduced Hepatic Carcinoembryonic Antigen-Related Cell Adhesion Molecule 1 Level in Obesity.

PubMed

Heinrich, Garrett; Muturi, Harrison T; Rezaei, Khadijeh; Al-Share, Qusai Y; DeAngelis, Anthony M; Bowman, Thomas A; Ghadieh, Hilda E; Ghanem, Simona S; Zhang, Deqiang; Garofalo, Robert S; Yin, Lei; Najjar, Sonia M

2017-01-01

Impairment of insulin clearance is being increasingly recognized as a critical step in the development of insulin resistance and metabolic disease. The carcinoembryonic antigen-related cell adhesion molecule 1 (CEACAM1) promotes insulin clearance. Null deletion or liver-specific inactivation of Ceacam1 in mice causes a defect in insulin clearance, insulin resistance, steatohepatitis, and visceral obesity. Immunohistological analysis revealed reduction of hepatic CEACAM1 in obese subjects with fatty liver disease. Thus, we aimed to determine whether this occurs at the hepatocyte level in response to systemic extrahepatic factors and whether this holds across species. Northern and Western blot analyses demonstrate that CEACAM1 mRNA and protein levels are reduced in liver tissues of obese individuals compared to their lean age-matched counterparts. Furthermore, Western analysis reveals a comparable reduction of CEACAM1 protein in primary hepatocytes derived from the same obese subjects. Similar to humans, Ceacam1 mRNA level, assessed by quantitative RT-PCR analysis, is significantly reduced in the livers of obese Zucker ( fa/fa , ZDF) and Koletsky ( f/f ) rats relative to their age-matched lean counterparts. These studies demonstrate that the reduction of hepatic CEACAM1 in obesity occurs at the level of hepatocytes and identify the reduction of hepatic CEACAM1 as a common denominator of obesity across multiple species.

Obesity and obesity-related behaviors among rural and urban adults in the USA.

PubMed

Trivedi, Tushar; Liu, Jihong; Probst, Janice; Merchant, Anwar; Jhones, Sonya; Martin, Amy Block

2015-01-01

Previous studies have reported a higher prevalence of obesity among rural Americans. However, it is not clear whether obesity-related behaviors can explain the higher level of obesity among rural adults. The purpose of this study was to examine the differences in obesity-related behaviors across rural-urban adult populations in the USA. Data were obtained from the 1999-2006 National Health and Nutrition Examination Survey, restricted to 14 039 participants aged 20 years or more. Body mass index (BMI) was calculated using measured height and weight, and individuals with BMI≥30 kg/m2 were categorized as obese. Physical activity recommendations were used to define participants' physical activity levels: no leisure-time physical activity, less than, meeting, and exceeding the recommended levels. Sedentary behaviors were measured by hours sitting and watching TV or videos or using a computer (outside of work). Dietary intake was assessed by one-day 24 hour dietary recall. Residence was measured at the census tract level using the Rural-Urban Commuting Area Codes. Multiple logistic regression models were used to examine urban-rural differences after adjusting for sociodemographic, health, dietary, and lifestyle factors. The prevalence of obesity was higher in rural than in urban residents (35.6% vs 30.4%, p<0.01), among both men (37.7% vs. 32.5%, p<0.01) and women (33.4% vs 28.2%, p<0.01). Compared to urban adults, more rural adults reported no leisure-time physical activity (38.8% vs 31.8%, p<0.01) and fewer rural adults met or exceeded physical activity recommendations (41.5% vs 47.2%, p<0.01). Rural adults had lower intake of fiber and fruits and higher intake of sweetened beverages. After adjusting for sociodemographic, health, diet, sedentary behaviors, and physical activity, the odds of being obese among rural adults were 1.19 times higher than that among urban adults (95% confidence interval: 1.06, 1.34). Higher level of obesity, physical inactivity, and poor

The Relations Between Immunity, Oxidative Stress and Inflammation Markers, in Childhood Obesity.

PubMed

Laura Anca, Popescu; Bogdana, Virgolici; Olivia, Timnea; Horia, Virgolici; Dumitru, Oraseanu; Leon, Zagrean

2014-10-01

Oxidative stress, inflammation and insulin resistance are the principal culprits in childhood obesity. Immune modifications are also important in the development of the obesity complications.The aim of this study is to find the relations for some immunity parameters with markers for oxidative stress and inflammation. Sixty obese children (10-16 years old) and thirty age and sex matched lean children were involved. The activities for erythrocyte superoxid dismutase (SOD), for erythrocyte glutathione peroxidase (GPx) and serum thioredoxin level were measured by ELISA, as oxidative stress markers. Circulating immune complexes (CIC), complement fractions C3, C4 and the self-antibodies, antismooth muscle antibodies (ASMA), antiliver-kidney microsome antibodies (LKM1) were measured by ELISA methods. Ceruloplasmin, haptoglobin and C reactive protein (CRP) were measured as inflammatory markers by immunoturbidimetric methods. ceruloplasmin (p<0.001), haptoglobin (p<0.001), CRP (p<0.05) and activity for SOD (p<0.001) were measured, while thioredoxin concentration (p<0.04) was reduced. The antibodies LKM1 and ASMA and GPx activity were not modified between groups. Positive correlations (for p<0.05) were calculated between SOD activity and LKM1 (r=0.37), GPx activity and ASMA (r=0.27), haptoglobin and C3 (r=0.33), ceruloplasmin and CIC (r=0.41), CRP and C3 (p<0.27) and negative correlations were calculated for C4 both with GPx activity (r= -0.28) and with thioredoxin level (r= -0.27). In the obese children versus the lean ones, higher levels for C3 (p<0.001), C4(p<0.001), CIC (p<0.05), In conclusion, this study demonstrates that immune modifications, inflammation and oxidative stress are related and they act in cluster in childhood obesity. Copyright © 2014. Published by Elsevier Inc.

Differential representation of liver proteins in obese human subjects suggests novel biomarkers and promising targets for drug development in obesity.

PubMed

Caira, Simonetta; Iannelli, Antonio; Sciarrillo, Rosaria; Picariello, Gianluca; Renzone, Giovanni; Scaloni, Andrea; Addeo, Pietro

2017-12-01

The proteome of liver biopsies from human obese (O) subjects has been compared to those of nonobese (NO) subjects using two-dimensional gel electrophoresis (2-DE). Differentially represented proteins were identified by matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF) mass spectrometry (MS)-based peptide mass fingerprinting (PMF) and nanoflow-liquid chromatography coupled to electrospray-tandem mass spectrometry (nLC-ESI-MS/MS). Overall, 61 gene products common to all of the liver biopsies were identified within 65 spots, among which 25 ones were differently represented between O and NO subjects. In particular, over-representation of short-chain acyl-CoA dehydrogenase, Δ(3,5)-Δ(2,4)dienoyl-CoA isomerase, acetyl-CoA acetyltransferase, glyoxylate reductase/hydroxypyruvate reductase, fructose-biphosphate aldolase B, peroxiredoxin I, protein DJ-1, catalase, α- and β-hemoglobin subunits, 3-mercaptopyruvate S-transferase, calreticulin, aminoacylase 1, phenazine biosynthesis-like domain-containing protein and a form of fatty acid-binding protein, together with downrepresentation of glutamate dehydrogenase, glutathione S-transferase A1, S-adenosylmethionine synthase 1A and a form of apolipoprotein A-I, was associated with the obesity condition. Some of these metabolic enzymes and antioxidant proteins have already been identified as putative diagnostic markers of liver dysfunction in animal models of steatosis or obesity, suggesting additional investigations on their role in these syndromes. Their differential representation in human liver was suggestive of their consideration as obesity human biomarkers and for the development of novel antiobesity drugs.

Dietary Aloe Reduces Adipogenesis via the Activation of AMPK and Suppresses Obesity-related Inflammation in Obese Mice.

PubMed

Shin, Eunju; Shin, Seulmee; Kong, Hyunseok; Lee, Sungwon; Do, Seon-Gil; Jo, Tae Hyung; Park, Young-In; Lee, Chong-Kil; Hwang, In-Kyeong; Kim, Kyungjae

2011-04-01

Metabolic disorders, including type II diabetes and obesity, present major health risks in industrialized countries. AMP-activated protein kinase (AMPK) has become the focus of a great deal of attention as a novel therapeutic target for the treatment of metabolic syndromes. In this study, we evaluated whether dietary aloe could reduce obesity-induced inflammation and adipogenesis. Male C57BL/6 obese mice fed a high-fat diet for 54 days received a supplement of aloe formula (PAG, ALS, Aloe QDM, and Aloe QDM complex) or pioglitazone (PGZ) and were compared with unsupplemented controls (high-fat diet; HFD) or mice fed a regular diet (RD). RT-PCR and western blot analysis were used to quantify the expression of obesity-induced inflammation. Aloe QDM complex down-regulated fat size through suppressed expression of scavenger receptors on adipose tissue macrophages (ATMs) compared with HFD. Both white adipose tissue (WATs) and muscle exhibited increased AMPK activation through aloe supplementation, and in particular, the Aloe QDM complex. Obesity-induced inflammatory cytokines (IL-1β and -6) and HIF1α mRNA and protein were decreased markedly, as was macrophage infiltration by the Aloe QDM complex. Further, the Aloe QDM complex decreased the translocation of NF-κB p65 from the cytosol in the WAT. Dietary aloe formula reduced obesity-induced inflammatory responses by activation of AMPK in muscle and suppression of proinflammatory cytokines in the WAT. Additionally, the expression of scavenger receptors in the ATM and activation of AMPK in WAT led to reduction in the percent of body fat. Thus, we suggest that the effect of the Aloe QDM complex in the WAT and muscle are related to activation of AMPK and its use as a nutritional intervention against T2D and obesity-related inflammation.

Dietary Aloe Reduces Adipogenesis via the Activation of AMPK and Suppresses Obesity-related Inflammation in Obese Mice

PubMed Central

Shin, Eunju; Shin, Seulmee; Kong, Hyunseok; Lee, Sungwon; Do, Seon-Gil; Jo, Tae Hyung; Park, Young-In; Lee, Chong-Kil; Hwang, In-Kyeong

2011-01-01

Background Metabolic disorders, including type II diabetes and obesity, present major health risks in industrialized countries. AMP-activated protein kinase (AMPK) has become the focus of a great deal of attention as a novel therapeutic target for the treatment of metabolic syndromes. In this study, we evaluated whether dietary aloe could reduce obesity-induced inflammation and adipogenesis. Methods Male C57BL/6 obese mice fed a high-fat diet for 54 days received a supplement of aloe formula (PAG, ALS, Aloe QDM, and Aloe QDM complex) or pioglitazone (PGZ) and were compared with unsupplemented controls (high-fat diet; HFD) or mice fed a regular diet (RD). RT-PCR and western blot analysis were used to quantify the expression of obesity-induced inflammation. Results Aloe QDM complex down-regulated fat size through suppressed expression of scavenger receptors on adipose tissue macrophages (ATMs) compared with HFD. Both white adipose tissue (WATs) and muscle exhibited increased AMPK activation through aloe supplementation, and in particular, the Aloe QDM complex. Obesity-induced inflammatory cytokines (IL-1β and -6) and HIF1α mRNA and protein were decreased markedly, as was macrophage infiltration by the Aloe QDM complex. Further, the Aloe QDM complex decreased the translocation of NF-κB p65 from the cytosol in the WAT. Conclusion Dietary aloe formula reduced obesity-induced inflammatory responses by activation of AMPK in muscle and suppression of proinflammatory cytokines in the WAT. Additionally, the expression of scavenger receptors in the ATM and activation of AMPK in WAT led to reduction in the percent of body fat. Thus, we suggest that the effect of the Aloe QDM complex in the WAT and muscle are related to activation of AMPK and its use as a nutritional intervention against T2D and obesity-related inflammation. PMID:21637388

Association of circulating adipokines with metabolic dyslipidemia in obese versus non-obese individuals.

PubMed

Rahimlou, Mehran; Mirzaei, Khadijeh; Keshavarz, Seyed Ali; Hossein-Nezhad, Arash

2016-01-01

Previous studies have shown that circulating adipokines may play an important role in the pathogenesis of some obesity related chronic disease such as dyslipidemia and type2 diabetes mellitus. The aim of the present study was to investigate the association between vaspin, omentin-1 and retinol binding protein-4 levels with metabolic dyslipidemia (MD) criteria in obese and non-obese individuals. The study was conducted on 170 obese and 81 non-obese individuals. After collecting the blood samples, serum levels metabolic parameters as well as three circulating adipokines and body composition were measured. No significant difference was noted regarding the mean serum levels of omentin-1 and vaspin between the obese and non-obese groups, while, serum level of RBP4 was significantly higher in the non-obese group. We found the 0.22 increased risk of MD in obese individuals with higher RBP4 concentration. After the adjustment for confounding factors, this association was still significant. No significant association was noted between MD and its components relative risks with omentin-1 and vaspin levels. Our study demonstrated that circulating RBP4 was significantly higher in the obese individuals which may increase the risk of MD in them. Further researches are needed to address this association. Copyright © 2015 Diabetes India. Published by Elsevier Ltd. All rights reserved.

C-reactive protein and its relation to high blood pressure in overweight or obese children and adolescents

PubMed Central

Noronha, Juliana Andreia F.; Medeiros, Carla Campos M.; Cardoso, Anajás da Silva; Gonzaga, Nathalia Costa; Ramos, Alessandra Teixeira; Ramos, André Luiz C.

2013-01-01

OBJECTIVE To investigate the association between C-reactive protein (CRP) and high blood pressure (BP) in overweight or obese children and adolescents. METHODS Cross-sectional study with 184 overweight or obese children and adolescents aged from two to 18 years old, from April, 2009 to April, 2010. The classification of nutritional status used the body mass index (BMI). Based on the Centers for Disease Control and Prevention curve, individuals were classified as: overweight (BMI between the 85th-95th percentiles), obesity (BMI between 95th-97th percentiles) and severe obesity (BMI >97th percentile). Abnormal values were considered for systolic BP (SBP) and/or diastolic (DBP) if ≥90th percentile of the BP curve recommended for children and adolescents in the V Brazilian Guidelines on Hypertension, for waist circumference (WC) if ≥90th percentile of the curve established by the National Cholesterol Education Program, and for high sensitive CRP (hs-CRP) if >3mg/dL. To evaluate the association of inadequate values of CRP and the studied groups, chi-square test and analysis of variance were applied, using the Statistical Package for the Social Sciences version 17.0 and adopting a significance level of 5%. RESULTS Among the evaluated sample, 66.3% were female, 63.5%, non-white, 64.1% had severe obesity, 78.3% had altered WC and 70.6% presented high BP. There was a significant association of CRP high levels with altered WC and BMI ≥97th percentile. In adolescents, high CRP was related to high SBP. CRP mean values were higher in individuals with elevated SBP. CONCLUSIONS Inadequate values of hs-CRP were associated with severe obesity and high SBP in the studied population. These markers can be used to identify children and adolescents at higher risk for developing atherosclerosis. PMID:24142315

The signaling mechanisms of hippocampal endoplasmic reticulum stress affecting neuronal plasticity-related protein levels in high fat diet-induced obese rats and the regulation of aerobic exercise.

PubMed

Cai, Ming; Wang, Hong; Li, Jing-Jing; Zhang, Yun-Li; Xin, Lei; Li, Feng; Lou, Shu-Jie

2016-10-01

High fat diet (HFD)-induced obesity has been shown to reduce the levels of neuronal plasticity-related proteins, specifically brain-derived neurotrophic factor (BDNF) and synaptophysin (SYN), in the hippocampus. However, the underlying mechanisms are not fully clear. Endoplasmic reticulum stress (ERS) has been reported to play a key role in regulating gene expression and protein production by affecting stress signaling pathways and ER functions of protein folding and post-translational modification in peripheral tissues of obese rodent models. Additionally, HFD that is associated with hyperglycemia could induce hippocampal ERS, thus impairing insulin signaling and cognitive health in HFD mice. One goal of this study was to determine whether hyperglycemia and hyperlipidemia could cause hippocampal ERS in HFD-induced obese SD rats, and explore the potential mechanisms of ERS regulating hippocampal BDNF and SYN proteins production. Additionally, although regular aerobic exercise could reduce central inflammation and elevate hippocampal BDNF and SYN levels in obese rats, the regulated mechanisms are poorly understood. Nrf2-HO-1 pathways play roles in anti-ERS, anti-inflammation and anti-apoptosis in peripheral tissues. Therefore, the other goal of this study was to determine whether aerobic exercise could activate Nrf2-HO-1 in hippocampus to alleviate obesity-induced hippocampal ERS, which would lead to increased BDNF and SYN levels. Male SD rats were fed on HFD for 8weeks to establish the obese model. Then, 8weeks of aerobic exercise treadmill intervention was arranged for the obese rats. Results showed that HFD-induced obesity caused hyperglycemia and hyperlipidemia, and significantly promoted hippocampal glucose transporter 3 (GLUT3) and fatty acid transport protein 1 (FATP1) protein expression. These results were associated with the activation of hippocampal ERS and ERS-mediated apoptosis. At the same time, we found that excessive hippocampal ERS not only

IL-10/STAT3 is reduced in childhood obesity with hypertriglyceridemia and is related to triglyceride level in diet-induced obese rats.

PubMed

Liu, Yuesheng; Xu, Dong; Yin, Chunyan; Wang, Sisi; Wang, Min; Xiao, Yanfeng

2018-06-13

The prevalence of childhood obesity and obesity-related metabolic disorder such as dyslipidemia has sharply increased in the past few decades. Chronic low-grade inflammation is associated with the development of comorbidities and poor prognosis in obesity. This study aims to evaluate interleukin-10 (IL-10) in childhood obesity with hypertriglyceridemia. We evaluated IL-10 and signal transducer and activator of transcription 3 (STAT3) mRNA expression in adipose tissue (AT) as well as serum IL-10 in 62 children of 3 groups and in high-fat diet (HFD) induced obese rat. Expression of IL-10 and STAT3 protein in AT of diet-induced obese rats were examined over feed period. Adipose IL-10 and STAT3 mRNA expression and serum IL-10 reduced in obese children with hypertriglyceridemia and in HFD obese rats. The protein expression of IL-10 and STAT3 decreased in AT of obese rats compared with the control rats at end time. Expression of IL-10 mRNA was negatively correlated to TG and LDL-C levels, and positively correlated to HDL-C, adiponectin and serum IL-10 levels. IL-10 expression and its downstream JAK-STAT pathway are down-regulated in obese children with hypertriglyceridemia and in HFD obese rats.

Dietary protein intake and quality in early life: impact on growth and obesity.

PubMed

Lind, Mads V; Larnkjær, Anni; Mølgaard, Christian; Michaelsen, Kim F

2017-01-01

Obesity is an increasing problem and high-protein intake early in life seems to increase later risk of obesity. This review summarizes recent publications in the area including observational and intervention studies and publications on underlying mechanisms. Recent observational and randomized controlled trials confirmed that high-protein intake in early life seems to increase early weight gain and the risk of later overweight and obesity. Recent studies have looked at the effect of different sources of protein, and especially high-animal protein intake seems to have an effect on obesity. Specific amino acids, such as leucine, have also been implicated in increasing later obesity risk maybe via specific actions on insulin-like growth factor I. Furthermore, additional underlying mechanisms including epigenetics have been linked to long-term obesogenic programming. Finally, infants with catch-up growth or specific genotypes might be particularly vulnerable to high-protein intake. Recent studies confirm the associations between high-protein intake during the first 2 years and later obesity. Furthermore, knowledge of the mechanisms involved and the role of different dietary protein sources and amino acids has increased, but intervention studies are needed to confirm the mechanisms. Avoiding high-protein intake in early life holds promise as a preventive strategy for childhood obesity.

Monocyte Chemoattractant Protein 1 (MCP-1) in Obesity and Diabetes

PubMed Central

Panee, Jun

2012-01-01

Monocyte chemoattractant protein-1 (MCP-1) is the first discovered and most extensively studied CC chemokine, and the amount of studies on its role in the etiologies of obesity- and diabetes-related diseases have increased exponentially during the past 2 decades. This review attempted to provide a panoramic perspective of the history, regulatory mechanisms, functions, and therapeutic strategies of this chemokine. The highlights of this review include the roles of MCP-1 in the development of obesity, diabetes, cardiovascular diseases, insulitis, diabetic nephropathy, and diabetic retinopathy. Therapies that specifically or non-specifically inhibit MCP-1 overproduction have been summarized. PMID:22766373

Phyllodulcin, a Natural Sweetener, Regulates Obesity-Related Metabolic Changes and Fat Browning-Related Genes of Subcutaneous White Adipose Tissue in High-Fat Diet-Induced Obese Mice.

PubMed

Kim, Eunju; Lim, Soo-Min; Kim, Min-Soo; Yoo, Sang-Ho; Kim, Yuri

2017-09-21

Phyllodulcin is a natural sweetener found in Hydrangea macrophylla var. thunbergii . This study investigated whether phyllodulcin could improve metabolic abnormalities in high-fat diet (HFD)-induced obese mice. Animals were fed a 60% HFD for 6 weeks to induce obesity, followed by 7 weeks of supplementation with phyllodulcin (20 or 40 mg/kg body weight (b.w.)/day). Stevioside (40 mg/kg b.w./day) was used as a positive control. Phyllodulcin supplementation reduced subcutaneous fat mass, levels of plasma lipids, triglycerides, total cholesterol, and low-density lipoprotein cholesterol and improved the levels of leptin, adiponectin, and fasting blood glucose. In subcutaneous fat tissues, supplementation with stevioside or phyllodulcin significantly decreased mRNA expression of lipogenesis-related genes, including CCAAT/enhancer-binding protein α ( C/EBPα ), peroxisome proliferator activated receptor γ ( PPARγ ), and sterol regulatory element-binding protein-1C ( SREBP-1c ) compared to the high-fat group. Phyllodulcin supplementation significantly increased the expression of fat browning-related genes, including PR domain containing 16 ( Prdm16 ), uncoupling protein 1 ( UCP1 ), and peroxisome proliferator-activated receptor γ coactivator 1-α ( PGC-1α ), compared to the high-fat group. Hypothalamic brain-derived neurotrophic factor-tropomyosin receptor kinase B (BDNF-TrkB) signaling was upregulated by phyllodulcin supplementation. In conclusion, phyllodulcin is a potential sweetener that could be used to combat obesity by regulating levels of leptin, fat browning-related genes, and hypothalamic BDNF-TrkB signaling.

A Macrocyclic Agouti-Related Protein/[Nle4,DPhe7]α-Melanocyte Stimulating Hormone Chimeric Scaffold Produces Subnanomolar Melanocortin Receptor Ligands.

PubMed

Ericson, Mark D; Freeman, Katie T; Schnell, Sathya M; Haskell-Luevano, Carrie

2017-01-26

The melanocortin system consists of five receptor subtypes, endogenous agonists, and naturally occurring antagonists. These receptors and ligands have been implicated in numerous biological pathways including processes linked to obesity and food intake. Herein, a truncation structure-activity relationship study of chimeric agouti-related protein (AGRP)/[Nle4,DPhe7]α-melanocyte stimulating hormone (NDP-MSH) ligands is reported. The tetrapeptide His-DPhe-Arg-Trp or tripeptide DPhe-Arg-Trp replaced the Arg-Phe-Phe sequence in the AGRP active loop derivative c[Pro-Arg-Phe-Phe-Xxx-Ala-Phe-DPro], where Xxx was the native Asn of AGRP or a diaminopropionic (Dap) acid residue previously shown to increase antagonist potency at the mMC4R. The Phe, Ala, and Dap/Asn residues were successively removed to generate a 14-member library that was assayed for agonist activity at the mouse MC1R, MC3R, MC4R, and MC5R. Two compounds possessed nanomolar agonist potency at the mMC4R, c[Pro-His-DPhe-Arg-Trp-Asn-Ala-Phe-DPro] and c[Pro-His-DPhe-Arg-Trp-Dap-Ala-DPro], and may be further developed to generate novel melanocortin probes and ligands for understanding and treating obesity.

An ATF4-ATG5 signaling in hypothalamic POMC neurons regulates obesity.

PubMed

Xiao, Yuzhong; Deng, Yalan; Yuan, Feixiang; Xia, Tingting; Liu, Hao; Li, Zhigang; Chen, Shanghai; Liu, Zhixue; Ying, Hao; Liu, Yi; Zhai, Qiwei; Guo, Feifan

2017-06-03

ATF4 (activating transcription factor 4) is an important transcription factor that has many biological functions, while its role in hypothalamic POMC (pro-opiomelanocortin-α) neurons in the regulation of energy homeostasis has not been explored. We recently discovered that mice with an Atf4 deletion specific to POMC neurons (PAKO mice) are lean and have higher energy expenditure. Furthermore, these mice are resistant to high-fat diet (HFD)-induced obesity and obesity-related metabolic disorders. Mechanistically, we found the expression of ATG5 (autophagy-related 5) is upregulated in POMC neurons of PAKO mice, and ATF4 regulates ATG5 expression by binding directly to its promoter. Mice with Atf4 and Atg5 double knockout in POMC neurons have reduced energy expenditure and gain more fat mass compared with PAKO mice under a HFD. Finally, the effect of Atf4 knockout in POMC neurons is possibly mediated by enhanced ATG5-dependent macroautophagy/autophagy and α-melanocyte-stimulating hormone (α-MSH) production in the hypothalamus. Together, this work not only identifies a beneficial role for ATF4 in hypothalamic POMC neurons in the regulation of obesity, but also provides a new potential therapeutic target for obesity and obesity-related metabolic diseases.

Impact of whey proteins on the systemic and local intestinal level of mice with diet induced obesity.

PubMed

Swiątecka, D; Złotkowska, D; Markiewicz, L H; Szyc, A M; Wróblewska, B

2017-04-19

Obesity is a serious public health problem and being multifactorial is difficult to tackle. Since the intestinal ecosystem's homeostasis is, at least partially, diet-dependent, its modulation may be triggered by food components that are designed to exert a modulatory action leading to a health-promoting effect. Milk whey proteins, are considered as such promising factors since they influence satiation as well as body weight and constitute the source of biologically active peptides which may modulate health status locally and systemically. This way, whey proteins are associated with obesity. Therefore, this paper is aimed at the estimation of the impact of whey proteins using a commercially available whey protein isolate on the physiological response of mice with diet-induced obesity. The physiological response was evaluated on the local-intestinal level, scrutinizing intestinal microbiota as one of the important factors in obesity and on the systemic level, analyzing the response of the organism. Whey proteins brought about the decrease of the fat mass with a simultaneous increase of the lean mass of animals with diet induced obesity, which is a promising, health-promoting effect. Whey proteins also proved to act beneficially helping restore the number of beneficial bifidobacteria in obese animals and decreasing the calorie intake and fat mass as well as the LDL level. Overall, supplementation of the high fat diet with whey proteins acted locally by restoration of the intestinal ecosystem, thus preventing dysbiosis and its effects and also acted systemically by strengthening the organism increasing the lean mass and thus hindering obesity-related detrimental effects.

G Protein-Coupled Estrogen Receptor in Energy Homeostasis and Obesity Pathogenesis

PubMed Central

Shi, Haifei; Dharshan Senthil Kumar, Shiva Priya; Liu, Xian

2013-01-01

Obesity and its related metabolic diseases have reached a pandemic level worldwide. There are sex differences in the prevalence of obesity and its related metabolic diseases, with men being more vulnerable than women; however, the prevalence of these disorders increases dramatically in women after menopause, suggesting that sex steroid hormone estrogens play key protective roles against development of obesity and metabolic diseases. Estrogens are important regulators of several aspects of metabolism, including body weight and body fat, caloric intake and energy expenditure, and glucose and lipid metabolism in both males and females. Estrogens act in complex ways on their nuclear estrogen receptors (ERs) ERα and ERβ and transmembrane ERs such as G protein-coupled estrogen receptor. Genetic tools, such as different lines of knockout mouse models, and pharmacological agents, such as selective agonists and antagonists, are available to study function and signaling mechanisms of ERs. We provide an overview of the evidence for the physiological and cellular actions of ERs in estrogen-dependent processes in the context of energy homeostasis and body fat regulation and discuss its pathology that leads to obesity and related metabolic states. PMID:23317786

Genetic variants of the unsaturated fatty acid receptor GPR120 relating to obesity in dogs

PubMed Central

MIYABE, Masahiro; GIN, Azusa; ONOZAWA, Eri; DAIMON, Mana; YAMADA, Hana; ODA, Hitomi; MORI, Akihiro; MOMOTA, Yutaka; AZAKAMI, Daigo; YAMAMOTO, Ichiro; MOCHIZUKI, Mariko; SAKO, Toshinori; TAMURA, Katsutoshi; ISHIOKA, Katsumi

2015-01-01

G protein-coupled receptor (GPR) 120 is an unsaturated fatty acid receptor, which is associated with various physiological functions. It is reported that the genetic variant of GPR120, p.Arg270His, is detected more in obese people, and this genetic variation functionally relates to obesity in humans. Obesity is a common nutritional disorder also in dogs, but the genetic factors have not ever been identified in dogs. In this study, we investigated the molecular structure of canine GPR120 and searched for candidate genetic variants which may relate to obesity in dogs. Canine GPR120 was highly homologous to those of other species, and seven transmembrane domains and two N-glycosylation sites were conserved. GPR120 mRNA was expressed in lung, jejunum, ileum, colon, hypothalamus, hippocampus, spinal cord, bone marrow, dermis and white adipose tissues in dogs, as those in mice and humans. Genetic variants of GPR120 were explored in client-owned 141 dogs, resulting in that 5 synonymous and 4 non-synonymous variants were found. The variant c.595C>A (p.Pro199Thr) was found in 40 dogs, and the gene frequency was significantly higher in dogs with higher body condition scores, i.e. 0.320 in BCS4–5 dogs, 0.175 in BCS3 dogs and 0.000 in BCS2 dogs. We conclude that c.595C>A (p.Pro199Thr) is a candidate variant relating to obesity, which may be helpful for nutritional management of dogs. PMID:25960032

Genetic variants of the unsaturated fatty acid receptor GPR120 relating to obesity in dogs.

PubMed

Miyabe, Masahiro; Gin, Azusa; Onozawa, Eri; Daimon, Mana; Yamada, Hana; Oda, Hitomi; Mori, Akihiro; Momota, Yutaka; Azakami, Daigo; Yamamoto, Ichiro; Mochizuki, Mariko; Sako, Toshinori; Tamura, Katsutoshi; Ishioka, Katsumi

2015-10-01

G protein-coupled receptor (GPR) 120 is an unsaturated fatty acid receptor, which is associated with various physiological functions. It is reported that the genetic variant of GPR120, p.Arg270His, is detected more in obese people, and this genetic variation functionally relates to obesity in humans. Obesity is a common nutritional disorder also in dogs, but the genetic factors have not ever been identified in dogs. In this study, we investigated the molecular structure of canine GPR120 and searched for candidate genetic variants which may relate to obesity in dogs. Canine GPR120 was highly homologous to those of other species, and seven transmembrane domains and two N-glycosylation sites were conserved. GPR120 mRNA was expressed in lung, jejunum, ileum, colon, hypothalamus, hippocampus, spinal cord, bone marrow, dermis and white adipose tissues in dogs, as those in mice and humans. Genetic variants of GPR120 were explored in client-owned 141 dogs, resulting in that 5 synonymous and 4 non-synonymous variants were found. The variant c.595C>A (p.Pro199Thr) was found in 40 dogs, and the gene frequency was significantly higher in dogs with higher body condition scores, i.e. 0.320 in BCS4-5 dogs, 0.175 in BCS3 dogs and 0.000 in BCS2 dogs. We conclude that c.595C>A (p.Pro199Thr) is a candidate variant relating to obesity, which may be helpful for nutritional management of dogs.

Effects of Obesity and Obesity-Related Molecules on Canine Mammary Gland Tumors.

PubMed

Lim, H-Y; Im, K-S; Kim, N-H; Kim, H-W; Shin, J-I; Yhee, J-Y; Sur, J-H

2015-11-01

Obesity can affect the clinical course of a number of diseases, including breast cancer in women and mammary gland tumors in female dogs, via the secretion of various cytokines and hormones. The objective of this study was to examine the expression patterns of obesity-related molecules such as aromatase, leptin, and insulin-like growth factor 1 receptor (IGF-1 R) in canine mammary carcinomas (CMCs) on the basis of the body condition score (BCS). Comparative analyses of the expression of these molecules, together with prognostic factors for CMCs, including hormone receptors (HRs; estrogen and progesterone receptors), lymphatic invasion, central necrosis of the tumor, and histologic grade, were performed on 56 CMCs. The mean age of CMC onset was lower in the overweight or obese group (8.7 ± 1.9 years) than in the lean or ideal body weight group (10.4 ± 2.7 years). The proportion of poorly differentiated (grade III) tumors was significantly higher in the overweight or obese female dogs. Aromatase expression was significantly higher in the overweight or obese group and was correlated with the expression of HRs (P = .025). These findings suggest that overweight or obese status might affect the development and behavior of CMCs by tumor-adipocyte interactions and increased HR-related tumor growth. © The Author(s) 2015.

Obesity-related systemic factors promote an invasive phenotype in prostate cancer cells.

PubMed

Price, R S; Cavazos, D A; De Angel, R E; Hursting, S D; deGraffenried, L A

2012-06-01

Obesity is associated with larger tumors, shorter time to PSA failure, and higher Gleason scores. However, the mechanism(s) by which obesity promotes aggressive prostate cancer remains unknown. We hypothesize that circulating factors related to obesity promote prostate cancer progression by modulating components of the metastatic cascade. Male C57BL/6 mice (6 weeks) were fed an ad libitum diet-induced obesity (60% fat) or control diet (10% fat) for 12 weeks. Serum was collected, metabolic and inflammatory proteins were measured by an antibody array. Sera were used to measure, in vitro, characteristics of a metastatic phenotype. Comparable to obese men, obese sera contained higher levels or leptin, vascular endothelial growth factor, PAI-1, interleukin-6 (IL-6) and lower levels of testosterone. In prostate cells, serum was used to assess: proliferation, invasion, migration, epithelial-mesenchymal-transition (EMT) and matrix metalloproteinase (MMP) activity. LNCaP and PacMetUT1 cells exposed to obese sera increased proliferation, whereas PrEC and DU145 were unaffected. LNCaP, PacMetUT1 and DU145 cancer cells exposed to obese sera resulted in increased invasion, migration and MMP-9 activity. Prostate cancer cells exposed to obese sera showed increased vimentin, dispersion of e-cadherin and β-catenin from the plasma membrane. We report, prostate cancer cells exposed to sera from obese mice increases proliferation, invasion, migration, MMP activity and induces changes in proteins critical for EMT.

Tumour biology of obesity-related cancers: understanding the molecular concept for better diagnosis and treatment.

PubMed

Teoh, Seong Lin; Das, Srijit

2016-11-01

Obesity continues to be a major global problem. Various cancers are related to obesity and proper understanding of their aetiology, especially their molecular tumour biology is important for early diagnosis and better treatment. Genes play an important role in the development of obesity. Few genes such as leptin, leptin receptor encoded by the db (diabetes), pro-opiomelanocortin, AgRP and NPY and melanocortin-4 receptors and insulin-induced gene 2 were linked to obesity. MicroRNAs control gene expression via mRNA degradation and protein translation inhibition and influence cell differentiation, cell growth and cell death. Overexpression of miR-143 inhibits tumour growth by suppressing B cell lymphoma 2, extracellular signal-regulated kinase-5 activities and KRAS oncogene. Cancers of the breast, uterus, renal, thyroid and liver are also related to obesity. Any disturbance in the production of sex hormones and insulin, leads to distortion in the balance between cell proliferation, differentiation and apoptosis. The possible mechanism linking obesity to cancer involves alteration in the level of adipokines and sex hormones. These mediators act as biomarkers for cancer progression and act as targets for cancer therapy and prevention. Interestingly, many anti-cancerous drugs are also beneficial in treating obesity and vice versa. We also reviewed the possible link in the mechanism of few drugs which act both on cancer and obesity. The present review may be important for molecular biologists, oncologists and clinicians treating cancers and also pave the way for better therapeutic options.

Prevalence of overweight, obesity, abdominal obesity and obesity-related risk factors in southern China.

PubMed

Hu, Lihua; Huang, Xiao; You, Chunjiao; Li, Juxiang; Hong, Kui; Li, Ping; Wu, Yanqing; Wu, Qinhua; Wang, Zengwu; Gao, Runlin; Bao, Huihui; Cheng, Xiaoshu

2017-01-01

The purpose of this study is to assess the prevalence of overweight/obesity, abdominal obesity and obesity-related risk factors in southern China. A cross-sectional survey of 15,364 participants aged 15 years and older was conducted from November 2013 to August 2014 in Jiangxi Province, China, using questionnaire forms and physical measurements. The physical measurements included body height, weight, waist circumference (WC), body fat percentage (BFP) and visceral adipose index (VAI). Multivariate logistic regression analysis was performed to evaluate the risk factors for overweight/obesity and abdominal obesity. The prevalence of overweight was 25.8% (25.9% in males and 25.7% in females), while that of obesity was 7.9% (8.4% in males and 7.6% in females). The prevalence of abdominal obesity was 10.2% (8.6% in males and 11.3% in females). The prevalence of overweight/obesity was 37.1% in urban residents and 30.2% in rural residents, and this difference was significant (P < 0.001). Urban residents had a significantly higher prevalence of abdominal obesity than rural residents (11.6% vs 8.7%, P < 0.001). Among the participants with an underweight/normal body mass index (BMI), 1.3% still had abdominal obesity, 16.1% had a high BFP and 1.0% had a high VAI. Moreover, among obese participants, 9.7% had a low /normal WC, 0.8% had a normal BFP and 15.9% had a normal VAI. Meanwhile, the partial correlation analysis indicated that the correlation coefficients between VAI and BMI, VAI and WC, and BMI and WC were 0.700, 0.666, and 0.721, respectively. A multivariate logistic regression analysis indicated that being female and having a high BFP and a high VAI were significantly associated with an increased risk of overweight/obesity and abdominal obesity. In addition, living in an urban area and older age correlated with overweight/obesity. This study revealed that obesity and abdominal obesity, which differed by gender and age, are epidemic in southern China. Moreover, there

FABP4 dynamics in obesity: discrepancies in adipose tissue and liver expression regarding circulating plasma levels.

PubMed

Queipo-Ortuño, María Isabel; Escoté, Xavier; Ceperuelo-Mallafré, Victoria; Garrido-Sanchez, Lourdes; Miranda, Merce; Clemente-Postigo, Mercedes; Pérez-Pérez, Rafael; Peral, Belen; Cardona, Fernando; Fernández-Real, Jose Manuel; Tinahones, Francisco J; Vendrell, Joan

2012-01-01

FABP4 is predominantly expressed in adipose tissue, and its circulating levels are linked with obesity and a poor atherogenic profile. In patients with a wide BMI range, we analyze FABP4 expression in adipose and hepatic tissues in the settings of obesity and insulin resistance. Associations between FABP4 expression in adipose tissue and the FABP4 plasma level as well as the main adipogenic and lipolytic genes expressed in adipose tissue were also analyzed. The expression of several lipogenic, lipolytic, PPAR family and FABP family genes was analyzed by real time PCR. FABP4 protein expression in total adipose tissues and its fractions were determined by western blot. In obesity FABP4 expression was down-regulated (at both mRNA and protein levels), with its levels mainly predicted by ATGL and inversely by the HOMA-IR index. The BMI appeared as the only determinant of the FABP4 variation in both adipose tissue depots. FABP4 plasma levels showed a significant progressive increase according to BMI but no association was detected between FABP4 circulating levels and SAT or VAT FABP4 gene expression. The gene expression of FABP1, FABP4 and FABP5 in hepatic tissue was significantly higher in tissue from the obese IR patients compared to the non-IR group. The inverse pattern in FABP4 expression between adipose and hepatic tissue observed in morbid obese patients, regarding the IR context, suggests that both tissues may act in a balanced manner. These differences may help us to understand the discrepancies between circulating plasma levels and adipose tissue expression in obesity.

FABP4 Dynamics in Obesity: Discrepancies in Adipose Tissue and Liver Expression Regarding Circulating Plasma Levels

PubMed Central

Ceperuelo-Mallafré, Victoria; Garrido-Sanchez, Lourdes; Miranda, Merce; Clemente-Postigo, Mercedes; Pérez-Pérez, Rafael; Peral, Belen; Cardona, Fernando; Fernández-Real, Jose Manuel; Tinahones, Francisco J.; Vendrell, Joan

2012-01-01

Background FABP4 is predominantly expressed in adipose tissue, and its circulating levels are linked with obesity and a poor atherogenic profile. Objective In patients with a wide BMI range, we analyze FABP4 expression in adipose and hepatic tissues in the settings of obesity and insulin resistance. Associations between FABP4 expression in adipose tissue and the FABP4 plasma level as well as the main adipogenic and lipolytic genes expressed in adipose tissue were also analyzed. Methods The expression of several lipogenic, lipolytic, PPAR family and FABP family genes was analyzed by real time PCR. FABP4 protein expression in total adipose tissues and its fractions were determined by western blot. Results In obesity FABP4 expression was down-regulated (at both mRNA and protein levels), with its levels mainly predicted by ATGL and inversely by the HOMA-IR index. The BMI appeared as the only determinant of the FABP4 variation in both adipose tissue depots. FABP4 plasma levels showed a significant progressive increase according to BMI but no association was detected between FABP4 circulating levels and SAT or VAT FABP4 gene expression. The gene expression of FABP1, FABP4 and FABP5 in hepatic tissue was significantly higher in tissue from the obese IR patients compared to the non-IR group. Conclusion The inverse pattern in FABP4 expression between adipose and hepatic tissue observed in morbid obese patients, regarding the IR context, suggests that both tissues may act in a balanced manner. These differences may help us to understand the discrepancies between circulating plasma levels and adipose tissue expression in obesity. PMID:23139800

The relation between childhood obesity and adenotonsillar hypertrophy.

PubMed

Daar, Ghaniya; Sarı, Kamran; Gencer, Zeliha Kapusuz; Ede, Hüseyin; Aydın, Reha; Saydam, Levent

2016-02-01

Childhood obesity is a common and significant public health problem all over the world. As a well-known fact obese children have an increased risk of obesity-associated comorbidities, including obstructive sleep apnea, diabetes, and cardiovascular disorders at an earlier age compared to their normal weight peers. They also have an increased risk of poor self-esteem, greater body dissatisfaction, and increased peer teasing that lead to a lower health-related quality of life. While the presence of adenoid hypertrophy and increased rate of obstructive sleep apnea frequently co-exists in majority of cases. We have limited knowledge about the effect of adenotonsillar hypertrophy on development of childhood obesity. In this study, we aimed to investigate the association between obesity, presence of adenotonsillar hypertrophy and the quality of life parameters in obese children as measured by the OSA-18 quality of life questionnaire. Fifty obese children aged between 3 and 18 years and 50 age- and gender-matched otherwise children were enrolled to the study. All subjects were routinely examined by the otolaryngologist before enrollment. The size of adenoid hypertrophy was measured using lateral cephalometric radiographs. The tonsils were also graded using the schema recommended by Brodsky et al. We used OSA-18 questionnaires to evaluate the subjects' quality of life issues. We found, 34 % of obese group had tonsillar hypertrophy while the rate was 6 % in control group. Similarly 16 % of obese group had tonsillar hypertrophy compared to only 4 % in non-obese group. It was also noted that total OSA-18 scores of obese group were significantly higher than those of non-obese group. In subgroup analysis of obese group, total OSA-18 score of obese subjects with either adenoid and/or tonsillar hypertrophy was significantly higher than that of obese subjects without adenoid or tonsillar hypertrophy. As the related literature suggests that the impact of adenotonsillar size on OSA

Anabolic sensitivity of postprandial muscle protein synthesis to the ingestion of a protein-dense food is reduced in overweight and obese young adults.

PubMed

Beals, Joseph W; Sukiennik, Richard A; Nallabelli, Julian; Emmons, Russell S; van Vliet, Stephan; Young, Justin R; Ulanov, Alexander V; Li, Zhong; Paluska, Scott A; De Lisio, Michael; Burd, Nicholas A

2016-10-01

Excess body fat diminishes muscle protein synthesis rates in response to hyperinsulinemic-hyperaminoacidemic clamps. However, muscle protein synthetic responses after the ingestion of a protein-dense food source across a range of body mass indexes (BMIs) have not been compared. We compared the myofibrillar protein synthetic response and underlying nutrient-sensing mechanisms after the ingestion of lean pork between obese, overweight, and healthy-weight adults. Ten healthy-weight [HW; BMI (in kg/m 2 ): 22.7 ± 0.4], 10 overweight (OW; BMI: 27.1 ± 0.5), and 10 obese (OB; BMI: 35.9 ± 1.3) adults received primed continuous l-[ring- 13 C 6 ]phenylalanine infusions. Blood and muscle biopsy samples were collected before and after the ingestion of 170 g pork (36 g protein and 3 g fat) to assess skeletal muscle anabolic signaling, amino acid transporters [large neutral and small neutral amino acid transporters (LAT1, SNAT2) and CD98], and myofibrillar protein synthesis. At baseline, OW and OB groups showed greater relative amounts of mammalian target of rapamycin complex 1 (mTORC1) protein than the HW group. Pork ingestion increased mTORC1 phosphorylation only in the HW group (P = 0.001). LAT1 and SNAT2 protein content increased during the postprandial period in all groups (time effect, P < 0.05). Basal myofibrillar protein synthetic responses were similar between groups (P = 0.43). However, myofibrillar protein synthetic responses (0-300 min) were greater in the HW group (1.6-fold; P = 0.005) after pork ingestion than in the OW and OB groups. There is a diminished myofibrillar protein synthetic response to the ingestion of protein-dense food in overweight and obese adults compared with healthy-weight controls. These data indicate that impaired postprandial myofibrillar protein synthetic response may be an early defect with increasing fat mass, potentially dependent on altered anabolic signals, that reduces muscle sensitivity to food ingestion. This trial was registered

Coptisine attenuates obesity-related inflammation through LPS/TLR-4-mediated signaling pathway in Syrian golden hamsters.

PubMed

Zou, Zong-Yao; Hu, Yin-Ran; Ma, Hang; Wang, Yan-Zhi; He, Kai; Xia, Shuang; Wu, Hao; Xue, Dong-Fang; Li, Xue-Gang; Ye, Xiao-Li

2015-09-01

It is known that obesity resulted from consumption of diets high in fat and calories and associated with a chronic low-grade inflammation. Because the fat, sterol and bile acid metabolism of male Syrian golden hamster are more similar to that of human, in the present study, high fat and high cholesterol (HFHC) induced obese hamsters were used to evaluate the anti-inflammation and hypolipidemic role of coptisine. The results showed that body weight, plasma lipid levels of total cholesterol (TC), triglyceride (TG), low density lipoprotein-cholesterol (LDL-c), very low density lipoprotein-cholesterol (VLDL-c), ApoB and pro-inflammatory cytokines including TNF-α, IL-6 and lipopolysaccharide (LPS) were significantly altered in hamsters fed with HFHC diet. A strong correlation was observed between the LPS level in serum and the level of LBP and pro-inflammatory cytokines. Coptisine from the concentrations of 60 to 700 mg/L dose-dependently inhibited Enterobacter cloacae growth, which can easily induce obesity and insulin resistance. The results of endotoxin neutralization assay suggest that coptisine is capable of reducing the LPS content under inflammation status. Real time RT-PCR analyses revealed that coptisine suppressed TLR-4 in visceral fat of hamsters and decreased CD14 expression in livers of hamsters. These encouraging findings make the development of coptisine a good candidate for preventing obesity-related diseases through the LPS/TLR-4-mediated signaling pathway. Copyright © 2015 Elsevier B.V. All rights reserved.

Nutraceutical Approach for Preventing Obesity-Related Colorectal and Liver Carcinogenesis

PubMed Central

Shimizu, Masahito; Kubota, Masaya; Tanaka, Takuji; Moriwaki, Hisataka

2012-01-01

Obesity and its related metabolic abnormalities, including insulin resistance, alterations in the insulin-like growth factor-1 (IGF-1)/IGF-1 receptor (IGF-1R) axis, and the state of chronic inflammation, increase the risk of colorectal cancer (CRC) and hepatocellular carcinoma (HCC). However, these findings also indicate that the metabolic disorders caused by obesity might be effective targets to prevent the development of CRC and HCC in obese individuals. Green tea catechins (GTCs) possess anticancer and chemopreventive properties against cancer in various organs, including the colorectum and liver. GTCs have also been known to exert anti-obesity, antidiabetic, and anti-inflammatory effects, indicating that GTCs might be useful for the prevention of obesity-associated colorectal and liver carcinogenesis. Further, branched-chain amino acids (BCAA), which improve protein malnutrition and prevent progressive hepatic failure in patients with chronic liver diseases, might be also effective for the suppression of obesity-related carcinogenesis because oral supplementation with BCAA reduces the risk of HCC in obese cirrhotic patients. BCAA shows these beneficial effects because they can improve insulin resistance. Here, we review the detailed relationship between metabolic abnormalities and the development of CRC and HCC. We also review evidence, especially that based on our basic and clinical research using GTCs and BCAA, which indicates that targeting metabolic abnormalities by either pharmaceutical or nutritional intervention may be an effective strategy to prevent the development of CRC and HCC in obese individuals. PMID:22312273

Alpha-Melanocyte-Stimulating Hormone and Agouti-Related Protein: Do They Play a Role in Appetite Regulation in Childhood Obesity?

PubMed

Vehapoğlu, Aysel; Türkmen, Serdar; Terzioğlu, Şule

2016-03-05

The hypothalamus plays a crucial role in the regulation of feeding behavior. The anorexigenic neuropeptide alpha-melanocyte-stimulating hormone (α-MSH) and the orexigenic neuropeptide agouti-related protein (AgRP) are among the major peptides produced in the hypothalamus. This study investigated the plasma concentrations of α-MSH and AgRP in underweight and obese children and their healthy peers. The associations between α-MSH and AgRP levels and anthropometric and nutritional markers of malnutrition and obesity were also assessed. Healthy sex-matched subjects aged 2 to 12 years were divided into 3 groups, as underweight (n=57), obese (n=61), and of normal weight (n=57). Plasma fasting concentrations of α-MSH and AgRP were measured by enzyme-linked immunosorbent assay. The differences between the three groups as to the relationships between plasma concentrations of α-MSH and AgRP and anthropometric data, serum biochemical parameters and homeostatic model assessment of insulin resistance were evaluated. Obese children had significantly lower α-MSH levels than underweight (1194±865 vs. 1904±1312 ng/mL, p=0.006) and normal weight (1194±865 vs. 1762±1463 ng/mL, p=0.036) children; there were no significant differences in the α-MSH levels between the underweight and normal weight children (p=0.811). Also, no significant differences were observed between the underweight and obese children regarding the AgRP levels (742±352 vs. 828±417 ng/mL, p=0.125). We found a significant positive correlation between plasma α-MSH and AgRP levels across the entire sample. This study is the first to demonstrate body weight-related differences in α-MSH and AgRP levels in children. Circulating plasma α-MSH levels in obese children were markedly lower than those of underweight and normal-weight children. This suggests that α-MSH could play a role in appetite regulation.

Effect of a long-term high-protein diet on survival, obesity development, and gut microbiota in mice.

PubMed

Kiilerich, Pia; Myrmel, Lene Secher; Fjære, Even; Hao, Qin; Hugenholtz, Floor; Sonne, Si Brask; Derrien, Muriel; Pedersen, Lone Møller; Petersen, Rasmus Koefoed; Mortensen, Alicja; Licht, Tine Rask; Rømer, Maria Unni; Vogel, Ulla Birgitte; Waagbø, Linn Jeanette; Giallourou, Natasa; Feng, Qiang; Xiao, Liang; Liu, Chuan; Liaset, Bjørn; Kleerebezem, Michiel; Wang, Jun; Madsen, Lise; Kristiansen, Karsten

2016-06-01

Female C57BL/6J mice were fed a regular low-fat diet or high-fat diets combined with either high or low protein-to-sucrose ratios during their entire lifespan to examine the long-term effects on obesity development, gut microbiota, and survival. Intake of a high-fat diet with a low protein/sucrose ratio precipitated obesity and reduced survival relative to mice fed a low-fat diet. By contrast, intake of a high-fat diet with a high protein/sucrose ratio attenuated lifelong weight gain and adipose tissue expansion, and survival was not significantly altered relative to low-fat-fed mice. Our findings support the notion that reduced survival in response to high-fat/high-sucrose feeding is linked to obesity development. Digital gene expression analyses, further validated by qPCR, demonstrated that the protein/sucrose ratio modulated global gene expression over time in liver and adipose tissue, affecting pathways related to metabolism and inflammation. Analysis of fecal bacterial DNA using the Mouse Intestinal Tract Chip revealed significant changes in the composition of the gut microbiota in relation to host age and dietary fat content, but not the protein/sucrose ratio. Accordingly, dietary fat rather than the protein/sucrose ratio or adiposity is a major driver shaping the gut microbiota, whereas the effect of a high-fat diet on survival is dependent on the protein/sucrose ratio. Copyright © 2016 the American Physiological Society.

Prevalence of obesity was related to HLA-DQ in 2-4-year-old children at genetic risk for type 1 diabetes.

PubMed

Yang, J; Lernmark, Å; Uusitalo, U M; Lynch, K F; Veijola, R; Winkler, C; Larsson, H E; Rewers, M; She, J-X; Ziegler, A G; Simell, O G; Hagopian, W A; Akolkar, B; Krischer, J P; Vehik, K

2014-12-01

Body size is postulated to modulate type 1 diabetes as either a trigger of islet autoimmunity or an accelerator to clinical onset after seroconversion. As overweight and obesity continue to rise among children, the aim of this study was to determine whether human leukocyte antigen DQ (HLA-DQ) genotypes may be related to body size among children genetically at risk for type 1 diabetes. Repeated measures of weight and height were collected from 5969 children 2-4 years of age enrolled in The Environmental Determinants of Diabetes in the Young prospective study. Overweight and obesity was determined by the International Obesity Task Force cutoff values that correspond to body mass index (BMI) of 25 and 30 kg m(-)(2) at age 18. The average BMI was comparable across specific HLA genotypes at every age point. The proportion of overweight was not different by HL A, but percent obesity varied by age with a decreasing trend among DQ2/8 carriers (P for trend=0.0315). A multivariable regression model suggested DQ2/2 was associated with higher obesity risk at age 4 (odds ratio, 2.41; 95% confidence interval, 1.21-4.80) after adjusting for the development of islet autoantibody and/or type 1 diabetes. The HLA-DQ2/2 genotype may predispose to obesity among 2-4-year-old children with genetic risk for type 1 diabetes.

Disparities in obesity prevalence and obesity-related behaviors among adolescents in Trinidad and Tobago.

PubMed

Wilson, Colwick; Woolford, Susan; Wilson, Leon; Williams, David; Oloo, Winetta

2017-09-29

Objective African Americans adolescents have disproportionately high rates of obesity compared to their Caucasian peers. Little is known about the rates of obesity among adolescents of African descent in countries with diverse populations. Therefore, we aimed to determine the prevalence of obesity and weight-related behaviors among adolescents in Trinidad and Tobago and to explore differences by race and gender. Methods In this cross-sectional study, students from a national stratified sample of high schools (n = 42) in Trinidad and Tobago completed a self-administered survey regarding their health habits. Body mass index (BMI) was calculated from measured height (via a portable stadiometer) and weight (via a digital scale), and BMI percentiles determined using Centers for Disease Control and Prevention (CDC) growth charts. Univariate calculations and χ2 analyses were performed to determine obesity prevalence and explore associations between obesity and self-reported demographic factors and weight-related behaviors. One-way analysis of variance (ANOVA) was used to test mean difference in weight status and multivariate analyses explored the role of gender and race after adjusting for covariates. Results Of the 3618 adolescents in the study, 56.3% were female. Race: 31.9% Black-Trinidadian, 33.7% Indo-Trinidadian and 33.4% Mixed-Race. Mean age was 17.6 years. The overall prevalence of obesity was 7%, but this differed by race (Black-Trinidadians 17%, Mixed-Trinidadians 2%, Indo-Trinidadians 1%). Black-Trinidadian girls were most likely to be obese (28.1%) and to engage in obesity related habits than their peers. Conclusion Black-Trinidadian girls have a significantly higher prevalence of obesity than their peers. Further work should explore culturally tailored interventions to address obesity prevention and treatment in this group.

Hepatocyte Toll-like receptor 4 regulates obesity-induced inflammation and insulin resistance

USDA-ARS?s Scientific Manuscript database

Chronic low-grade inflammation is a hallmark of obesity and thought to contribute to the development of obesity-related insulin resistance. Toll-like receptor 4 (Tlr4) is a key mediator of pro-inflammatory responses. Mice lacking Tlr4s are protected from diet-induced insulin resistance and inflammat...

Obesity-related differences in neural correlates of force control.

PubMed

Mehta, Ranjana K; Shortz, Ashley E

2014-01-01

Greater body segment mass due to obesity has shown to impair gross and fine motor functions and reduce balance control. While recent studies suggest that obesity may be linked with altered brain functions involved in fine motor tasks, this association is not well investigated. The purpose of this study was to examine the neural correlates of motor performance in non-obese and obese adults during force control of two upper extremity muscles. Nine non-obese and eight obese young adults performed intermittent handgrip and elbow flexion exertions at 30% of their respective muscle strengths for 4 min. Functional near infrared spectroscopy was employed to measure neural activity in the prefrontal cortex bilaterally, joint steadiness was computed using force fluctuations, and ratings of perceived exertions (RPEs) were obtained to assess perceived effort. Obesity was associated with higher force fluctuations and lower prefrontal cortex activation during handgrip exertions, while RPE scores remained similar across both groups. No obesity-related differences in neural activity, force fluctuation, or RPE scores were observed during elbow flexion exertions. The study is one of the first to examine obesity-related differences on prefrontal cortex activation during force control of the upper extremity musculature. The study findings indicate that the neural correlates of motor activity in the obese may be muscle-specific. Future work is warranted to extend the investigation to monitoring multiple motor-function related cortical regions and examining obesity differences with different task parameters (e.g., longer duration, increased precision demands, larger muscles, etc.).

[Effect of metformin on the expression of tumor necrosis factor-α, Toll like receptors 2/4 and C reactive protein in obese type-2 diabetic patients].

PubMed

Andrews, Mónica; Soto, Néstor; Arredondo, Miguel

2012-11-01

The pharmacological action of metformin goes beyond mere glycemic control, decreasing markers of inflammation and contributing to the reduction of oxidative stress. To evaluate biochemical, anthropometric and pro-inflammatory markers in obese type 2 diabetic patients treated or not with metformin. Obese patients with type 2 diabetes were invited to participate in the study if they were aged more than 40 years, were not receiving insulin, did not have cardiovascular diseases and were not taking anti-inflammatory drugs. A pharmacological history was taken and patients were stratified in two groups whether they were using metformin or not. A fasting blood sample was obtained to measure blood glucose, insulin, lipid levels, C reactive protein (hsCRP) and to isolate peripheral blood mononuclear cells. RNA was isolated from these cells to measure expression of tumor necrosis factor-α (TNF-α), Interleukin-6 (IL-6), nuclear factor kappa-light-chain-enhancer of activated B cells (NF-kB), Toll-Like Receptor 2/4 (TLR 2/4) and beta-2-microglobulin (B2M). Thirty participants were studied. Of these, 16 subjects aged 54.4 ± 5.5years were treated with metformin and 14 subjects aged 54.9 ± 6.4 years did not receive the drug. Participants receiving metformin had lower levels of hsCRP and lower mRNA relative abundance of TNF-α and TLR 2/4. There were no differences in glucose levels or lipid profile between both groups. Obese diabetic patients treated with metformin had lower levels of hsCRP expression of TNF-α and TLR 2/4, than their counterparts not receiving the drug.

Association of MC4R variants with obesity-related traits in Hispanic children

USDA-ARS?s Scientific Manuscript database

Melanocortin 4 receptor (MC4R) has been implicated in the regulation of appetite and energy expenditure. In children, MC4R mutations have been associated with severe obesity. The main objective of this study was to investigate the potential functional effects of variants in MC4R gene on the variatio...

Plasma ANGPTL-4 is Associated with Obesity and Glucose Tolerance: Cross-Sectional and Longitudinal Findings.

PubMed

Barja-Fernandez, Silvia; Moreno-Navarrete, José María; Folgueira, Cintia; Xifra, Gemma; Sabater, Mònica; Castelao, Cecilia; FernØ, Johan; Leis, Rosaura; Diéguez, Carlos; Casanueva, Felipe F; Ricart, Wifredo; Seoane, Luisa M; Fernandez-Real, José Manuel; Nogueiras, Rubén

2018-05-01

Angiopoietin-like protein 4 (ANGPTL-4) regulates plasma lipoprotein levels, but its relevance in human obesity and type 2 diabetes (T2D) is largely unknown. We aim to investigate the regulation of circulating ANGPTL-4 levels in obesity, T2D, and after changes in body weight. Circulating ANGPTL-4 levels were measured in two different cohorts. First, in a cross-sectional study, we evaluated ANGPTL-4 levels in lean and obese patients with normoglycemia or with altered glucose tolerance (AGT; n = 282). Second, in a longitudinal intervention study, 51 obese participants were evaluated. A hypocaloric diet was prescribed, with follow-up 2 years later. ANGPTL-4 levels were significantly increased in obese patients with AGT compared to lean participants. Moreover, ANGPTL-4 was positively correlated with BMI, waist circumference, fat mass, HbA1c, HOMA-IR, fasting triglycerides, and with inflammatory markers. Participants gaining weight after the follow-up showed increased ANGPTL-4 levels in parallel to increased BMI, fat mass, and fasting glucose, while ANGPTL-4 levels were reduced in participants losing weight. Our data support a relevant role of ANGPTL-4 in human obesity and its involvement in long-term body weight changes. © 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Age-related consequences of childhood obesity.

PubMed

Kelsey, Megan M; Zaepfel, Alysia; Bjornstad, Petter; Nadeau, Kristen J

2014-01-01

The severity and frequency of childhood obesity has increased significantly over the past three to four decades. The health effects of increased body mass index as a child may significantly impact obese youth as they age. However, many of the long-term outcomes of childhood obesity have yet to be studied. This article examines the currently available longitudinal data evaluating the effects of childhood obesity on adult outcomes. Consequences of obesity include an increased risk of developing the metabolic syndrome, cardiovascular disease, type 2 diabetes and its associated retinal and renal complications, nonalcoholic fatty liver disease, obstructive sleep apnea, polycystic ovarian syndrome, infertility, asthma, orthopedic complications, psychiatric disease, and increased rates of cancer, among others. These disorders can start as early as childhood, and such early onset increases the likelihood of early morbidity and mortality. Being obese as a child also increases the likelihood of being obese as an adult, and obesity in adulthood also leads to obesity-related complications. This review outlines the evidence for childhood obesity as a predictor of adult obesity and obesity-related disorders, thereby emphasizing the importance of early intervention to prevent the onset of obesity in childhood.

Hypocaloric, high-protein nutrition therapy for critically ill patients with obesity.

PubMed

Dickerson, Roland N

2014-12-01

We published the first article that addressed hypocaloric, high-protein enteral nutrition therapy for critically ill patients with obesity more than 10 years ago. This study demonstrated that it was possible to successfully achieve this mode of therapy with a commercially available high-protein enteral formula and concurrent use of protein supplements. This study was also the first to demonstrate improved clinical outcomes with the use of hypocaloric, high-protein nutrition therapy. The results of this study, its unique findings, and shortcomings are discussed. Subsequent studies have added clarity to the effective use of this therapy, including its use in home parenteral nutrition patients, patients with class III obesity, and older patients with obesity. © 2014 American Society for Parenteral and Enteral Nutrition.

Distinct effects of calorie restriction on adipose tissue cytokine and angiogenesis profiles in obese and lean mice

PubMed Central

2012-01-01

Background Obesity associates with low-grade inflammation and adipose tissue remodeling. Using sensitive high-throughput protein arrays we here investigated adipose tissue cytokine and angiogenesis-related protein profiles from obese and lean mice, and in particular, the influence of calorie restriction (CR). Methods Tissue samples from visceral fat were harvested from obese mice fed with a high-fat diet (60% of energy), lean controls receiving low-fat control diet as well as from obese and lean mice kept under CR (energy intake 70% of ad libitum intake) for 50 days. Protein profiles were analyzed using mouse cytokine and angiogenesis protein array kits. Results In obese and lean mice, CR was associated with 11.3% and 15.6% reductions in body weight, as well as with 4.0% and 4.6% reductions in body fat percentage, respectively. Obesity induced adipose tissue cytokine expressions, the most highly upregulated cytokines being IL-1ra, IL-2, IL-16, MCP-1, MIG, RANTES, C5a, sICAM-1 and TIMP-1. CR increased sICAM-1 and TIMP-1 expression both in obese and lean mice. Overall, CR showed distinct effects on cytokine expressions; in obese mice CR largely decreased but in lean mice increased adipose tissue cytokine expressions. Obesity was also associated with increased expressions of angiogenesis-related proteins, in particular, angiogenin, endoglin, endostatin, endothelin-1, IGFBP-3, leptin, MMP-3, PAI-1, TIMP-4, CXCL16, platelet factor 4, DPPIV and coagulation factor III. CR increased endoglin, endostatin and platelet factor 4 expressions, and decreased IGFBP-3, NOV, MMP-9, CXCL16 and osteopontin expressions both in obese and lean mice. Interestingly, in obese mice, CR decreased leptin and TIMP-4 expressions, whereas in lean mice their expressions were increased. CR decreased MMP-3 and PAI-1 only in obese mice, whereas CR decreased FGF acidic, FGF basic and coagulation factor III, and increased angiogenin and DPPIV expression only in lean mice. Conclusions CR exerts

Prevalence of overweight, obesity, abdominal obesity and obesity-related risk factors in southern China

PubMed Central

Hu, Lihua; Huang, Xiao; You, Chunjiao; Li, Juxiang; Hong, Kui; Li, Ping; Wu, Yanqing; Wu, Qinhua; Wang, Zengwu; Gao, Runlin; Bao, Huihui

2017-01-01

Objectives The purpose of this study is to assess the prevalence of overweight/obesity, abdominal obesity and obesity-related risk factors in southern China. Methods A cross-sectional survey of 15,364 participants aged 15 years and older was conducted from November 2013 to August 2014 in Jiangxi Province, China, using questionnaire forms and physical measurements. The physical measurements included body height, weight, waist circumference (WC), body fat percentage (BFP) and visceral adipose index (VAI). Multivariate logistic regression analysis was performed to evaluate the risk factors for overweight/obesity and abdominal obesity. Results The prevalence of overweight was 25.8% (25.9% in males and 25.7% in females), while that of obesity was 7.9% (8.4% in males and 7.6% in females). The prevalence of abdominal obesity was 10.2% (8.6% in males and 11.3% in females). The prevalence of overweight/obesity was 37.1% in urban residents and 30.2% in rural residents, and this difference was significant (P < 0.001). Urban residents had a significantly higher prevalence of abdominal obesity than rural residents (11.6% vs 8.7%, P < 0.001). Among the participants with an underweight/normal body mass index (BMI), 1.3% still had abdominal obesity, 16.1% had a high BFP and 1.0% had a high VAI. Moreover, among obese participants, 9.7% had a low /normal WC, 0.8% had a normal BFP and 15.9% had a normal VAI. Meanwhile, the partial correlation analysis indicated that the correlation coefficients between VAI and BMI, VAI and WC, and BMI and WC were 0.700, 0.666, and 0.721, respectively. A multivariate logistic regression analysis indicated that being female and having a high BFP and a high VAI were significantly associated with an increased risk of overweight/obesity and abdominal obesity. In addition, living in an urban area and older age correlated with overweight/obesity. Conclusion This study revealed that obesity and abdominal obesity, which differed by gender and age, are

Uncovering Suitable Reference Proteins for Expression Studies in Human Adipose Tissue with Relevance to Obesity

PubMed Central

Pérez-Pérez, Rafael; López, Juan A.; García-Santos, Eva; Camafeita, Emilio; Gómez-Serrano, María; Ortega-Delgado, Francisco J.; Ricart, Wifredo; Fernández-Real, José M.; Peral, Belén

2012-01-01

Background Protein expression studies based on the two major intra-abdominal human fat depots, the subcutaneous and the omental fat, can shed light into the mechanisms involved in obesity and its co-morbidities. Here we address, for the first time, the identification and validation of reference proteins for data standardization, which are essential for accurate comparison of protein levels in expression studies based on fat from obese and non-obese individuals. Methodology and Findings To uncover adipose tissue proteins equally expressed either in omental and subcutaneous fat depots (study 1) or in omental fat from non-obese and obese individuals (study 2), we have reanalyzed our previously published data based on two-dimensional fluorescence difference gel electrophoresis. Twenty-four proteins (12 in study 1 and 12 in study 2) with similar expression levels in all conditions tested were selected and identified by mass spectrometry. Immunoblotting analysis was used to confirm in adipose tissue the expression pattern of the potential reference proteins and three proteins were validated: PARK7, ENOA and FAA. Western Blot analysis was also used to test customary loading control proteins. ENOA, PARK7 and the customary loading control protein Beta-actin showed steady expression profiles in fat from non-obese and obese individuals, whilst FAA maintained steady expression levels across paired omental and subcutaneous fat samples. Conclusions ENOA, PARK7 and Beta-actin are proper reference standards in obesity studies based on omental fat, whilst FAA is the best loading control for the comparative analysis of omental and subcutaneous adipose tissues either in obese and non-obese subjects. Neither customary loading control proteins GAPDH and TBB5 nor CALX are adequate standards in differential expression studies on adipose tissue. The use of the proposed reference proteins will facilitate the adequate analysis of proteins differentially expressed in the context of obesity

Contribution of Common Genetic Variants to Obesity and Obesity-Related Traits in Mexican Children and Adults

PubMed Central

Villalobos-Comparán, Marisela; Villarreal-Molina, Teresa; Romero-Hidalgo, Sandra; López-Contreras, Blanca; Gutiérrez-Vidal, Roxana; Vega-Badillo, Joel; Jacobo-Albavera, Leonor; Posadas-Romeros, Carlos; Canizalez-Román, Adrián; Río-Navarro, Blanca Del; Campos-Pérez, Francisco; Acuña-Alonzo, Victor; Aguilar-Salinas, Carlos; Canizales-Quinteros, Samuel

2013-01-01

Background Several studies have identified multiple obesity-associated loci mainly in European populations. However, their contribution to obesity in other ethnicities such as Mexicans is largely unknown. The aim of this study was to examine 26 obesity-associated single-nucleotide polymorphisms (SNP) in a sample of Mexican mestizos. Methods 9 SNPs in biological candidate genes showing replications (PPARG, ADRB3, ADRB2, LEPR, GNB3, UCP3, ADIPOQ, UCP2, and NR3C1), and 17 SNPs in or near genes associated with obesity in first, second and third wave GWAS (INSIG2, FTO, MC4R, TMEM18, FAIM2/BCDIN3, BDNF, SH2B1, GNPDA2, NEGR1, KCTD15, SEC16B/RASAL2, NPC1, SFRF10/ETV5, MAF, PRL, MTCH2, and PTER) were genotyped in 1,156 unrelated Mexican-Mestizos including 683 cases (441 obese class I/II and 242 obese class III) and 473 normal-weight controls. In a second stage we selected 12 of the SNPs showing nominal associations with obesity, to seek associations with quantitative obesity-related traits in 3 cohorts including 1,218 Mexican Mestizo children, 945 Mexican Mestizo adults, and 543 Indigenous Mexican adults. Results After adjusting for age, sex and admixture, significant associations with obesity were found for 6 genes in the case-control study (ADIPOQ, FTO, TMEM18, INSIG2, FAIM2/BCDIN3 and BDNF). In addition, SH2B1 was associated only with class I/II obesity and MC4R only with class III obesity. SNPs located at or near FAIM2/BCDIN3, TMEM18, INSIG2, GNPDA2 and SEC16B/RASAL2 were significantly associated with BMI and/or WC in the combined analysis of Mexican-mestizo children and adults, and FTO locus was significantly associated with increased BMI in Indigenous Mexican populations. Conclusions Our findings replicate the association of 8 obesity-related SNPs with obesity risk in Mexican adults, and confirm the role of some of these SNPs in BMI in Mexican adults and children. PMID:23950976

Hypocaloric high-protein diet improves fatty liver and hypertriglyceridemia in sucrose-fed obese rats via two pathways.

PubMed

Uebanso, Takashi; Taketani, Yutaka; Fukaya, Makiko; Sato, Kazusa; Takei, Yuichiro; Sato, Tadatoshi; Sawada, Naoki; Amo, Kikuko; Harada, Nagakatsu; Arai, Hidekazu; Yamamoto, Hironori; Takeda, Eiji

2009-07-01

The mechanism by which replacement of some dietary carbohydrates with protein during weight loss favors lipid metabolism remains obscure. In this study, we investigated the effect of an energy-restricted, high-protein/low-carbohydrate diet on lipid metabolism in obese rats. High-sucrose-induced obese rats were assigned randomly to one of two energy-restricted dietary interventions: a carbohydrate-based control diet (CD) or a high-protein diet (HPD). Lean rats of the same age were assigned as normal control. There was significantly greater improvement in fatty liver and hypertriglyceridemia with the HPD diet relative to the CD diet. Expression of genes regulated by fibroblast growth factor-21 (FGF21) and involved in liver lipolysis and lipid utilitization, such as lipase and acyl-CoA oxidase, increased in obese rats fed the HPD. Furthermore, there was an inverse correlation between levels of FGF21 gene expression (regulated by glucagon/insulin balance) and increased triglyceride concentrations in liver from obese rats. Expression of hepatic stearoyl-CoA desaturase-1 (SCD1), regulated primarily by the dietary carbohydrate, was also markedly reduced in the HPD group (similar to plasma triglyceride levels in fasting animals) relative to the CD group. In conclusion, a hypocaloric high-protein diet improves fatty liver and hypertriglyceridemia effectively relative to a carbohydrate diet. The two cellular pathways at work behind these benefits include stimulation of hepatic lipolysis and lipid utilization mediated by FGF21 and reduction of hepatic VLDL-TG production by SCD1 regulation.

Beyond the "I" in the obesity epidemic: a review of social relational and network interventions on obesity.

PubMed

Leroux, Janette S; Moore, Spencer; Dubé, Laurette

2013-01-01

Recent research has shown the importance of networks in the spread of obesity. Yet, the translation of research on social networks and obesity into health promotion practice has been slow. To review the types of obesity interventions targeting social relational factors. Six databases were searched in January 2013. A Boolean search was employed with the following sets of terms: (1) social dimensions: social capital, cohesion, collective efficacy, support, social networks, or trust; (2) intervention type: intervention, experiment, program, trial, or policy; and (3) obesity in the title or abstract. Titles and abstracts were reviewed. Articles were included if they described an obesity intervention with the social relational component central. Articles were assessed on the social relational factor(s) addressed, social ecological level(s) targeted, the intervention's theoretical approach, and the conceptual placement of the social relational component in the intervention. Database searches and final article screening yielded 30 articles. Findings suggested that (1) social support was most often targeted; (2) few interventions were beyond the individual level; (3) most interventions were framed on behaviour change theories; and (4) the social relational component tended to be conceptually ancillary to the intervention. Theoretically and practically, social networks remain marginal to current interventions addressing obesity.

C1q/TNF-Related Protein-9 (CTRP9) Levels Are Associated With Obesity and Decrease Following Weight Loss Surgery

PubMed Central

Steele, Kimberley E.; Peterson, Leigh A.; Zeng, Xiange; Jaffe, Andrew E.; Schweitzer, Michael A.; Magnuson, Thomas H.; Wong, G. William

2016-01-01

Context: C1q/TNF-related protein-9 (CTRP9) is a novel adipokine that has beneficial metabolic and cardiovascular effects in various animal models. Alterations in circulating CTRP9 have also been observed in patients with cardiovascular disease and diabetes, but little is known about the impact of obesity and bariatric surgery on CTRP9 concentrations. Objective: The aim of this study was to compare CTRP9 levels in obese and lean subjects and to determine whether circulating CTRP9 levels in morbidly obese patients are altered by bariatric surgery. Design, Setting, and Participants: Fifty-nine obese bariatric surgical patients and 62 lean controls were recruited to participate in a cross-sectional study at an academic medical center. The obese patients were further invited to participate in a cohort study, and 21 returned for analysis at 3 and 6 months postsurgery. Intervention: Bariatric surgery (Roux-en-Y gastric bypass and vertical sleeve gastrectomy) was the intervention for this study. Main Outcome Measures: Fasting serum was obtained from all subjects on entry to the study and was analyzed in the core laboratory for hemoglobin A1c, glucose, aspartate aminotransferase, alanine aminotransferase, total cholesterol, high- and low-density lipoprotein cholesterol, and triglycerides; CTRP9, insulin, adiponectin, and leptin were measured by ELISA. Serum from the patients in the cohort study was also analyzed at 3 and 6 months. Results: Serum CTRP9 was significantly higher in the obese group compared to the lean group. CTRP9 was associated with obesity, even after controlling for age, gender, and ethnicity. Following bariatric surgery, there was a significant decrease in weight at 3 and 6 months postprocedure, accompanied by decreases in CTRP9, hemoglobin A1c and leptin, and an increase in serum adiponectin. Conclusions: CTRP9 levels are elevated in obesity and significantly decrease following weight loss surgery. Our data suggest that CTRP9 may play a compensatory role

C1q/TNF-related protein 6 (CTRP6) links obesity to adipose tissue inflammation and insulin resistance.

PubMed

Lei, Xia; Seldin, Marcus M; Little, Hannah C; Choy, Nicholas; Klonisch, Thomas; Wong, G William

2017-09-08

Obesity is associated with chronic low-grade inflammation, and metabolic regulators linking obesity to inflammation have therefore received much attention. Secreted C1q/TNF-related proteins (CTRPs) are one such group of regulators that regulate glucose and fat metabolism in peripheral tissues and modulate inflammation in adipose tissue. We have previously shown that expression of CTRP6 is up-regulated in leptin-deficient mice and, conversely, down-regulated by the anti-diabetic drug rosiglitazone. Here, we provide evidence for a novel role of CTRP6 in modulating both inflammation and insulin sensitivity. We found that in obese and diabetic humans and mouse models, CTRP6 expression was markedly up-regulated in adipose tissue and that stromal vascular cells, such as macrophages, are a major CTRP6 source. Overexpressing mouse or human CTRP6 impaired glucose disposal in peripheral tissues in response to glucose and insulin challenge in wild-type mice. Conversely, Ctrp6 gene deletion improved insulin action and increased metabolic rate and energy expenditure in diet-induced obese mice. Mechanistically, CTRP6 regulates local inflammation and glucose metabolism by targeting macrophages and adipocytes, respectively. In cultured macrophages, recombinant CTRP6 dose-dependently up-regulated the expression and production of TNF-α. Conversely, CTRP6 deficiency reduced circulating inflammatory cytokines and pro-inflammatory macrophages in adipose tissue. CTRP6-overexpressing mice or CTRP6-treated adipocytes had reduced insulin-stimulated Akt phosphorylation and glucose uptake. In contrast, loss of CTRP6 enhanced insulin-stimulated Akt activation in adipose tissue. Together, these results establish CTRP6 as a novel metabolic/immune regulator linking obesity to adipose tissue inflammation and insulin resistance. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

Polymorphism and methylation of the MC4R gene in obese and non-obese dogs.

PubMed

Mankowska, Monika; Nowacka-Woszuk, Joanna; Graczyk, Aneta; Ciazynska, Paulina; Stachowiak, Monika; Switonski, Marek

2017-08-01

The dog is considered to be a useful biomedical model for human diseases and disorders, including obesity. One of the numerous genes associated with human polygenic obesity is MC4R, encoding the melanocortin 4 receptor. The aim of our study was to analyze polymorphisms and methylation of the canine MC4R in relation to adiposity. Altogether 270 dogs representing four breeds predisposed to obesity: Labrador Retriever (n = 187), Golden Retriever (n = 38), Beagle (n = 28) and Cocker Spaniel (n = 17), were studied. The dogs were classified into three groups: lean, overweight and obese, according to the 5-point Body Condition Score (BCS) scale. In the cohort of Labradors a complete phenotypic data (age, sex, neutering status, body weight and BCS) were collected for 127 dogs. The entire coding sequence as well as 5' and 3'-flanking regions of the studied gene were sequenced and six polymorphic sites were reported. Genotype frequencies differed considerably between breeds and Labrador Retrievers appeared to be the less polymorphic. Moreover, distribution of some polymorphic variants differed significantly (P < 0.05) between small cohorts with diverse BCS in Golden Retrievers (c.777T>C, c.868C>T and c.*33C>G) and Beagles (c.-435T>C and c.637G>T). On the contrary, in Labradors no association between the studied polymorphisms and BCS or body weight was observed. Methylation analysis, using bisulfite DNA conversion followed by Sanger sequencing, was carried out for 12 dogs with BCS = 3 and 12 dogs with BCS = 5. Two intragenic CpG islands, containing 19 cytosines, were analyzed and the methylation profile did not differ significantly between lean and obese animals. We conclude that an association of the MC4R gene polymorphism with dog obesity or body weight is unlikely, in spite of the fact that some associations were found in small cohorts of Beagles and Golden Retrievers. Also methylation level of this gene is not related with dog adiposity.

Immune function, mitogenicity, and angiogenic growth factor concentrations in lean and obese rodent sera: implications in obesity-related prostate tumor biology.

PubMed

Mydlo, J H; Gerstein, M I; Harris, C F; Braverman, A S

2003-01-01

Some studies suggest that several tumors have a greater incidence in those patients with a high fat diet, such as colon, breast, and prostate. However, we wanted to determine the effects of obesity alone, independent of diet, on the progression of prostate tumor growth. Using a genetic model of obese and lean Zucker rats, we wanted to demonstrate any sera differences in the concentration of basic fibroblast growth factor (FGF-2) and vascular endothelial cell growth factor (VEGF), two important factors involved in the growth and progression of prostate cancer. We also wanted to investigate if there were any differences in immune function between the two sera, which could also account for uninhibited tumor growth, as well as differences in mitogenic stimulation. Female Zucker rat obese and lean sera were analyzed using ELISA assays for FGF-2, VEGF, and macrophage inflammatory protein-1 alpha (MIP-1a), as a measure of macrophage function. In addition, the sera of lean and obese sera were plated on wells growing LNCaP prostate cancer cells to determine differences in mitogenicity. We found a greater concentration of FGF-2 in the sera from obese Zucker rats compared to lean Zucker rats: 6.32+/-0.56 vs 3.48+/-0.34 pg/ml, respectively, P<0.05). We also demonstrated a greater concentration of VEGF in obese rat sera compared to lean sera: 54.4+/-4.1 vs 38.0+/-2.9 pg/mL, respectively, P<0.05). We detected a trend in mitogenic stimulation among LNCaP cells along the higher concentrations of the dose-response curve (0.72+/-0.06 vs 0.51+/-0.5). However, this was not statistically significant. In addition, we did not find a significant difference in MIP-1a macrophage activity levels between sera. To conclude, we speculate that the greater concentrations of VEGF and FGF-2 in the sera of obese rodents vs lean rodents may account for some of the differences seen in obesity-related tumor growth seen in the human condition. However, the lack of any sera differences of immune function

Role of hormonal and inflammatory alterations in obesity-related reproductive dysfunction at the level of the hypothalamic-pituitary-ovarian axis.

PubMed

Goldsammler, Michelle; Merhi, Zaher; Buyuk, Erkan

2018-05-09

Besides being a risk factor for multiple metabolic disorders, obesity could affect female reproduction. While increased adiposity is associated with hormonal changes that could disrupt the function of the hypothalamus and the pituitary, compelling data suggest that obesity-related hormonal and inflammatory changes could directly impact ovarian function. To review the available data related to the mechanisms by which obesity, and its associated hormonal and inflammatory changes, could affect the female reproductive function with a focus on the hypothalamic-pituitary-ovarian (HPO) axis. PubMed database search for publications in English language until October 2017 pertaining to obesity and female reproductive function was performed. The obesity-related changes in hormone levels, in particular leptin, adiponectin, ghrelin, neuropeptide Y and agouti-related protein, are associated with reproductive dysfunction at both the hypothalamic-pituitary and the ovarian levels. The pro-inflammatory molecules advanced glycation end products (AGEs) and monocyte chemotactic protein-1 (MCP-1) are emerging as relatively new players in the pathophysiology of obesity-related ovarian dysfunction. There is an intricate crosstalk between the adipose tissue and the inflammatory system with the HPO axis function. Understanding the mechanisms behind this crosstalk could lead to potential therapies for the common obesity-related reproductive dysfunction.

Protein kinase Cβ activates fat mass and obesity-associated protein by influencing its ubiquitin/proteasome degradation.

PubMed

Tai, Haoran; Wang, Xiaobo; Zhou, Jiao; Han, Xiaojuan; Fang, Tingting; Gong, Hui; Huang, Ning; Chen, Honghan; Qin, Jianqiong; Yang, Ming; Wei, Xiawei; Yang, Li; Xiao, Hengyi

2017-10-01

Protein kinase Cβ (PKCβ) is a serine-threonine kinase associated with obesity and diabetic complications; its activation contributes to weight gain, and deletion of its gene results in resistance to genetic- and diet-induced obesity. Fat mass and obesity-associated (FTO) protein is a recently identified RNA demethylase, and its overexpression in mice leads to increased body weight as well as fat mass. Although sharing some features in anabolism regulation, PKCβ and FTO have not been investigated together; therefore, their relationship has not been established. We report that PKCβ positively regulates FTO on the posttranslation level, evidenced by the facts that PKCβ activation contributes to high-glucose-induced FTO up-regulation, and overexpression of PKCβ suppresses ubiquitin-proteasome degradation of FTO, whereas PKCβ inactivation acts in the opposite manner. It was also found that PKCβ can phosphorylate FTO on threonine, and this phosphorylation requires both catalytic and regulatory domains of PKCβ. Moreover, PKCβ inhibition can suppress 3T3-L1 cell differentiation in normal and FTO-overexpressing cells but not in FTO-silenced or -inhibited cells. We propose that PKCβ acts to suppress the degradation of FTO protein and reveals the associated role of PKCβ and FTO in adipogenesis, suggesting a new pathway that affects the development of obesity and metabolic diseases.-Tai, H., Wang, X., Zhou, J., Han, X., Fang, T., Gong, H., Huang, N., Chen, H., Qin, J., Yang, M., Wei, X., Yang, L., Xiao, H. Protein kinase Cβ activates fat mass and obesity-associated protein by influencing its ubiquitin/proteasome degradation. © FASEB.

Mixed compared with single-source proteins in high-protein diets affect kidney structure and function differentially in obese fa/fa Zucker rats.

PubMed

Devassy, Jessay G; Wojcik, Jennifer L; Ibrahim, Naser H M; Zahradka, Peter; Taylor, Carla G; Aukema, Harold M

2017-02-01

Questions remain regarding the potential negative effects of dietary high protein (HP) on kidney health, particularly in the context of obesity in which the risk for renal disease is already increased. To examine whether some of the variability in HP effects on kidney health may be due to source of protein, obese fa/fa Zucker rats were given HP (35% of energy from protein) diets containing either casein, soy protein, or a mixed source of animal and plant proteins for 12 weeks. Control lean and obese rats were given diets containing casein at normal protein (15% of energy from protein) levels. Body weight and blood pressure were measured, and markers of renal structural changes, damage, and function were assessed. Obesity alone resulted in mild renal changes, as evidenced by higher kidney weights, proteinuria, and glomerular volumes. In obese rats, increasing the protein level using the single, but not mixed, protein sources resulted in higher renal fibrosis compared with the lean rats. The mixed-protein HP group also had lower levels of serum monocyte chemoattractant protein-1, even though this diet further increased kidney and glomerular size. Soy and mixed-protein HP diets also resulted in a small number of damaged glomeruli, while soy compared with mixed-protein HP diet delayed the increase in blood pressure over time. Since obesity itself confers added risk of renal disease, an HP diet from mixed-protein sources that enables weight loss but has fewer risks to renal health may be advantageous.

Differential regulation of lipid and protein metabolism in obese vs. lean subjects before and after a 72-h fast.

PubMed

Bak, Ann Mosegaard; Møller, Andreas Buch; Vendelbo, Mikkel Holm; Nielsen, Thomas Svava; Viggers, Rikke; Rungby, Jørgen; Pedersen, Steen Bønløkke; Jørgensen, Jens Otto Lunde; Jessen, Niels; Møller, Niels

2016-07-01

Increased availability of lipids may conserve muscle protein during catabolic stress. Our study was designed to define 1) intracellular mechanisms leading to increased lipolysis and 2) whether this scenario is associated with decreased amino acid and urea fluxes, and decreased muscle amino acid release in obese subjects under basal and fasting conditions. We therefore studied nine lean and nine obese subjects twice, after 12 and 72 h of fasting, using measurements of mRNA and protein expression and phosphorylation of lipolytic and protein metabolic signaling molecules in fat and muscle together with whole body and forearm tracer techniques. Obese subjects displayed increased whole body lipolysis, decreased urea production rates, and decreased forearm muscle protein breakdown per 100 ml of forearm tissue, differences that persisted after 72 h of fasting. Lipolysis per fat mass unit was reduced in obese subjects and, correspondingly, adipose tissue hormone-sensitive lipase (HSL) phosphorylation and mRNA and protein levels of the adipose triglyceride lipase (ATGL) coactivator CGI58 were decreased. Fasting resulted in higher HSL phosphorylations and lower protein levels of the ATGL inhibitor G0S2. Muscle protein expressions of mammalian target of rapamycin (mTOR) and 4EBP1 were lower in obese subjects, and MuRf1 mRNA was higher with fasting in lean but not obese subjects. Phosphorylation and signaling of mTOR decreased with fasting in both groups, whereas ULK1 protein and mRNA levels increased. In summary, obese subjects exhibit increased lipolysis due to a large fat mass with blunted prolipolytic signaling, together with decreased urea and amino acid fluxes both in the basal and 72-h fasted state; this is compatible with preservation of muscle and whole body protein. Copyright © 2016 the American Physiological Society.

Association between obesity and glomerular hyperfiltration: the confounding effect of smoking and sodium and protein intakes.

PubMed

Ogna, Adam; Forni Ogna, Valentina; Bochud, Murielle; Guessous, Idris; Paccaud, Fred; Burnier, Michel; Wuerzner, Gregoire

2016-04-01

Glomerular hyperfiltration has been suggested as a possible mechanism linking obesity and chronic kidney disease (CKD), independently of classical risk factors. We explored the association of overweight and obesity with glomerular hyperfiltration in a large sample of the Swiss adult population, accounting for several confounders including dietary factors. Data from a 2010 to 2012 cross-sectional population-based survey in Switzerland were used. Creatinine clearance (CrCl) was determined from 24-h urine collection; CrCl > 140 ml/min was used to define glomerular hyperfiltration. Participants were categorized into lean (<25 kg/m(2)), overweight (25-29.9 kg/m(2)) and obese (≥30 kg/m(2)) according to body mass index (BMI). A total of 1339 participants were included in the analysis [median (IQR) age 49.4 (34.3-63.5) years, 48.9 % men]. The prevalences of overweight and obesity were 32.2 and 14.2 %, respectively. Median CrCl was 102[84-121] ml/min in lean, 110 [87-136] ml/min in overweight and 124 [97-150] ml/min in obese participants (p < 0.001). The prevalence of glomerular hyperfiltration increased across BMI categories (10.4, 20.8 and 34.7 %, respectively; p < 0.001). This positive association remained significant after adjusting for age, sex, hypertension, diabetes, smoking and dietary factors (sodium and protein intakes): odds ratio [95 %CI] 2.39 [1.52-3.76] (p < 0.001) for overweight versus lean and 4.10[2.31-7.27] (p < 0.001) for obesity versus lean. BMI categories and glomerular hyperfiltration are positively associated, independently of other known CKD risk factors and dietary confounders, suggesting that glomerular hyperfiltration may represent an early renal phenotype in obesity. Our observations confirm the significant association of glomerular hyperfiltration with sodium and protein intakes and identify sodium intake as an important modifying factor of the association between hyperfiltration and obesity.

Anti-Obesity Effects of Aster spathulifolius Extract in High-Fat Diet-Induced Obese Rats.

PubMed

Kim, Sa-Jic; Bang, Chae-Young; Guo, Yuan-Ri; Choung, Se-Young

2016-04-01

The aim of this study was to investigate the anti-obesity and antihyperlipidemic efficacy and molecular mechanisms of Aster spathulifolius Maxim extract (ASE) in rats with high-fat diet (HFD)-induced obesity. Rats were separately fed a normal diet or a HFD for 8 weeks, then they were treated with ASE (62.5, 125, or 250 mg/kg) for another 4.5 weeks. The ASE supplementation significantly lowered body weight gain, visceral fat pad weights, serum lipid levels, as well as hepatic lipid levels in HFD-induced obese rats. Histological analysis showed that the ASE-treated group showed lowered numbers of lipid droplets and smaller size of adipocytes compared to the HFD group. To understand the mechanism of action of ASE, the expression of genes and proteins involved in obesity were measured in liver and skeletal muscle. The expression of fatty acid oxidation and thermogenesis-related genes (e.g., PPAR-α, ACO, CPT1, UCP2, and UCP3) of HFD-induced obese rats were increased by ASE treatment. On the other hand, ASE treatment resulted in decreased expression of fat intake-related gene ACC2 and lipogenesis-related genes (e.g., SREBP-1c, ACC1, FAS, SCD1, GPATR, AGPAT, and DGAT). Furthermore, ASE treatment increased the level of phosphorylated AMPKα in obese rats. Similarly, the level of phosphorylated ACC, a target protein of AMPKα in ASE groups, was increased by ASE treatment compared with the HFD group. These results suggest that ASE attenuated visceral fat accumulation and improved hyperlipidemia in HFD-induced obese rats by increasing lipid metabolism through the regulation of AMPK activity and the expression of genes and proteins involved in lipolysis and lipogenesis.

Pharmacological Characterization of 30 Human Melanocortin-4 Receptor Polymorphisms with the Endogenous Proopiomelanocortin Derived Agonists, Synthetic Agonists, and the Endogenous Agouti-Related Protein (AGRP) Antagonist

PubMed Central

Xiang, Zhimin; Proneth, Bettina; Dirain, Marvin L.; Litherland, Sally A.; Haskell-Luevano, Carrie

2010-01-01

The melanocortin-4 receptor (MC4R) is a G-protein coupled receptor (GPCR) that is expressed in the central nervous system and has a role in regulating feeding behavior, obesity, energy homeostasis, male erectile response, and blood pressure. Since the report of the MC4R knockout mouse in 1997, the field has been searching for links between this genetic bio marker and human obesity and type 2 diabetes. More then 80 single nucleotide polymorphisms (SNPs) have been identified from human patients, both obese and non-obese controls. Many significant studies have been performed examining the pharmacological characteristics of these hMC4R SNPs in attempts to identify a molecular defects/insights that might link a genetic factor to the obese phenotype observed in patients possessing these mutations. Our laboratory has previously reported the pharmacological characterization of 40 of these polymorphic hMC4 receptors with multiple endogenous and synthetic ligands. The goal of the current study is to perform a similar comprehensive side-by-side characterization of 30 additional human hMC4R with single nucleotide polymorphisms using multiple endogenous agonists [α-, β, γ2-melanocyte stimulating hormones (MSH) and adrenocorticotropin (ACTH)], the antagonist agouti-related protein hAGRP(87-132), and synthetic agonists [NDP-MSH, MTII, and the tetrapeptide Ac-His-DPhe-Arg-Trp-NH2 (JRH887-9)]. These in vitro data, in some cases, provide a putative molecular link between dysfunctional hMC4R's and human obesity. These 30 hMC4R SNPs include R7H, R18H, R18L, S36Y, P48S, V50M, F51L, E61K, I69T, D90N, S94R, G98R, I121T, A154D, Y157S, W174C, G181D, F202L, A219V, I226T, G231S, G238D, N240S, C271R, S295P, P299L, E308K, I317V, L325F and 750DelGA. All but the N240S hMC4R were identified in obese patients. Additionally, we have characterized a double I102T/V103I hMC4R. In addition to the pharmacological characterization, the hMC4R variants were evaluated for cell surface expression by flow

Obesity related factors in school-aged children.

PubMed

Soltani, Parvaneh Reza; Ghanbari, Atefeh; Rad, Afagh Hasanzadeh

2013-05-01

Overweight and obesity is becoming an increasingly prevalent problem in both developed and developing world, and is one of the most serious public health challenges of the 21(st) century. Although various studies demonstrated pediatric obesity-related factors, but, due to its ongoing hazardous effects, researchers aimed to assess obesity-related factors in school-aged children in Rasht, Iran. This was a case-control study which was performed in eight primary schools of Rasht. A cluster sampling method was used to select 320 students including 80 in case (BMI ≥85(th) percentile for age and gender) and 240 in control group (BMI = 5(th)-85(th) percentile for age and gender). Data were collected by a scale, a tape meter, and a form which consisted of obesity-related factors, and were analyzed by Chi-square, Mann-Whitney, and stepwise multivariate regression tests in SPSS 19. Findings showed that the mean and standard deviation of birth weight (g) in case and control groups were 3671 ± 5.64 and 190 ± 5.46, respectively (P = 0.000). 82.5% of case and 92.9% of control group had exclusive breastfeeding for 4-6 months (P = 0.024). Also, multivariate regression analysis indicated that birth weight, age, exclusive breastfeeding, and frequency of meals have significant effects on body mass index (BMI). It seems that more accurate interventions for primordial prevention are essential to reduce childhood obesity risk factors, including promotion of pre-pregnancy and prenatal care to have neonates who are appropriate for gestational age and also improving exclusive breastfeeding in the first 6 months of life. In addition, identifying children at risk for adolescent obesity provides physicians and midwives with an opportunity for earlier intervention with the goal of limiting the progression of abnormal weight gain.

Serum C-reactive protein and white blood cell count in morbidly obese surgical patients.

PubMed

Chen, Sheng-Bin; Lee, Yi-Chih; Ser, Kong-Han; Chen, Jung-Chien; Chen, Shu Chung; Hsieh, Hsing-Fang; Lee, Wei-Jei

2009-04-01

Obesity has been widely recognized as a chronic inflammatory condition and associated with elevated inflammatory indicators including C-reactive protein (CRP) and white blood cell count (WBC). Recent studies have shown elevated CRP or WBC is a significant risk factor for cardiac events and stroke but the clinical significance of CRP and WBC has not been clearly studied in morbidly obese patients. This study is aimed at the clinical significance of WBC and CRP in morbidly obese patients and the change after bariatric surgery. The study was a prospectively controlled clinical study. From December 1, 2001 to January 31, 2006, of 640 (442 females and 198 males) consecutive morbid obese patients enrolled in a surgically supervised weight loss program with at least 1 year's follow-up were examined. Of the patients, 476 (74.4%) had elevated CRP and 100 (15.6%) had elevated WBC at preoperative study. CRP and WBC were significantly related and both increased with increasing body mass index (BMI). CRP is also increased with increasing waist, glucose level, hemoglobin, albumin, Ca, insulin, C-peptide, and metabolic syndrome while WBC is increased with metabolic syndrome but decreased with increasing age. Multivariate analysis confirmed fasting glucose level and hemoglobin are independent predictors of the elevation of CRP while age is the only independent predictor for elevated WBC. Both WBC and CRP levels decreased rapidly after obesity surgery. These improvements resulted in a 69.8% reduction of CRP and 26.4% reduction of WBC 1 year after surgery. Although individuals who underwent laparoscopic gastric bypass lost significantly more weight (36.8 +/- 11.7 kg vs. 17.3 +/- 10.8 kg; p = 0.000) and achieved a lower BMI (27.8 +/- 4.6 vs. 35.0 +/- 5.5; p = 0.000) than individuals who underwent laparoscopic gastric banding, there was no difference in the resolution of elevated CRP 1 year after surgery (95.9% vs. 84.5%; p = 0.169) and WBC (99.4% vs. 98.3%; p = 0.323). Both baseline

Biological effects of bariatric surgery on obesity-related comorbidities

PubMed Central

Noria, Sabrena F.; Grantcharov, Teodor

2013-01-01

The prevalence of obesity has increased so rapidly over the last few decades that it is now considered a global epidemic. Obesity, defined as a body mass index (BMI) of 30 or more, is associated with several comorbid conditions that decrease life expectancy and increase health care costs. Diet therapies have been reported to be ineffective in the long-term treatment of obesity, and guidelines for the surgical therapy of morbid obesity (BMI ≥ 40 or BMI ≥ 35 in the presence of substantial comorbidities) have since been established. Considering the number of bariatric surgical procedures has dramatically increased since these guidelines were established, we review the types of bariatric surgical procedures and their impact on diabetes, sleep apnea, dyslipidemia and hypertension — 4 major obesity-related comorbidities. PMID:23351555

High dietary fat-induced obesity in Wistar rats and type 2 diabetes in nonobese Goto-Kakizaki rats differentially affect retinol binding protein 4 expression and vitamin A metabolism.

PubMed

Shirai, Tomomi; Shichi, Yuta; Sato, Miyuki; Tanioka, Yuri; Furusho, Tadasu; Ota, Toru; Tadokoro, Tadahiro; Suzuki, Tsukasa; Kobayashi, Ken-Ichi; Yamamoto, Yuji

2016-03-01

Obesity is a major risk factor for type 2 diabetes, which is caused mainly by insulin resistance. Retinol binding protein 4 (RBP4) is the only specific transport protein for retinol in the serum. RBP4 level is increased in the diabetic state and high-fat condition, indicating that retinol metabolism may be affected under these conditions. However, the precise effect of diabetes and high fat-induced obesity on retinol metabolism is unknown. In this study, we examined differences in retinol metabolite levels in rat models of diet-induced obesity and type 2 diabetes (Goto-Kakizaki [GK] rat). Four-week-old male Wistar and GK rats were given either a control diet (AIN-93G) or a high-fat diet (HFD, 40% fat kJ). After 15 weeks of feeding, the RBP4 levels increased by 2-fold in the serum of GK rats but not HFD-fed rats. The hepatic retinol concentration of HFD-fed rats was approximately 50% that of the controls (P < .01). In contrast, the renal retinol concentrations of GK rats increased by 70% (P < .01). However, expression of RARβ in the kidney, which was induced in a retinoic acid-dependent manner, was downregulated by 90% (P < .01) in GK rats. In conclusion, diabetes and obesity affected retinol metabolism differently, and the effects were different in different peripheral tissues. The impact of HFD may be limited to the storage of hepatic vitamin A as retinyl palmitate. In particular, our data indicate that renal retinoic acid production might represent an important target for the treatment of type 2 diabetes mellitus. Copyright © 2016 Elsevier Inc. All rights reserved.

Pharmacological characterization of 30 human melanocortin-4 receptor polymorphisms with the endogenous proopiomelanocortin-derived agonists, synthetic agonists, and the endogenous agouti-related protein antagonist.

PubMed

Xiang, Zhimin; Proneth, Bettina; Dirain, Marvin L; Litherland, Sally A; Haskell-Luevano, Carrie

2010-06-08

The melanocortin-4 receptor (MC4R) is a G-protein-coupled receptor (GPCR) that is expressed in the central nervous system and has a role in regulating feeding behavior, obesity, energy homeostasis, male erectile response, and blood pressure. Since the report of the MC4R knockout mouse in 1997, the field has been searching for links between this genetic biomarker and human obesity and type 2 diabetes. More then 80 single nucleotide polymorphisms (SNPs) have been identified from human patients, both obese and nonobese controls. Many significant studies have been performed examining the pharmacological characteristics of these hMC4R SNPs in attempts to identify a molecular defects/insights that might link a genetic factor to the obese phenotype observed in patients possessing these mutations. Our laboratory has previously reported the pharmacological characterization of 40 of these polymorphic hMC4 receptors with multiple endogenous and synthetic ligands. The goal of the current study is to perform a similar comprehensive side-by-side characterization of 30 additional human hMC4R with single nucleotide polymorphisms using multiple endogenous agonists [alpha-, beta-, and gamma(2)-melanocyte stimulating hormones (MSH) and adrenocorticotropin (ACTH)], the antagonist agouti-related protein hAGRP(87-132), and synthetic agonists [NDP-MSH, MTII, and the tetrapeptide Ac-His-dPhe-Arg-Trp-NH(2) (JRH887-9)]. These in vitro data, in some cases, provide a putative molecular link between dysfunctional hMC4R's and human obesity. These 30 hMC4R SNPs include R7H, R18H, R18L, S36Y, P48S, V50M, F51L, E61K, I69T, D90N, S94R, G98R, I121T, A154D, Y157S, W174C, G181D, F202L, A219 V, I226T, G231S, G238D, N240S, C271R, S295P, P299L, E308K, I317V, L325F, and 750DelGA. All but the N240S hMC4R were identified in obese patients. Additionally, we have characterized a double I102T/V103I hMC4R. In addition to the pharmacological characterization, the hMC4R variants were evaluated for cell surface

Obesity-related metabolite profiles of black women spanning the epidemiologic transition.

PubMed

Dugas, Lara R; Chorell, Elin; Plange-Rhule, Jacob; Lambert, Estelle V; Cao, Guichan; Cooper, Richard S; Layden, Brian T; Scholten, Denise; Olsson, Tommy; Luke, Amy; Goedecke, Julia H

2016-03-01

In developed countries, specific metabolites have been associated with obesity and metabolic diseases, e.g. type 2 diabetes. It is unknown whether a similar profile persists across populations of African-origin, at increased risk for obesity and related diseases. In a cross-sectional study of normal-weight and obese black women (33.3 ± 6.3 years) from the US ( N = 69, 65 % obese), South Africa (SA, N = 97, 49 % obese) and Ghana ( N = 82, 33 % obese) serum metabolite profiles were characterized via gas chromatography-time of flight/mass spectrometry. In US and SA women, BMI correlated with branched-chain and aromatic amino acids, as well as dopamine and aminoadipic acid. The relationship between BMI and lipid metabolites differed by site; BMI correlated positively with palmitoleic acid (16:1) in the US; negatively with stearic acid (18:0) in SA, and positively with arachidonic acid (20:4) in Ghana. BMI was also positively associated with sugar-related metabolites in the US; i.e. uric acid, and mannitol, and with glucosamine, glucoronic acid and mannitol in SA. While we identified a common amino acid metabolite profile associated with obesity in black women from the US and SA, we also found site-specific obesity-related metabolites suggesting that the local environment is a key moderator of obesity.

The Role of Aldosterone in Obesity-Related Hypertension

PubMed Central

Kawarazaki, Wakako

2016-01-01

Obese subjects often have hypertension and related cardiovascular and renal diseases, and this has become a serious worldwide health problem. In obese subjects, impaired renal-pressure natriuresis causes sodium retention, leading to the development of salt-sensitive hypertension. Physical compression of the kidneys by visceral fat and activation of the sympathetic nervous system, renin–angiotensin systems (RAS), and aldosterone/mineralocorticoid receptor (MR) system are involved in this mechanism. Obese subjects often exhibit hyperaldosteronism, with increased salt sensitivity of blood pressure (BP). Adipose tissue excretes aldosterone-releasing factors, thereby stimulating aldosterone secretion independently of the systemic RAS, and aldosterone/MR activation plays a key role in the development of hypertension and organ damage in obesity. In obese subjects, both salt sensitivity of BP, enhanced by obesity-related metabolic disorders including aldosterone excess, and increased dietary sodium intake are closely related to the incidence of hypertension. Some salt sensitivity-related gene variants affect the risk of obesity, and together with salt intake, its combination is possibly associated with the development of hypertension in obese subjects. With high salt levels common in modern diets, salt restriction and weight control are undoubtedly important. However, not only MR blockade but also new diagnostic modalities and therapies targeting and modifying genes that are related to salt sensitivity, obesity, or RAS regulation are expected to prevent obesity and obesity-related hypertension. PMID:26927805

A casein diet added isoflavone-enriched soy protein favorably affects biomarkers of steatohepatitis in obese Zucker rats.

PubMed

Gudbrandsen, Oddrun Anita; Wergedahl, Hege; Berge, Rolf Kristian

2009-05-01

Dietary supplementation of a soy protein enriched with isoflavones (HDI) has been shown to improve fatty liver in obese rats. The main objective of this study was to investigate whether HDI would influence the inflammatory status in livers of obese rats with fatty liver. Male obese Zucker fa/fa rats were fed casein (controls) or casein supplemented with HDI (containing 4.00 g of genistein and 4.50 g of daidzein per kilogram of diet) for 6 wk. The HDI-fed rats had a markedly lower hepatic concentration of triacylglycerol when compared with controls. The decreased aspartate transaminase/alanine transaminase ratio in plasma, together with lower circulating levels of alkaline phosphatase and bile acids after HDI feeding, implied an improved hepatitis. This was supported by decreased plasma and hepatic mRNA levels of tumor necrosis factor-alpha, lower plasma levels of interleukin-1beta and monocyte chemoattractant protein-1, and an increased anti-inflammatory fatty acid index in plasma. HDI also seemed to protect the rats from oxidative damage, because the level of lipid peroxides in triacylglycerol-rich lipoproteins after in vitro copper oxidation was lower for HDI-fed rats when compared with controls. These results show that isoflavone-enriched soy protein favorably affects biomarkers of hepatic inflammation in obese Zucker fa/fa rats with fatty liver. Thus, dietary soy proteins enriched in isoflavones may be a promising agent to improve steatohepatitis in patients.

Physical health-related quality of life in relation to metabolic health and obesity among men and women in Germany.

PubMed

Truthmann, Julia; Mensink, Gert B M; Bosy-Westphal, Anja; Hapke, Ulfert; Scheidt-Nave, Christa; Schienkiewitz, Anja

2017-06-10

This study examined sex-specific differences in physical health-related quality of life (HRQoL) across subgroups of metabolic health and obesity. We specifically asked whether (1) obesity is related to lower HRQoL independent of metabolic health status and potential confounders, and (2) whether associations are similar in men and women. We used cross-sectional data from the German Health Interview and Examination Survey 2008-11. Physical HRQoL was measured using the Short Form-36 version 2 physical component summary (PCS) score. Based on harmonized ATPIII criteria for the definition of the metabolic health and a body mass index ≥ 30 kg/m 2 to define obesity, individuals were classified as metabolically healthy non-obese (MHNO), metabolically unhealthy non-obese (MUNO), metabolically healthy obese (MHO), and metabolically unhealthy obese (MUO). Sex-specific analyses including multivariable linear regression analyses were based on PCS as the dependent variable, metabolic health and obesity category as the independent variable with three categories and MHNO as the reference, and age, education, lifestyle and comorbidities as confounders. This study included 6860 participants (3298 men, 3562 women). Compared to MHNO, all other metabolic health and obesity categories had significantly lower PCS in both sexes. As reflected by the beta coefficients [95% confidence interval] from bivariable linear regression models, a significant inverse association with PCS was strongest for MUO (men: -7.0 [-8.2; -5.8]; women: -9.0 [-10.2; -7.9]), intermediate for MUNO (men: -4.2 [-5.3; -3.1]; women: -5.6 [-6.8; -4.4]) and least pronounced for MHO (men: -2.2 [-3.6; -0.8]; women -3.9 [-5.4; -2.5]). Differences in relation to MHNO remained statistically significant for all groups after adjusting for confounders, but decreased in particular for MUNO (men:-1.3 [-2.3; -0.3]; women: -1.5 [-2.7; -0.3]. Obesity was significantly related to lower physical HRQoL, independent of metabolic

C1q/TNF-related Protein 4 (CTRP4) Is a Unique Secreted Protein with Two Tandem C1q Domains That Functions in the Hypothalamus to Modulate Food Intake and Body Weight*

PubMed Central

Byerly, Mardi S.; Petersen, Pia S.; Ramamurthy, Santosh; Seldin, Marcus M.; Lei, Xia; Provost, Elayne; Wei, Zhikui; Ronnett, Gabriele V.; Wong, G. William

2014-01-01

CTRP4 is a unique member of the C1q family, possessing two tandem globular C1q domains. Its physiological function is poorly defined. Here, we show that CTRP4 is an evolutionarily conserved, ∼34-kDa secretory protein expressed in the brain. In human, mouse, and zebrafish brain, CTRP4 expression begins early in development and is widespread in the central nervous system. Neurons, but not astrocytes, express and secrete CTRP4, and secreted proteins form higher-order oligomeric complexes. CTRP4 is also produced by peripheral tissues and circulates in blood. Its serum levels are increased in leptin-deficient obese (ob/ob) mice. Functional studies suggest that CTRP4 acts centrally to modulate energy metabolism. Refeeding following an overnight fast induced the expression of CTRP4 in the hypothalamus. Central administration of recombinant protein suppressed food intake and altered the whole-body energy balance in both chow-fed and high-fat diet-fed mice. Suppression of food intake by CTRP4 is correlated with a decreased expression of orexigenic neuropeptide (Npy and Agrp) genes in the hypothalamus. These results establish CTRP4 as a novel nutrient-responsive central regulator of food intake and energy balance. PMID:24366864

Hypocaloric, high-protein nutrition therapy in older vs younger critically ill patients with obesity.

PubMed

Dickerson, Roland N; Medling, Theresa L; Smith, Ashley C; Maish, George O; Croce, Martin A; Minard, Gayle; Brown, Rex O

2013-01-01

Older patients require more protein than younger patients to achieve anabolism, but age-associated renal dysfunction may limit the amount of protein that can be safely provided. This study examined whether older, critically ill trauma patients with obesity can safely achieve nitrogen equilibrium and have positive clinical outcomes similar to younger obese patients during hypocaloric, high-protein nutrition therapy. Adult patients with traumatic injury and obesity (body mass index [BMI] >30 kg/m(2)), admitted to the Presley Trauma Center from January 2009 to April 2011, were evaluated. Patients were targeted to receive hypocaloric, high-protein nutrition therapy (<25 kcal/kg ideal body weight [IBW]/d and >2 g/kg IBW/d of protein) for >10 days. Patients were stratified as older (≥60 years) or younger (18-59 years). Seventy-four patients (33 older, 41 younger) were studied. Older and younger patients were similar in BMI and injury severity. When given isonitrogenous regimens (2.3 ± 0.2 g/kg IBW/d), nitrogen balance was similar between older and younger patients (-3.2 ± 5.7 g/d vs -4.9 ± 9.0 g/d; P = .363). Older patients experienced a greater mean serum urea nitrogen concentration than younger patients (30 ± 14 mg/dL vs 20 ± 9 mg/dL; P = .001) during nutrition therapy. Clinical outcomes were not different between groups. Older critically ill trauma patients exhibited an equivalent net protein response as younger patients during hypocaloric, high-protein nutrition therapy. Older patients are at greater risk for developing azotemia. Close monitoring is warranted.

Leptin and leptin receptor-related monogenic obesity.

PubMed

Dubern, Beatrice; Clement, Karine

2012-10-01

The studies based on candidate genes and encoded proteins known to cause severe obesity in rodents, have shown that these genes also contribute to human early-onset obesity especially for those involved in the leptin pathway: the leptin (LEP) and leptin receptor (LEPR) genes. Since 1997, less than 20 individuals carrying a LEP gene mutation have been identified. Patients are mostly characterized by severe early-onset obesity with severe hyperphagia and associated phenotype such hypogonadotrophic hypogonadism, high rate of infection associated with a deficiency in T cell and abnormalities of sympathetic nerve function. Therapeutic option (subcutaneous daily injection of leptin) is available for patients with LEP deficiency. It results in weight loss, mainly of fat mass, with a major effect on reducing food intake and on other dysfunctions including immunity and induction of puberty even in adults. In LEPR deficient subjects, phenotypic similarities with the LEP-deficient subjects were noticed, especially the exhibited rapid weight gain in the first few months of life, with severe hyperphagia and the endocrine abnormalities (hypogonadotrophic hypogonadism, insufficient somatotrophic or thyreotropic secretion). Leptin treatment is useless in the LEPR deficient subjects. Factors that could possibly bypass normal leptin delivery systems are being developed but are not yet currently available for the treatment of these patients. Measurement of circulating leptin may help for the diagnosis of such obesity: it is undetectable in LEP mutation carriers or extremely elevated in LEPR mutation carriers. Thus, LEPR gene screening might be also considered in subjects with the association of severe obesity with endocrine dysfunctions such as hypogonadism and with leptin related to corpulence level. Copyright © 2012 Elsevier Masson SAS. All rights reserved.

Exogenous fatty acid binding protein 4 promotes human prostate cancer cell progression.

PubMed

Uehara, Hisanori; Takahashi, Tetsuyuki; Oha, Mina; Ogawa, Hirohisa; Izumi, Keisuke

2014-12-01

Epidemiologic studies have found that obesity is associated with malignant grade and mortality in prostate cancer. Several adipokines have been implicated as putative mediating factors between obesity and prostate cancer. Fatty acid binding protein 4 (FABP4), a member of the cytoplasmic fatty acid binding protein multigene family, was recently identified as a novel adipokine. Although FABP4 is released from adipocytes and mean circulating concentrations of FABP4 are linked with obesity, effects of exogenous FABP4 on prostate cancer progression are unclear. In this study, we examined the effects of exogenous FABP4 on human prostate cancer cell progression. FABP4 treatment promoted serum-induced prostate cancer cell invasion in vitro. Furthermore, oleic acid promoted prostate cancer cell invasion only if FABP4 was present in the medium. These promoting effects were reduced by FABP4 inhibitor, which inhibits FABP4 binding to fatty acids. Immunostaining for FABP4 showed that exogenous FABP4 was taken up into DU145 cells in three-dimensional culture. In mice, treatment with FABP4 inhibitor reduced the subcutaneous growth and lung metastasis of prostate cancer cells. Immunohistochemical analysis showed that the number of apoptotic cells, positive for cleaved caspase-3 and cleaved PARP, was increased in subcutaneous tumors of FABP4 inhibitor-treated mice, as compared with control mice. These results suggest that exogenous FABP4 might promote human prostate cancer cell progression by binding with fatty acids. Additionally, exogenous FABP4 activated the PI3K/Akt pathway, independently of binding to fatty acids. Thus, FABP4 might be a key molecule to understand the mechanisms underlying the obesity-prostate cancer progression link. © 2014 UICC.

The use of measures of obesity in childhood for predicting obesity and the development of obesity-related diseases in adulthood: a systematic review and meta-analysis.

PubMed

Simmonds, Mark; Burch, Jane; Llewellyn, Alexis; Griffiths, Claire; Yang, Huiqin; Owen, Christopher; Duffy, Steven; Woolacott, Nerys

2015-06-01

It is uncertain which simple measures of childhood obesity are best for predicting future obesity-related health problems and the persistence of obesity into adolescence and adulthood. To investigate the ability of simple measures, such as body mass index (BMI), to predict the persistence of obesity from childhood into adulthood and to predict obesity-related adult morbidities. To investigate how accurately simple measures diagnose obesity in children, and how acceptable these measures are to children, carers and health professionals. Multiple sources including MEDLINE, EMBASE and The Cochrane Library were searched from 2008 to 2013. Systematic reviews and a meta-analysis were carried out of large cohort studies on the association between childhood obesity and adult obesity; the association between childhood obesity and obesity-related morbidities in adulthood; and the diagnostic accuracy of simple childhood obesity measures. Study quality was assessed using Quality Assessment of Diagnostic Accuracy Studies-2 (QUADAS-2) and a modified version of the Quality in Prognosis Studies (QUIPS) tool. A systematic review and an elicitation exercise were conducted on the acceptability of the simple measures. Thirty-seven studies (22 cohorts) were included in the review of prediction of adult morbidities. Twenty-three studies (16 cohorts) were included in the tracking review. All studies included BMI. There were very few studies of other measures. There was a strong positive association between high childhood BMI and adult obesity [odds ratio 5.21, 95% confidence interval (CI) 4.50 to 6.02]. A positive association was found between high childhood BMI and adult coronary heart disease, diabetes and a range of cancers, but not stroke or breast cancer. The predictive accuracy of childhood BMI to predict any adult morbidity was very low, with most morbidities occurring in adults who were of healthy weight in childhood. Predictive accuracy of childhood obesity was moderate for

Diet compounds, glycemic index and obesity-related cardiac effects.

PubMed

Diniz, Yeda S; Burneiko, Regina M; Seiva, Fabio R F; Almeida, Flávia Q A; Galhardi, Cristiano Machado; Filho, José Luiz V B Novelli; Mani, Fernanda; Novelli, Ethel L B

2008-02-20

Diet compounds may influence obesity-related cardiac oxidative stress and metabolic sifting. Carbohydrate-rich diet may be disadvantageous from fat-rich diet to cardiac tissue and glycemic index rather than lipid profile may predict the obesity-related cardiac effects. Male Wistar rats were divided into three groups (n=8/group): (C) receiving standard chow (3.0 kcal/g); (CRD) receiving carbohydrate-rich diet (4.0 kcal/g), and (FRD) receiving fat-rich diet (4.0 kcal/g). Rats were sacrificed after the oral glucose tolerance test (OGTT) at 60 days of dietary treatments. Lipid profile and oxidative stress parameters were determined in serum. Myocardial samples were used to determine oxidative stress, metabolic enzymes, glycogen and triacylglycerol. FRD rats showed higher final body weight and body mass index than CRD and C. Serum cholesterol and low-density lipoprotein were higher in FRD than in CRD, while triacylglycerol and oxidized low-density lipoprotein cholesterol were higher in CRD than in FRD. CRD rats had the highest myocardial lipid hydroperoxide and diminished superoxide dismutase and catalase activities. Myocardial glycogen was lower and triacylglycerol was higher in CRD than in C and FRD rats. Although FRD rats had depressed myocardial-reducing power, no significant changes were observed in myocardial energy metabolism. Myocardial beta-hydroxyacyl coenzyme-A dehydrogenase and citrate synthase, as well as the enhanced lactate dehydrogenase/citrate synthase ratio indicated that fatty acid degradation was decreased in CRD rats. Glycemic index was positively correlated with obesity-related cardiac effects. Isoenergetic carbohydrate-rich and fat-rich diets induced different degree of obesity and differently affected lipid profile. Carbohydrate-rich diet was deleterious relative to fat-rich diet in the heart enhancing lipoperoxidation and shifting the metabolic pathway for energy production. Glycemic index rather than dyslipidemic profile may predict the obesity

Obesity-related metabolite profiles of black women spanning the epidemiologic transition

PubMed Central

Plange-Rhule, Jacob; Lambert, Estelle V.; Cao, Guichan; Cooper, Richard S.; Layden, Brian T.; Scholten, Denise; Olsson, Tommy; Luke, Amy; Goedecke, Julia H.

2016-01-01

In developed countries, specific metabolites have been associated with obesity and metabolic diseases, e.g. type 2 diabetes. It is unknown whether a similar profile persists across populations of African-origin, at increased risk for obesity and related diseases. In a cross-sectional study of normal-weight and obese black women (33.3 ± 6.3 years) from the US (N = 69, 65 % obese), South Africa (SA, N = 97, 49 % obese) and Ghana (N = 82, 33 % obese) serum metabolite profiles were characterized via gas chromatography-time of flight/mass spectrometry. In US and SA women, BMI correlated with branched-chain and aromatic amino acids, as well as dopamine and aminoadipic acid. The relationship between BMI and lipid metabolites differed by site; BMI correlated positively with palmitoleic acid (16:1) in the US; negatively with stearic acid (18:0) in SA, and positively with arachidonic acid (20:4) in Ghana. BMI was also positively associated with sugar-related metabolites in the US; i.e. uric acid, and mannitol, and with glucosamine, glucoronic acid and mannitol in SA. While we identified a common amino acid metabolite profile associated with obesity in black women from the US and SA, we also found site-specific obesity-related metabolites suggesting that the local environment is a key moderator of obesity. PMID:27346989

The utility of childhood and adolescent obesity assessment in relation to adult health.

PubMed

Goldhaber-Fiebert, Jeremy D; Rubinfeld, Rachel E; Bhattacharya, Jay; Robinson, Thomas N; Wise, Paul H

2013-02-01

High childhood obesity prevalence has raised concerns about future adult health, generating calls for obesity screening of young children. To estimate how well childhood obesity predicts adult obesity and to forecast obesity-related health of future US adults. Longitudinal statistical analyses; microsimulations combining multiple data sets. National Longitudinal Survey of Youth, Population Study of Income Dynamics, and National Health and Nutrition Evaluation Surveys. The authors estimated test characteristics and predictive values of childhood body mass index to identify 2-, 5-, 10-, and 15 year-olds who will become obese adults. The authors constructed models relating childhood body mass index to obesity-related diseases through middle age stratified by sex and race. Twelve percent of 18-year-olds were obese. While screening at age 5 would miss 50% of those who become obese adults, screening at age 15 would miss 9%. The predictive value of obesity screening below age 10 was low even when maternal obesity was included as a predictor. Obesity at age 5 was a substantially worse predictor of health in middle age than was obesity at age 15. For example, the relative risk of developing diabetes as adults for obese white male 15-year-olds was 4.5 versus otherwise similar nonobese 15-year-olds. For obese 5-year-olds, the relative risk was 1.6. Main results do not include Hispanics due to sample size. Past relationships between childhood and adult obesity and health may change in the future. Early childhood obesity assessment adds limited information to later childhood assessment. Targeted later childhood approaches or universal strategies to prevent unhealthy weight gain should be considered.

Association of canine obesity with reduced serum levels of C-reactive protein.

PubMed

Veiga, Angela P M; Price, Christopher A; de Oliveira, Simone T; Dos Santos, Andréa P; Campos, Rómulo; Barbosa, Patricia R; González, Félix H D

2008-03-01

The prevalence of obesity is increasing in dogs as well as in humans. C-reactive protein (CRP) is an important tool for the detection of inflammation and/or early tissue damage and is linked to obesity in humans. The objective of the present study was to determine if serum CRP levels are altered in obese dogs. Fifteen lean (control group) and 16 overweight (obese group) dogs were examined. Blood samples were collected under fasted conditions for serum determination of CRP, glucose, insulin, cholesterol, triglyceride, and fructosamine. Results indicated that obese dogs were insulin resistant because serum insulin and insulin/glucose ratios were higher than in lean dogs (P < or = 0.05). Serum CRP concentrations were lower in obese dogs than in controls (P < or = 0.001). C-reactive protein was negatively correlated with insulin/glucose ratio (R = -0.42) and cholesterol (R = -0.39; P < or = 0.05). Furthermore, levels of cholesterol, triglycerides, and fructosamine were increased in the obese group compared with the control group. Based on these results, it can be postulated that CRP production is inhibited by obesity and insulin resistance in dogs.

Uncoupling of Obesity from Insulin Resistance Through a Targeted Mutation in aP2, the Adipocyte Fatty Acid Binding Protein

NASA Astrophysics Data System (ADS)

Hotamisligil, Gokhan S.; Johnson, Randall S.; Distel, Robert J.; Ellis, Ramsey; Papaioannou, Virginia E.; Spiegelman, Bruce M.

1996-11-01

Fatty acid binding proteins (FABPs) are small cytoplasmic proteins that are expressed in a highly tissue-specific manner and bind to fatty acids such as oleic and retinoic acid. Mice with a null mutation in aP2, the gene encoding the adipocyte FABP, were developmentally and metabolically normal. The aP2-deficient mice developed dietary obesity but, unlike control mice, they did not develop insulin resistance or diabetes. Also unlike their obese wild-type counterparts, obese aP2-/- animals failed to express in adipose tissue tumor necrosis factor-α (TNF-α), a molecule implicated in obesity-related insulin resistance. These results indicate that aP2 is central to the pathway that links obesity to insulin resistance, possibly by linking fatty acid metabolism to expression of TNF-α.

Associations of variants in FTO and near MC4R with obesity traits in South Asian Indians.

PubMed

Vasan, Senthil K; Fall, Tove; Neville, Matthew J; Antonisamy, Belavendra; Fall, Caroline H; Geethanjali, Finney S; Gu, Harvest F; Raghupathy, Palany; Samuel, Prasanna; Thomas, Nihal; Brismar, Kerstin; Ingelsson, Erik; Karpe, Fredrik

2012-11-01

Recent genome-wide association studies show that loci in FTO and melanocortin 4 receptor (MC4R) associate with obesity-related traits. Outside Western populations the associations between these variants have not always been consistent and in Indians it has been suggested that FTO relates to diabetes without an obvious intermediary obesity phenotype. We investigated the association between genetic variants in FTO (rs9939609) and near MC4R (rs17782313) with obesity- and type 2 diabetes (T2DM)-related traits in a longitudinal birth cohort of 2,151 healthy individuals from the Vellore birth cohort in South India. The FTO locus displayed significant associations with several conventional obesity-related anthropometric traits. The per allele increase is about 1% for BMI, waist circumference (WC), hip circumference (HC), and waist-hip ratio. Consistent associations were observed for adipose tissue-specific measurements such as skinfold thickness reinforcing the association with obesity-related traits. Obesity associations for the MC4R locus were weak or nonsignificant but a signal for height (P < 0.001) was observed. The effect on obesity-related traits for FTO was seen in adulthood, but not at younger ages. The loci also showed nominal associations with increased blood glucose but these associations were lost on BMI adjustment. The effect of FTO on obesity-related traits was driven by an urban environmental influence. We conclude that rs9939609 variant in the FTO locus is associated with measures of adiposity and metabolic consequences in South Indians with an enhanced effect associated with urban living. The detection of these associations in Indians is challenging because conventional anthropometric obesity measures work poorly in the Indian "thin-fat" phenotype.

Relationship between Acute Phase Proteins and Serum Fatty Acid Composition in Morbidly Obese Patients

PubMed Central

Fernandes, Ricardo; Beserra, Bruna Teles Soares; Cunha, Raphael Salles Granato; Hillesheim, Elaine; Camargo, Carolina de Quadros; Pequito, Danielle Cristina Tonello; de Castro, Isabela Coelho; Fernandes, Luiz Cláudio; Nunes, Everson Araújo; Trindade, Erasmo Benício Santos de Moraes

2013-01-01

Background. Obesity is considered a low-grade inflammatory state and has been associated with increased acute phase proteins as well as changes in serum fatty acids. Few studies have assessed associations between acute phase proteins and serum fatty acids in morbidly obese patients. Objective. To investigate the relationship between acute phase proteins (C-Reactive Protein, Orosomucoid, and Albumin) and serum fatty acids in morbidly obese patients. Methods. Twenty-two morbidly obese patients were enrolled in this study. Biochemical and clinical data were obtained before bariatric surgery, and fatty acids measured in preoperative serum. Results. Orosomucoid was negatively correlated with lauric acid (P = 0.027) and eicosapentaenoic acid (EPA) (P = 0.037) and positively with arachidonic acid (AA) (P = 0.035), AA/EPA ratio (P = 0.005), and n-6/n-3 polyunsaturated fatty acids ratio (P = 0.035). C-Reactive Protein (CRP) was negatively correlated with lauric acid (P = 0.048), and both CRP and CRP/Albumin ratio were negatively correlated with margaric acid (P = 0.010, P = 0.008, resp.). Albumin was positively correlated with EPA (P = 0.027) and margaric acid (P = 0.008). Other correlations were not statistically significant. Conclusion. Our findings suggest that serum fatty acids are linked to acute phase proteins in morbidly obese patients. PMID:24167354

Renoprotective mechanisms of soy protein intake in the obese Zucker rat

PubMed Central

Trujillo, Joyce; Cruz, Cristino; Tovar, Armando; Vaidya, Vishal; Zambrano, Elena; Bonventre, Joseph V.; Gamba, Gerardo; Torres, Nimbe; Bobadilla, Norma A.

2008-01-01

We previously showed that long-term consumption of a soy protein diet (SoyP) reduces renal damage in obese Zucker (ObeseZ) rats by restoring urinary NO2 and NO3 excretion (UNO2/NO3V), suggesting that nitric oxide (NO) deficiency may contribute to the renal progression observed in this model. In addition, there is compelling evidence that hyperleptinemia produced deleterious effects on the kidney through its interaction with the short leptin receptor (ObRa). This study was designed to evaluate the contribution of the NO/endothelial NO synthase (eNOS) system, renal oxidative stress, and ObRa expression to the renoprotection conferred by the consumption of a SoyP in ObeseZ rats. Ten lean and ten male ObeseZ rats were included. One-half of each group was fed with a 20% SoyP and the other half with a 20% casein protein diet (CasP) over the course of 160 days. eNOS protein levels and phosphorylation, renal lipoperoxidation (rLPO), and antioxidant enzyme activity were assessed. In addition, renal ObRa, TGF-β, and kidney injury molecule (Kim-1) mRNA levels, as well as urinary Kim-1 levels, were measured. Renal injury observed in ObeseZ rats fed with CasP was not associated with changes in eNOS expression or phosphorylation. However, this group did present with increased rLPO, reduced catalase activity, and upregulation of ObRa, TGF-β1, and Kim-1. In contrast, ObeseZ rats fed with a SoyP exhibited a reduction in NOS-Thr495 phosphorylation and rLPO, as well as an enhanced catalase activity. These findings were associated with a significant reduction of ObRa, TGF-β1, and Kim-1 mRNA levels and urinary Kim-1 protein. Our results show that renoprotection by SoyP in ObeseZ rats is in part mediated by increased NO availability secondary to a reduction in eNOS-T495 phosphorylation and oxidative stress, together with a significant reduction in ObRa and TGF-β expression. PMID:18815216

The Effect of Casein Protein Prior to Sleep on Fat Metabolism in Obese Men

PubMed Central

Kinsey, Amber W.; Cappadona, Stacy R.; Panton, Lynn B.; Allman, Brittany R.; Contreras, Robert J.; Hickner, Robert C.; Ormsbee, Michael J.

2016-01-01

We have previously shown that ingesting protein at night before sleep is either beneficial or non-detrimental to metabolism, health, and body composition in obese women. However, the overnight protein-induced lipolytic actions and mechanism for improved metabolism and body composition have not been fully established. Therefore, in a crossover design, twelve obese men (age, 27.0 ± 2.2 years) were randomly assigned to ingest (within 30 min of sleep) casein protein (CAS, 120 kcal) or a non-nutritive placebo (PLA) before going to sleep. Markers of fat metabolism (lipolysis, substrate utilization, growth hormone), insulin, glucose, resting energy expenditure (REE), and appetite (questionnaire and ghrelin) were measured. During sleep and the next morning, interstitial glycerol from the subcutaneous abdominal adipose tissue (SCAAT) was measured using microdialysis. There were no differences in SCAAT glycerol (overnight: CAS, 177.4 ± 26.7; PLA, 183.8 ± 20.2 μmol/L; morning: CAS, 171.6 ± 19.1; PLA, 161.5 ± 18.6 μmol/L), substrate utilization, REE, or any blood markers between CAS and PLA. Desire to eat was greater for CAS compared to baseline (p = 0.03), but not different from PLA (baseline: 39 ± 6, CAS: 62 ± 8, PLA: 55 ± 5 mm). CAS consumption before sleep did not affect fat or glucose metabolism, REE, or suppress appetite in hyperinsulemic obese men. CAS may be consumed before sleep without impeding overnight or morning fat metabolism in young, obese men. PMID:27472361

Obesity-related genetic variants, human pigmentation, and risk of melanoma

PubMed Central

Li, Xin; Liang, Liming; Zhang, Mingfeng; Song, Fengju; Nan, Hongmei; Wang, Li-E; Wei, Qingyi; Lee, Jeffrey E.; Amos, Christopher I.; Qureshi, Abrar A.; Han, Jiali

2013-01-01

Previous biological studies showed evidence of a genetic link between obesity and pigmentation in both animal models and humans. Our study investigated the individual and joint associations between obesity-related single nucleotide polymorphisms (SNPs) and both human pigmentation and risk of melanoma. Eight obesity-related SNPs in the FTO, MAP2K5, NEGR1, FLJ35779, ETV5, CADM2, and NUDT3 genes were nominally significantly associated with hair color among 5,876 individuals of European ancestry. The genetic score combining 35 independent obesity-risk loci was significantly associated with darker hair color (beta-coefficient per ten alleles=0.12, P-value=4 10−5). However, single SNPs or genetic scores showed non-significant association with tanning ability. We further examined the SNPs at the FTO locus for their associations with pigmentation and risk of melanoma. Among the 783 SNPs in the FTO gene with imputation R-square quality metric >0.8 using the 1000 genome data set, ten and three independent SNPs were significantly associated with hair color and tanning ability respectively. Moreover, five independent FTO SNPs showed nominally significant association with risk of melanoma in 1,804 cases and 1,026 controls. But none of them was associated with obesity or in linkage disequilibrium with obesity-related variants. FTO locus may confer variation in human pigmentation and risk of melanoma, which may be independent of its effect on obesity. PMID:23539184

High-protein diet selectively reduces fat mass and improves glucose tolerance in Western-type diet-induced obese rats

PubMed Central

Stengel, Andreas; Goebel-Stengel, Miriam; Wang, Lixin; Hu, Eugenia; Karasawa, Hiroshi; Pisegna, Joseph R.

2013-01-01

Obesity is an increasing health problem. Because drug treatments are limited, diets remain popular. High-protein diets (HPD) reduce body weight (BW), although the mechanisms are unclear. We investigated physiological mechanisms altered by switching diet induced obesity (DIO) rats from Western-type diet (WTD) to HPD. Male rats were fed standard (SD) or WTD (45% calories from fat). After developing DIO (50% of rats), they were switched to SD (15% calories from protein) or HPD (52% calories from protein) for up to 4 weeks. Food intake (FI), BW, body composition, glucose tolerance, insulin sensitivity, and intestinal hormone plasma levels were monitored. Rats fed WTD showed an increased FI and had a 25% greater BW gain after 9 wk compared with SD (P < 0.05). Diet-induced obese rats switched from WTD to HPD reduced daily FI by 30% on day 1, which lasted to day 9 (−9%) and decreased BW during the 2-wk period compared with SD/SD (P < 0.05). During these 2 wk, WTD/HPD rats lost 72% more fat mass than WTD/SD (P < 0.05), whereas lean mass was unaltered. WTD/HPD rats had lower blood glucose than WTD/SD at 30 min postglucose gavage (P < 0.05). The increase of pancreatic polypeptide and peptide YY during the 2-h dark-phase feeding was higher in WTD/HPD compared with WTD/SD (P < 0.05). These data indicate that HPD reduces BW in WTD rats, which may be related to decreased FI and the selective reduction of fat mass accompanied by improved glucose tolerance, suggesting relevant benefits of HPD in the treatment of obesity. PMID:23883680

Novel thioredoxin-related transmembrane protein TMX4 has reductase activity.

PubMed

Sugiura, Yoshimi; Araki, Kazutaka; Iemura, Shun-ichiro; Natsume, Tohru; Hoseki, Jun; Nagata, Kazuhiro

2010-03-05

In the endoplasmic reticulum (ER), a number of thioredoxin (Trx) superfamily proteins are present to enable correct disulfide bond formation of secretory and membrane proteins via Trx-like domains. Here, we identified a novel transmembrane Trx-like protein 4 (TMX4), in the ER of mammalian cells. TMX4, a type I transmembrane protein, was localized to the ER and possessed a Trx-like domain that faced the ER lumen. A maleimide alkylation assay showed that a catalytic CXXC motif in the TMX4 Trx-like domain underwent changes in its redox state depending on cellular redox conditions, and, in the normal state, most of the endogenous TMX4 existed in the oxidized form. Using a purified recombinant protein containing the Trx-like domain of TMX4 (TMX4-Trx), we confirmed that this domain had reductase activity in vitro. The redox potential of this domain (-171.5 mV; 30 degrees C at pH 7.0) indicated that TMX4 could work as a reductase in the environment of the ER. TMX4 had no effect on the acceleration of ER-associated degradation. Because TMX4 interacted with calnexin and ERp57 by co-immunoprecipitation assay, the role of TMX4 may be to enable protein folding in cooperation with these proteins consisting of folding complex in the ER.

Gender-Related Differential Effects of Obesity on Health-Related Quality of Life via Obesity-Related Comorbidities: A Mediation Analysis of a French Nationwide Survey.

PubMed

Audureau, Etienne; Pouchot, Jacques; Coste, Joël

2016-05-01

Negative effects of obesity on health-related quality of life (HRQoL) have been reported, especially in women, but the relative contribution of cardiometabolic and other obesity-related comorbidities to such effects remains unclear. Our objective was to model the association by sex between body mass index and HRQoL and to precisely quantify the indirect effects mediated by obesity-related comorbidities. Data were drawn from the latest French Decennial Health Survey, a nationwide cross-sectional study conducted in 2003 (21 239 adults aged 25-64 years analyzed). HRQoL was measured by the 36-item short-form health survey questionnaire. A mediation analysis based on the counterfactual framework was performed to quantify the proportion of obesity effects on HRQoL mediated by related comorbidities, including cardiometabolic risk factors (diabetes mellitus, hypertension, dyslipidemia) and diseases (ischemic heart disease, cerebrovascular, and peripheral vascular disease), musculoskeletal disorders, and asthma. After multiple linear regression, inverse associations were found between increasing body mass index category and physically oriented and most mentally oriented 36-item short-form health survey dimensions, with evidence of greater effects in women. Mediation analysis revealed that obesity effects were significantly mediated by several comorbidities, more apparently in men (eg, proportion of obesity class II total effect mediated via cardiometabolic factors: general health 27.0% [men] versus 13.6% [women]; proportion of obesity class II total effect mediated via total count of comorbidities: physical functioning 17.8% [men] versus 7.7% [women] and general health 37.1% [men] versus 20.3% [women]). Women have a greater overall impact of obesity on HRQoL, but with proportionally lower effects mediated by cardiometabolic and other obesity-related conditions, suggesting the possible role of other specific psychosocial processes. © 2016 American Heart Association, Inc.

Association of Nuclear Factor-Erythroid 2-Related Factor 2, Thioredoxin Interacting Protein, and Heme Oxygenase-1 Gene Polymorphisms with Diabetes and Obesity in Mexican Patients.

PubMed

Jiménez-Osorio, Angélica Saraí; González-Reyes, Susana; García-Niño, Wylly Ramsés; Moreno-Macías, Hortensia; Rodríguez-Arellano, Martha Eunice; Vargas-Alarcón, Gilberto; Zúñiga, Joaquín; Barquera, Rodrigo; Pedraza-Chaverri, José

2016-01-01

The nuclear factor-erythroid 2- (NF-E2-) related factor 2 (Nrf2) is abated and its ability to reduce oxidative stress is impaired in type 2 diabetes and obesity. Thus, the aim of this study was to explore if polymorphisms in Nrf2 and target genes are associated with diabetes and obesity in Mexican mestizo subjects. The rs1800566 of quinone oxidoreductase 1 (NQO1) gene, rs7211 of thioredoxin interacting protein (TXNIP) gene, rs2071749 of heme oxygenase-1 (HMOX1) gene, and the rs6721961 and the rs2364723 from Nrf2 gene were genotyped in 627 diabetic subjects and 1020 controls. The results showed that the rs7211 polymorphism is a protective factor against obesity in nondiabetic subjects (CC + CT versus TT, OR = 0.40, P = 0.005) and in women (CC versus CT + TT, OR = 0.7, P = 0.016). TT carriers had lower high-density lipoprotein cholesterol levels and lower body mass index. The rs2071749 was positively associated with obesity (AA versus AG + GG, OR = 1.25, P = 0.026). Finally, the rs6721961 was negatively associated with diabetes in men (CC versus CA + AA, OR = 0.62, P = 0.003). AA carriers showed lower glucose concentrations. No association was found for rs1800566 and rs2364723 polymorphisms. In conclusion, the presence of Nrf2 and related genes polymorphisms are associated with diabetes and obesity in Mexican patients.

Nutritional Status of Maintenance Dialysis Patients: Low Lean Body Mass Index and Obesity Are Common, Protein-Energy Wasting Is Uncommon.

PubMed

Koefoed, Mette; Kromann, Charles Boy; Juliussen, Sophie Ryberg; Hvidtfeldt, Danni; Ekelund, Bo; Frandsen, Niels Erik; Marckmann, Peter

2016-01-01

Maintenance dialysis patients are at increased risk of abnormal nutritional status due to numerous causative factors, both nutritional and non-nutritional. The present study assessed the current prevalence of protein-energy wasting, low lean body mass index and obesity in maintenance dialysis patients, and compared different methods of nutritional assessment. In a cross-sectional study conducted in 2014 at Roskilde Hospital, Denmark, we performed anthropometry (body weight, skinfolds, mid-arm, waist, and hip circumferences), and determined plasma albumin and normalized protein catabolic rate in order to assess the prevalence of protein-energy wasting, low lean body mass index and obesity in these patients. Seventy-nine eligible maintenance dialysis patients participated. The prevalence of protein-energy wasted patients was 4% (95% CI: 2-12) as assessed by the coexistence of low lean body mass index and low fat mass index. Low lean body mass index was seen in 32% (95% CI: 22-44). Obesity prevalence as assessed from fat mass index was 43% (95% CI: 32-55). Coexistence of low lean body mass index and obesity was seen in 10% (95% CI: 5-19). The prevalence of protein-energy wasting and obesity varied considerably, depending on nutritional assessment methodology. Our data indicate that protein-energy wasting is uncommon, whereas low lean body mass index and obesity are frequent conditions among patients in maintenance dialysis. A focus on how to increase and preserve lean body mass in dialysis patients is suggested in the future. In order to clearly distinguish between shortage, sufficiency and abundance of protein and/or fat deposits in maintenance dialysis patients, we suggest the simple measurements of lean body mass index and fat mass index.

Inhibitory G proteins and their receptors: emerging therapeutic targets for obesity and diabetes

PubMed Central

Kimple, Michelle E; Neuman, Joshua C; Linnemann, Amelia K; Casey, Patrick J

2014-01-01

The worldwide prevalence of obesity is steadily increasing, nearly doubling between 1980 and 2008. Obesity is often associated with insulin resistance, a major risk factor for type 2 diabetes mellitus (T2DM): a costly chronic disease and serious public health problem. The underlying cause of T2DM is a failure of the beta cells of the pancreas to continue to produce enough insulin to counteract insulin resistance. Most current T2DM therapeutics do not prevent continued loss of insulin secretion capacity, and those that do have the potential to preserve beta cell mass and function are not effective in all patients. Therefore, developing new methods for preventing and treating obesity and T2DM is very timely and of great significance. There is now considerable literature demonstrating a link between inhibitory guanine nucleotide-binding protein (G protein) and G protein-coupled receptor (GPCR) signaling in insulin-responsive tissues and the pathogenesis of obesity and T2DM. These studies are suggesting new and emerging therapeutic targets for these conditions. In this review, we will discuss inhibitory G proteins and GPCRs that have primary actions in the beta cell and other peripheral sites as therapeutic targets for obesity and T2DM, improving satiety, insulin resistance and/or beta cell biology. PMID:24946790

Fatty acid binding protein 4 enhances prostate cancer progression by upregulating matrix metalloproteinases and stromal cell cytokine production

PubMed Central

Huang, Mingguo; Narita, Shintaro; Inoue, Takamitsu; Koizumi, Atsushi; Saito, Mitsuru; Tsuruta, Hiroshi; Numakura, Kazuyuki; Satoh, Shigeru; Nanjo, Hiroshi; Sasaki, Takehiko; Habuchi, Tomonori

2017-01-01

Fatty acid binding protein 4 (FABP4) is an abundant protein in adipocytes, and its production is influenced by high-fat diet (HFD) or obesity. The prostate stromal microenvironment induces proinflammatory cytokine production, which is key for the development and progression of prostate cancer (PCa). Here, we show that high FABP4 expression and its secretion by PCa cells directly stimulated PCa cell invasiveness by upregulating matrix metalloproteinases through phosphatidylinositol 3-kinase and mitogen-activated protein kinase signaling pathways. In addition, prostate stromal cells augmented PCa cell invasiveness by secreting interleukin-8 and -6 in response to FABP4. This was abrogated by the FABP4 specific inhibitor, BMS309403. Furthermore, a mouse xenograft experiment showed HFD enhanced PCa metastasis and invasiveness by the upregulation of FABP4 and interleukin-8. Clinically, the serum level of FABP4 was significantly associated with an aggressive type of PCa rather than obesity. Taken together, FABP4 may enhance PCa progression and invasiveness by upregulating matrix metalloproteinases and cytokine production in the PCa stromal microenvironment, especially under HFD or obesity. PMID:29340091

Obesity and Obese-related Chronic Low-grade Inflammation in Promotion of Colorectal Cancer Development.

PubMed

Pietrzyk, Lukasz; Torres, Anna; Maciejewski, Ryszard; Torres, Kamil

2015-01-01

Colorectal cancer (CRC) is a worldwide health problem, being the third most commonly detected cancer in males and the second in females. Rising CRC incidence trends are mainly regarded as a part of the rapid 'Westernization' of life-style and are associated with calorically excessive high-fat/low-fibre diet, consumption of refined products, lack of physical activity, and obesity. Most recent epidemiological and clinical investigations have consistently evidenced a significant relationship between obesity-driven inflammation in particular steps of colorectal cancer development, including initiation, promotion, progression, and metastasis. Inflammation in obesity occurs by several mechanisms. Roles of imbalanced metabolism (MetS), distinct immune cells, cytokines, and other immune mediators have been suggested in the inflammatory processes. Critical mechanisms are accounted to proinflammatory cytokines (e.g. IL-1, IL-6, IL-8) and tumor necrosis factor-α (TNF-α). These molecules are secreted by macrophages and are considered as major agents in the transition between acute and chronic inflammation and inflammation-related CRC. The second factor promoting the CRC development in obese individuals is altered adipokine concentrations (leptin and adiponectin). The role of leptin and adiponectin in cancer cell proliferation, invasion, and metastasis is attributable to the activation of several signal transduction pathways (JAK/STAT, mitogen-activated protein kinase (MAPK), phosphatidylinositol 3 kinase (PI3K), mTOR, and 5'AMPK signaling pathways) and multiple dysregulation (COX-2 downregulation, mRNA expression).

Sex differences in obesity related cancer incidence in relation to type 2 diabetes diagnosis (ZODIAC-49).

PubMed

Schrijnders, Dennis; Hendriks, Steven H; Kleefstra, Nanne; Vissers, Pauline A J; Johnson, Jeffrey A; de Bock, Geertruida H; Bilo, Henk J G; Landman, Gijs W D

2018-01-01

Diabetes and obesity seem to be partly overlapping risk factors for the development of obesity-related cancer (mainly breast, prostate and colorectal cancer) in patients with type 2 diabetes (T2DM). In the general population, women have a lower risk for obesity-related cancer compared to men. Previous studies involving cardiovascular disease have shown that T2DM eliminates a female advantage of lower CVD risk in the general population compared to men. It is unclear whether the same could be true for obesity-related cancer. This study aimed to this investigate obesity-related cancer incidence in women and men known with T2DM as compared to the Dutch general population. This study included 69,583 patients with T2DM selected from a prospective primary care cohort, which was linked to the Dutch National Cancer Registry to obtain cancer specific data. Obesity-related cancers included liver, kidney, colorectal, gallbladder, pancreas, ovarian, endometrial, advanced prostate cancer, post-menopausal breast cancer and oesophageal adenocarcinoma. Primary outcome was sex-stratified, age and year of cancer diagnosis adjusted standardized incidence ratios (SIRs) for three time periods: 5 years before, the year after diagnosis and the next 4 years after T2DM diagnosis. The Dutch general population was used as reference group. Women with T2DM were at an increased risk for obesity-related cancer compared to women in the general population already 5 years before diabetes diagnosis (SIR 1.77; 95%CI: 1.63-1.91). In both men and women, there was a peak in obesity-related cancer incidence following diabetes diagnosis (SIR: 1.38; 95%CI 1.11-1.64 and SIR: 2.21; 95%CI 1.94-2.30, respectively). From the second to the fifth year after diabetes diagnosis the obesity-related cancer incidence was higher in women compared to women in the general population (SIR: 2.12; 95%CI 1.94-2.30). Women with T2DM seem to have a substantially higher obesity-related cancer risk. As opposed to men, in women

Sex differences in obesity related cancer incidence in relation to type 2 diabetes diagnosis (ZODIAC-49)

PubMed Central

Hendriks, Steven H.; Kleefstra, Nanne; Vissers, Pauline A. J.; de Bock, Geertruida H.; Bilo, Henk J. G.; Landman, Gijs W. D.

2018-01-01

Background Diabetes and obesity seem to be partly overlapping risk factors for the development of obesity-related cancer (mainly breast, prostate and colorectal cancer) in patients with type 2 diabetes (T2DM). In the general population, women have a lower risk for obesity-related cancer compared to men. Previous studies involving cardiovascular disease have shown that T2DM eliminates a female advantage of lower CVD risk in the general population compared to men. It is unclear whether the same could be true for obesity-related cancer. This study aimed to this investigate obesity-related cancer incidence in women and men known with T2DM as compared to the Dutch general population. Methods This study included 69,583 patients with T2DM selected from a prospective primary care cohort, which was linked to the Dutch National Cancer Registry to obtain cancer specific data. Obesity-related cancers included liver, kidney, colorectal, gallbladder, pancreas, ovarian, endometrial, advanced prostate cancer, post-menopausal breast cancer and oesophageal adenocarcinoma. Primary outcome was sex-stratified, age and year of cancer diagnosis adjusted standardized incidence ratios (SIRs) for three time periods: 5 years before, the year after diagnosis and the next 4 years after T2DM diagnosis. The Dutch general population was used as reference group. Results Women with T2DM were at an increased risk for obesity-related cancer compared to women in the general population already 5 years before diabetes diagnosis (SIR 1.77; 95%CI: 1.63–1.91). In both men and women, there was a peak in obesity-related cancer incidence following diabetes diagnosis (SIR: 1.38; 95%CI 1.11–1.64 and SIR: 2.21; 95%CI 1.94–2.30, respectively). From the second to the fifth year after diabetes diagnosis the obesity-related cancer incidence was higher in women compared to women in the general population (SIR: 2.12; 95%CI 1.94–2.30). Conclusions Women with T2DM seem to have a substantially higher obesity-related

[Attitudes of dietitians in relation to obese individuals - an exploratory study].

PubMed

Cori, Giuliana da Costa; Petty, Maria Luiza Blanques; Alvarenga, Marle dos Santos

2015-02-01

The scope of this study was to assess attitudes of dietitians in relation to obesity; involving beliefs about the characteristics attributed to obese people, the reasons that lead to obesity and obesity itself. Dietitians (N = 344; 97.1% women) were contacted via their professional council and filled out the online survey. The survey questions were translated and adapted from international studies on this subject and the responses were analyzed for concordance rate. The results pointed to strong stigmatization of obesity and prejudice against the obese, attributing characteristics such as greed (67.4%), unattractiveness (52.0%), ungainliness (55.1%), lack of willpower (43.6%) and laziness (42.3%). The most important causal factors were considered to be emotional and mood changes, food addiction and low self-esteem. Research on this topic should be enhanced since these attitudes can affect the efficacy of treatment and also to foster broad discussion and training regarding the significance of obesity and to ensure more individualized and humanized treatment for obese patients.

Dietary Protein Modifies the Effect of the MC4R Genotype on 2-Year Changes in Appetite and Food Craving: The POUNDS Lost Trial.

PubMed

Huang, Tao; Zheng, Yan; Hruby, Adela; Williamson, Donald A; Bray, George A; Shen, Yiru; Sacks, Frank M; Qi, Lu

2017-03-01

Background: The melanocortin-4 receptor (MC4R) plays a pivotal role in the regulation of appetite and eating behavior. Variants in the MC4R gene have been related to appetite and obesity. Objective: We aimed to examine whether weight-loss diets modified the effect of the "obesity-predisposing" MC4R genotype on appetite-related measures in a randomized controlled trial. Methods: A total of 811 overweight and obese subjects [25 ≤ body mass index (BMI; kg/m 2 ) ≤ 40] aged 30-70 y were included in the 2-y POUNDS Lost (Preventing Overweight Using Novel Dietary Strategies) trial. We genotyped MC4R rs7227255 in 735 overweight adults and assessed appetite-related characteristics, including craving, fullness, hunger, and prospective consumption, as well as a composite appetite score. We examined the effects of the genotype-by-weight-loss diet intervention interaction on appetite variables by using general linear models in both the whole population and in white participants only. Results: We found that dietary protein intake (low compared with high: 15% of energy compared with 25% of energy, respectively) significantly modified MC4R genetic effects on changes in appetite score and craving ( P -interaction = 0.03 and 0.02, respectively) at 2 y, after adjustment for age, sex, ethnicity, baseline BMI, weight change, and baseline perspective phenotype. The obesity-predisposing A allele was associated with a greater increase in overall appetite score (β = 0.10, P = 0.05) and craving (β = 0.13, P = 0.008) compared with the non-A allele among participants who consumed a high-protein diet. MC4R genotype did not modify the effects of fat or carbohydrate intakes on appetite measures. Similar interaction patterns were observed in whites. Conclusion: Our data suggest that individuals with the MC4R rs7227255 A allele rather than the non-A allele might experience greater increases in appetite and food craving when consuming a high-protein weight-loss diet. This trial was registered

Nutritional Status of Maintenance Dialysis Patients: Low Lean Body Mass Index and Obesity Are Common, Protein-Energy Wasting Is Uncommon

PubMed Central

Koefoed, Mette; Kromann, Charles Boy; Juliussen, Sophie Ryberg; Hvidtfeldt, Danni; Ekelund, Bo; Frandsen, Niels Erik; Marckmann, Peter

2016-01-01

Background and Aims Maintenance dialysis patients are at increased risk of abnormal nutritional status due to numerous causative factors, both nutritional and non-nutritional. The present study assessed the current prevalence of protein-energy wasting, low lean body mass index and obesity in maintenance dialysis patients, and compared different methods of nutritional assessment. Methods In a cross-sectional study conducted in 2014 at Roskilde Hospital, Denmark, we performed anthropometry (body weight, skinfolds, mid-arm, waist, and hip circumferences), and determined plasma albumin and normalized protein catabolic rate in order to assess the prevalence of protein-energy wasting, low lean body mass index and obesity in these patients. Results Seventy-nine eligible maintenance dialysis patients participated. The prevalence of protein-energy wasted patients was 4% (95% CI: 2–12) as assessed by the coexistence of low lean body mass index and low fat mass index. Low lean body mass index was seen in 32% (95% CI: 22–44). Obesity prevalence as assessed from fat mass index was 43% (95% CI: 32–55). Coexistence of low lean body mass index and obesity was seen in 10% (95% CI: 5–19). The prevalence of protein-energy wasting and obesity varied considerably, depending on nutritional assessment methodology. Conclusions Our data indicate that protein-energy wasting is uncommon, whereas low lean body mass index and obesity are frequent conditions among patients in maintenance dialysis. A focus on how to increase and preserve lean body mass in dialysis patients is suggested in the future. In order to clearly distinguish between shortage, sufficiency and abundance of protein and/or fat deposits in maintenance dialysis patients, we suggest the simple measurements of lean body mass index and fat mass index. PMID:26919440

High muscle lipid content in obesity is not due to enhanced activation of key triglyceride esterification enzymes or the suppression of lipolytic proteins

PubMed Central

Li, Minghua; Paran, Christopher; Wolins, Nathan E.

2011-01-01

The mechanisms underlying alterations in muscle lipid metabolism in obesity are poorly understood. The primary aim of this study was to compare the abundance and/or activities of key proteins that regulate intramyocellular triglyceride (IMTG) concentration in the skeletal muscle obtained from obese (OB; n = 8, BMI 38 ± 1 kg/m2) and nonobese (NOB; n = 9, BMI 23 ± 1 kg/m2) women. IMTG concentration was nearly twofold greater in OB vs. NOB subjects (75 ± 15 vs. 40 ± 8 μmol/g dry wt, P < 0.05). In contrast, the activity and protein abundance of key enzymes that regulate the esterification of IMTG (i.e., glycerol-3-phosphate acyltransferase and diacylglycerol acyltransferase) were not elevated. We also found no differences between groups in muscle adipose triglyceride lipase and hormone-sensitive lipase (HSL) protein abundance and no differences in phosphorylation of specific sites known to affect HSL activity. However, we did find the elevated IMTG in obesity to be accompanied by a greater abundance of the fatty acid transporter FAT/CD36 in the membrane fraction of muscle from OB vs. NOB subjects (P < 0.05), suggestive of an elevated fatty acid transport capacity. Additionally, protein abundance of the lipid-trafficking protein perilipin 3 was lower (P < 0.05) in muscle from OB vs. NOB when expressed relative to IMTG content. Our findings indicate that the elevated IMTG content found in obese women was not due to an upregulation of key lipogenic proteins or to the suppression of lipolytic proteins. The impact of a low perilipin protein abundance relative to the amount of IMTG in obesity remains to be clarified. PMID:21285405

Obesity and Obesity-Related Secondary Conditions in Adolescents with Intellectual/Developmental Disabilities

ERIC Educational Resources Information Center

Rimmer, J. H.; Yamaki, K.; Davis Lowry, B. M.; Wang, E.; Vogel, L. C.

2010-01-01

Background: To explore the prevalence of obesity and related secondary conditions associated with obesity in adolescents with intellectual/developmental disabilities (IDD). Methods: In total, 461 parents of adolescents with IDD (M = 14.9 year, SD = 1.9) across 49 US states completed a web-based survey containing questions related to their child's…

Expression of syntaxin 8 in visceral adipose tissue is increased in obese patients with type 2 diabetes and related to markers of insulin resistance and inflammation.

PubMed

Lancha, Andoni; López-Garrido, Santiago; Rodríguez, Amaia; Catalán, Victoria; Ramírez, Beatriz; Valentí, Víctor; Moncada, Rafael; Silva, Camilo; Gil, María J; Salvador, Javier; Frühbeck, Gema; Gómez-Ambrosi, Javier

2015-01-01

Obesity is associated with increased adipose tissue inflammation as well as with the development of type 2 diabetes (T2D). Syntaxin 8 (STX8) is a protein required for the transport of endosomes. In this study we analyzed the relationship of STX8 with the presence of T2D in the context of obesity. With this purpose, 21 subjects (seven lean [LN], eight obese normoglycemic [OB-NG] and six obese with type 2 diabetes [OB-T2D]) were included in the study. Gene and protein expression levels of STX8 and GLUT4 were analyzed in visceral adipose tissue (VAT). mRNA (p = 0.008) and protein (p <0.001) expression levels of STX8 were significantly increased in VAT of OB-T2D patients. Moreover, gene expression levels of SLC2A4 (GLUT4) were downregulated (p = 0.002) in VAT of obese patients. We found that STX8 was positively correlated (p <0.05) with fasting glucose concentrations, plasma glucose 2 h after an OGTT and C-reactive protein. Interestingly, the expression of STX8 was negatively correlated (p <0.05) with the expression of SLC2A4 in VAT. Increased STX8 expression in VAT appears to be associated with the presence of T2D in obese patients through a mechanism that may involve GLUT4. Copyright © 2015 IMSS. Published by Elsevier Inc. All rights reserved.

Gender-related Differences in Food Craving and Obesity

PubMed Central

Hallam, Jessica; Boswell, Rebecca G.; DeVito, Elise E.; Kober, Hedy

2016-01-01

Food craving is often defined as a strong desire to eat. Much work has shown that it consistently and prospectively predicts eating and weight-related outcomes, contributing to the growing obesity epidemic. Although there are clear gender differences in the prevalence and health consequences of obesity, relatively little recent work has investigated gender differences in craving, or any sex-hormone-based differences as they relate to phases of the menstrual cycle. Here, we propose that gender-related differences in food craving contribute to gender-related differences in obesity. Drawing on findings in the addiction literature, we highlight ways to incorporate gender-based differences in food craving into treatment approaches, potentially improving the efficacy of obesity and weight loss treatment. Overall, this review aims to emphasize the importance of investigating gender differences in food craving, with a view towards informing the development of more effective treatments for obesity and weight loss. PMID:27354843

Protein kinases: mechanisms and downstream targets in inflammation-mediated obesity and insulin resistance.

PubMed

Nandipati, Kalyana C; Subramanian, Saravanan; Agrawal, Devendra K

2017-02-01

Obesity-induced low-grade inflammation (metaflammation) impairs insulin receptor signaling. This has been implicated in the development of insulin resistance. Insulin signaling in the target tissues is mediated by stress kinases such as p38 mitogen-activated protein kinase, c-Jun NH2-terminal kinase, inhibitor of NF-kB kinase complex β (IKKβ), AMP-activated protein kinase, protein kinase C, Rho-associated coiled-coil containing protein kinase, and RNA-activated protein kinase. Most of these kinases phosphorylate several key regulators in glucose homeostasis. The phosphorylation of serine residues in the insulin receptor and IRS-1 molecule results in diminished enzymatic activity in the phosphatidylinositol 3-kinase (PI3K)/Akt pathway. This has been one of the key mechanisms observed in the tissues that are implicated in insulin resistance especially in type 2 diabetes mellitus (T2-DM). Identifying the specific protein kinases involved in obesity-induced chronic inflammation may help in developing the targeted drug therapies to minimize the insulin resistance. This review is focused on the protein kinases involved in the inflammatory cascade and molecular mechanisms and their downstream targets with special reference to obesity-induced T2-DM.

Interplay of atherogenic factors, protein intake and betatrophin levels in obese-metabolic syndrome patients treated with hypocaloric diets.

PubMed

Crujeiras, A B; Zulet, M A; Abete, I; Amil, M; Carreira, M C; Martínez, J A; Casanueva, F F

2016-03-01

The understanding of the potential role of betatrophin in human metabolic disorders is a current challenge. The present research evaluated circulating betatrophin levels in obese patients with metabolic syndrome (MetSyn) features under energy-restricted weight-loss programs and in normal weight in order to establish the putative interplay between the levels of this hormone, diet and metabolic risk factors linked to obesity and associated comorbidities. One hundred forty-three participants were enrolled in the study (95 obese-MetSyn; age 49.5±9.4 years; body mass index (BMI) 35.7±4.5 kg m(-2) and 48 normal weight; age 35.71±8.8 years; BMI 22.9±2.2 kg m(-2)). A nutritional therapy consisting in two hypocaloric strategies (control diet based on the AHA recommendations and the RESMENA (MEtabolic Syndrome REduction in Navarra) diet, a novel dietary program with changes in the macronutrient distribution) was only prescribed to obese-MetSyn participants who were randomly allocated to the dietary strategies. Dietary records, anthropometrical and biochemical variables as well as betatrophin levels were analyzed before (pre-intervention, week 0), at 8 weeks (post-intervention, week 8) and after 4 additional months of self-control period (follow-up, week 24). Betatrophin levels were higher in obese-MetSyn patients than normal-weight subjects (1.24±0.43 vs 0.97±0.69 ng ml(-1), respectively, P=0.012), and levels were positively associated with body composition, metabolic parameters, leptin and irisin in all participants at baseline. Notably, low pre-intervention (week 0) betatrophin levels in obese patients were significantly associated with higher dietary-induced changes in atherogenic risk factors after 8 weeks. Moreover, protein intake, especially proteins from animal sources, was an independent determinant of betatrophin levels after dietary treatment (B=-0.27; P=0.012). Betatrophin is elevated in obese patients with MetSyn features and is associated with

Heart-Type Fatty Acid Binding Protein Is Associated with Proteinuria in Obesity

PubMed Central

Chen, Hui-Mei; Zheng, Chun-Xia; Gao, Qing; Ge, Yong-Chun; Liu, Zhi-Hong

2012-01-01

Rationale Lipid metabolism contributes to the formation of obesity-related glomerulopathy (ORG). Heart-type fatty acid binding protein (H-FABP or FABP3) is involved in lipid metabolism and was predicted to relate to renal lesions in obesity. Methods A total of 28 patients with ORG were investigated, and renal tissue from 7 kidney donors served as controls. Db/db mice with albuminuria were treated with Simvastatin for 12 weeks. Results Immunohistochemistry demonstrated the H-FABP staining in glomerular and tubular areas of patients with ORG, and the percentage of H-FABP in the glomerular area was significantly higher than in controls (15.8±1.62 versus 4.51±0.56%, P<0.001). Moreover, H-FABP expression correlated with proteinuria, high-density lipoprotein (HDL) cholesterol, waist circumference and the homeostatic model assessment – insulin resistance (HOMA-IR) among patients with ORG. Enhanced expression of H-FABP was also detected in the db/db mice, and expression increased from 8 to 20 weeks of age and was weakly related to increased albuminuria (r = 0.433; P = 0.020). Furthermore, H-FABP was co-localized with synaptopodin and demonstrated a podocyte pattern distribution. After Simvastation treatment, the urine albumin levels decreased with lipid levels and H-FABP expression in the glomeruli. The expression of H-FABP was related to Simvastatin treatment, albuminuria and triglycerides, while it was only linked with triglycerides and albuminuria (r = 0.643, P = 0.036). Conclusions This study confirmed an association of H-FABP with the pathogenesis of clinical and experimental ORG, and suggests that such a process might be related to podocytes and lipid dysmetabolism. PMID:23029183

Central role for melanocortin-4 receptors in offspring hypertension arising from maternal obesity

PubMed Central

Samuelsson, Anne-Maj S.; Mullier, Amandine; Maicas, Nuria; Oosterhuis, Nynke R.; Eun Bae, Sung; Novoselova, Tatiana V.; Chan, Li F.; Pombo, Joaquim M.; Taylor, Paul D.; Joles, Jaap A.; Coen, Clive W.; Balthasar, Nina; Poston, Lucilla

2016-01-01

Melanocortin-4 receptor (Mc4r)–expressing neurons in the autonomic nervous system, particularly in the paraventricular nucleus of the hypothalamus (PVH), play an essential role in blood pressure (BP) control. Mc4r-deficient (Mc4rKO) mice are severely obese but lack obesity-related hypertension; they also show a reduced pressor response to salt loading. We have previously reported that lean juvenile offspring born to diet-induced obese rats (OffOb) exhibit sympathetic-mediated hypertension, and we proposed a role for postnatally raised leptin in its etiology. Here, we test the hypothesis that neonatal hyperleptinemia due to maternal obesity induces persistent changes in the central melanocortin system, thereby contributing to offspring hypertension. Working on the OffOb paradigm in both sexes and using transgenic technology to restore Mc4r in the PVH of Mc4rKO (Mc4rPVH) mice, we have now shown that these mice develop higher BP than Mc4rKO or WT mice. We have also found that experimental hyperleptinemia induced in the neonatal period in Mc4rPVH and WT mice, but not in the Mc4rKO mice, leads to heightened BP and severe renal dysfunction. Thus, Mc4r in the PVH appears to be required for early-life programming of hypertension arising from either maternal obesity or neonatal hyperleptinemia. Early-life exposure of the PVH to maternal obesity through postnatal elevation of leptin may have long-term consequences for cardiovascular health. PMID:27791019

Expression studies of six human obesity-related genes in seven tissues from divergent pig breeds.

PubMed

Cirera, S; Jensen, M S; Elbrønd, V S; Moesgaard, S G; Christoffersen, B Ø; Kadarmideen, H N; Skovgaard, K; Bruun, C V; Karlskov-Mortensen, P; Jørgensen, C B; Fredholm, M

2014-02-01

Obesity has reached epidemic proportions globally and has become the cause of several major health risks worldwide. Presently, more than 100 loci have been related to obesity and metabolic traits in humans by genome-wide association studies. The complex genetic architecture behind obesity has triggered a need for the development of better animal models than rodents. The pig has emerged as a very promising biomedical model to study human obesity traits. In this study, we have characterized the expression patterns of six obesity-related genes, leptin (LEP), leptin receptor (LEPR), melanocortin 4 receptor (MC4R), fat mass and obesity associated (FTO), neuronal growth regulator 1 (NEGR)1 and adiponectin (ADIPOQ), in seven obesity-relevant tissues (liver; muscle; pancreas; hypothalamus; and retroperitoneal, subcutaneous and mesenteric adipose tissues) in two pig breeds (production pigs and Göttingen minipigs) that deviate phenotypically and genetically from each other with respect to obesity traits. We observe significant differential expression for LEP, LEPR and ADIPOQ in muscle and in all three adipose tissues. Interestingly, in pancreas, LEP expression is only detected in the fat minipigs. FTO shows significant differential expression in all tissues analyzed, and NEGR1 shows significant differential expression in muscle, pancreas, hypothalamus and subcutaneous adipose tissue. The MC4R transcript can be detected only in hypothalamus. In general, the expression profiles of the investigated genes are in accordance with those observed in human studies. Our study shows that both the differences between the investigated breeds and the phenotypic state with respect to obesity/leanness play a large role for differential expression of the obesity-related genes. © 2013 The Authors, Animal Genetics © 2013 Stichting International Foundation for Animal Genetics.

Dietary Protein Modifies the Effect of the MC4R Genotype on 2-Year Changes in Appetite and Food Craving: The POUNDS Lost Trial123

PubMed Central

Huang, Tao; Zheng, Yan; Hruby, Adela; Williamson, Donald A; Bray, George A; Shen, Yiru; Sacks, Frank M; Qi, Lu

2017-01-01

Background: The melanocortin-4 receptor (MC4R) plays a pivotal role in the regulation of appetite and eating behavior. Variants in the MC4R gene have been related to appetite and obesity. Objective: We aimed to examine whether weight-loss diets modified the effect of the “obesity-predisposing” MC4R genotype on appetite-related measures in a randomized controlled trial. Methods: A total of 811 overweight and obese subjects [25 ≤ body mass index (BMI; kg/m2) ≤ 40] aged 30–70 y were included in the 2-y POUNDS Lost (Preventing Overweight Using Novel Dietary Strategies) trial. We genotyped MC4R rs7227255 in 735 overweight adults and assessed appetite-related characteristics, including craving, fullness, hunger, and prospective consumption, as well as a composite appetite score. We examined the effects of the genotype-by-weight-loss diet intervention interaction on appetite variables by using general linear models in both the whole population and in white participants only. Results: We found that dietary protein intake (low compared with high: 15% of energy compared with 25% of energy, respectively) significantly modified MC4R genetic effects on changes in appetite score and craving (P-interaction = 0.03 and 0.02, respectively) at 2 y, after adjustment for age, sex, ethnicity, baseline BMI, weight change, and baseline perspective phenotype. The obesity-predisposing A allele was associated with a greater increase in overall appetite score (β = 0.10, P = 0.05) and craving (β = 0.13, P = 0.008) compared with the non-A allele among participants who consumed a high-protein diet. MC4R genotype did not modify the effects of fat or carbohydrate intakes on appetite measures. Similar interaction patterns were observed in whites. Conclusion: Our data suggest that individuals with the MC4R rs7227255 A allele rather than the non-A allele might experience greater increases in appetite and food craving when consuming a high-protein weight-loss diet. This trial was

Pathways linking obesity to health-related quality of life.

PubMed

Park, Sangshin

2017-08-01

Obesity is a well-recognized risk factor for impaired health-related quality of life (HRQOL). Nevertheless, few studies have investigated the mechanisms underlying the obesity-HRQOL associations. In this study, we explored potential mediators of the associations between obesity and HRQOL. Body mass index (BMI), an indicator of obesity, and HRQOL data were available for the 34,565 individuals 20 years of age and older participating in the cross-sectional Korea National Health and Nutrition Examination Survey 2007-2012. HRQOL was measured by the EuroQol five-dimension descriptive system. Path analysis was performed to assess the contributions of obesity-related diseases and self-rated health (SRH) on the relationships between obesity and HRQOL. In men, obesity was negatively associated with HRQOL through diabetes mellitus, hypertension, and dyslipidemia and positively associated with HRQOL through SRH. These opposite indirect effects offset one another and produced a non-significant association between obesity and HRQOL in men. However, in women, obesity was directly associated with HRQOL and indirectly associated with HRQOL through diabetes mellitus and SRH. Since these associations were in the same negative direction, the negative obesity-HRQOL association was clearly observed in women. Obesity was negatively associated with HRQOL through obesity-related diseases in both genders. However, in men, the positive association between obesity and SRH resulted in a non-significant association of obesity with HRQOL.

A global perspective for managing obesity and improving health: conventional treatment and surgical options: 4th Annual Obesity Summit, London, April 2016.

PubMed

Ahmad, Adeel Nazir; Edwards, Kimberley L

2016-12-01

4th Annual Obesity Summit, London, 12-14 April 2016 There are more than 1.9 billion overweight people worldwide, culminating in high rates of Type 2 diabetes; and cardiovascular, digestive and other health problems. This makes obesity a startling phenomenon and a significant global health epidemic. To address this, The 2016 Obesity Summit, 4th in the series of obesity-related annual events organized by EuroSciCon, was held from 12 to 14 April 2016 at Cineworld, The O2 in London. This conference set the stage for three days of stimulating high-quality presentations on the advancements in obesity in an informal academic setting. Approximately 156 delegates including students, researchers, healthcare professionals and scientists from 36 countries around the world attended the event. This meeting report summarizes some of the most outstanding presentations.

A Latent Class Analysis of Weight-Related Health Behaviors among 2- and 4-year College Students, and Associated Risk of Obesity

PubMed Central

Mathur, C; Stigler, M; Lust, K; Laska, M

2016-01-01

Little is known about the complex patterning of weight-related health behaviors in 2- and 4-year college students. The objective of this study was to identify and describe unique classes of weight-related health behaviors among college youth. Latent class analysis was used to identify homogenous, mutually exclusive classes of nine health behaviors which represent multiple theoretically/clinically relevant dimensions of obesity risk among 2- versus 4-year college students using cross-sectional statewide surveillance data (n= 17,584). Additionally, differences in class membership on selected sociodemographic characteristics were examined using a model-based approach. Analysis was conducted separately for both college groups, and 5 and 4 classes were identified for 2-and 4-year college students, respectively. Four classes were similar across 2-and 4-year college groups and were characterized as “mostly healthy dietary habits, active”, “moderately high screen time, active”, “moderately healthy dietary habits, inactive”, and “moderately high screen time, inactive”. “Moderately healthy dietary habits, high screen time” was the additional class unique to 2-year college students. These classes differed on a number of sociodemographic characteristics, including the proportion in each class who were classified as obese. Implications for prevention scientists and future intervention programs are considered. PMID:24990599

Adenovirus 36 and Obesity: An Overview.

PubMed

Ponterio, Eleonora; Gnessi, Lucio

2015-07-08

There is an epidemic of obesity starting about 1980 in both developed and undeveloped countries definitely associated with multiple etiologies. About 670 million people worldwide are obese. The incidence of obesity has increased in all age groups, including children. Obesity causes numerous diseases and the interaction between genetic, metabolic, social, cultural and environmental factors are possible cofactors for the development of obesity. Evidence emerging over the last 20 years supports the hypothesis that viral infections may be associated with obesity in animals and humans. The most widely studied infectious agent possibly linked to obesity is adenovirus 36 (Adv36). Adv36 causes obesity in animals. In humans, Adv36 associates with obesity both in adults and children and the prevalence of Adv36 increases in relation to the body mass index. In vivo and in vitro studies have shown that the viral E4orf1 protein (early region 4 open reading frame 1, Adv) mediates the Adv36 effect including its adipogenic potential. The Adv36 infection should therefore be considered as a possible risk factor for obesity and could be a potential new therapeutic target in addition to an original way to understand the worldwide rise of the epidemic of obesity. Here, the data indicating a possible link between viral infection and obesity with a particular emphasis to the Adv36 will be reviewed.

Adenovirus 36 and Obesity: An Overview

PubMed Central

Ponterio, Eleonora; Gnessi, Lucio

2015-01-01

There is an epidemic of obesity starting about 1980 in both developed and undeveloped countries definitely associated with multiple etiologies. About 670 million people worldwide are obese. The incidence of obesity has increased in all age groups, including children. Obesity causes numerous diseases and the interaction between genetic, metabolic, social, cultural and environmental factors are possible cofactors for the development of obesity. Evidence emerging over the last 20 years supports the hypothesis that viral infections may be associated with obesity in animals and humans. The most widely studied infectious agent possibly linked to obesity is adenovirus 36 (Adv36). Adv36 causes obesity in animals. In humans, Adv36 associates with obesity both in adults and children and the prevalence of Adv36 increases in relation to the body mass index. In vivo and in vitro studies have shown that the viral E4orf1 protein (early region 4 open reading frame 1, Adv) mediates the Adv36 effect including its adipogenic potential. The Adv36 infection should therefore be considered as a possible risk factor for obesity and could be a potential new therapeutic target in addition to an original way to understand the worldwide rise of the epidemic of obesity. Here, the data indicating a possible link between viral infection and obesity with a particular emphasis to the Adv36 will be reviewed. PMID:26184280

Surveillance of obesity-related policies in multiple environments: the Missouri Obesity, Nutrition, and Activity Policy Database, 2007-2009.

PubMed

Haire-Joshu, Debra; Elliott, Michael; Schermbeck, Rebecca; Taricone, Elsa; Green, Scoie; Brownson, Ross C

2010-07-01

The objective of this study was to develop the Missouri Obesity, Nutrition, and Activity Policy Database, a geographically representative baseline of Missouri's existing obesity-related local policies on healthy eating and physical activity. The database is organized to reflect 7 local environments (government, community, health care, worksite, school, after school, and child care) and to describe the prevalence of obesity-related policies in these environments. We employed a stratified nested cluster design using key informant interviews and review of public records to sample 2,356 sites across the 7 target environments for the presence or absence of obesity-related policies. The school environment had the most policies (88%), followed by after school (47%) and health care (32%). Community, government, and child care environments reported smaller proportions of obesity-related policies but higher rates of funding for these policies. Worksite environments had low numbers of obesity-related policies and low funding levels (17% and 6%, respectively). Sixteen of the sampled counties had high obesity-related policy occurrence; 65 had moderate and 8 had low occurrences. Except in Missouri schools, the presence of obesity-related policies is limited. More obesity-related policies are needed so that people have access to environments that support the model behaviors necessary to halt the obesity epidemic. The Missouri Obesity, Nutrition, and Activity Policy Database provides a benchmark for evaluating progress toward the development of obesity-related policies across multiple environments in Missouri.

Deficiency in adipocyte chemokine receptor CXCR4 exacerbates obesity and compromises thermoregulatory responses of brown adipose tissue in a mouse model of diet-induced obesity

PubMed Central

Yao, Longbiao; Heuser-Baker, Janet; Herlea-Pana, Oana; Zhang, Nan; Szweda, Luke I.; Griffin, Timothy M.; Barlic-Dicen, Jana

2014-01-01

The chemokine receptor CXCR4 is expressed on adipocytes and macrophages in adipose tissue, but its role in this tissue remains unknown. We evaluated whether deficiency in either adipocyte or myeloid leukocyte CXCR4 affects body weight (BW) and adiposity in a mouse model of high-fat-diet (HFD)-induced obesity. We found that ablation of adipocyte, but not myeloid leukocyte, CXCR4 exacerbated obesity. The HFD-fed adipocyte-specific CXCR4-knockout (AdCXCR4ko) mice, compared to wild-type C57BL/6 control mice, had increased BW (average: 52.0 g vs. 35.5 g), adiposity (average: 49.3 vs. 21.0% of total BW), and inflammatory leukocyte content in white adipose tissue (WAT), despite comparable food intake. As previously reported, HFD feeding increased uncoupling protein 1 (UCP1) expression (fold increase: 3.5) in brown adipose tissue (BAT) of the C57BL/6 control mice. However, no HFD-induced increase in UCP1 expression was observed in the AdCXCR4ko mice, which were cold sensitive. Thus, our study suggests that adipocyte CXCR4 limits development of obesity by preventing excessive inflammatory cell recruitment into WAT and by supporting thermogenic activity of BAT. Since CXCR4 is conserved between mouse and human, the newfound role of CXCR4 in mouse adipose tissue may parallel the role of this chemokine receptor in human adipose tissue.—Yao, L., Heuser-Baker, J., Herlea-Pana, O., Zhang, N., Szweda, L. I., Griffin, T. M., Barlic-Dicen, J. Deficiency in adipocyte chemokine receptor CXCR4 exacerbates obesity and compromises thermoregulatory responses of brown adipose tissue in a mouse model of diet-induced obesity. PMID:25016030

Obesity-related cardiovascular risk factors: intervention recommendations to decrease adolescent obesity

NASA Technical Reports Server (NTRS)

Calderon, Kristine S.; Yucha, Carolyn B.; Schaffer, Susan D.

2005-01-01

The incidence of adolescent obesity is increasing dramatically in the United States with associated risks of hypertension, adverse lipid profiles, and Type II diabetes. Unless reversed, this trend predicts an epidemic of adult cardiovascular disease. Interventions at home, at school, and in the community are required to empower teens to increase physical activity and to modify eating habits. This article describes assessment for obesity-related health problems as well as scientific guidelines and research-based intervention strategies to decrease obesity in adolescents.

ALOX5AP Overexpression in Adipose Tissue Leads to LXA4 Production and Protection Against Diet-Induced Obesity and Insulin Resistance.

PubMed

Elias, Ivet; Ferré, Tura; Vilà, Laia; Muñoz, Sergio; Casellas, Alba; Garcia, Miquel; Molas, Maria; Agudo, Judith; Roca, Carles; Ruberte, Jesús; Bosch, Fatima; Franckhauser, Sylvie

2016-08-01

Eicosanoids, such as leukotriene B4 (LTB4) and lipoxin A4 (LXA4), may play a key role during obesity. While LTB4 is involved in adipose tissue inflammation and insulin resistance, LXA4 may exert anti-inflammatory effects and alleviate hepatic steatosis. Both lipid mediators derive from the same pathway, in which arachidonate 5-lipoxygenase (ALOX5) and its partner, arachidonate 5-lipoxygenase-activating protein (ALOX5AP), are involved. ALOX5 and ALOX5AP expression is increased in humans and rodents with obesity and insulin resistance. We found that transgenic mice overexpressing ALOX5AP in adipose tissue had higher LXA4 rather than higher LTB4 levels, were leaner, and showed increased energy expenditure, partly due to browning of white adipose tissue (WAT). Upregulation of hepatic LXR and Cyp7a1 led to higher bile acid synthesis, which may have contributed to increased thermogenesis. In addition, transgenic mice were protected against diet-induced obesity, insulin resistance, and inflammation. Finally, treatment of C57BL/6J mice with LXA4, which showed browning of WAT, strongly suggests that LXA4 is responsible for the transgenic mice phenotype. Thus, our data support that LXA4 may hold great potential for the future development of therapeutic strategies for obesity and related diseases. © 2016 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered.

4G/5G polymorphism modulates PAI-1 circulating levels in obese women.

PubMed

Fernandes, Karla S; Sandrim, Valéria C

2012-05-01

The increase in plasminogen activator inhibitor type 1 (PAI-1) has been described as a risk factor to thrombosis-related diseases. In addition, it has been demonstrated that the variant 4G of polymorphism 4G/5G located in promoter region of PAI-1 gene is associated with higher PAI-1 levels. We investigate the role of this polymorphism on circulating PAI-1 concentration in a population of 57 obese women (23%, 4G/4G; 49%, 4G/5G and 28%, 5G/5G genotypes). Our results demonstrate a genotype-specific modulation on PAI-1 levels in obese women, thus 5G/5G genotype presented significantly lower levels of plasma PAI-1 when compared to 4G/4G group (46 ± 19 ng/mL vs. 63 ± 13 ng/mL, respectively). Our findings indicate that obese carriers of 4G/4G genotype may have increased risk to develop thrombotic diseases.

Lipoxin A4 Attenuates Obesity-Induced Adipose Inflammation and Associated Liver and Kidney Disease.

PubMed

Börgeson, Emma; Johnson, Andrew M F; Lee, Yun Sok; Till, Andreas; Syed, Gulam Hussain; Ali-Shah, Syed Tasadaque; Guiry, Patrick J; Dalli, Jesmond; Colas, Romain A; Serhan, Charles N; Sharma, Kumar; Godson, Catherine

2015-07-07

The role of inflammation in obesity-related pathologies is well established. We investigated the therapeutic potential of LipoxinA4 (LXA4:5(S),6(R),15(S)-trihydroxy-7E,9E,11Z,13E,-eicosatetraenoic acid) and a synthetic 15(R)-Benzo-LXA4-analog as interventions in a 3-month high-fat diet (HFD; 60% fat)-induced obesity model. Obesity caused distinct pathologies, including impaired glucose tolerance, adipose inflammation, fatty liver, and chronic kidney disease (CKD). Lipoxins (LXs) attenuated obesity-induced CKD, reducing glomerular expansion, mesangial matrix, and urinary H2O2. Furthermore, LXA4 reduced liver weight, serum alanine-aminotransferase, and hepatic triglycerides. LXA4 decreased obesity-induced adipose inflammation, attenuating TNF-α and CD11c(+) M1-macrophages (MΦs), while restoring CD206(+) M2-MΦs and increasing Annexin-A1. LXs did not affect renal or hepatic MΦs, suggesting protection occurred via attenuation of adipose inflammation. LXs restored adipose expression of autophagy markers LC3-II and p62. LX-mediated protection was demonstrable in adiponectin(-/-) mice, suggesting that the mechanism was adiponectin independent. In conclusion, LXs protect against obesity-induced systemic disease, and these data support a novel therapeutic paradigm for treating obesity and associated pathologies. Copyright © 2015 Elsevier Inc. All rights reserved.

Protein kinases: mechanisms and downstream targets in inflammation mediated obesity and insulin resistance

PubMed Central

Nandipati, Kalyana C; Subramanian, Saravanan; Agrawal, Devendra K

2016-01-01

Obesity induced low-grade inflammation (metaflammation) impairs insulin receptor signaling (IRS). This has been implicated in the development of insulin resistance. Insulin signaling in the target tissues is mediated by stress kinases such as p38 mitogen-activated protein kinase (MAPK), c-Jun NH2-terminal kinase (JNK), inhibitor of NF-kB kinase complex beta (IKKβ), AMP activated protein kinase (AMPK), protein kinase C (PKC), Rho associated coiled-coil containing protein kinase (ROCK) and RNA-activated protein kinase (PKR), etc. Most of these kinases phosphorylate several key regulators in glucose homeostasis. The phosphorylation of serine residues in the insulin receptor (IR) and IRS-1 molecule results in diminished enzymatic activity in the phosphatidylinositol 3-kinase (PI3K)/Akt pathway. This has been one of the key mechanisms observed in the tissues that are implicated in insulin resistance especially in Type II Diabetes Mellitus (T2-DM). Identifying the specific protein kinases involved in obesity induced chronic inflammation may help in developing the targeted drug therapies to minimize the insulin resistance. This review is focused on the protein kinases involved in the inflammatory cascade and molecular mechanisms and their downstream targets with special reference to obesity induced T2-DM. PMID:27868170

Obesity and injury-related absenteeism in a population-based firefighter cohort.

PubMed

Poston, Walker S C; Jitnarin, Nattinee; Haddock, C Keith; Jahnke, Sara A; Tuley, Brianne C

2011-10-01

A consistent relationship has been demonstrated between obesity and absenteeism in the workplace. However, most studies have focused on primarily sedentary occupational groups. Firefighting is a physically demanding profession that involves significant potential for exposure to dangerous situations and strenuous work. No studies to date have evaluated the impact of obesity on risk for absenteeism among firefighters. We examined the cross-sectional association between BMI and obesity and injury-related absenteeism. BMI, body fat percentage (BF%), waist circumference (WC), injury, and injury-related absenteeism were assessed in 478 career male firefighters. One hundred and fifteen firefighters reported an injury in the previous year and the number of days absent from work due to their injury. BMI was an independent predictor of absenteeism due to injury even after adjustment for confounding variables. Firefighters meeting the definition of class II and III obesity had nearly five times (odds ratio (OR) = 4.89; 95% confidence interval (CI) = 3.63-6.58) the number missed work days due to injury when compared to their normal weight counterparts and their elevated risk was greater than firefighters with class I obesity (OR = 2.71; 95% CI = 2.01-3.65) or those who were overweight (OR = 2.55; 95% CI = 1.90-3.41). The attributable per capita costs of class II and III obesity-related absenteeism over the last year were $1,682.90 per firefighter, $254.00 per firefighter for class I obesity, and $74.41 per firefighter for overweight. Our findings suggest that class II and III obesity were associated with substantial attributable costs to employers and our cost estimates probably underestimate the actual financial burden.

Obesity and Injury-Related Absenteeism in a Population-Based Firefighter Cohort

PubMed Central

Poston, Walker S.C.; Jitnarin, Nattinee; Haddock, C. Keith; Jahnke, Sara A.; Tuley, Brianne C.

2018-01-01

A consistent relationship has been demonstrated between obesity and absenteeism in the workplace. However, most studies have focused on primarily sedentary occupational groups. Firefighting is a physically demanding profession that involves significant potential for exposure to dangerous situations and strenuous work. No studies to date have evaluated the impact of obesity on risk for absenteeism among firefighters. We examined the cross-sectional association between BMI and obesity and injury-related absenteeism. BMI, body fat percentage (BF%), waist circumference (WC), injury, and injury-related absenteeism were assessed in 478 career male firefighters. One hundred and fifteen firefighters reported an injury in the previous year and the number of days absent from work due to their injury. BMI was an independent predictor of absenteeism due to injury even after adjustment for confounding variables. Firefighters meeting the definition of class II and III obesity had nearly five times (odds ratio (OR) = 4.89; 95% confidence interval (CI) = 3.63–6.58) the number missed work days due to injury when compared to their normal weight counterparts and their elevated risk was greater than firefighters with class I obesity (OR = 2.71; 95% CI = 2.01–3.65) or those who were overweight (OR = 2.55; 95% CI = 1.90–3.41). The attributable per capita costs of class II and III obesity-related absenteeism over the last year were $1,682.90 per firefighter, $254.00 per firefighter for class I obesity, and $74.41 per firefighter for overweight. Our findings suggest that class II and III obesity were associated with substantial attributable costs to employers and our cost estimates probably underestimate the actual financial burden. PMID:21633400

Differential DNA Methylation in Relation to Age and Health Risks of Obesity.

PubMed

Mansego, María Luisa; Milagro, Fermín I; Zulet, María Ángeles; Moreno-Aliaga, María J; Martínez, José Alfredo

2015-07-24

The aim of this study was to evaluate whether genome-wide levels of DNA methylation are associated with age and the health risks of obesity (HRO); defined according to BMI categories as "Low HRO" (overweight and class 1 obesity) versus "High HRO" (class 2 and class 3 obesity). Anthropometric measurements were assessed in a subsample of 48 volunteers from the Metabolic Syndrome Reduction in Navarra (RESMENA) study and 24 women from another independent study, Effects of Lipoic Acid and Eicosapentaenoic Acid in Human Obesity (OBEPALIP study). In the pooled population; the methylation levels of 55 CpG sites were significantly associated with age after Benjamini-Hochberg correction. In addition, DNA methylation of three CpG sites located in ELOVL2; HOXC4 and PI4KB were further negatively associated with their mRNA levels. Although no differentially methylated CpG sites were identified in relation to HRO after multiple testing correction; several nominally significant CpG sites were identified in genes related to insulin signaling; energy and lipid metabolism. Moreover, statistically significant associations between BMI or mRNA levels and two HRO-related CpG sites located in GPR133 and ITGB5 are reported. As a conclusion, these findings from two Spanish cohorts add knowledge about the important role of DNA methylation in the age-related regulation of gene expression. In addition; a relevant influence of age on DNA methylation in white blood cells was found, as well as, on a trend level, novel associations between DNA methylation and obesity.

A latent class analysis of weight-related health behaviors among 2- and 4-year college students and associated risk of obesity.

PubMed

Mathur, Charu; Stigler, Melissa; Lust, Katherine; Laska, Melissa

2014-12-01

Little is known about the complex patterning of weight-related health behaviors in 2- and 4-year college students. The objective of this study was to identify and describe unique classes of weight-related health behaviors among college students. Latent class analysis was used to identify homogenous, mutually exclusive classes of nine health behaviors that represent multiple theoretically/clinically relevant dimensions of obesity risk among 2- versus 4-year college students using cross-sectional statewide surveillance data (N = 17,584). Additionally, differences in class membership on selected sociodemographic characteristics were examined using a model-based approach. Analysis was conducted separately for both college groups, and five and four classes were identified for 2- and 4-year college students, respectively. Four classes were similar across 2- and 4-year college groups and were characterized as "mostly healthy dietary habits, active"; "moderately high screen time, active"; "moderately healthy dietary habits, inactive"; and "moderately high screen time, inactive." "Moderately healthy dietary habits, high screen time" was the additional class unique to 2-year college students. These classes differed on a number of sociodemographic characteristics, including the proportion in each class who were classified as obese. Implications for prevention scientists and future intervention programs are considered. © 2014 Society for Public Health Education.

A randomized trial of energy-restricted high-protein versus high-carbohydrate, low-fat diet in morbid obesity.

PubMed

Dalle Grave, Riccardo; Calugi, Simona; Gavasso, Ilaria; El Ghoch, Marwan; Marchesini, Giulio

2013-09-01

Conflicting evidence exists as to weight loss produced by diets with different carbohydrate/protein ratio. The aim was to compare the long-term effects of high-protein vs. high-carbohydrate diet (HPD, HCD), combined with cognitive behavior therapy (CBT). In a randomized trial, 88 obese participants (mean age, 46.7; mean BMI, 45.6 kg m(-2) ) were enrolled in a 3-week inpatient and 48-week outpatient treatment, with continuous CBT during the study period. All subjects consumed a restricted diet (1,200 kcal day(-1) for women, 1,500 for men; 20% energy from fat, <10% saturated fat). HPD derived 34% energy from proteins, 46% from carbohydrates; HCD 17% from proteins, 64% from carbohydrates. The primary outcome was 1-year percent weight loss. Secondary outcomes were attrition rates and changes in cardiovascular risk factors and psychological profile. Attrition rates were similar between groups (25.6%). In the intention-to-treat analysis, weight loss averaged 15.0% in HPD and 13.3% in HCD at 1 year, without any difference throughout the study period. Both diets produced a similar improvement in secondary outcomes. The relative carbohydrate and protein content of the diet, when combined with intensive CBT, does not significantly affect attrition rate, weight loss and psychosocial outcome in patients with severe obesity. Copyright © 2013 The Obesity Society.

Cortisol dysregulation in obesity-related metabolic disorders

PubMed Central

Baudrand, Rene; Vaidya, Anand

2015-01-01

Purpose of review The understanding of how adrenal function is challenged by the interplay of our genetic and environmental milieu has highlighted the importance of inappropriate cortisol regulation in cardiometabolic disorders. Increased adipose tissue in obesity is associated with hypothalamic-pituitary-adrenal axis over-activation, increased cortisol production at the local tissue level, and probably higher mineralocorticoid receptor activation in certain tissues. Recent findings Due to the clinical resemblance of obesity-related metabolic disorders with the Cushing syndrome, new studies have investigated the intracellular regulation and metabolism of cortisol, new measurements in scalp hair as a tool for long-term exposure and the cortisol-mineralocorticoid receptor pathway. Thus, current and future pharmacological interventions in obesity may include specific inhibition of steroidogenic and regulatory enzymes as well as antagonists of the mineralocorticoid and glucocorticoid receptors. Summary This review highlights recent investigations focusing on the role of dysregulated cortisol physiology in obesity as a potential modifiable mechanism in the pathogenesis of obesity related cardiometabolic disorders. PMID:25871955

Neurocognitive correlates of obesity and obesity-related behaviors in children and adolescents.

PubMed

Liang, J; Matheson, B E; Kaye, W H; Boutelle, K N

2014-04-01

Childhood obesity rates have risen dramatically over the past few decades. Although obesity has been linked to poorer neurocognitive functioning in adults, much less is known about this relationship in children and adolescents. Therefore, we conducted a systematic review to examine the relationship between obesity and obesity-related behaviors with neurocognitive functioning in youth. We reviewed articles from 1976 to 2013 using PsycInfo, PubMed, Medline and Google Scholar. Search terms included cognitive function, neurocognitive function/performance, executive function, impulsivity, self-regulation, effortful control, cognitive control, inhibition, delayed gratification, memory, attention, language, motor, visuo-spatial, academic achievement, obesity, overweight, body mass index, waist-hip ratio, adiposity and body fat. Articles were excluded if participants had health problems known to affect cognitive functioning, the study used imaging as the only outcome measure, they were non-peer-reviewed dissertations, theses, review papers, commentaries, or they were non-English articles. Sixty-seven studies met inclusion criteria for this review. Overall, we found data that support a negative relationship between obesity and various aspects of neurocognitive functioning, such as executive functioning, attention, visuo-spatial performance, and motor skill. The existing literature is mixed on the effects among obesity, general cognitive functioning, language, learning, memory, and academic achievement. Executive dysfunction is associated with obesity-related behaviors, such as increased intake, disinhibited eating, and less physical activity. Physical activity is positively linked with motor skill. More longitudinal research is needed to determine the directionality of such relationships, to point towards crucial intervention time periods in the development of children, and to inform effective treatment programs.

Neurocognitive correlates of obesity and obesity-related behaviors in children and adolescents

PubMed Central

Liang, J.; Matheson, BE.; Kaye, WH.; Boutelle, KN.

2015-01-01

Childhood obesity rates have risen dramatically over the past few decades. Although obesity has been linked to poorer neurocognitive functioning in adults, much less is known about this relationship in children and adolescents. Therefore, we conducted a systematic review to examine the relationship between obesity and obesity-related behaviors with neurocognitive functioning in youth. We reviewed articles from 1976 to 2013 using PsycInfo, PubMed, Medline and Google Scholar. Search terms included cognitive function, neurocognitive function/performance, executive function, impulsivity, self-regulation, effortful control, cognitive control, inhibition, delayed gratification, memory, attention, language, motor, visuo-spatial, academic achievement, obesity, overweight, body mass index, waist-hip ratio, adiposity and body fat. Articles were excluded if participants had health problems known to affect cognitive functioning, the study used imaging as the only outcome measure, they were non-peer-reviewed dissertations, theses, review papers, commentaries, or they were non-English articles. Sixty-seven studies met inclusion criteria for this review. Overall, we found data that support a negative relationship between obesity and various aspects of neurocognitive functioning, such as executive functioning, attention, visuo-spatial performance, and motor skill. The existing literature is mixed on the effects among obesity, general cognitive functioning, language, learning, memory, and academic achievement. Executive dysfunction is associated with obesity-related behaviors, such as increased intake, disinhibited eating, and less physical activity. Physical activity is positively linked with motor skill. More longitudinal research is needed to determine the directionality of such relationships, to point towards crucial intervention time periods in the development of children, and to inform effective treatment programs. PMID:23913029

Adipocyte-Macrophage Cross-Talk in Obesity.

PubMed

Engin, Ayse Basak

2017-01-01

Obesity is characterized by the chronic low-grade activation of the innate immune system. In this respect, macrophage-elicited metabolic inflammation and adipocyte-macrophage interaction has a primary importance in obesity. Large amounts of macrophages are accumulated by different mechanisms in obese adipose tissue. Hypertrophic adipocyte-derived chemotactic monocyte chemoattractant protein-1 (MCP-1)/C-C chemokine receptor 2 (CCR2) pathway also promotes more macrophage accumulation into the obese adipose tissue. However, increased local extracellular lipid concentrations is a final mechanism for adipose tissue macrophage accumulation. A paracrine loop involving free fatty acids and tumor necrosis factor-alpha (TNF-alpha) between adipocytes and macrophages establishes a vicious cycle that aggravates inflammatory changes in the adipose tissue. Adipocyte-specific caspase-1 and production of interleukin-1beta (IL-1beta) by macrophages; both adipocyte and macrophage induction by toll like receptor-4 (TLR4) through nuclear factor-kappaB (NF-kappaB) activation; free fatty acid-induced and TLR-mediated activation of c-Jun N-terminal kinase (JNK)-related pro-inflammatory pathways in CD11c+ immune cells; are effective in macrophage accumulation and in the development of adipose tissue inflammation. Old adipocytes are removed by macrophages through trogocytosis or sending an "eat me" signal. The obesity-induced changes in adipose tissue macrophage numbers are mainly due to increases in the triple-positive CD11b+ F4/80+ CD11c+ adipose tissue macrophage subpopulation. The ratio of M1-to-M2 macrophages is increased in obesity. Furthermore, hypoxia along with higher concentrations of free fatty acids exacerbates macrophage-mediated inflammation in obesity. The metabolic status of adipocytes is a major determinant of macrophage inflammatory output. Macrophage/adipocyte fatty-acid-binding proteins act at the interface of metabolic and inflammatory pathways. Both macrophages and

Obesity and its Relation With Diabetes and Hypertension: A Cross-Sectional Study Across 4 Geographical Regions.

PubMed

Patel, Shivani A; Ali, Mohammed K; Alam, Dewan; Yan, Lijing L; Levitt, Naomi S; Bernabe-Ortiz, Antonio; Checkley, William; Wu, Yangfeng; Irazola, Vilma; Gutierrez, Laura; Rubinstein, Adolfo; Shivashankar, Roopa; Li, Xian; Miranda, J Jaime; Chowdhury, Muhammad Ashique Haider; Siddiquee, Ali Tanweer; Gaziano, Thomas A; Kadir, M Masood; Prabhakaran, Dorairaj

2016-03-01

The implications of rising obesity for cardiovascular health in middle-income countries has generated interest, in part because associations between obesity and cardiovascular health seem to vary across ethnic groups. We assessed general and central obesity in Africa, East Asia, South America, and South Asia. We further investigated whether body mass index (BMI) and waist circumference differentially relate to cardiovascular health; and associations between obesity metrics and adverse cardiovascular health vary by region. Using baseline anthropometric data collected between 2008 and 2012 from 7 cohorts in 9 countries, we estimated the proportion of participants with general and central obesity using BMI and waist circumference classifications, respectively, by study site. We used Poisson regression to examine the associations (prevalence ratios) of continuously measured BMI and waist circumference with prevalent diabetes and hypertension by sex. Pooled estimates across studies were computed by sex and age. This study analyzed data from 31,118 participants aged 20 to 79 years. General obesity was highest in South Asian cities and central obesity was highest in South America. The proportion classified with general obesity (range 11% to 50%) tended to be lower than the proportion classified as centrally obese (range 19% to 79%). Every standard deviation higher of BMI was associated with 1.65 and 1.60 times higher probability of diabetes and 1.42 and 1.28 times higher probability of hypertension, for men and women, respectively, aged 40 to 69 years. Every standard deviation higher of waist circumference was associated with 1.48 and 1.74 times higher probability of diabetes and 1.34 and 1.31 times higher probability of hypertension, for men and women, respectively, aged 40 to 69 years. Associations of obesity measures with diabetes were strongest in South Africa among men and in South America among women. Associations with hypertension were weakest in South Africa among

Alteration of Bone Mineral Density Differs Between Genders in Obese Subjects After Laparoscopic Sleeve Gastrectomy: Bone Morphogenetic Protein 4 May Count.

PubMed

Wang, Xingchun; Li, Liang; Zhu, Cuiling; Gao, Jingyang; Qu, Shen

2018-05-12

Laparoscopic sleeve gastrectomy (LSG) has proven to be successful in weight reduction but with potential loss of bone mass. Previous studies indicated that bone morphogenetic protein 4 (BMP4) plays an important role in both bone formation and glucose-lipid metabolism. This study aimed to investigate the changes in bone mineral density (BMD), bone metabolic parameters, and serum BMP4 levels in obese Chinese subjects after LSG. Seventy-one obese patients (34 males, age 31.70 ± 9.61 years and 37 females, age 32.80 ± 11.45 years) were enrolled. BMD (at the right hip, femoral neck, and lumbar spine 1-4 (L1-L4)) was measured by dual-energy X-ray absorptiometry, bone metabolic markers, and routine anthropometric/laboratory biochemical parameters at baseline, 3, 6, and 12 months after LSG (abbreviated as 3, 6, and 12 M post-LSG, respectively) were recorded. Serum BMP4 levels were measured by enzyme-linked immunosorbent assay. LSG led to dramatic weight loss with improved glucose-lipid metabolism in all patients. In females, BMD was significantly decreased at the right hip at all time points studied and at the femoral neck at 6 and 12 M post-LSG (P < 0.05 or P < 0.01). In males, BMD was not significantly changed (all P > 0.05). Intriguingly, serum BMP4 levels were reduced slightly at 3 M post-LSG (P = 0.463) and were significantly at 6 M post-LSG (from 75.51 ± 16.54 to 65.40 ± 10.51 pg/mL, P = 0.048) in females, but unchanged in males (all P > 0.05). Vitamin D and 25-hydroxy vitamin D were increased in males at 12 M post-LSG (all P < 0.05). Osteocalcin was increased in males at all time points studied and in females at 3 and 6 M post-LSG (all P < 0.05). Type I collagen was increased in males at 3 and 6 M post-LSG and in females at all the time points studied (all P < 0.05). The effect of LSG on BMD differs between genders, decreasing significantly in females while remaining unchanged in males. Moreover

Inflammation profile in overweight/obese adolescents in Europe: an analysis in relation to iron status.

PubMed

Ferrari, M; Cuenca-García, M; Valtueña, J; Moreno, L A; Censi, L; González-Gross, M; Androutsos, O; Gilbert, C C; Huybrechts, I; Dallongeville, J; Sjöström, M; Molnar, D; De Henauw, S; Gómez-Martínez, S; de Moraes, A C F; Kafatos, A; Widhalm, K; Leclercq, C

2015-02-01

The objectives of this study were to investigate the relationship between inflammatory parameters (CRP, c-reactive protein; AGP, α1-acid glycoprotein), iron status indicators (SF, serum ferritin; sTfR, soluble transferrin receptor) and body mass index (BMI) z-score, fat-free mass (FFM) and fat mass (FM) in European adolescents. Differences in intake for some nutrients (total iron, haem and non-haem iron, vitamin C, calcium, proteins) were assessed according to BMI categories, and the association of nutrient intakes with BMI z-score, FM and FFM was evaluated. A total of 876 adolescents participating in the Healthy Lifestyle in Europe by Nutrition in Adolescence-Cross Sectional Study were included in the study sample. Mean CRP values (standard error; s.e.) were significantly higher in overweight/obese adolescents (1.7±0.3 and 1.4±0.3 mg/l in boys and girls, respectively) than in thin/normal-weight adolescents (1.1±0.2 and 1.0±0.1 mg/l in boys and girls, respectively) (P<0.05). For boys, mean SF values (s.e.) were significantly higher in overweight/obese adolescents (46.9±2.7 μg/l) than in thin/normal-weight adolescents (35.7±1.7 μg/l) (P<0.001), whereas median sTfR values did not differ among BMI categories for both boys and girls. Multilevel regression analyses showed that BMI z-score and FM were significantly related to CRP and AGP (P<0.05). Dietary variables did not differ significantly among BMI categories, except for the intake of vegetable proteins, which, for boys, was higher in thin/normal-weight adolescents than in overweight/obese adolescents (P<0.05). The adiposity of the European adolescents was sufficient to cause chronic inflammation but not sufficient to impair iron status and cause iron deficiency.

Pediatric Obesity-Related Asthma: The Role of Metabolic Dysregulation.

PubMed

Vijayakanthi, Nandini; Greally, John M; Rastogi, Deepa

2016-05-01

The burden of obesity-related asthma among children, particularly among ethnic minorities, necessitates an improved understanding of the underlying disease mechanisms. Although obesity is an independent risk factor for asthma, not all obese children develop asthma. Several recent studies have elucidated mechanisms, including the role of diet, sedentary lifestyle, mechanical fat load, and adiposity-mediated inflammation that may underlie the obese asthma pathophysiology. Here, we review these recent studies and emerging scientific evidence that suggest metabolic dysregulation may play a role in pediatric obesity-related asthma. We also review the genetic and epigenetic factors that may underlie susceptibility to metabolic dysregulation and associated pulmonary morbidity among children. Lastly, we identify knowledge gaps that need further exploration to better define pathways that will allow development of primary preventive strategies for obesity-related asthma in children. Copyright © 2016 by the American Academy of Pediatrics.

Pediatric Obesity-Related Asthma: The Role of Metabolic Dysregulation

PubMed Central

Vijayakanthi, Nandini; Greally, John M.

2016-01-01

The burden of obesity-related asthma among children, particularly among ethnic minorities, necessitates an improved understanding of the underlying disease mechanisms. Although obesity is an independent risk factor for asthma, not all obese children develop asthma. Several recent studies have elucidated mechanisms, including the role of diet, sedentary lifestyle, mechanical fat load, and adiposity-mediated inflammation that may underlie the obese asthma pathophysiology. Here, we review these recent studies and emerging scientific evidence that suggest metabolic dysregulation may play a role in pediatric obesity-related asthma. We also review the genetic and epigenetic factors that may underlie susceptibility to metabolic dysregulation and associated pulmonary morbidity among children. Lastly, we identify knowledge gaps that need further exploration to better define pathways that will allow development of primary preventive strategies for obesity-related asthma in children. PMID:27244776

Relation with HOMA-IR and thyroid hormones in obese Turkish women with metabolic syndrome.

PubMed

Topsakal, S; Yerlikaya, E; Akin, F; Kaptanoglu, B; Erürker, T

2012-03-01

The aim of this study was to investigate the relationship between insulin resistance and thyroid function in obese pre- and postmenopausal women with or without metabolic syndrome (MetS). 141 obese women were divided into two groups, HOMA-IR<2.7 and HOMA-IR>2.7, to evaluate relation with HOMA-IR and fatness, hormone and blood parameters. They were then divided into four groups as pre- and postmenopausal with or without MetS. Various fatness, hormone and blood parameters were examined. Statistically significant difference was found in weight, body mass index (BMI), waist circumference, fat%, fasting insulin, TSH, FT3, FT4, FSH, Anti-microsomal antibody (ANTIM) and triglycerides levels in HOMA-IR<2.7 and HOMA-IR>2.7 obese Turkish women. This study showed that age, weight, BMI, waist circumference, fat%, fasting insulin, FT3, ANTIM, FSH, LH, total cholesterol, triglycerides, HDL, HOMA-IR, systolic and diastolic blood pressure levels were related in preand post menopausal status in obese women with or without MetS. Obesity may influence the levels of thyroid hormones and increases the risk of MetS in women. Postmenopausal status with MetS is associated with an increased TSH, FT3 and FT4 levels and HOMA-IR in obese women. Strong relation was observed with MetS and TSH and FT3 levels.

p38 mitogen-activated protein kinase is involved in arginase-II-mediated eNOS-Uncoupling in Obesity

PubMed Central

2014-01-01

Background Endothelial nitric oxide synthase (eNOS)-uncoupling links obesity-associated insulin resistance and type-II diabetes to the increased incidence of cardiovascular disease. Studies have indicated that increased arginase is involved in eNOS-uncoupling through competing with the substrate L-arginine. Given that arginase-II (Arg-II) exerts some of its biological functions through crosstalk with signal transduction pathways, and that p38 mitogen-activated protein kinase (p38mapk) is involved in eNOS-uncoupling, we investigated here whether p38mapk is involved in Arg-II-mediated eNOS-uncoupling in a high fat diet (HFD)-induced obesity mouse model. Methods Obesity was induced in wild type (WT) and Arg-II-deficient (Arg-II-/-) mice on C57BL/6 J background by high-fat diet (HFD, 55% fat) for 14 weeks starting from age of 7 weeks. The entire aortas were isolated and subjected to 1) immunoblotting analysis of the protein level of eNOS, Arg-II and p38mapk activation; 2) arginase activity assay; 3) endothelium-dependent and independent vasomotor responses; 4) en face staining of superoxide anion and NO production with Dihydroethidium and 4,5-Diaminofluorescein Diacetate, respectively, to assess eNOS-uncoupling. To evaluate the role of p38mapk, isolated aortas were treated with p38mapk inhibitor SB203580 (10 μmol/L, 1 h) prior to the analysis. In addition, the role of p38mapk in Arg-II-induced eNOS-uncoupling was investigated in cultured human endothelial cells overexpressing Arg-II in the absence or presence of shRNA against p38mapk. Results HFD enhanced Arg-II expression/activity and p38mapk activity, which was associated with eNOS-uncoupling as revealed by decreased NO and enhanced L-NAME-inhibitable superoxide in aortas of WT obese mice. In accordance, WT obese mice revealed decreased endothelium-dependent relaxations to acetylcholine despite of higher eNOS protein level, whereas Arg-II-/- obese mice were protected from HFD-induced eNOS-uncoupling and

Obesity-related parameters and colorectal adenoma development.

PubMed

Kim, Tae Jun; Kim, Jee Eun; Choi, Yoon-Ho; Hong, Sung Noh; Kim, Young-Ho; Chang, Dong Kyung; Rhee, Poong-Lyul; Kim, Min-Ji; Jung, Sin-Ho; Son, Hee Jung

2017-12-01

Obesity increases the risk of colorectal adenoma and colorectal cancer. However, the obesity-related parameters that are best for assessing the risk of colorectal adenoma development remain unclear. We analyzed the parameters that may best describe the association between obesity and colorectal adenoma development. In this retrospective cohort study, 3405 individuals underwent screening colonoscopy during routine health examinations. We measured body mass index; waist circumference; and metabolic parameters such as high-density lipoprotein-cholesterol, glucose, triglyceride, and systolic blood pressure. We analyzed the risk of developing colorectal adenoma, relative to obesity-related parameters, over a mean interval of 5.8 years from baseline colonoscopy. In a multivariate analysis, waist circumference was the only obesity-related marker associated with an increased risk of metachronous colorectal adenoma. Men with waist circumferences ≥85 cm and women with waist circumference ≥82 cm had a 31% increased risk of metachronous colorectal adenoma compared to those with smaller waist circumferences [odds ratio (OR) 1.31; 95% confidence interval (CI, 1.09-1.57)]. Other factors associated with metachronous colorectal adenoma were age (OR, 1.03; 95% CI 1.02-1.04), male sex (OR 1.49; 95% CI 1.17-1.88), alcohol consumption ≥3/week (OR 1.33; 95% CI 1.10-1.62), the number of adenoma at baseline (OR 1.21; 95% CI 1.10-1.33), and the presence of advanced adenoma at baseline (OR 1.60; 95% CI 1.24-2.06). Our findings suggest that central obesity, represented by waist circumference, is a significant predictor of metachronous colorectal adenoma, independent of body mass index and other metabolic variables.

Dietary fiber prevents obesity-related liver lipotoxicity by modulating sterol-regulatory element binding protein pathway in C57BL/6J mice fed a high-fat/cholesterol diet.

PubMed

Han, Shufen; Jiao, Jun; Zhang, Wei; Xu, Jiaying; Wan, Zhongxiao; Zhang, Weiguo; Gao, Xiaoran; Qin, Liqiang

2015-10-29

Adequate intake of dietary fibers has proven metabolic and cardiovascular benefits, molecular mechanisms remain still limited. This study was aimed to investigate the effects of cereal dietary fiber on obesity-related liver lipotoxicity in C57BL/6J mice fed a high-fat/cholesterol (HFC) diet and underlying mechanism. Forty-eight adult male C57BL/6J mice were randomly given a reference chow diet, or a high fat/cholesterol (HFC) diet supplemented with or without oat fiber or wheat bran fiber for 24 weeks. Our results showed mice fed oat or wheat bran fiber exhibited lower weight gain, lipid profiles and insulin resistance, compared with HFC diet. The two cereal dietary fibers potently decreased protein expressions of sterol regulatory element binding protein-1 and key factors involved in lipogenesis, including fatty acid synthase and acetyl-CoA carboxylase in target tissues. At molecular level, the two cereal dietary fibers augmented protein expressions of peroxisome proliferator-activated receptor alpha and gamma, liver X receptor alpha, and ATP-binding cassette transporter A1 in target tissues. Our findings indicated that cereal dietary fiber supplementation abrogated obesity-related liver lipotoxicity and dyslipidemia in C57BL/6J mice fed a HFC diet. In addition, the efficacy of oat fiber is greater than wheat bran fiber in normalizing these metabolic disorders and pathological profiles.

Dietary fiber prevents obesity-related liver lipotoxicity by modulating sterol-regulatory element binding protein pathway in C57BL/6J mice fed a high-fat/cholesterol diet

PubMed Central

Han, Shufen; Jiao, Jun; Zhang, Wei; Xu, Jiaying; Wan, Zhongxiao; Zhang, Weiguo; Gao, Xiaoran; Qin, Liqiang

2015-01-01

Adequate intake of dietary fibers has proven metabolic and cardiovascular benefits, molecular mechanisms remain still limited. This study was aimed to investigate the effects of cereal dietary fiber on obesity-related liver lipotoxicity in C57BL/6J mice fed a high-fat/cholesterol (HFC) diet and underlying mechanism. Forty-eight adult male C57BL/6J mice were randomly given a reference chow diet, or a high fat/choleserol (HFC) diet supplemented with or without oat fiber or wheat bran fiber for 24 weeks. Our results showed mice fed oat or wheat bran fiber exhibtied lower weight gain, lipid profiles and insulin resistance, compared with HFC diet. The two cereal dietary fibers potently decreased protein expressions of sterol regulatory element binding protein-1 and key factors involved in lipogenesis, including fatty acid synthase and acetyl-CoA carboxylase in target tissues. At molecular level, the two cereal dietary fibers augmented protein expressions of peroxisome proliferator-activated receptor alpha and gamma, liver X receptor alpha, and ATP-binding cassette transporter A1 in target tissues. Our findings indicated that cereal dietary fiber supplementation abrogated obesity-related liver lipotoxicity and dyslipidemia in C57BL/6J mice fed a HFC diet. In addition, the efficacy of oat fiber is greater than wheat bran fiber in normalizing these metabolic disorders and pathological profiles. PMID:26510459

C-B3-02: Association of FTO, INSIG2, MC4R, and PCSK1 Obesity SNPs With Binge Eating in Morbidly Obese Patients

PubMed Central

Gerhard, Glenn S; Still, Christopher D; Wood, G Craig; Chu, Xin; Erdman, Robert; Susek, Meghan; Gerst, Heather; Derr, Kim; AlAgha, Mouna; Hartman, Christina; Carey, David; Benotti, Peter

2010-01-01

Background/Aims: Obesity has a strong genetic component. Recent genome-wide association studies have identified single nucleotide polymorphisms (SNPs) in or near over a dozen genes that are related to body mass index (BMI). Despite the association of these SNPs with BMI, the mechanism by which they influence the determination of body weight is not yet known. Recently, the fat- mass and obesity-associated (FTO) obesity SNP was related to energy intake and preference for foods of high caloric density in children. FTO genotype was not associated with resting energy expenditure. We have extended this type of analysis to eating behaviors in the morbidly obese. Methods: DNA was obtained from approximately 900 morbidly obese (BMI>40 kg/m2) patients and used to genotype obesity SNPs in or near the FTO, INSIG2, MC4R, and PCSK1 genes. Binge eating status (normal, episodic overeating, or any binge eating) was determined using the validated Questionnaire on Eating and Weight Patterns (QEWP). Binge eating status was correlated with each individual genotype, the combined obesity allele burden, and the combined homozygous obesity gene burden. Results: Binge eating data was obtained from 640 patients who had completed the QEWP. Of these 640, 116 (18%) were classified as manifesting binge eating behavior. No association was present between heterozygous or homozygous FTO (P=0.59), MC4R (P=0.30), or PSK1 (P=0.77) obesity SNPs. However, 29% of those who were homozygous for the INSIG2 obesity SNP were classified as binge eaters, versus 17% of heterozygous or homozygous normal patients (P=0.006). Association was also found with binge eating status and the presence of 2 or more homozygous obesity genotypes (28% versus 17%, P=0.041), likely due to the INSIG2 gene. Cumulative obesity allele burden (0–8 alleles for the 4 genes) was not associated with binge eating status (P=0.42). Conclusions: The INSIG2 obesity SNP appears to influence binge eating behavior in morbidly obese adults. The

Voluntary exercise prevents the obese and diabetic metabolic syndrome of the melanocortin-4 receptor knockout mouse.

PubMed

Haskell-Luevano, Carrie; Schaub, Jay W; Andreasen, Amy; Haskell, Kim R; Moore, Marcus C; Koerper, Lorraine M; Rouzaud, Francois; Baker, Henry V; Millard, William J; Walter, Glenn; Litherland, S A; Xiang, Zhimin

2009-02-01

Exercise is a mechanism for maintenance of body weight in humans. Morbidly obese human patients have been shown to possess single nucleotide polymorphisms in the melanocortin-4 receptor (MC4R). MC4R knockout mice have been well characterized as a genetic model that possesses phenotypic metabolic disorders, including obesity, hyperphagia, hyperinsulinemia, and hyperleptinemia, similar to those observed in humans possessing dysfunctional hMC4Rs. Using this model, we examined the effect of voluntary exercise of MC4R knockout mice that were allowed access to a running wheel for a duration of 8 wk. Physiological parameters that were measured included body weight, body composition of fat and lean mass, food consumption, body length, and blood levels of cholesterol and nonfasted glucose, insulin, and leptin. At the termination of the experiment, hypothalamic mRNA expression levels of neuropeptide Y (NPY), agouti-related protein (AGRP), proopiomelanocortin (POMC), cocaine- and amphetamine-regulated transcript (CART), orexin, brain-derived neurotropic factor (BDNF), phosphatase with tensin homology (Pten), melanocortin-3 receptor (MC3R), and NPY-Y1R were determined. In addition, islet cell distribution and function in the pancreas were examined. In the exercising MC4R knockout mice, the pancreatic islet cell morphology and other physiological parameters resembled those observed in the wild-type littermate controls. Gene expression profiles identified exercise as having a significant effect on hypothalamic POMC, orexin, and MC3R levels. Genotype had a significant effect on AGRP, POMC, CART, and NPY-Y1R, with an exercise and genotype interaction effect on NPY gene expression. These data support the hypothesis that voluntary exercise can prevent the genetic predisposition of melanocortin-4 receptor-associated obesity and diabetes.

Belief in Food Addiction and Obesity-Related Policy Support.

PubMed

Schulte, Erica M; Tuttle, Hannah M; Gearhardt, Ashley N

2016-01-01

This study examines whether belief in the food addiction construct is associated with support for obesity-related policies (e.g., restrictions on foods served in schools and workplace cafeterias, subsidies on fruits and vegetables), while simultaneously examining other factors associated with policy support (e.g., political party affiliation). Cross-sectional. Online Community. 200 individuals were recruited through Amazon Mechanical Turk. Participants (n = 193) responded to three questions about belief in food addiction and a measure evaluating support for 13 obesity-related policy initiatives. Individuals also completed the modified Yale Food Addiction Scale (mYFAS), self-reported height and weight, and provided demographic information (age, gender, race, political party affiliation). Belief in food addiction was significantly associated with greater support for obesity-related initiatives, even when accounting for the significant associations of age, gender, and political party. Belief in food addiction and political party both had moderate effect sizes for predicting support for obesity-related policy. There was an interaction between age and belief in food addiction, with significant associations with policy support for both younger and older individuals, though the effect was larger for younger participants. The current study provides evidence that belief in food addiction is associated with increased obesity-related policy support, comparable to the influence of one's political party. Growing evidence for the role of an addictive process in obesity may have important implications for public support of obesity-related policy initiatives.

Belief in Food Addiction and Obesity-Related Policy Support

PubMed Central

2016-01-01

Objectives This study examines whether belief in the food addiction construct is associated with support for obesity-related policies (e.g., restrictions on foods served in schools and workplace cafeterias, subsidies on fruits and vegetables), while simultaneously examining other factors associated with policy support (e.g., political party affiliation). Design Cross-sectional. Setting Online Community. Participants 200 individuals were recruited through Amazon Mechanical Turk. Measurements Participants (n = 193) responded to three questions about belief in food addiction and a measure evaluating support for 13 obesity-related policy initiatives. Individuals also completed the modified Yale Food Addiction Scale (mYFAS), self-reported height and weight, and provided demographic information (age, gender, race, political party affiliation). Results Belief in food addiction was significantly associated with greater support for obesity-related initiatives, even when accounting for the significant associations of age, gender, and political party. Belief in food addiction and political party both had moderate effect sizes for predicting support for obesity-related policy. There was an interaction between age and belief in food addiction, with significant associations with policy support for both younger and older individuals, though the effect was larger for younger participants. Conclusion The current study provides evidence that belief in food addiction is associated with increased obesity-related policy support, comparable to the influence of one’s political party. Growing evidence for the role of an addictive process in obesity may have important implications for public support of obesity-related policy initiatives. PMID:26808427

Sex steroid-induced changes in circulating monocyte chemoattractant protein-1 levels may contribute to metabolic dysfunction in obese men.

PubMed

Ruige, Johannes B; Bekaert, Marlies; Lapauw, Bruno; Fiers, Tom; Lehr, Stefan; Hartwig, Sonja; Herzfeld de Wiza, Daniella; Schiller, Martina; Passlack, Waltraud; Van Nieuwenhove, Yves; Pattyn, Piet; Cuvelier, Claude; Taes, Youri E; Sell, Henrike; Eckel, Juergen; Kaufman, Jean-Marc; Ouwens, D Margriet

2012-07-01

Low testosterone accompanied by elevated estradiol associates with the development of metabolic dysfunction in men. The aim of the study was to explore the hypothesis that alterations in sex steroid levels induce metabolic dysfunction through adipokines. Circulating levels of sex steroids and 28 adipokines were determined in a cross-sectional study of morbidly obese men and aged-matched controls, as well as in a randomized clinical trial with healthy young men in which obesity-related alterations in sex steroid levels were mimicked by treatment with an aromatase inhibitor plus estradiol patches. Morbidly obese men had lower testosterone levels than normal-weight controls. Estradiol levels were increased in morbidly obese men (without DM2) as compared to normal-weight controls. Circulating levels of multiple proinflammatory cytokines, including IL-1Ra, IL-5, IL-6, IL-10, leptin, monocyte chemoattractant protein 1 (MCP1), and macrophage inflammatory protein 1α, positively associated with estradiol and negatively with testosterone. The associations with estradiol, but not with testosterone, remained significant after adjusting for adipocyte cell size. In a separate clinical trial, the direct adverse effects of lowering testosterone and raising estradiol on MCP1 were substantiated in vivo. Initial alterations in sex steroid levels may contribute to metabolic dysfunction through adverse effects on adipokine levels in obese men. The direct adverse effects on MCP1, a chemokine highly linked to the development of metabolic dysfunction, were substantiated in a trial mimicking obesity-related alterations of sex steroid levels in healthy young males.

Piperidine alkaloids from Piperretrofractum Vahl. protect against high-fat diet-induced obesity by regulating lipid metabolism and activating AMP-activated protein kinase

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

Kim, Kyung Jin; Lee, Myoung-Su; Jo, Keunae

Highlights: {yields} Piperidine alkaloids from Piperretrofractum Vahl. (PRPAs), including piperine, pipernonaline, and dehydropipernonaline, are isolated as the anti-obesity constituents. {yields} PRPA administration significantly reduces body weight gain without altering food intake and fat pad mass. {yields} PRPA reduces high-fat diet-induced triglyceride accumulation in liver. {yields} PRPAs attenuate HFD-induced obesity by activating AMPK and PPAR{delta}, and regulate lipid metabolism, suggesting their potential anti-obesity effects. -- Abstract: The fruits of Piperretrofractum Vahl. have been used for their anti-flatulent, expectorant, antitussive, antifungal, and appetizing properties in traditional medicine, and they are reported to possess gastroprotective and cholesterol-lowering properties. However, their anti-obesity activity remainsmore » unexplored. The present study was conducted to isolate the anti-obesity constituents from P. retrofractum Vahl. and evaluate their effects in high-fat diet (HFD)-induced obese mice. Piperidine alkaloids from P. retrofractum Vahl. (PRPAs), including piperine, pipernonaline, and dehydropipernonaline, were isolated as the anti-obesity constituents through a peroxisome proliferator-activated receptor {delta} (PPAR{delta}) transactivation assay. The molecular mechanism was investigated in 3T3-L1 adipocytes and L6 myocytes. PRPA treatment activated AMP-activated protein kinase (AMPK) signaling and PPAR{delta} protein and also regulated the expression of lipid metabolism-related proteins. In the animal model, oral PRPA administration (50, 100, or 300 mg/kg/day for 8 weeks) significantly reduced HFD-induced body weight gain without altering the amount of food intake. Fat pad mass was reduced in the PRPA treatment groups, as evidenced by reduced adipocyte size. In addition, elevated serum levels of total cholesterol, low-density lipoprotein cholesterol, total lipid, leptin, and lipase were suppressed by PRPA treatment. PRPA

CTLA-4Ig immunotherapy of obesity-induced insulin resistance by manipulation of macrophage polarization in adipose tissues

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

Fujii, Masakazu, E-mail: masakazu731079@yahoo.co.jp; Inoguchi, Toyoshi, E-mail: toyoshi@intmed3.med.kyushu-u.ac.jp; Innovation Center for Medical Redox Navigation, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582

Highlights: •CTLA-4Ig completely alleviates HFD-induced insulin resistance. •CTLA-4Ig reduces epididymal and subcutaneous fat tissue weight and adipocyte size. •CTLA-4Ig alters ATM polarization from inflammatory M1 to anti-inflammatory M2. •CTLA-4Ig may lead to a novel anti-obesity/inflammation/insulin resistance agent. •We identified the mechanism of the novel favorable effects of CTLA-4lg. -- Abstract: It has been established that obesity alters the metabolic and endocrine function of adipose tissue and, together with accumulation of adipose tissue macrophages, contributes to insulin resistance. Although numerous studies have reported that shifting the polarization of macrophages from M1 to M2 can alleviate adipose tissue inflammation, manipulation of macrophagemore » polarization has not been considered as a specific therapy. Here, we determined whether cytotoxic T-lymphocyte-associated antigen-4IgG1 (CTLA-4Ig) can ameliorate insulin resistance by induction of macrophages from proinflammatory M1 to anti-inflammatory M2 polarization in the adipose tissues of high fat diet-induced insulin-resistant mice. CTLA4-Ig treatment prevented insulin resistance by changing gene expression to M2 polarization, which increased the levels of arginase 1. Furthermore, flow cytometric analysis confirmed the alteration of polarization from CD11c (M1)- to CD206 (M2)-positive cells. Concomitantly, CTLA-4Ig treatment resulted in weight reductions of epididymal and subcutaneous adipose tissues, which may be closely related to overexpression of apoptosis inhibitors in macrophages. Moreover, proinflammatory cytokine and chemokine levels decreased significantly. In contrast, CCAAT enhancer binding protein α, peroxisome proliferator-activated receptor γ, and adiponectin expression increased significantly in subcutaneous adipose tissue. This novel mechanism of CTLA-4lg immunotherapy may lead to an ideal anti-obesity/inflammation/insulin resistance agent.« less

Comparison of the effects of weight loss from a high-protein versus standard-protein energy-restricted diet on strength and aerobic capacity in overweight and obese men.

PubMed

Wycherley, Thomas P; Buckley, Jonathan D; Noakes, Manny; Clifton, Peter M; Brinkworth, Grant D

2013-02-01

To compare the effects of two low-fat, hypoenergetic diets differing in carbohydrate-to-protein ratio, on strength and aerobic capacity measures in overweight and obese men. In a parallel design, 56 men (age, 45.5 ± 8.7 years; BMI, 33.6 ± 3.9 kg/m(2)) were randomly assigned to a low-fat, energy-restricted diet (7,000 kJ/day) with either high protein (HP: protein/carbohydrate/fat % energy, 35:40:25) or standard protein (SP, 17:58:25). Body weight, body composition, muscle strength and aerobic capacity were assessed at baseline and after 12 weeks. Forty-two participants completed the study (HP, n = 21; SP, n = 21). Both groups experienced similar reductions in body weight (HP, -10.7 ± 5.3 kg [-9.8%]; SP, -8.7 ± 3.5 kg [-8.4%]) and fat-free mass (HP, -2.8 ± 3.6 kg; SP, -3.2 ± 2.7 kg; P < 0.001 time; P > 0.14 time × group interaction). There was a trend for a greater reduction in fat mass in the HP diet group, (-7.7 ± 4.3 kg [-21.2%] vs. -5.4 ± 3.3 kg [-15.1%]; P < 0.001 time; P = 0.06 time × group interaction). Absolute peak oxygen uptake did not change in either group (P = 0.39 time; P = 0.50 time × group interaction). Overall, in both groups, relative peak oxygen uptake increased (2.9 ± 2.8 ml kg(-1) min(-1) [8.9%]), peak isometric knee extensor strength increased (14.1 ± 35.7 Nm [7.1%]) and peak handgrip strength decreased (-1.6 ± 4.1 kg [-3%]) (P ≤ 0.02 time for all), with no diet effect (P ≤ 0.23 time × group interaction). In overweight and obese men, both a HP and SP diet reduced body weight and improved body composition with similar effects on strength and aerobic capacity.

Traffic-related air pollution and childhood obesity in an Italian birth cohort.

PubMed

Fioravanti, Sara; Cesaroni, Giulia; Badaloni, Chiara; Michelozzi, Paola; Forastiere, Francesco; Porta, Daniela

2018-01-01

Air pollution is associated with several adverse health outcomes in children, such as respiratory illnesses and cognitive development impairment. There are suggestions of an effect of traffic-related air pollution on the occurrence of childhood obesity, but the results are not consistent. The aim of the study is to analyse whether air pollution and vehicular traffic exposure, during the first four years of life, influence obesity- related measures among 4 and 8-year-old children from a prospective birth cohort in Rome. A cohort of newborns, enrolled in 2003-2004 within the GASPII project, was followed at 4 and 8 years of age with parental interviews and clinical examinations. Air pollution was assessed at residential address using Land Use Regression models (for NO 2 , NOx, PM 10 , PM 2.5 , PMcoarse, PM2.5 absorbance and one traffic variable (Total traffic load of all roads in a 100m buffer)). The outcomes under study were body mass index (BMI Z-scores according to WHO recommendations, considered both categorical and continuous) measured at 4 and 8 years, and, waist circumference, waist-to-hip ratio, total and HDL cholesterol measured at 8 years. The associations were evaluated through both cross-sectional and longitudinal approaches, using logistic regression models, Generalized Estimating Equation models (GEE) and linear regression models, as appropriate. Moreover, Inverse Probability Weighting (IPW) methodology was used to account for selection bias at enrolment and at follow-up. A total of 719 infants were enrolled and 581 (80.8%) and 499 (69.4%) were followed at 4 and 8 years, respectively. The prevalence of overweight/obesity was 9.3% and 36.9% at 4 and 8 years. No evidence of an association was found between vehicular traffic and being overweight/obese. Similarly, there was no evidence of an association between exposure to air pollutants and all other ponderal excess parameters. The study shows no association between exposure to vehicular traffic and

Fatty Acid-Binding Protein 4 (FABP4): Pathophysiological Insights and Potent Clinical Biomarker of Metabolic and Cardiovascular Diseases

PubMed Central

Furuhashi, Masato; Saitoh, Shigeyuki; Shimamoto, Kazuaki; Miura, Tetsuji

2014-01-01

Over the past decade, evidences of an integration of metabolic and inflammatory pathways, referred to as metaflammation in several aspects of metabolic syndrome, have been accumulating. Fatty acid-binding protein 4 (FABP4), also known as adipocyte FABP (A-FABP) or aP2, is mainly expressed in adipocytes and macrophages and plays an important role in the development of insulin resistance and atherosclerosis in relation to metaflammation. Despite lack of a typical secretory signal peptide, FABP4 has been shown to be released from adipocytes in a non-classical pathway associated with lipolysis, possibly acting as an adipokine. Elevation of circulating FABP4 levels is associated with obesity, insulin resistance, diabetes mellitus, hypertension, cardiac dysfunction, atherosclerosis, and cardiovascular events. Furthermore, ectopic expression and function of FABP4 in several types of cells and tissues have been recently demonstrated. Here, we discuss both the significant role of FABP4 in pathophysiological insights and its usefulness as a biomarker of metabolic and cardiovascular diseases. PMID:25674026

Fatty Acid-Binding Protein 4 (FABP4): Pathophysiological Insights and Potent Clinical Biomarker of Metabolic and Cardiovascular Diseases.

PubMed

Furuhashi, Masato; Saitoh, Shigeyuki; Shimamoto, Kazuaki; Miura, Tetsuji

2014-01-01

Over the past decade, evidences of an integration of metabolic and inflammatory pathways, referred to as metaflammation in several aspects of metabolic syndrome, have been accumulating. Fatty acid-binding protein 4 (FABP4), also known as adipocyte FABP (A-FABP) or aP2, is mainly expressed in adipocytes and macrophages and plays an important role in the development of insulin resistance and atherosclerosis in relation to metaflammation. Despite lack of a typical secretory signal peptide, FABP4 has been shown to be released from adipocytes in a non-classical pathway associated with lipolysis, possibly acting as an adipokine. Elevation of circulating FABP4 levels is associated with obesity, insulin resistance, diabetes mellitus, hypertension, cardiac dysfunction, atherosclerosis, and cardiovascular events. Furthermore, ectopic expression and function of FABP4 in several types of cells and tissues have been recently demonstrated. Here, we discuss both the significant role of FABP4 in pathophysiological insights and its usefulness as a biomarker of metabolic and cardiovascular diseases.

Anti-obesity efficacy of nanoemulsion oleoresin capsicum in obese rats fed a high-fat diet

PubMed Central

Kim, Joo-Yeon; Lee, Mak-Soon; Jung, Sunyoon; Joo, Hyunjin; Kim, Chong-Tai; Kim, In-Hwan; Seo, Sangjin; Oh, Soojung; Kim, Yangha

2014-01-01

Purpose This study determined the effects of oleoresin capsicum (OC) and nanoemulsion OC (NOC) on obesity in obese rats fed a high-fat diet. Methods The rats were randomly separated into three groups: a high-fat (HF) diet group, HF + OC diet group, and HF + NOC diet group. All groups were fed the diet and water ad libitum for 14 weeks. Results NOC reduced the body weight and adipose tissue mass, whereas OC did not. OC and NOC reduced mRNA levels of adipogenic genes, including peroxisome proliferator-activated receptor (PPAR)-γ, sterol regulatory element-binding protein-1c, and fatty acid-binding protein in white adipose tissue. The mRNA levels of genes related to β-oxidation or thermogenesis including PPAR-α, palmitoyltransferase-1α, and uncoupling protein-2 were increased by the OC and NOC relative to the HF group. Both OC and NOC clearly stimulated AMP-activated protein kinase (AMPK) activity. In particular, PPAR-α, palmitoyltransferase-1α, uncoupling protein-2 expression, and AMPK activity were significantly increased in the NOC group compared to in the OC group. NOC decreased glycerol-3-phosphate dehydrogenase activity whereas OC did not. Conclusion From these results, NOC could be suggested as a potential anti-obesity agent in obese rats fed a HF diet. The effects of the NOC on obesity were associated with changes of multiple gene expression, activation of AMPK, and inhibition of glycerol-3-phosphate dehydrogenase in white adipose tissue. PMID:24403834

Anti-obesity efficacy of nanoemulsion oleoresin capsicum in obese rats fed a high-fat diet.

PubMed

Kim, Joo-Yeon; Lee, Mak-Soon; Jung, Sunyoon; Joo, Hyunjin; Kim, Chong-Tai; Kim, In-Hwan; Seo, Sangjin; Oh, Soojung; Kim, Yangha

2014-01-01

This study determined the effects of oleoresin capsicum (OC) and nanoemulsion OC (NOC) on obesity in obese rats fed a high-fat diet. THE RATS WERE RANDOMLY SEPARATED INTO THREE GROUPS: a high-fat (HF) diet group, HF + OC diet group, and HF + NOC diet group. All groups were fed the diet and water ad libitum for 14 weeks. NOC reduced the body weight and adipose tissue mass, whereas OC did not. OC and NOC reduced mRNA levels of adipogenic genes, including peroxisome proliferator-activated receptor (PPAR)-γ, sterol regulatory element-binding protein-1c, and fatty acid-binding protein in white adipose tissue. The mRNA levels of genes related to β-oxidation or thermogenesis including PPAR-α, palmitoyltransferase-1α, and uncoupling protein-2 were increased by the OC and NOC relative to the HF group. Both OC and NOC clearly stimulated AMP-activated protein kinase (AMPK) activity. In particular, PPAR-α, palmitoyltransferase-1α, uncoupling protein-2 expression, and AMPK activity were significantly increased in the NOC group compared to in the OC group. NOC decreased glycerol-3-phosphate dehydrogenase activity whereas OC did not. From these results, NOC could be suggested as a potential anti-obesity agent in obese rats fed a HF diet. The effects of the NOC on obesity were associated with changes of multiple gene expression, activation of AMPK, and inhibition of glycerol-3-phosphate dehydrogenase in white adipose tissue.

Proatherogenic Lipid Profile in Early Childhood: Association with Weight Status at 4 Years and Parental Obesity.

PubMed

Riaño-Galán, Isolina; Fernández-Somoano, Ana; Rodríguez-Dehli, Cristina; Valvi, Damaskini; Vrijheid, Martine; Tardón, Adonina

2017-08-01

To determine lipid profiles in early childhood and evaluate their association with weight status at 4 years of age. Additionally, we evaluated whether the risk of overweight or having an altered lipid profile was associated with parental weight status. Five hundred eighty two mothers and their 4-year-old children from 2 Spanish population-based cohorts were studied. Weight status in children at 4 years of age was classified as overweight or obese using the International Obesity Task Force criteria. Plasma total cholesterol, triglycerides, high-density lipoprotein cholesterol, and low-density lipoprotein cholesterol were determined in children and lipid ratios were calculated. A proatherogenic lipid profile was defined as having the 3 lipid ratios in the third tertile. A total of 12.9% of children were overweight and 6.4% were obese. Weight status at 4 years of age was related to maternal prepregnancy body mass index, paternal body mass index, gestational diabetes, and birth weight, but not with other sociodemographic characteristics of the mother. We found no association with gestational age, sex of the child, or breastfeeding. The risk of overweight/obesity was increased 4.17-fold if mothers were overweight/obese (95% CI 1.76-9.88) and 5.1-fold (95% CI 2.50-10.40) if both parents were overweight/obese. There were 133 children (22.8%) with a proatherogenic lipid profile. The risk of a proatherogenic lipid profile was increased 2.44-fold (95% CI 1.54-3.86) if they were overweight/obese at 4 years of age and 2-fold if the father was overweight/obese (95% CI 1.22-3.35). Four-year-old overweight/obese children have higher lipid risk profiles. Offspring of overweight/obese parents have an increased risk for obesity and a proatherogenic lipid profile. Copyright © 2017 The Author(s). Published by Elsevier Inc. All rights reserved.

Obese and Allergic Related Asthma Phenotypes Among Children Across the United States.

PubMed

Ross, Mindy K; Romero, Tahmineh; Sim, Myung S; Szilagyi, Peter G

2018-04-19

Pediatric asthma is heterogeneous with phenotypes that reflect differing underlying inflammation and pathophysiology. Little is known about the national prevalence of certain obesity and allergy related asthma phenotypes or associated characteristics. We therefore assessed the national prevalence, risk factors, and parent-reported severity of four asthma phenotypes: not-allergic-not-obese, allergic-not-obese, obese-not-allergic, and allergic-and-obese. We analyzed data from the 2007-2008 National Survey of Children's Health (NSCH) of 10-17 year-olds with parent-reported asthma. We described sociodemographic and health risk factors of each phenotype and then applied logistic and ordinal regression models to identify associated risk factors and level of severity of the phenotypes. Among 4,427 children with asthma in this NSCH cohort, the association between race and phenotype is statistically significant (p<0.0001); white children with asthma were most likely to have allergic-not-obese asthma while black and Hispanic children with asthma were most likely to have the obese-non-allergic phenotype (p<0.001). ADD/ADHD was more likely to be present in allergic-not-obese children (OR 1.50, CI 1.14-1.98, p = 0.004). The phenotype with the highest risk for more severe compared to mild asthma was the obese-and-allergic asthma phenotype (OR 3.34, CI 2.23-5.01, p<0.001). Allergic-not-obese asthma comprised half of our studied asthma phenotypes, while obesity-related asthma (with or without allergic components) comprised one-fifth of asthma phenotypes in this cohort representative of the U.S. Children with both obese and allergic asthma are most likely to have severe asthma. Future management of childhood asthma might consider more tailoring of treatment and management plans based upon different childhood asthma phenotypes.

MAP4K4 and IL-6+ Th17 cells play important roles in non-obese type 2 diabetes.

PubMed

Chuang, Huai-Chia; Tan, Tse-Hua

2017-01-07

Obesity is a causal factor of type 2 diabetes (T2D); however, people without obesity (including lean, normal weight, or overweight) may still develop T2D. Non-obese T2D is prevalent in Asia and also frequently occurs in Europe. Recently, multiple evidences oppose the notion that either obesity or central obesity (visceral fat accumulation) promotes non-obese T2D. Several factors such as inflammation and environmental factors contribute to non-obese T2D. According to the data derived from gene knockout mice and T2D clinical samples in Asia and Europe, the pathogenesis of non-obese T2D has been unveiled recently. MAP4K4 downregulation in T cells results in enhancement of the IL-6 + Th17 cell population, leading to insulin resistance and T2D in both human and mice. Moreover, MAP4K4 single nucleotide polymorphisms and epigenetic changes are associated with T2D patients. Interactions between MAP4K4 gene variants and environmental factors may contribute to MAP4K4 attenuation in T cells, leading to non-obese T2D. Future investigations of the pathogenesis of non-obese T2D shall lead to development of precision medicine for non-obese T2D.

[Impact of obesity-related gene polymorphism on risk of obesity and metabolic disorder in childhood].

PubMed

Zhang, Meixian; Zhao, Xiaoyuan; Xi, Bo; Shen, Yue; Wu, Lijun; Cheng, Hong; Hou, Dongqing; Mi, Jie

2014-09-01

To examine the impact of single nucleotide polymorphisms in obesity-related genes on risk of obesity and metabolic disorder in childhood. A total of 3 503 Chinese children aged 6 to 18 years participated in the study, including 1 229 obese, 655 overweight and 1 619 normal weight children (diagnosed by the Chinese age- and sex- specific BMI cutoffs). Body size parameters were assessed and venipuncture blood samples were collected after a 12-hour overnight fast. Plasma glucose, insulin and serum lipid profiles were measured.Genomic DNA was isolated from peripheral blood white cells using the salt fractionation method. A total of 11 single nucleotide polymorphisms were genotyped by TaqMan allelic discrimination assays with the GeneAmp 7900 sequence detection system (Applied Biosystems, Foster City, CA, USA) (FTO rs9939609, MC4R rs17782313, GNPDA2 rs10938397, FAIM2 rs7138803, BDNF rs6265, NPC1 rs1805081, PCSK1 rs6235, KCTD15 rs29941, BAT2 rs2844479, SEC16B rs10913469 and SH2B1 rs4788102). Multiple factor analysis was performed to estimate the association between the variant and obesity-related traits. The false discovery rate (FDR) approach was used to correct for multiple comparisons. After sex, age and pubertal stage adjustment and correction for multiple testing, the rs9939609-A, rs17782313-C, rs10938397-G, and rs7138803-A alleles were associated with higher BMI (β = 0.352-0.747), fat mass percentage(β = 0.568-1.113), waist circumference (β = 0.885-1.649) and waist-to-height ratio(β = 0.005-0.010) (all P values < 0.01) in Chinese children. The rs6265-G allele increased BMI(β = 0.251, P = 0.020). The rs9939609-A, rs17782313-C, and rs10938397-G and rs6265-G alleles were also associated with risk of obesity (OR = 1.386, 95%CI:1.171-1.642; OR = 1.367, 95%CI:1.196-1.563; OR = 1.242, 95%CI:1.102-1.400; OR = 1.156, 95%CI:1.031-1.296).Rs7138803 was associated with risk of obesity only in boys (OR = 1.234, 95%CI:1.043-1.460). GNPDA2 rs10938397-G allele was associated

Pro-HEART - a randomized clinical trial to test the effectiveness of a high protein diet targeting obese individuals with heart failure: rationale, design and baseline characteristics.

PubMed

Motie, Marjan; Evangelista, Lorraine S; Horwich, Tamara; Hamilton, Michele; Lombardo, Dawn; Cooper, Dan M; Galassetti, Pietro R; Fonarow, Gregg C

2013-11-01

There is ample research to support the potential benefits of a high protein diet on clinical outcomes in overweight/obese, diabetic subjects. However, nutritional management of overweight/obese individuals with heart failure (HF) and type 2 diabetes mellitus (DM) or metabolic syndrome (MS) is poorly understood and few clinical guidelines related to nutritional approaches exist for this subgroup. This article describes the design, methods, and baseline characteristics of study participants enrolled in Pro-HEART, a randomized clinical trial to determine the short term and long term effects of a high protein diet (30% protein [~110 g/day], 40% carbohydrates [150 g/day], 30% fat [~50 g/day]) versus a standard protein diet (15% protein [~55 g/day], 55% carbohydrates [~200 g/day], 30% fat [~50 g/day]) on body weight and adiposity, cardiac structure and function, functional status, lipid profile, glycemic control, and quality of life. Between August, 2009 and May, 2013, 61 individuals agreed to participate in the study; 52 (85%) - mean age 58.2 ± 9.8 years; 15.4% Blacks; 57.7% Whites; 19.2% Hispanics; 7.7% Asians; 73.1% male; weight 112.0 ± 22.6 kg - were randomized to a 3-month intensive weight management program of either a high protein or standard protein diet; data were collected at baseline, 3 months, and 15 months. This study has the potential to reveal significant details about the role of macronutrients in weight management of overweight/obese individuals with HF and DM or MS. © 2013 Elsevier Inc. All rights reserved.

Obesity-related decrease in intraoperative blood flow is associated with maturation failure of radiocephalic arteriovenous fistula.

PubMed

Kim, Jwa-Kyung; Jeong, Jae Han; Song, Young Rim; Kim, Hyung Jik; Lee, Won Yong; Kim, Kun Il; Kim, Sung Gyun

2015-10-01

Successful arteriovenous fistula (AVF) maturation is often challenging in obese patients. Optimal initial intraoperative blood flow (IOBF) is essential for adequate AVF maturation. This study was conducted to elucidate the effect of obesity on IOBF and radiocephalic AVF maturation. Patients with a newly created radiocephalic AVF were included (N = 252). Obesity was defined as a baseline body mass index (BMI) ≥25 kg/m(2), and primary maturation failure was defined as failure to use the AVF successfully by 3 months after its creation. IOBF was measured immediately after construction of the AVF with a VeriQ system (MediStim, Oslo, Norway). The mean BMI was 24.1 ± 3.9 kg/m(2), and the prevalence of obesity was 31.3%. Particularly, 8.3% (21 patients) had a BMI ≥30 kg/m(2). Primary maturation failure occurred in 100 patients (39.7%), and an IOBF <190 mL/min was closely associated with the risk of maturation failure (relative risk, 3.05; 95% confidence interval, 1.52-6.11). Compared with nonobese patients, obese subjects had a significantly higher prevalence of diabetes and elevated high-sensitivity C-reactive protein levels, whereas diameters of vessels were similar. When the patients were further divided into three groups as BMI <25, 25 to 29.9, and ≥30 kg/m(2), patients in the higher BMI group showed significantly lower IOBF and higher maturation failure rate. According to multivariate analysis, the statistically significant variables that determined maturation failure were obesity, previous vascular disease, increased high-sensitivity C-reactive protein levels, and IOBF <190 mL/min. Obese patients had a significantly lower IOBF, and both obesity and low IOBF contributed to the primary maturation failure of AVF. Obesity-associated inflammation and atherosclerosis might play roles in this association. Copyright © 2015 Society for Vascular Surgery. Published by Elsevier Inc. All rights reserved.

Kefir Peptides Prevent Hyperlipidemia and Obesity in High-Fat-Diet-Induced Obese Rats via Lipid Metabolism Modulation.

PubMed

Tung, Yu-Tang; Chen, Hsiao-Ling; Wu, Hsin-Shan; Ho, Mei-Hsuan; Chong, Kowit-Yu; Chen, Chuan-Mu

2018-02-01

Obesity has reached epidemic proportions worldwide. Obesity is a complex metabolic disorder that is linked to numerous serious health complications with high morbidity. The present study evaluated the effects of kefir peptides on high fat diet (HFD)-induced obesity in rats. Kefir peptides markedly improved obesity, including body weight gain, inflammatory reactions and the formation of adipose tissue fat deposits around the epididymis and kidney, and adipocyte size. Treating high fat diet (HFD)-induced obese rats with kefir peptides significantly reduced the fatty acid synthase protein and increased the p-acetyl-CoA carboxylase protein to block lipogenesis in the livers. Kefir peptides also increased fatty acid oxidation by increasing the protein expressions of phosphorylated AMP-activated protein kinase, peroxisome proliferator-activated receptor-α, and hepatic carnitine palmitoyltransferase-1 in the livers. In addition, administration of kefir peptides significantly decreased the inflammatory response (TNF-α, IL-1β, and TGF-β) to modulate oxidative damage. These results demonstrate that kefir peptides treatment improves obesity via inhibition of lipogenesis, modulation of oxidative damage, and stimulation of lipid oxidation. Therefore, kefir peptides may act as an anti-obesity agent to prevent body fat accumulation and obesity-related metabolic diseases. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Estrogen receptor protein content is different in abdominal than gluteal subcutaneous adipose tissue of overweight-to-obese premenopausal women.

PubMed

Gavin, Kathleen M; Cooper, Elizabeth E; Hickner, Robert C

2013-08-01

Premenopausal women demonstrate a distinctive gynoid body fat distribution and circulating estrogen status is associated with the maintenance of this adiposity patterning. Estrogen's role in modulation of regional adiposity may occur through estrogen receptors (ERs), which are present in human adipose tissue. The purpose of this study was to determine regional differences in the protein content of ERα, ERβ, and the G protein-coupled estrogen receptor (GPER) between the abdominal (AB) and gluteal (GL) subcutaneous adipose tissue of overweight-to-obese premenopausal women. Biopsies of the subcutaneous AB and GL adipose tissue were performed in 15 premenopausal women (7 Caucasian/8 African American, 25.1 ± 1.8 years, BMI 29.5 ± 0.5kg/m(2)). Adipose tissue protein content was measured by western blot analysis and correlation analyses were conducted to assess the relationship between ER protein content and anthropometric indices/body composition measurements. We found that ERα protein was higher in AB than GL (AB 1.0 ± 0.2 vs GL 0.67 ± 0.1 arbitrary units [AU], P=0.02), ERβ protein was higher in GL than AB (AB 0.78 ± 0.12 vs GL 1.3 ± 0.2 AU, P=0.002), ERα/ERβ ratio was higher in AB than GL (AB 1.9 ± 0.4 vs GL 0.58 ± 0.08 AU, P=0.007), and GPER protein content was similar in AB and GL (P=0.80) subcutaneous adipose tissue. Waist-to-hip ratio was inversely related to gluteal ERβ (r(2)=0.315, P=0.03) and positively related to gluteal ERα/ERβ ratio (r(2)=0.406, P=0.01). These results indicate that depot specific ER content may be an important underlying determinant of regional effects of estrogen in upper and lower body adipose tissue of overweight-to-obese premenopausal women. Copyright © 2013 Elsevier Inc. All rights reserved.

Endocrine Disruptors Leading to Obesity and Related Diseases.

PubMed

Petrakis, Demetrios; Vassilopoulou, Loukia; Mamoulakis, Charalampos; Psycharakis, Christos; Anifantaki, Aliki; Sifakis, Stavros; Docea, Anca Oana; Tsiaoussis, John; Makrigiannakis, Antonios; Tsatsakis, Aristides M

2017-10-24

The review aims to comprehensively present the impact of exposure to endocrine disruptors (EDs) in relation to the clinical manifestation of obesity and related diseases, including diabetes mellitus, metabolic syndrome, cardiovascular diseases, carcinogenesis and infertility. EDs are strong participants in the obesity epidemic scenery by interfering with cellular morphological and biochemical processes; by inducing inflammatory responses; and by presenting transcriptional and oncogenic activity. Obesity and lipotoxicity enhancement occur through reprogramming and/or remodeling of germline epigenome by exposure to EDs. Specific population groups are vulnerable to ED exposure due to current dietary and environmental conditions. Obesity, morbidity and carcinogenicity induced by ED exposure are an evolving reality. Therefore, a new collective strategic approach is deemed essential, for the reappraisal of current global conditions pertaining to energy management.

The missense variation landscape of FTO, MC4R, and TMEM18 in obese children of African Ancestry.

PubMed

Deliard, Sandra; Panossian, Saarene; Mentch, Frank D; Kim, Cecilia E; Hou, Cuiping; Frackelton, Edward C; Bradfield, Jonathan P; Glessner, Joseph T; Zhang, Haitao; Wang, Kai; Sleiman, Patrick M A; Chiavacci, Rosetta M; Berkowitz, Robert I; Hakonarson, Hakon; Zhao, Jianhua; Grant, Struan F A

2013-01-01

Common variation at the loci harboring fat mass and obesity (FTO), melanocortin receptor 4 (MC4R), and transmembrane protein 18 (TMEM18) is consistently reported as being statistically most strongly associated with obesity. Investigations if these loci also harbor rarer missense variants that confer substantially higher risk of common childhood obesity in African American (AA) children were conducted. The exons of FTO, MC4R, and TMEM18 in an initial subset of our cohort were sequenced, that is, 200 obese (BMI ≥ 95 th percentile) and 200 lean AA children (BMI ≤ 5 th percentile). Any missense exonic variants that were uncovered went on to be further genotyped in a further 768 obese and 768 lean (BMI≤50th percentile) children of the same ethnicity. A number of exonic variants were observed from our sequencing effort: seven in FTO, of which four were non-synonymous (A163T, G182A, M400V, and A405V), thirteen in MC4R, of which six were non-synonymous (V103I, N123S, S136A, F202L, N240S, and I251L), and four in TMEM18, of which two were non-synonymous (P2S and V113L). Follow-up genotyping of these missense variants revealed only one significant difference in allele frequency between cases and controls, namely with N240S in MC4R (Fisher's exact P = 0.0001). In summary, moderately rare missense variants within the FTO, MC4R, and TMEM18 genes observed in our study did not confer risk of common childhood obesity in African Americans except for a degree of evidence for one known loss-of-function variant in MC4R. Copyright © 2012 The Obesity Society.

Correlation of TLR4 and KLF7 in Inflammation Induced by Obesity.

PubMed

Wang, Cuizhe; Ha, Xiaodan; Li, Wei; Xu, Peng; Gu, Yajuan; Wang, Tingting; Wang, Yan; Xie, Jianxin; Zhang, Jun

2017-02-01

Objective Recent studies have revealed a link between toll-like receptors (TLRs), Kruppel-like factors (KLFs), and the adipose tissue inflammation associated with obesity. TLR4 is associated with chronic inflammation in obesity. KLF7 is known to play an important role in the differentiation of adipocytes, but its role in visceral adipose tissue inflammation has not yet been investigated. Thus, the objective of this study was to determine the correlation of TLR4 and KLF7 in inflammation induced by obesity. Methods A total of 32 Wistar male rat subjects were fed in the center for experimental animals of Shihezi University. The rats were divided into normal control (NC) and high-fat diet (HFD) group. Surgical instruments were used to collect rats' visceral adipose tissue samples in the 10th week after HFD feeding. Ninety-five Uygur subjects between 20 and 90 years old were enrolled in the present study. The subjects were divided into two groups: the normal control group (NC, 18.0 kg/m 2  ≤ BMI ≤ 23.9 kg/m 2 , n = 50) and the obesity group (OB, BMI ≥ 28 kg/m 2 , n = 45), and visceral adipose tissue was collected from the subjects. Anthropometric and clinical parameters were measured using standard procedures; biochemical indices were detected using the glucose oxidase-peroxidase method and a standardized automatic biochemistry analyzer; the plasma levels of inflammatory factors and adipocytokines were measured by enzyme-linked immunosorbent assay (ELISA); the mRNA and protein expression levels of key genes involved in the inflammatory signaling pathway were measured by real-time PCR and Western blot. Results In rats, compared with the NC group, the weight, Lee's index, waist circumference, visceral fat mass, and the plasma level of Glu, TG, FFA, and TNF-α were higher in the HFD group, while the plasma levels of LPT and APN were significantly lower in the HFD group in the 10th week. Furthermore, compared with the NC group, visceral adipose

Colchicine to decrease NLRP3-activated inflammation and improve obesity-related metabolic dysregulation

PubMed Central

Demidowich, Andrew P.; Davis, Angela I.; Dedhia, Nicket; Yanovski, Jack A.

2016-01-01

Obesity is a major risk-factor for the development of insulin resistance, type 2 diabetes, and cardiovascular disease. Circulating molecules associated with obesity, such as saturated fatty acids and cholesterol crystals, stimulate the innate immune system to incite a chronic inflammatory state. Studies in mouse models suggest that suppressing the obesity-induced chronic inflammatory state may prevent or reverse obesity-associated metabolic dysregulation. Human studies, however, have been far less positive, possibly because targeted interventions were too far downstream of the inciting inflammatory events. Recently, it has been shown that, within adipose tissue macrophages, assembly of a multi-protein member of the innate immune system, the NOD-like receptor family pyrin domain containing 3 (NLRP3) inflammasome, is essential for the induction of this inflammatory state. Microtubules enable the necessary spatial arrangement of the components of the NLRP3 inflammasome in the cell, leading to its activation and propagation of the inflammatory cascade. Colchicine, a medication classically used for gout, mediates its anti-inflammatory effect by inhibiting tubulin polymerization, and has been shown to attenuate macrophage NLRP3 inflammasome arrangement and activation in vitro and in vivo. Given these findings, we hypothesize that, in at-risk individuals (those with obesity-induced inflammation and metabolic dysregulation), long-term colchicine use will lead to suppression of inflammation and thus cause improvements in insulin sensitivity and other obesity-related metabolic impairments. PMID:27241260

A High-Protein Diet Reduces Weight Gain, Decreases Food Intake, Decreases Liver Fat Deposition, and Improves Markers of Muscle Metabolism in Obese Zucker Rats

PubMed Central

French, William W.; Dridi, Sami; Shouse, Stephanie A.; Wu, Hexirui; Hawley, Aubree; Lee, Sun-Ok; Gu, Xuan; Baum, Jamie I.

2017-01-01

A primary factor in controlling and preventing obesity is through dietary manipulation. Diets higher in protein have been shown to improve body composition and metabolic health during weight loss. The objective of this study was to examine the effects of a high-protein diet versus a moderate-protein diet on muscle, liver and fat metabolism and glucose regulation using the obese Zucker rat. Twelve-week old, male, Zucker (fa/fa) and lean control (Fa/fa) rats were randomly assigned to either a high-protein (40% energy) or moderate-protein (20% energy) diet for 12 weeks, with a total of four groups: lean 20% protein (L20; n = 8), lean 40% protein (L40; n = 10), obese 20% protein (O20; n = 8), and obese 40% protein (O40; n = 10). At the end of 12 weeks, animals were fasted and euthanized. There was no difference in food intake between L20 and L40. O40 rats gained less weight and had lower food intake (p < 0.05) compared to O20. O40 rats had lower liver weight (p < 0.05) compared to O20. However, O40 rats had higher orexin (p < 0.05) levels compared to L20, L40 and O20. Rats in the L40 and O40 groups had less liver and muscle lipid deposition compared to L20 and L40 diet rats, respectively. O40 had decreased skeletal muscle mechanistic target of rapamycin complex 1 (mTORC1) phosphorylation and peroxisome proliferator-activated receptor gamma (PPARγ) mRNA expression compared to O20 (p < 0.05), with no difference in 5′ AMP-activated protein kinase (AMPK), eukaryotic translation initiation factor 4E binding protein 1 (4EBP1), protein kinase B (Akt) or p70 ribosomal S6 kinase (p70S6K) phosphorylation. The data suggest that high-protein diets have the potential to reduce weight gain and alter metabolism, possibly through regulation of an mTORC1-dependent pathway in skeletal muscle. PMID:28594375

A High-Protein Diet Reduces Weight Gain, Decreases Food Intake, Decreases Liver Fat Deposition, and Improves Markers of Muscle Metabolism in Obese Zucker Rats.

PubMed

French, William W; Dridi, Sami; Shouse, Stephanie A; Wu, Hexirui; Hawley, Aubree; Lee, Sun-Ok; Gu, Xuan; Baum, Jamie I

2017-06-08

A primary factor in controlling and preventing obesity is through dietary manipulation. Diets higher in protein have been shown to improve body composition and metabolic health during weight loss. The objective of this study was to examine the effects of a high-protein diet versus a moderate-protein diet on muscle, liver and fat metabolism and glucose regulation using the obese Zucker rat. Twelve-week old, male, Zucker (fa/fa) and lean control (Fa/fa) rats were randomly assigned to either a high-protein (40% energy) or moderate-protein (20% energy) diet for 12 weeks, with a total of four groups: lean 20% protein (L20; n = 8), lean 40% protein (L40; n = 10), obese 20% protein (O20; n = 8), and obese 40% protein (O40; n = 10). At the end of 12 weeks, animals were fasted and euthanized. There was no difference in food intake between L20 and L40. O40 rats gained less weight and had lower food intake ( p < 0.05) compared to O20. O40 rats had lower liver weight ( p < 0.05) compared to O20. However, O40 rats had higher orexin ( p < 0.05) levels compared to L20, L40 and O20. Rats in the L40 and O40 groups had less liver and muscle lipid deposition compared to L20 and L40 diet rats, respectively. O40 had decreased skeletal muscle mechanistic target of rapamycin complex 1 (mTORC1) phosphorylation and peroxisome proliferator-activated receptor gamma (PPARγ) mRNA expression compared to O20 ( p < 0.05), with no difference in 5' AMP-activated protein kinase (AMPK), eukaryotic translation initiation factor 4E binding protein 1 (4EBP1), protein kinase B (Akt) or p70 ribosomal S6 kinase (p70S6K) phosphorylation. The data suggest that high-protein diets have the potential to reduce weight gain and alter metabolism, possibly through regulation of an mTORC1-dependent pathway in skeletal muscle.

Interactome of Obesity: Obesidome : Genetic Obesity, Stress Induced Obesity, Pathogenic Obesity Interaction.

PubMed

Geronikolou, Styliani A; Pavlopoulou, Athanasia; Cokkinos, Dennis; Chrousos, George

2017-01-01

Obesity is a chronic disease of increasing prevalence reaching epidemic proportions. Genetic defects as well as epigenetic effects contribute to the obesity phenotype. Investigating gene (e.g. MC4R defects)-environment (behavior, infectious agents, stress) interactions is a relative new field of great research interest. In this study, we have made an effort to create an interactome (henceforth referred to as "obesidome"), where extrinsic stressors response, intrinsic predisposition, immunity response to inflammation and autonomous nervous system implications are integrated. These pathways are presented in one interactome network for the first time. In our study, obesity-related genes/gene products were found to form a complex interactions network.

The Potential Role of Aerobic Exercise-Induced Pentraxin 3 on Obesity-Related Inflammation and Metabolic Dysregulation.

PubMed

Slusher, Aaron L; Huang, Chun-Jung; Acevedo, Edmund O

2017-01-01

Obesity is defined as the excess accumulation of intra-abdominal body fat, resulting in a state of chronic, low-grade proinflammation that can directly contribute to the development of insulin resistance. Pentraxin 3 (PTX3) is an acute-phase protein that is expressed by a variety of tissue and cell sources and provides an anti-inflammatory property to downregulate the production of proinflammatory cytokines, in particular interleukin-1 beta and tumor necrosis factor alpha. Although PTX3 may therapeutically aid in altering the proinflammatory milieu in obese individuals, and despite elevated expression of PTX3 mRNA observed in adipose tissue, the circulating level of PTX3 is reduced with obesity. Interestingly, aerobic activity has been demonstrated to elevate PTX3 levels. Therefore, the purpose of this review is to discuss the therapeutic potential of PTX3 to positively regulate obesity-related inflammation and discuss the proposition for utilizing aerobic exercise as a nonpharmacological anti-inflammatory treatment strategy to enhance circulating PTX3 concentrations in obese individuals.

Cyanidin 3-glucoside ameliorates hyperglycemia and insulin sensitivity due to downregulation of retinol binding protein 4 expression in diabetic mice.

PubMed

Sasaki, Rie; Nishimura, Natsumi; Hoshino, Hiromi; Isa, Yasuka; Kadowaki, Maho; Ichi, Takahito; Tanaka, Akihito; Nishiumi, Shin; Fukuda, Itsuko; Ashida, Hitoshi; Horio, Fumihiko; Tsuda, Takanori

2007-12-03

Adipocyte dysfunction is strongly associated with the development of obesity and insulin resistance. It is accepted that the regulation of adipocytokine expression is one of the most important targets for the prevention of obesity and improvement of insulin sensitivity. In this study, we have demonstrated that anthocyanin (cyanidin 3-glucoside; C3G) which is a pigment widespread in the plant kingdom, ameliorates hyperglycemia and insulin sensitivity due to the reduction of retinol binding protein 4 (RBP4) expression in type 2 diabetic mice. KK-A(y) mice were fed control or control +0.2% of a C3G diet for 5 weeks. Dietary C3G significantly reduced blood glucose concentration and enhanced insulin sensitivity. The adiponectin and its receptors expression were not responsible for this amelioration. C3G significantly upregulated the glucose transporter 4 (Glut4) and downregulated RBP4 in the white adipose tissue, which is accompanied by downregulation of the inflammatory adipocytokines (monocyte chemoattractant protein-1 and tumor necrosis factor-alpha) in the white adipose tissue of the C3G group. These findings indicate that C3G has significant potency in an anti-diabetic effect through the regulation of Glut4-RBP4 system and the related inflammatory adipocytokines.

Inhibition of Mdmx (Mdm4) in vivo induces anti-obesity effects.

PubMed

Kon, Ning; Wang, Donglai; Li, Tongyuan; Jiang, Le; Qiang, Li; Gu, Wei

2018-01-26

Although cell-cycle arrest, senescence and apoptosis remain as major canonical activities of p53 in tumor suppression, the emerging role of p53 in metabolism has been a topic of great interest. Nevertheless, it is not completely understood how p53-mediated metabolic activities are regulated in vivo and whether this part of the activities has an independent role beyond tumor suppression. Mdmx (also called Mdm4), like Mdm2, acts as a major suppressor of p53 but the embryonic lethality of mdmx-null mice creates difficulties to evaluate its physiological significance in metabolism. Here, we report that the embryonic lethality caused by the deficiency of mdmx , in contrast to the case for mdm2 , is fully rescued in the background of p53 3KR/3KR , an acetylation-defective mutant unable to induce cell-cycle arrest, senescence and apoptosis. p53 3KR/3KR /mdmx -/- mice are healthy but skinny without obvious developmental defects. p53 3KR/3KR /mdmx -/- mice are resistant to fat accumulation in adipose tissues upon high fat diet. Notably, the levels of p53 protein are only slightly increased and can be further induced upon DNA damage in p53 3KR/3KR /mdmx -/- mice, suggesting that Mdmx is only partially required for p53 degradation in vivo . Further analyses indicate that the anti-obesity phenotypes in p53 3KR/3KR /mdmx -/- mice are caused by activation of lipid oxidation and thermogenic programs in adipose tissues. These results demonstrate the specific effects of the p53/Mdmx axis in lipid metabolism and adipose tissue remodeling and reveal a surprising role of Mdmx inhibition in anti-obesity effects beyond, commonly expected, tumor suppression. Thus, our study has significant implications regarding Mdmx inhibitors in the treatment of obesity related diseases.

Variants in the human intestinal fatty acid binding protein 2 gene in obese subjects.

PubMed

Sipiläinen, R; Uusitupa, M; Heikkinen, S; Rissanen, A; Laakso, M

1997-08-01

Fatty acid binding protein 2 gene (FABP2) has been proposed to be an important candidate gene for insulin resistance; therefore, it also could be a promising candidate gene for obesity. We screened the whole coding region of the FABP2 gene in 40 obese nondiabetic Finnish subjects. Furthermore, we investigated the effects of the codon 54 polymorphism of this gene (Ala-->Thr) on insulin levels and basal metabolic rate in 170 obese subjects. The frequencies of the variants found in exon 4 (GTA-->GTG) and 3'-noncoding region (GCGCA-->GCACA), as well as the allele frequencies for the variable lengths of the ATT repeat sequence in intron 2 did not differ between the obese subjects and nonobese controls. The frequency of threonine-encoding allele in codon 54 of the FABP2 gene did not differ between obese and control subjects (28 vs. 29%, respectively). In the obese group there were no differences in gender distribution, age, weight, body mass index, lean body mass, percentage of body fat, waist circumference, and waist-to-hip ratio among the individuals homozygous for Ala54, heterozygous for Thr54, and homozygous for Thr54-encoding alleles. Similarly, fasting serum insulin, glucose, lipids and lipoprotein concentrations, basal metabolic rate (adjusted for lean body mass and age), respiratory quotient, and rates of glucose and lipid oxidation did not differ among the groups. We conclude that obesity is not associated with specific variants in the FABP2 gene. Furthermore, the codon 54 Ala to Thr polymorphism of this gene does not influence insulin levels or basal metabolic rate in obese Finns.

Relation of Obesity to New-Onset Atrial Fibrillation and Atrial Flutter in Adults.

PubMed

Foy, Andrew J; Mandrola, John; Liu, Guodong; Naccarelli, Gerald V

2018-05-01

Prospective cohort studies involving older adults report an association of obesity and new-onset atrial fibrillation and atrial flutter. To assess this relation, we performed a longitudinal cohort study from January 1, 2006 to December 31, 2013, using a national claims database that tracks all inpatient, outpatient, and pharmacy claims data. The primary end point of new-onset atrial fibrillation was compared between obese and nonobese cohorts. We used logistic regression to determine the strength of association between obesity and new-onset atrial fibrillation controlling for age, gender, hypertension, and diabetes. Overall, 67,278 subjects were included in the cohort, divided evenly between those with and without a diagnosis of obesity. Obese subjects were significantly more likely to have hypertension (29.5% vs 14.6%) and diabetes (12.7% vs 5.2%) at study onset. Over 8 years of follow-up, we recorded a new diagnosis of atrial fibrillation in 1,511 (2.2%) subjects. Obesity was strongly associated with a new diagnosis of atrial fibrillation after controlling for age, gender, hypertension, and diabetes (odds ratio 1.4, 95% confidence interval 1.3 to 1.6). In conclusion, this information contributes to the growing evidence supporting the causal relation between obesity and atrial fibrillation, and emphasizes the need of addressing obesity as part of our therapeutic strategy to prevent atrial fibrillation. Copyright © 2018 Elsevier Inc. All rights reserved.

Novel genes in brain tissues of EAE-induced normal and obese mice: Upregulation of metal ion-binding protein genes in obese-EAE mice.

PubMed

Hasan, Mahbub; Seo, Ji-Eun; Rahaman, Khandoker Asiqur; Min, Hophil; Kim, Ki Hun; Park, Ju-Hyung; Sung, Changmin; Son, Junghyun; Kang, Min-Jung; Jung, Byung Hwa; Park, Won Sang; Kwon, Oh-Seung

2017-02-20

Experimental autoimmune encephalomyelitis (EAE) is an inflammatory autoimmune disease of the central nervous system resulting from degeneration of the myelin sheath. This study is aimed to identify differentially expressed genes (DEGs) in the brain of EAE-induced normal diet (ND) mice and high-fat diet (HFD)-induced obese mice, and to identify novel genes responsible for elucidating the mechanism of the disease. Purified mRNA samples from the brain tissue were analyzed for gene microarray and validated by real-time RT-PCR. DEGs were identified if significant changes greater than 1.5-fold or less than 0.66-fold were observed (p<0.05). Pathway construction and functional categorization were performed using the Kyoto encyclopedia of genes and genomes pathways and gene ontology (GO) analysis. HFD-EAE mice showed more severe disease symptoms than ND-EAE mice. From GO study, fold changes of HFD-EAE to ND-EAE genes indicated that the genes were significantly associated to the pathways related with the immune response, antigen presentation, and complement activation. The genes related with metal ion-binding proteins were upregulated in HFD-EAE and ND-EAE mice. Upregulation of Cul9, Mast2, and C4b expression is significantly higher in HFD-EAE mice than ND-EAE mice. Cul9, Mast2, C4b, Psmb8, Ly86, and Ms4a6d were significantly upregulated in both ND- and HFD-EAE mice. Fcgr4, S3-12, Gca, and Zdhhc4 were upregulated only in ND-EAE, and Xlr4b was upregulated only in HFD-EAE mice. And significant upregulated genes of metal ion-binding proteins (Cul9 and Mast2) were observed in HFD-EAE mice. Copyright © 2016 IBRO. Published by Elsevier Ltd. All rights reserved.

Biochemical and metabolic mechanisms by which dietary whey protein may combat obesity and Type 2 diabetes.

PubMed

Jakubowicz, Daniela; Froy, Oren

2013-01-01

Consumption of milk and dairy products has been associated with reduced risk of metabolic disorders and cardiovascular disease. Milk contains two primary sources of protein, casein (80%) and whey (20%). Recently, the beneficial physiological effects of whey protein on the control of food intake and glucose metabolism have been reported. Studies have shown an insulinotropic and glucose-lowering properties of whey protein in healthy and Type 2 diabetes subjects. Whey protein seems to induce these effects via bioactive peptides and amino acids generated during its gastrointestinal digestion. These amino acids and peptides stimulate the release of several gut hormones, such as cholecystokinin, peptide YY and the incretins gastric inhibitory peptide and glucagon-like peptide 1 that potentiate insulin secretion from β-cells and are associated with regulation of food intake. The bioactive peptides generated from whey protein may also serve as endogenous inhibitors of dipeptidyl peptidase-4 (DPP-4) in the proximal gut, preventing incretin degradation. Indeed, recently, DPP-4 inhibitors were identified in whey protein hydrolysates. This review will focus on the emerging properties of whey protein and its potential clinical application for obesity and Type 2 diabetes. Copyright © 2013 Elsevier Inc. All rights reserved.

Extreme obesity is associated with variation in genes related to the circadian rhythm of food intake and hypothalamic signaling.

PubMed

Mariman, Edwin C M; Bouwman, Freek G; Aller, Erik E J G; van Baak, Marleen A; Wang, Ping

2015-06-01

The hypothalamus is important for regulation of energy intake. Mutations in genes involved in the function of the hypothalamus can lead to early-onset severe obesity. To look further into this, we have followed a strategy that allowed us to identify rare and common gene variants as candidates for the background of extreme obesity from a relatively small cohort. For that we focused on subjects with a well-selected phenotype and on a defined gene set and used a rich source of genetic data with stringent cut-off values. A list of 166 genes functionally related to the hypothalamus was generated. In those genes complete exome sequence data from 30 extreme obese subjects (60 genomes) were screened for novel rare indel, nonsense, and missense variants with a predicted negative impact on protein function. In addition, (moderately) common variants in those genes were analyzed for allelic association using the general population as reference (false discovery rate<0.05). Six novel rare deleterious missense variants were found in the genes for BAIAP3, NBEA, PRRC2A, RYR1, SIM1, and TRH, and a novel indel variant in LEPR. Common variants in the six genes for MBOAT4, NPC1, NPW, NUCB2, PER1, and PRRC2A showed significant allelic association with extreme obesity. Our findings underscore the complexity of the genetic background of extreme obesity involving rare and common variants of genes from defined metabolic and physiologic processes, in particular regulation of the circadian rhythm of food intake and hypothalamic signaling. Copyright © 2015 the American Physiological Society.

Impact of obesity-related genes in Spanish population

PubMed Central

2013-01-01

Background The objective was to investigate the association between BMI and single nucleotide polymorphisms previously identified of obesity-related genes in two Spanish populations. Forty SNPs in 23 obesity-related genes were evaluated in a rural population characterized by a high prevalence of obesity (869 subjects, mean age 46 yr, 62% women, 36% obese) and in an urban population (1425 subjects, mean age 54 yr, 50% women, 19% obese). Genotyping was assessed by using SNPlex and PLINK for the association analysis. Results Polymorphisms of the FTO were significantly associated with BMI, in the rural population (beta 0.87, p-value <0.001). None of the other SNPs showed significant association after Bonferroni correction in the two populations or in the pooled analysis. A weighted genetic risk score (wGRS) was constructed using the risk alleles of the Tag-SNPs with a positive Beta parameter in both populations. From the first to the fifth quintile of the score, the BMI increased 0.45 kg/m2 in Hortega and 2.0 kg/m2 in Pizarra. Overall, the obesity predictive value was low (less than 1%). Conclusion The risk associated with polymorphisms is low and the overall effect on BMI or obesity prediction is minimal. A weighted genetic risk score based on genes mainly acting through central nervous system mechanisms was associated with BMI but it yields minimal clinical prediction for the obesity risk in the general population. PMID:24267414

Impact of obesity-related genes in Spanish population.

PubMed

Martínez-García, Fernando; Mansego, María L; Rojo-Martínez, Gemma; De Marco-Solar, Griselda; Morcillo, Sonsoles; Soriguer, Federico; Redón, Josep; Pineda Alonso, Monica; Martín-Escudero, Juan C; Cooper, Richard S; Chaves, Felipe J

2013-11-23

The objective was to investigate the association between BMI and single nucleotide polymorphisms previously identified of obesity-related genes in two Spanish populations. Forty SNPs in 23 obesity-related genes were evaluated in a rural population characterized by a high prevalence of obesity (869 subjects, mean age 46 yr, 62% women, 36% obese) and in an urban population (1425 subjects, mean age 54 yr, 50% women, 19% obese). Genotyping was assessed by using SNPlex and PLINK for the association analysis. Polymorphisms of the FTO were significantly associated with BMI, in the rural population (beta 0.87, p-value <0.001). None of the other SNPs showed significant association after Bonferroni correction in the two populations or in the pooled analysis. A weighted genetic risk score (wGRS) was constructed using the risk alleles of the Tag-SNPs with a positive Beta parameter in both populations. From the first to the fifth quintile of the score, the BMI increased 0.45 kg/m2 in Hortega and 2.0 kg/m2 in Pizarra. Overall, the obesity predictive value was low (less than 1%). The risk associated with polymorphisms is low and the overall effect on BMI or obesity prediction is minimal. A weighted genetic risk score based on genes mainly acting through central nervous system mechanisms was associated with BMI but it yields minimal clinical prediction for the obesity risk in the general population.

Glutathionylation of hepatic and visceral adipose proteins decreases in obese-prone, glucose intolerant rats

USDA-ARS?s Scientific Manuscript database

Obesity and insulin resistance are associated with increases in oxidative stress and lipid peroxidation. On the other hand, adipocytes from obese animals have elevated GSH content, and insulin resistance can be reversed by GSH depletion. Oxidation of active site cysteines of protein tyrosine phospha...

Inhibition of 11β-hydroxysteroid dehydrogenase type 1 ameliorates obesity-related insulin resistance.

PubMed

Shao, Shiying; Zhang, Xiaojie; Zhang, Muxun

2016-09-09

Excess 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) may be implicated in the development of obesity related metabolic disorders. The present study measured the expression level of 11β-HSD1 in visceral adipose tissues from 23 patients undergoing abdominal operation. Correlation of 11β-HSD1 expression with BMI, waist-to-hip ratio (WHR), HOMA-IR, and serum lipids was evaluated by spearman correlation analysis. High-fat diet-induced obese (DIO) rats were orally dosed with BVT.2733 for 4 weeks. Weight, plasma insulin, and lipids were detected at the end of the treatment. The effects of 11β-HSD1 inhibition on the key insulin-signaling cascade and adipocytokines were measured by western blot and ELISA respectively. 11β-HSD1 was increased in patients with central obesity, the expression level of which was closely related with WHR (r = 0.5851), BMI (r = 0.4952), and HOMA-IR (r = 0.4637). Obesity related insulin resistance in high-fat DIO rats, as reflected by a marked decrease in IRS-1, IRS-2, GLUT4, and PI3K, could be attenuated by 11β-HSD1 inhibition. Furthermore, the down-regulation of 11β-HSD1 could correct the disordered profiles of adipocytokines including adiponectin, IL-6, and TNF-α. These findings indicated that 11β-HSD1 inhibition can give a potential benefit in reducing obesity and lowering insulin resistance by modulating the insulin-signaling pathway and adipocytokine production. Copyright © 2016. Published by Elsevier Inc.

Dietary fish protein hydrolysates containing bioactive motifs affect serum and adipose tissue fatty acid compositions, serum lipids, postprandial glucose regulation and growth in obese Zucker fa/fa rats.

PubMed

Drotningsvik, Aslaug; Mjøs, Svein A; Pampanin, Daniela M; Slizyte, Rasa; Carvajal, Ana; Remman, Tore; Høgøy, Ingmar; Gudbrandsen, Oddrun A

2016-10-01

The world's fisheries and aquaculture industries produce vast amounts of protein-containing by-products that can be enzymatically hydrolysed to smaller peptides and possibly be used as additives to functional foods and nutraceuticals targeted for patients with obesity-related metabolic disorders. To investigate the effects of fish protein hydrolysates on markers of metabolic disorders, obese Zucker fa/fa rats consumed diets with 75 % of protein from casein/whey (CAS) and 25 % from herring (HER) or salmon (SAL) protein hydrolysate from rest raw material, or 100 % protein from CAS for 4 weeks. The fatty acid compositions were similar in the experimental diets, and none of them contained any long-chain n-3 PUFA. Ratios of lysine:arginine and methionine:glycine were lower in HER and SAL diets when compared with CAS, and taurine was detected only in fish protein hydrolysate diets. Motifs with reported hypocholesterolemic or antidiabetic activities were identified in both fish protein hydrolysates. Rats fed HER diet had lower serum HDL-cholesterol and LDL-cholesterol, and higher serum TAG, MUFA and n-3:n-6 PUFA ratio compared with CAS-fed rats. SAL rats gained more weight and had better postprandial glucose regulation compared with CAS rats. Serum lipids and fatty acids were only marginally affected by SAL, but adipose tissue contained less total SFA and more total n-3 PUFA when compared with CAS. To conclude, diets containing hydrolysed rest raw material from herring or salmon proteins may affect growth, lipid metabolism, postprandial glucose regulation and fatty acid composition in serum and adipose tissue in obese Zucker rats.

Impact of the Polymorphism Near MC4R (rs17782313) on Obesity- and Metabolic-Related Traits in Women Participating in an Aerobic Training Program.

PubMed

Leońska-Duniec, Agata; Jastrzębski, Zbigniew; Zarębska, Aleksandra; Smółka, Wojciech; Cięszczyk, Paweł

2017-09-01

The C/T polymorphism (rs17782313) mapped 188 kb downstream of the melanocortin-4 receptor gene (MC4R) shows a strong relationship with an increased body mass index (BMI) and the risk of type 2 diabetes. However, the information on polymorphism's potential modifying effect on obesity- and metabolic-related traits achieved through training is still unknown. Therefore, we decided to check if selected body measurements observed in physically active participants would be modulated by the genotype. The genotype distribution was examined in a group of 201 Polish women measured for chosen traits before and after the completion of a 12 week moderate-intensive aerobic training program. A statistically significant relationship between the glucose level and the genotype was identified (p = 0.046). Participants with CC and CT genotypes had a higher glucose level during the entire study period compared with the TT genotype. However, our results did not confirm the relationship between the C allele and an increased BMI or other obesity-related traits. Additionally, we did not observe a near MC4R C/T polymorphism x physical activity interaction. However, our results revealed that majority of obesity-related variables changed significantly during the 12 week training program. The effect sizes (d) of these changes ranged from small to medium (d = 0.11-0.80), whereas the largest effect (d = 0.80; i.e. medium) was reported for the fat mass content (FM). We found a relationship between the near MC4R C/T polymorphism and an increased glucose level, and it is thus a candidate to influence type 2 diabetes. Interestingly, after the 12 week training program, participants with the C (risk) allele with fasting hyperglycemia had a normal glucose level. Although, this change was not statistically significant, it shows an important trend which needs further investigation.

[Visfatin in obese patients, relation with cardiovascular risk factors, a cross sectional study].

PubMed

de Luis, Daniel A; Ballesteros, María; Ruiz, Enrique; Muñoz, Carmen; Penacho, Angeles; Iglesias, Pedro; Guzmán, Antonio López; Abreu, Cristina; Maldonado, Alfonso; Delgado, Manuel; Martín, Lucía San; Puigdevall, Victor; Romero, Enrique; Sagrado, Manuel González; Izaola, Olatz; Conde, Rosa

2011-07-23

Obesity and insulin resistance are associated with cardiovascular risk factors. The aim of the present study was to explore the relation of visfatin with insulin resistance, cardiovascular risk factors and anthropometry in obese patients without comorbidities. A population of 270 obese patients was analyzed in a prospective way. In all patients we performed a biochemical analysis (lipid profile, insulin, HOMA and visfatina), and a nutritional evaluation (dietary intake, conventional anthropometry and bioimpedance). Patients were divided in two groups by median visfatin value (8,32 ng/ml), group I (patients with the low values, average value 7,11 (0,7) ng/ml) and group II (patients with the high values, average value 13,5 (10,1) ng/ml). Patients in the group I had higher weight, body mass index, waist circumference, and waist to hip ratio than patients in group II. Patients in group I had lower LDL-cholesterol and C reactive protein than patients in group II. Correlation analysis showed a positive correlation between visfatin levels and LDL cholesterol (r=0.194; p<0.05) and C reactive protein (r=0.266; p<0.05) and a negative corelation with weight (r=-0.162; p<0.05). In the logistic analysis with age-, sex- and dietary intake- adjusted basal visfatin concentration as a dependent variable, the next variables remained in the model; weight with an odds ratio (OR) 0,97 (IC95% 0,95-0,99), LDL cholesterol 1,012(1,010-1.023) and C reactive protein 1,15 (1.03-1.3). LDL cholesterol and c reactive protein levels are positively correlated with visfatin levels. Weight is negatively correlated with visfatin levels, in an independent way and adjusted by age, sex and dietary intake. Copyright © 2010 Elsevier España, S.L. All rights reserved.

Roux-en-Y gastric bypass surgery suppresses hypothalamic PTP1B protein level and alleviates leptin resistance in obese rats

PubMed Central

Liu, Jia-Yu; Mu, Song; Zhang, Shu-Ping; Guo, Wei; Li, Qi-Fu; Xiao, Xiao-Qiu; Zhang, Jun; Wang, Zhi-Hong

2017-01-01

The present study aimed to explore the effect of Roux-en-Y gastric bypass (RYGB) surgery on protein tyrosine phosphatase 1B (PTP1B) expression levels and leptin activity in hypothalami of obese rats. Obese rats induced by a high-fat diet (HFD) that underwent RYGB (n=11) or sham operation (SO, n=9), as well as an obese control cohort (Obese, n=10) and an additional normal-diet group (ND, n=10) were used. Food efficiency was measured at 8 weeks post-operation. Plasma leptin levels were evaluated and hypothalamic protein tyrosine phosphatase 1B (PTP1B) levels and leptin signaling activity were examined at the genetic and protein levels. The results indicated that food efficiency was typically lower in RYGB rats compared with that in the Obese and SO rats. In the RYGB group, leptin receptor expression and proopiomelanocortin was significantly higher, while Neuropeptide Y levels were lower than those in the Obese and SO groups. Furthermore, the gene and protein expression levels of PTP1B in the RYGB group were lower, while levels of phosphorylated signal transducer and activator of transcription 3 protein were much higher compared with those in the Obese and SO groups. In conclusion, RYGB surgery significantly suppressed hypothalamic PTP1B protein expression. PTP1B regulation may partially alleviate leptin resistance. PMID:28947917

Roux-en-Y gastric bypass surgery suppresses hypothalamic PTP1B protein level and alleviates leptin resistance in obese rats.

PubMed

Liu, Jia-Yu; Mu, Song; Zhang, Shu-Ping; Guo, Wei; Li, Qi-Fu; Xiao, Xiao-Qiu; Zhang, Jun; Wang, Zhi-Hong

2017-09-01

The present study aimed to explore the effect of Roux-en-Y gastric bypass (RYGB) surgery on protein tyrosine phosphatase 1B (PTP1B) expression levels and leptin activity in hypothalami of obese rats. Obese rats induced by a high-fat diet (HFD) that underwent RYGB (n=11) or sham operation (SO, n=9), as well as an obese control cohort (Obese, n=10) and an additional normal-diet group (ND, n=10) were used. Food efficiency was measured at 8 weeks post-operation. Plasma leptin levels were evaluated and hypothalamic protein tyrosine phosphatase 1B (PTP1B) levels and leptin signaling activity were examined at the genetic and protein levels. The results indicated that food efficiency was typically lower in RYGB rats compared with that in the Obese and SO rats. In the RYGB group, leptin receptor expression and proopiomelanocortin was significantly higher, while Neuropeptide Y levels were lower than those in the Obese and SO groups. Furthermore, the gene and protein expression levels of PTP1B in the RYGB group were lower, while levels of phosphorylated signal transducer and activator of transcription 3 protein were much higher compared with those in the Obese and SO groups. In conclusion, RYGB surgery significantly suppressed hypothalamic PTP1B protein expression. PTP1B regulation may partially alleviate leptin resistance.

Determinants of Perceived Stress in Individuals with Obesity: Exploring the Relationship of Potentially Obesity-Related Factors and Perceived Stress.

PubMed

Junne, Florian; Ziser, Katrin; Giel, Katrin Elisabeth; Schag, Kathrin; Skoda, Eva; Mack, Isabelle; Niess, Andreas; Zipfel, Stephan; Teufel, Martin

2017-01-01

Associations of specific types of stress with increased food intake and subsequent weight gain have been demonstrated in animal models as well as in experimental and epidemiological studies on humans. This study explores the research question of to what extent potentially obesity-related factors determine perceived stress in individuals with obesity. N = 547 individuals with obesity participated in a cross-sectional study assessing perceived stress as the outcome variable and potential determinants of stress related to obesity. Based on the available evidence, a five factorial model of 'obesity-related obesogenic stressors' was hypothesized, including the dimensions, 'drive for thinness', 'impulse regulation', 'ineffectiveness', 'social insecurity', and 'body dissatisfaction'. The model was tested using multiple linear regression analyses. The five factorial model of 'potentially obesity-related stressors' resulted in a total variance explanation of adjusted R² = 0.616 for males and adjusted R² = 0.595 for females for perceived stress. The relative variance contribution of the five included factors differed substantially for the two sexes. The findings of this cross-sectional study support the hypothesized, potentially obesity-related factors: 'drive for thinness', 'impulse regulation', 'ineffectiveness', 'social insecurity', and 'body dissatisfaction' as relevant determinants of perceived stress in individuals with obesity. © 2017 The Author(s) Published by S. Karger GmbH, Freiburg.

Eating habits, obesity related behaviors, and effects of Danhak exercise in elderly Koreans

PubMed Central

Ha, Ae Wha; Kim, Jong Hyun; Shin, Dong Joo; Choi, Dal Woong; Park, Soo Jin; Kang, Nam-E

2010-01-01

The aims of this study were to evaluate obesity-related dietary behaviors and to determine long-term exercise effects on obesity and blood lipid profiles in elderly Korean subjects. A total of 120 subjects, aged 60-75 yr, were recruited, and obesity-related dietary behaviors were determined. An exercise intervention was conducted with 35 qualified elderly females for 6 months, and body composition and blood lipids were measured 6 times at 4 week intervals. At baseline, mean BMI (kg/m2) was 24.8 for males and 23.1 for females. The females had better eating habits than the males and were more concerned with reading nutrition labels on food products (P < 0.001); they also preferred convenience foods less than the male subjects (P < 0.05). Obese individuals were more likely than overweight or normal weight individuals to misperceive their weight (P < 0.001). Those with a high BMI responded feeling more depressed (P < 0.01), lacking self-confidence (P < 0.01), and feeling isolated (P < 0.01), as well as having more difficulty doing outdoor activities (P < 0.01). After exercise, body fat (%) and WHR were significantly reduced (P < 0.05), while body weight and BMI were also decreased without statistical significance. Total cholesterol and blood HDL were significantly improved (207.1 mg/dl vs. 182.6 mg/dl, HDL: 45.6 mg/dl vs. 50.6 mg/dl, P < 0.05). Other benefits obtained from exercise were improvements in self-confidence (26.4%), movement (22.6%), stress-relief (18.9%), and depression (13.2%). In conclusion, elderly females had better eating habits and were more concerned with nutrition information and healthy diets compared to elderly males. However, misperceptions of weight and obesity-related stress tended to be very high in females who were overweight and obese, which can be a barrier to maintain normal weight. Long-term Danhak practice, a traditional Korean exercise, was effective at reducing body fat (%) and abdominal obesity, and improved lipid profiles, self

Role of diabetes- and obesity-related protein in the regulation of osteoblast differentiation

PubMed Central

Linares, Gabriel R.; Xing, Weirong; Burghardt, Hans; Baumgartner, Bernhard; Chen, Shin-Tai; Ricart, Wifredo; Fernández-Real, José Manuel; Zorzano, Antonio

2011-01-01

Although thyroid hormone (TH) is known to exert important effects on the skeleton, the nuclear factors constituting the TH receptor coactivator complex and the molecular pathways by which TH mediates its effects on target gene expression in osteoblasts remain poorly understood. A recent study demonstrated that the actions of TH on myoblast differentiation are dependent on diabetes- and obesity-related protein (DOR). However, the role of DOR in osteoblast differentiation is unknown. We found DOR expression increased during in vitro differentiation of bone marrow stromal cells into osteoblasts and also in MC3T3-E1 cells treated with TH. However, DOR expression decreased during cellular proliferation. To determine whether DOR acts as a modulator of TH action during osteoblast differentiation, we examined whether overexpression or knockdown of DOR in MC3T3-E1 cells affects the ability of TH to induce osteoblast differentiation by evaluating alkaline phosphatase (ALP) activity. ALP activity was markedly increased in DOR-overexpressing cells treated with TH. In contrast, loss of DOR dramatically reduced TH stimulation of ALP activity in MC3T3-E1 cells and primary calvaria osteoblasts transduced with lentiviral DOR shRNA. Consistent with reduced ALP activity, mRNA levels of osteocalcin, ALP, and Runx2 were decreased significantly in DOR shRNA cells. In addition, a common single nucleotide polymorphism (SNP), DOR1 found on the promoter of human DOR gene, was associated with circulating osteocalcin levels in nondiabetic subjects. Based on these data, we conclude that DOR plays an important role in TH-mediated osteoblast differentiation, and a DOR SNP associates with plasma osteocalcin in men. PMID:21467300

Effect of plant-based diets on obesity-related inflammatory profiles: a systematic review and meta-analysis of intervention trials.

PubMed

Eichelmann, F; Schwingshackl, L; Fedirko, V; Aleksandrova, K

2016-11-01

Plant-based dietary interventions have been proposed to reduce obesity induced chronic low-grade inflammation and hence prevent chronic disease risk; however, human evidence remains unclear. This systematic review and meta-analysis of intervention trials aimed to assess the effect of plant-based diets on obesity-related inflammatory biomarker profiles. Medline, EMBASE and Cochrane Central Register of Controlled Trials (CENTRAL) were searched for articles published until January 2016 and mean differences in biomarkers of inflammatory status were assessed for: C-reactive protein (CRP), interleukin-6 (IL-6), tumour necrosis factor-alpha (TNF-ɑ), soluble intercellular adhesion molecule 1 (sICAM), leptin, adiponectin and resistin. Of initially identified 2,583 publications, 29 met the meta-analysis inclusion criteria [a total of 2,689 participants]. Consumption of plant-based diets was associated with a reduction in the mean concentrations of the following biomarkers: CRP [effect size, -0.55 mg/l, 95% confidence intervals (CI): -0.78; -0.32, I 2  = 94.4%], IL-6 [effect size, -0.25 ng/l, 95% CI: -0.56; 0.06, I 2  = 74%], and, to some degree, sICAM (-25.07 ng/ml [95% CI: -52.32; 2.17, I 2  = 93.2%]). No substantial effects were revealed for TNF-ɑ, resistin, adiponectin and leptin. Plant-based diets are associated with an improvement in obesity-related inflammatory profiles and could provide means for therapy and prevention of chronic disease risk. © 2016 World Obesity.

Loss of angiopoietin-like 4 (ANGPTL4) in mice with diet-induced obesity uncouples visceral obesity from glucose intolerance partly via the gut microbiota.

PubMed

Janssen, Aafke W F; Katiraei, Saeed; Bartosinska, Barbara; Eberhard, Daniel; Willems van Dijk, Ko; Kersten, Sander

2018-06-01

Angiopoietin-like 4 (ANGPTL4) is an important regulator of triacylglycerol metabolism, carrying out this role by inhibiting the enzymes lipoprotein lipase and pancreatic lipase. ANGPTL4 is a potential target for ameliorating cardiometabolic diseases. Although ANGPTL4 has been implicated in obesity, the study of the direct role of ANGPTL4 in diet-induced obesity and related metabolic dysfunction is hampered by the massive acute-phase response and development of lethal chylous ascites and peritonitis in Angptl4 -/- mice fed a standard high-fat diet. The aim of this study was to better characterise the role of ANGPTL4 in glucose homeostasis and metabolic dysfunction during obesity. We chronically fed wild-type (WT) and Angptl4 -/- mice a diet rich in unsaturated fatty acids and cholesterol, combined with fructose in drinking water, and studied metabolic function. The role of the gut microbiota was investigated by orally administering a mixture of antibiotics (ampicillin, neomycin, metronidazole). Glucose homeostasis was assessed via i.p. glucose and insulin tolerance tests. Mice lacking ANGPTL4 displayed an increase in body weight gain, visceral adipose tissue mass, visceral adipose tissue lipoprotein lipase activity and visceral adipose tissue inflammation compared with WT mice. However, they also unexpectedly had markedly improved glucose tolerance, which was accompanied by elevated insulin levels. Loss of ANGPTL4 did not affect glucose-stimulated insulin secretion in isolated pancreatic islets. Since the gut microbiota have been suggested to influence insulin secretion, and because ANGPTL4 has been proposed to link the gut microbiota to host metabolism, we hypothesised a potential role of the gut microbiota. Gut microbiota composition was significantly different between Angptl4 -/- mice and WT mice. Interestingly, suppression of the gut microbiota using antibiotics largely abolished the differences in glucose tolerance and insulin levels between WT and Angptl4

Increased Obesity-Associated Circulating Levels of the Extracellular Matrix Proteins Osteopontin, Chitinase-3 Like-1 and Tenascin C Are Associated with Colon Cancer

PubMed Central

Catalán, Victoria; Gómez-Ambrosi, Javier; Rodríguez, Amaia; Ramírez, Beatriz; Izaguirre, Maitane; Hernández-Lizoain, José Luis; Baixauli, Jorge; Martí, Pablo; Valentí, Víctor; Moncada, Rafael; Silva, Camilo; Salvador, Javier; Frühbeck, Gema

2016-01-01

Background Excess adipose tissue represents a major risk factor for the development of colon cancer with inflammation and extracellular matrix (ECM) remodeling being proposed as plausible mechanisms. The aim of this study was to investigate whether obesity can influence circulating levels of inflammation-related extracellular matrix proteins in patients with colon cancer (CC), promoting a microenvironment favorable for tumor growth. Methods Serum samples obtained from 79 subjects [26 lean (LN) and 53 obese (OB)] were used in the study. Enrolled subjects were further subclassified according to the established diagnostic protocol for CC (44 without CC and 35 with CC). Anthropometric measurements as well as circulating metabolites and hormones were determined. Circulating concentrations of the ECM proteins osteopontin (OPN), chitinase-3-like protein 1 (YKL-40), tenascin C (TNC) and lipocalin-2 (LCN-2) were determined by ELISA. Results Significant differences in circulating OPN, YKL-40 and TNC concentrations between the experimental groups were observed, being significantly increased due to obesity (P<0.01) and colon cancer (P<0.05). LCN-2 levels were affected by obesity (P<0.05), but no differences were detected regarding the presence or not of CC. A positive association (P<0.05) with different inflammatory markers was also detected. Conclusions To our knowledge, we herein show for the first time that obese patients with CC exhibit increased circulating levels of OPN, YKL-40 and TNC providing further evidence for the influence of obesity on CC development via ECM proteins, representing promising diagnostic biomarkers or target molecules for therapeutics. PMID:27612200

Fighting obesity or obese persons? Public perceptions of obesity-related health messages.

PubMed

Puhl, R; Peterson, J L; Luedicke, J

2013-06-01

This study examined public perceptions of obesity-related public health media campaigns with specific emphasis on the extent to which campaign messages are perceived to be motivating or stigmatizing. In summer 2011, data were collected online from a nationally representative sample of 1014 adults. Participants viewed a random selection of 10 (from a total of 30) messages from major obesity public health campaigns from the United States, the United Kingdom and Australia, and rated each campaign message according to positive and negative descriptors, including whether it was stigmatizing or motivating. Participants also reported their familiarity with each message and their intentions to comply with the message content. Participants responded most favorably to messages involving themes of increased fruit and vegetable consumption, and general messages involving multiple health behaviors. Messages that have been publicly criticized for their stigmatizing content received the most negative ratings and the lowest intentions to comply with message content. Furthermore, messages that were perceived to be most positive and motivating made no mention of the word 'obesity' at all, and instead focused on making healthy behavioral changes without reference to body weight. These findings have important implications for framing messages in public health campaigns to address obesity, and suggest that certain types of messages may lead to increased motivation for behavior change among the public, whereas others may be perceived as stigmatizing and instill less motivation to improve health.

Glucagon-like peptide-1 analogue prevents nonalcoholic steatohepatitis in non-obese mice.

PubMed

Yamamoto, Takaya; Nakade, Yukiomi; Yamauchi, Taeko; Kobayashi, Yuji; Ishii, Norimitsu; Ohashi, Tomohiko; Ito, Kiyoaki; Sato, Ken; Fukuzawa, Yoshitaka; Yoneda, Masashi

2016-02-28

To investigate whether a glucagon-like peptide-1 (GLP-1) analogue inhibits nonalcoholic steatohepatitis (NASH), which is being increasingly recognized in Asia, in non-obese mice. A methionine-choline-deficient diet (MCD) along with exendin-4 (20 μg/kg per day, ip), a GLP-1 analogue, or saline was administered to male db/db mice (non-obese NASH model). Four or eight weeks after commencement of the diet, the mice were sacrificed and their livers were excised. The excised livers were examined by histochemistry for evidence of hepatic steatosis and inflammation. Hepatic triglyceride (TG) and free fatty acid (FFA) content was measured, and the expression of hepatic fat metabolism- and inflammation-related genes was evaluated. Oxidative stress-related parameters and macrophage recruitment were also examined using immunohistochemistry. Four weeks of MCD feeding induced hepatic steatosis and inflammation and increased the hepatic TG and FFA content. The expression of fatty acid transport protein 4 (FATP4), a hepatic FFA influx-related gene; macrophage recruitment; and the level of malondialdehyde (MDA), an oxidative stress marker, were significantly augmented by a 4-wk MCD. The levels of hepatic sterol regulatory element-binding protein-1c (SREBP-1c) mRNA (lipogenesis-related gene) and acyl-coenzyme A oxidase 1 (ACOX1) mRNA (β-oxidation-related gene) had decreased at 4 wk and further decreased at 8 wk. However, the level of microsomal triglyceride transfer protein mRNA (a lipid excretion-related gene) remained unchanged. The administration of exendin-4 significantly attenuated the MCD-induced increase in hepatic steatosis, hepatic TG and FFA content, and FATP4 expression as well as the MCD-induced augmentation of hepatic inflammation, macrophage recruitment, and MDA levels. Additionally, it further decreased the hepatic SREBP-1c level and alleviated the MCD-mediated inhibition of the ACOX1 mRNA level. These results suggest that GLP-1 inhibits hepatic steatosis and

Glucagon-like peptide-1 analogue prevents nonalcoholic steatohepatitis in non-obese mice

PubMed Central

Yamamoto, Takaya; Nakade, Yukiomi; Yamauchi, Taeko; Kobayashi, Yuji; Ishii, Norimitsu; Ohashi, Tomohiko; Ito, Kiyoaki; Sato, Ken; Fukuzawa, Yoshitaka; Yoneda, Masashi

2016-01-01

AIM: To investigate whether a glucagon-like peptide-1 (GLP-1) analogue inhibits nonalcoholic steatohepatitis (NASH), which is being increasingly recognized in Asia, in non-obese mice. METHODS: A methionine-choline-deficient diet (MCD) along with exendin-4 (20 μg/kg per day, ip), a GLP-1 analogue, or saline was administered to male db/db mice (non-obese NASH model). Four or eight weeks after commencement of the diet, the mice were sacrificed and their livers were excised. The excised livers were examined by histochemistry for evidence of hepatic steatosis and inflammation. Hepatic triglyceride (TG) and free fatty acid (FFA) content was measured, and the expression of hepatic fat metabolism- and inflammation-related genes was evaluated. Oxidative stress-related parameters and macrophage recruitment were also examined using immunohistochemistry. RESULTS: Four weeks of MCD feeding induced hepatic steatosis and inflammation and increased the hepatic TG and FFA content. The expression of fatty acid transport protein 4 (FATP4), a hepatic FFA influx-related gene; macrophage recruitment; and the level of malondialdehyde (MDA), an oxidative stress marker, were significantly augmented by a 4-wk MCD. The levels of hepatic sterol regulatory element-binding protein-1c (SREBP-1c) mRNA (lipogenesis-related gene) and acyl-coenzyme A oxidase 1 (ACOX1) mRNA (β-oxidation-related gene) had decreased at 4 wk and further decreased at 8 wk. However, the level of microsomal triglyceride transfer protein mRNA (a lipid excretion-related gene) remained unchanged. The administration of exendin-4 significantly attenuated the MCD-induced increase in hepatic steatosis, hepatic TG and FFA content, and FATP4 expression as well as the MCD-induced augmentation of hepatic inflammation, macrophage recruitment, and MDA levels. Additionally, it further decreased the hepatic SREBP-1c level and alleviated the MCD-mediated inhibition of the ACOX1 mRNA level. CONCLUSION: These results suggest that GLP-1

Colchicine to decrease NLRP3-activated inflammation and improve obesity-related metabolic dysregulation.

PubMed

Demidowich, Andrew P; Davis, Angela I; Dedhia, Nicket; Yanovski, Jack A

2016-07-01

Obesity is a major risk-factor for the development of insulin resistance, type 2 diabetes, and cardiovascular disease. Circulating molecules associated with obesity, such as saturated fatty acids and cholesterol crystals, stimulate the innate immune system to incite a chronic inflammatory state. Studies in mouse models suggest that suppressing the obesity-induced chronic inflammatory state may prevent or reverse obesity-associated metabolic dysregulation. Human studies, however, have been far less positive, possibly because targeted interventions were too far downstream of the inciting inflammatory events. Recently, it has been shown that, within adipose tissue macrophages, assembly of a multi-protein member of the innate immune system, the NOD-like receptor family pyrin domain containing 3 (NLRP3) inflammasome, is essential for the induction of this inflammatory state. Microtubules enable the necessary spatial arrangement of the components of the NLRP3 inflammasome in the cell, leading to its activation and propagation of the inflammatory cascade. Colchicine, a medication classically used for gout, mediates its anti-inflammatory effect by inhibiting tubulin polymerization, and has been shown to attenuate macrophage NLRP3 inflammasome arrangement and activation in vitro and in vivo. Given these findings, we hypothesize that, in at-risk individuals (those with obesity-induced inflammation and metabolic dysregulation), long-term colchicine use will lead to suppression of inflammation and thus cause improvements in insulin sensitivity and other obesity-related metabolic impairments. Published by Elsevier Ltd.

Endoplasmic Reticulum Stress and Obesity.

PubMed

Yilmaz, Erkan

2017-01-01

In recent years, the world has seen an alarming increase in obesity and closely associated with insulin resistance which is a state of low-grade inflammation, the latter characterized by elevated levels of proinflammatory cytokines in blood and tissues. A shift in energy balance alters systemic metabolic regulation and the important role that chronic inflammation, endoplasmic reticulum (ER) dysfunction, and activation of the unfolded protein response (UPR) play in this process.Why obesity is so closely associated with insulin resistance and inflammation is not understood well. This suggests that there are probably other causes for obesity-related insulin resistance and inflammation. One of these appears to be endoplasmic reticulum (ER) stress.The ER is a vast membranous network responsible for the trafficking of a wide range of proteins and plays a central role in integrating multiple metabolic signals critical in cellular homeostasis. Conditions that may trigger unfolded protein response activation include increased protein synthesis, the presence of mutant or misfolded proteins, inhibition of protein glycosylation, imbalance of ER calcium levels, glucose and energy deprivation, hypoxia, pathogens or pathogen-associated components and toxins. Thus, characterizing the mechanisms contributing to obesity and identifying potential targets for its prevention and treatment will have a great impact on the control of associated conditions, particularly T2D.

Obesity Alters Molecular and Functional Cardiac Responses to Ischemia-Reperfusion and Glucagon-Like Peptide-1 Receptor Agonism

PubMed Central

Sassoon, Daniel J; Goodwill, Adam G; Noblet, Jillian N; Conteh, Abass M; Herring, B. Paul; McClintick, Jeanette N; Tune, Johnathan D; Mather, Kieren J

2016-01-01

This study tested the hypothesis that obesity alters the cardiac response to ischemia/reperfusion and/or glucagon like peptide-1 (GLP-1) receptor activation, and that these differences are associated with alterations in the obese cardiac proteome and microRNA (miR) transcriptome. Ossabaw swine were fed normal chow or obesogenic diet for 6 months. Cardiac function was assessed at baseline, during a 30-min coronary occlusion, and during 2 hours of reperfusion in anesthetized swine treated with saline or exendin-4 for 24 hours. Cardiac biopsies were obtained from normal and ischemia/reperfusion territories. Fat-fed animals were heavier, and exhibited hyperinsulinemia, hyperglycemia, and hypertriglyceridemia. Plasma troponin-I concentration (index of myocardial injury) was increased following ischemia/reperfusion and decreased by exendin-4 treatment in both groups. Ischemia/reperfusion produced reductions in systolic pressure and stroke volume in lean swine. These indices were higher in obese hearts at baseline and relatively maintained throughout ischemia/reperfusion. Exendin-4 administration increased systolic pressure in lean swine but did not affect blood pressure in obese swine. End-diastolic volume was reduced by exendin-4 following ischemia/reperfusion in obese swine. These divergent physiologic responses were associated with obesity-related differences in proteins related to myocardial structure/function (e.g. titin) and calcium handling (e.g. SERCA2a, histidine-rich Ca2+ binding protein). Alterations in expression of cardiac miRs in obese hearts included miR-15, miR-27, miR-130, miR-181, and let-7. Taken together, these observations validate this discovery approach and reveal novel associations that suggest previously undiscovered mechanisms contributing to the effects of obesity on the heart and contributing to the actions of GLP-1 following ischemia/reperfusion. PMID:27234258

Determinants of Perceived Stress in Individuals with Obesity: Exploring the Relationship of Potentially Obesity-Related Factors and Perceived Stress

PubMed Central

Junne, Florian; Ziser, Katrin; Giel, Katrin Elisabeth; Schag, Kathrin; Skoda, Eva; Mack, Isabelle; Niess, Andreas; Zipfel, Stephan; Teufel, Martin

2017-01-01

Objective Associations of specific types of stress with increased food intake and subsequent weight gain have been demonstrated in animal models as well as in experimental and epidemiological studies on humans. This study explores the research question of to what extent potentially obesity-related factors determine perceived stress in individuals with obesity. Methods N = 547 individuals with obesity participated in a cross-sectional study assessing perceived stress as the outcome variable and potential determinants of stress related to obesity. Based on the available evidence, a five factorial model of ‘obesity-related obesogenic stressors’ was hypothesized, including the dimensions, ‘drive for thinness’, ‘impulse regulation’, ‘ineffectiveness’, ‘social insecurity’, and ‘body dissatisfaction’. The model was tested using multiple linear regression analyses. Results The five factorial model of ‘potentially obesity-related stressors’ resulted in a total variance explanation of adjusted R² = 0.616 for males and adjusted R² = 0.595 for females for perceived stress. The relative variance contribution of the five included factors differed substantially for the two sexes. Conclusion The findings of this cross-sectional study support the hypothesized, potentially obesity-related factors: ‘drive for thinness’, ‘impulse regulation’, ‘ineffectiveness’, ‘social insecurity’, and ‘body dissatisfaction’ as relevant determinants of perceived stress in individuals with obesity. PMID:28433993

Food-related lifestyles and their association to obesity in five European countries.

PubMed

Pérez-Cueto, Federico J A; Verbeke, Wim; de Barcellos, Marcia Dutra; Kehagia, Olga; Chryssochoidis, George; Scholderer, Joachim; Grunert, Klaus G

2010-02-01

This paper's objective is to investigate the associations between obesity and Food-Related Lifestyles (FRL) in five European countries. A cross-sectional web-based survey was carried out in Belgium, Denmark, Germany, Greece and Poland, January 2008, with quota samples on gender (male, female), age categories (20-44 and 45-70 years), and locality of residence (urban, rural). A total of 2437 respondents (51% women, 49% men; mean age 41.4 years, SD 13.1) participated. Obtained data included socio-demographic information, measure of the food-related lifestyle scale and self-reported weights and heights. Body Mass Index (in kg/m(2)) was calculated as weight (in kg) divided by the squared height (in m(2)). Individuals were classified as obese if BMI > or = 30. Logistic regressions were fitted for the aggregated sample and then by country with obese as dependent and socio-demographics and FRL were included as independents. The prevalence of obesity in the five countries is 22%. Europeans giving more importance to 'self-fulfilment' (odds = 1.18), 'planning of meals' (odds = 1.15), and preferring 'snacks vs. meals' (odds = 1.24) are more likely to be obese. Respondents were less likely to be obese if they attached lower levels of importance to the use of 'shopping lists' (odds = 0.87). The overall picture is that a stronger interest in health, organic products and freshness, within the FLR domain of quality aspects, is associated with 'not being obese'. This study has identified specific FRL dimensions as potential predictors of obesity. The resulting consumers' profiling can be used for targeted interventions for weight management in Europe. 2009 Elsevier Ltd. All rights reserved.

Obesity and motor skills among 4 to 6-year-old children in the United States: nationally-representative surveys.

PubMed

Castetbon, Katia; Andreyeva, Tatiana

2012-03-15

Few population-based studies have assessed relationships between body weight and motor skills in young children. Our objective was to estimate the association between obesity and motor skills at 4 years and 5-6 years of age in the United States. We used repeated cross-sectional assessments of the national sample from the Early Childhood Longitudinal Survey-Birth Cohort (ECLS-B) of preschool 4-year-old children (2005-2006; n = 5 100) and 5-6-year-old kindergarteners (2006-2007; n = 4 700). Height, weight, and fine and gross motor skills were assessed objectively via direct standardized procedures. We used categorical and continuous measures of body weight status, including obesity (Body Mass Index (BMI) ≥ 95th percentile) and BMI z-scores. Multivariate logistic and linear models estimated the association between obesity and gross and fine motor skills in very young children adjusting for individual, social, and economic characteristics and parental involvement. The prevalence of obesity was about 15%. The relationship between motor skills and obesity varied across types of skills. For hopping, obese boys and girls had significantly lower scores, 20% lower in obese preschoolers and 10% lower in obese kindergarteners than normal weight counterparts, p < 0.01. Obese girls could jump 1.6-1.7 inches shorter than normal weight peers (p < 0.01). Other gross motor skills and fine motor skills of young children were not consistently related to BMI z-scores and obesity. Based on objective assessment of children's motor skills and body weight and a full adjustment for confounding covariates, we find no reduction in overall coordination and fine motor skills in obese young children. Motor skills are adversely associated with childhood obesity only for skills most directly related to body weight.

Obesity and motor skills among 4 to 6-year-old children in the united states: nationally-representative surveys

PubMed Central

2012-01-01

Background Few population-based studies have assessed relationships between body weight and motor skills in young children. Our objective was to estimate the association between obesity and motor skills at 4 years and 5-6 years of age in the United States. We used repeated cross-sectional assessments of the national sample from the Early Childhood Longitudinal Survey-Birth Cohort (ECLS-B) of preschool 4-year-old children (2005-2006; n = 5 100) and 5-6-year-old kindergarteners (2006-2007; n = 4 700). Height, weight, and fine and gross motor skills were assessed objectively via direct standardized procedures. We used categorical and continuous measures of body weight status, including obesity (Body Mass Index (BMI) ≥ 95th percentile) and BMI z-scores. Multivariate logistic and linear models estimated the association between obesity and gross and fine motor skills in very young children adjusting for individual, social, and economic characteristics and parental involvement. Results The prevalence of obesity was about 15%. The relationship between motor skills and obesity varied across types of skills. For hopping, obese boys and girls had significantly lower scores, 20% lower in obese preschoolers and 10% lower in obese kindergarteners than normal weight counterparts, p < 0.01. Obese girls could jump 1.6-1.7 inches shorter than normal weight peers (p < 0.01). Other gross motor skills and fine motor skills of young children were not consistently related to BMI z-scores and obesity. Conclusions Based on objective assessment of children's motor skills and body weight and a full adjustment for confounding covariates, we find no reduction in overall coordination and fine motor skills in obese young children. Motor skills are adversely associated with childhood obesity only for skills most directly related to body weight. PMID:22420636

The Psychosocial Factors Related to Obesity: A Study Among Overweight, Obese, and Morbidly Obese Women in India

PubMed Central

Agrawal, Praween; Gupta, Kamla; Mishra, Vinod; Agrawal, Sutapa

2015-01-01

Psychosocial factors among overweight, obese, and morbidly obese women in Delhi, India were examined. A follow-up survey was conducted of 325 ever-married women aged 20–54 years, systematically selected from 1998–99 National Family Health Survey samples, who were re-interviewed after 4 years in 2003. Information on day-to-day problems, body image dissatisfaction, sexual dissatisfaction, and stigma and discrimination were collected and anthropometric measurements were obtained from women to compute their current body mass index. Three out of four overweight women (BMI between 25 and 29.9 kg/m2) were not happy with their body image, compared to four out of five obese women (BMI of 30 kg/m2 or greater), and almost all (95 percent) morbidly obese women (BMI of 35 kg/m2 or greater) (p < .0001). It was found that morbidly obese and obese women were five times (adjusted odds ratio [aOR] 5.29, 95% confidence interval [CI] 2.02–13.81, p < .001) and two times (aOR 2.30, 95% CI 1.20–4.42, p < .001), respectively, as likely to report day-to-day problems; twelve times (aOR 11.88, 95% CI 2.62–53.87, p < .001) and three times, respectively, as likely (aOR 2.92, 95% CI 1.45–5.88, p = .001) to report dissatisfaction with body image; and nine times (aOR 9.41, 95% CI 2.96–29.94, p < .001) and three times (aOR 2.93, 95% CI 1.03–8.37, p = .001), respectively, as likely to report stigma and discrimination as overweight women. PMID:25905678

[Interaction of FABP4 with plasma membrane proteins of endothelial cells].

PubMed

Saavedra, Paula; Girona, Josefa; Aragonès, Gemma; Cabré, Anna; Guaita, Sandra; Heras, Mercedes; Masana, Lluís

2015-01-01

Fatty acid binding protein (FABP4) is an adipose tissue-secreted adipokine implicated in the regulation of the energetic metabolism and inflammation. High levels of circulating FABP4 have been described in people with obesity, atherogenic dyslipidemia, diabetes and metabolic syndrome. Recent studies have demonstrated that FABP4 could have a direct effect on peripheral tissues and, specifically, on vascular function. It is still unknown how the interaction between FABP4 and the endothelial cells is produced to prompt these effects on vascular function. The objective of this work is studying the interaction between FABP4 and the plasma membrane proteins of endothelial cells. HUVEC cells were incubated with and without FABP4 (100 ng/ml) for 5 minutes. Immunolocalization of FABP4 was studied by confocal microscopy. The results showed that FABP4 colocalizates with CD31, a membrane protein marker. A strategy which combines 6XHistidine-tag FABP4 (FABP4-His), incubations with or without FABP4-His (100 ng/ml), formaldehyde cross-linking, cellular membrane protein extraction and western blot, was designed to study the FABP4 interactions with membrane proteins of HUVECs. The results showed different western blot profiles depending of the incubation with or without FABP4-His. The immunoblot revelead three covalent protein complexes of about 108, 77 and 33 kDa containing FAPB4 and its putative receptor. The existence of a specific binding protein complex able to bind FABP4 to endothelial cells is supported by these results. The obtained results will permit us advance in the molecular knowledge of FABP4 effects as well as use this protein and its receptor as therapeutic target to prevent cardiovascular. Copyright © 2014 Sociedad Española de Arteriosclerosis. Published by Elsevier España. All rights reserved.

Relationship between diabetes mellitus, hypertension and obesity, and health-related quality of life in Gaziantep, a central south-eastern city in Turkey.

PubMed

Ucan, Ozlem; Ovayolu, Nimet

2010-09-01

The main goal of nursing care should be to increase health-related quality of life as well as improve the medical status of patients with chronic disease. For this reason, this study aims to evaluate and compare the health-related quality of life of patients with diabetes mellitus, hypertension and obesity in Gaziantep, a south-eastern city in Turkey. Diabetes mellitus, hypertension and obesity are the most decisive factors in terms of adversely affecting health-related quality of life. A cross-sectional, descriptive design was used. In this study, the research population included a total of 1601 diabetes mellitus, hypertension and obesity patients. To evaluate health-related quality of life of patients, Short Form-36 (SF-36) was used. Student's t-test, one-way anova and chi-square analyses were used for comparisons between groups. In total, 18·1% of patients had combined obesity, hypertension and diabetes mellitus; 16·1% had hypertension and diabetes mellitus. Approximately 16·1% had only hypertension; 15·4% had obesity and hypertension; 13·3% had diabetes mellitus; 12·7% had obesity and diabetes mellitus; and 8·4% had obesity. The health-related quality of life physical component mean scores of patients with combined obesity and hypertension were lower than that of the other groups (p < 0·05). Health-related quality of life physical component mean scores were determined as 34·5 (SD 0·4), and mental component mean scores were determined as 43·9 (SD 4·4). Health-related quality of life physical component mean scores of moderately active patients were higher, while older age and lower educational and income levels had a negative effect on health-related quality of life (p < 0·05). Diabetes, hypertension and obesity decrease patient health-related quality of life while physical activity increases it. The coexistence of obesity and hypertension, in particular, has a more negative effect on health-related quality of life. Patients with hypertension

Novel insights of dietary polyphenols and obesity

PubMed Central

Wang, Shu; Moustaid-Moussa, Naima; Chen, Lixia; Mo, Huanbiao; Shastri, Anuradha; Su, Rui; Bapat, Priyanka; Kwun, InSook; Shen, Chwan-Li

2013-01-01

Prevalence of obesity has steadily increased over the past three decades both in the United States and worldwide. Recent studies have shown the role of dietary polyphenols in the prevention of obesity and obesity-related chronic diseases. Here we evaluated the impact of commonly consumed polyphenols, including green tea catechins and epigallocatechin gallates, resveratrol, and curcumin, on obesity and obesity-related-inflammation. Cellular studies demonstrated that these dietary polyphenols reduce viability of adipocytes and proliferation of preadipocytes, suppress adipocyte differentiation and triglyceride accumulation, stimulate lipolysis and fatty acid β-oxidation, and reduce inflammation. Concomitantly, the polyphenols modulate signaling pathways including the AMP-activated protein kinase, peroxisome proliferator activated receptor γ, CCAAT/enhancer binding protein α, PPAR gamma activator 1-alpha, sirtuin 1, sterol regulatory element binding protein-1c, uncoupling proteins 1 and 2, and nuclear factor kappa B that regulate adipogenesis, antioxidant and anti-inflammatory responses. Animal studies strongly suggest that commonly consumed polyphenols described in this review have a pronounced effect on obesity as shown by lower body weight, fat mass, and triglycerides through enhancing energy expenditure and fat utilization, and modulating glucose hemostasis. Limited human studies have been conducted in this area, and are inconsistent about the anti-obesity impact of dietary polyphenols, probably due to the various study designs and lengths, variation among subjects (age, gender, ethnicity), chemical forms of the dietary polyphenols used and confounding factors such as other weight reducing agents. Future randomized controlled trials are warranted to reconcile the discrepancies between preclinical efficacies and inconclusive clinic outcomes of these polyphenols. PMID:24314860

Association of Parental Obesity and Diabetes Mellitus With Circulating Adipokines in Nonobese Nondiabetic Offspring.

PubMed

Zachariah, Justin P; Quiroz, Rene; Enserro, Danielle; Andersson, Charlotte; Keaney, John F; Sullivan, Lisa M; Vasan, Ramachandran S

2017-07-16

Adipokines are implicated in the development of obesity-related traits. We hypothesized that nonobese participants without diabetes mellitus (DM) whose parents were obese or had DM would have altered circulating adipokines compared with those without parental history of these conditions. Participants in the community-based Framingham Third Generation cohort who were not obese (body mass index <30) and not diabetic with both parents in the Framingham Offspring cohort were included in this analysis (n=2034, mean age 40 years, 54% women). Circulating concentrations of fetuin A, RBP4 (retinol binding protein 4), FABP4 (fatty acid binding protein 4), leptin, LEP-R (leptin receptor), and adiponectin were assayed. Parental DM was defined as occurring before age 60 years, and obesity was defined as body mass index ≥30 before age 60 years. General estimating equations were used to compare concentrations of adipokines among participants with 0, 1, or 2 parents affected by obesity or DM (separate analyses for each), adjusting for known correlates of adipokines. Overall, 44% had at least 1 parent who was obese and 15% had parents with DM. Parental obesity was associated with higher serum levels of FABP4 and LEP-R in their offspring ( P =0.02 for both). Parental DM was associated with lower adiponectin but higher RBP4 concentrations in offspring ( P ≤0.02 for both). In our community-based sample, a parental history of DM or obesity was associated with an altered adipokine profile in nonobese nondiabetic offspring. Additional studies are warranted to evaluate whether such preclinical biomarker alterations presage future risk of disease. © 2017 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley.

Cell Death and Heart Failure in Obesity: Role of Uncoupling Proteins

PubMed Central

Ruiz-Ramírez, Angélica; López-Acosta, Ocarol; Barrios-Maya, Miguel Angel

2016-01-01

Metabolic diseases such as obesity, metabolic syndrome, and type II diabetes are often characterized by increased reactive oxygen species (ROS) generation in mitochondrial respiratory complexes, associated with fat accumulation in cardiomyocytes, skeletal muscle, and hepatocytes. Several rodents studies showed that lipid accumulation in cardiac myocytes produces lipotoxicity that causes apoptosis and leads to heart failure, a dynamic pathological process. Meanwhile, several tissues including cardiac tissue develop an adaptive mechanism against oxidative stress and lipotoxicity by overexpressing uncoupling proteins (UCPs), specific mitochondrial membrane proteins. In heart from rodent and human with obesity, UCP2 and UCP3 may protect cardiomyocytes from death and from a state progressing to heart failure by downregulating programmed cell death. UCP activation may affect cytochrome c and proapoptotic protein release from mitochondria by reducing ROS generation and apoptotic cell death. Therefore the aim of this review is to discuss recent findings regarding the role that UCPs play in cardiomyocyte survival by protecting against ROS generation and maintaining bioenergetic metabolism homeostasis to promote heart protection. PMID:27642497

The Potential Role of Aerobic Exercise-Induced Pentraxin 3 on Obesity-Related Inflammation and Metabolic Dysregulation

PubMed Central

Acevedo, Edmund O.

2017-01-01

Obesity is defined as the excess accumulation of intra-abdominal body fat, resulting in a state of chronic, low-grade proinflammation that can directly contribute to the development of insulin resistance. Pentraxin 3 (PTX3) is an acute-phase protein that is expressed by a variety of tissue and cell sources and provides an anti-inflammatory property to downregulate the production of proinflammatory cytokines, in particular interleukin-1 beta and tumor necrosis factor alpha. Although PTX3 may therapeutically aid in altering the proinflammatory milieu in obese individuals, and despite elevated expression of PTX3 mRNA observed in adipose tissue, the circulating level of PTX3 is reduced with obesity. Interestingly, aerobic activity has been demonstrated to elevate PTX3 levels. Therefore, the purpose of this review is to discuss the therapeutic potential of PTX3 to positively regulate obesity-related inflammation and discuss the proposition for utilizing aerobic exercise as a nonpharmacological anti-inflammatory treatment strategy to enhance circulating PTX3 concentrations in obese individuals. PMID:28400677

Relation between local food environments and obesity among adults

PubMed Central

Spence, John C; Cutumisu, Nicoleta; Edwards, Joy; Raine, Kim D; Smoyer-Tomic, Karen

2009-01-01

Background Outside of the United States, evidence for associations between exposure to fast-food establishments and risk for obesity among adults is limited and equivocal. The purposes of this study were to investigate whether the relative availability of different types of food retailers around people's homes was associated with obesity among adults in Edmonton, Canada, and if this association varied as a function of distance between food locations and people's homes. Methods Data from a population health survey of 2900 adults (18 years or older) conducted in 2002 was linked with geographic measures of access to food retailers. Based upon a ratio of the number of fast-food restaurants and convenience stores to supermarkets and specialty food stores, a Retail Food Environment Index (RFEI) was calculated for 800 m and 1600 m buffers around people's homes. In a series of logistic regressions, associations between the RFEI and the level of obesity among adults were examined. Results The median RFEI for adults in Edmonton was 4.00 within an 800 m buffer around their residence and 6.46 within a 1600 m buffer around their residence. Approximately 14% of the respondents were classified as being obese. The odds of a resident being obese were significantly lower (OR = 0.75, 95%CI 0.59 – 0.95) if they lived in an area with the lowest RFEI (below 3.0) in comparison to the highest RFEI (5.0 and above). These associations existed regardless of the covariates included in the model. No significant associations were observed between RFEI within a 1600 m buffer of the home and obesity. Conclusion The lower the ratio of fast-food restaurants and convenience stores to grocery stores and produce vendors near people's homes, the lower the odds of being obese. Thus the proximity of the obesogenic environment to individuals appears to be an important factor in their risk for obesity. PMID:19538709

The utility of childhood and adolescent obesity assessment in relation to adult health

PubMed Central

Goldhaber-Fiebert, Jeremy D.; Rubinfeld, Rachel E.; Bhattacharya, Jay; Robinson, Thomas N.; Wise, Paul H.

2014-01-01

The high prevalence of childhood obesity has raised concerns regarding long-term patterns of adult health and has generated calls for obesity screening of young children. This study examined patterns of obesity and the predictive utility of obesity screening for children of different ages in terms of adult health outcomes. Using the National Longitudinal Survey of Youth, the Population Study of Income Dynamics, and National Health and Nutrition Evaluation Surveys, we estimated the sensitivity, specificity and predictive value of childhood BMI to identify 2, 5, 10, or 15 year-olds who will become obese adults. We constructed models assessing the relationship of childhood BMI to obesity-related diseases through middle age stratified by sex and race/ethnicity. 12% of 18 year-olds were obese. While 50% of these adolescents would not have been identified by screening at age 5, 9% would have been missed at age 15. Approximately 70% of obese children at age 5 became non-obese at age 18. The predictive utility of obesity screening below the age of 10 was low, even when maternal obesity was also included. The elevated risk of diabetes, obesity, and hypertension in middle age predicted by obesity at age 15 was significantly higher than at age 5 (e.g., the RR of diabetes for obese white male 15 year-olds was 4.5; for 5 year-olds, it was 1.6). Early childhood obesity assessment adds limited predictive utility to strategies that also include later childhood assessment. Targeted approaches in later childhood or universal strategies to prevent unhealthy weight gain should be considered. PMID:22647830

Protein metabolism in obese patients during very low-calorie mixed diets containing different amounts of proteins and carbohydrates.

PubMed

Pasquali, R; Casimirri, F; Melchionda, N

1987-12-01

To assess long-term nitrogen sparing capacity of very low-calorie mixed diets, we administered two isoenergetic (2092KJ) liquid formula regimens of different composition for 8 weeks to two matched groups of massively obese patients (group 1: proteins 60 g, carbohydrate 54 g; group 2: proteins 41 g, carbohydrates 81 g). Weight loss was similar in both groups. Daily nitrogen balance (g) during the second month resulted more a negative in group 2 with respect to group 1. However, within the groups individual nitrogen sparing capacity varied markedly; only a few in group 1 and one in group 2 were able to attain nitrogen equilibrium throughout the study. Daily urine excretion of 3-methylhistidine fell significantly in group 1 but did not change in group 2. Unlike total proteins, albumins, and transferrin, serum levels of retinol-binding protein, thyroxin-binding globulin, and complement-C3 fell significantly in both groups but per cent variations of complement-C3 were more pronounced in the first group. Prealbumin levels fell persistently in group 1 and transiently in group 2. The results indicate that even with this type of diet an adequate amount of dietary protein represents the most important factor in minimizing whole body protein catabolism during long-term semistarvation in massively obese patients. Moreover, they confirm the possible role of dietary carbohydrates in the regulation of some visceral protein metabolism.

[Relationship between high-sensitivity C-reactive protein and obesity/metabolic syndrome in children].

PubMed

Chen, Fangfang; Wang, Wenpeng; Teng, Yue; Hou, Dongqing; Zhao, Xiaoyuan; Yang, Ping; Yan, Yinkun; Mi, Jie

2014-06-01

To explore the relationship between high-sensitivity C-reactive protein (hsCRP) and obesity/metabolic syndrome (MetS) related factors in children. 403 children aged 10-14 and born in Beijing were involved in this study. Height, weight, waist circumference, fat mass percentage (Fat%), blood pressure (BP), hsCRP, triglyceride (TG), total cholesterol (TC), fasting plasma glucose (FPG), high and low density lipoprotein cholesterol (HDL-C, LDL-C) were observed among these children. hsCRP was transformed with base 10 logarithm (lgCRP). MetS was defined according to the International Diabetes Federation 2007 definition. Associations between MetS related components and hsCRP were tested using partial correlation analysis, analysis of covariance and linear regression models. 1) lgCRP was positively correlated with BMI, waist circumference, Fat%,BP, FPG, LDL-C and TC while negatively correlated with HDL-C. With BMI under control, the relationships disappeared, but LDL-C (r = 0.102). 2) The distributions of lgCRP showed obvious differences in all the metabolic indices, in most groups, respectively. With BMI under control, close relationships between lgCRP and high blood pressure/high TG disappeared and the relationship with MetS weakened. 3) Through linear regression models, factors as waist circumference, BMI, Fat% were the strongest factors related to hsCRP, followed by systolic BP, HDL-C, diastolic BP, TG and LDL-C. With BMI under control, the relationships disappeared, but LDL-C(β = 0.045). hsCRP was correlated with child obesity, lipid metabolism and MetS. Waist circumference was the strongest factors related with hsCRP. Obesity was the strongest and the independent influencing factor of hsCRP.

Vitamin E and vitamin C do not reduce insulin sensitivity but inhibit mitochondrial protein expression in exercising obese rats

PubMed Central

Picklo, Matthew J.; Thyfault, John P.

2016-01-01

Controversy exists as to whether supplementation with the antioxidants vitamin E and vitamin C blocks adaptation to exercise. Exercise is a first-line means to treat obesity and its complications. While diet-induced obesity alters mitochondrial function and induces insulin resistance (IR), no data exist as to whether supplementation with vitamin E and vitamin C modify responses to exercise in pre-existing obesity. We tested the hypothesis that dietary supplementation with vitamin E (0.4 g α-tocopherol acetate/kg) and vitamin C (0.5 g/kg) blocks exercise-induced improvements on IR and mitochondrial content in obese rats maintained on a high-fat (45% fat energy (en)) diet. Diet-induced obese, sedentary rats had a 2-fold higher homeostasis model assessment of insulin resistance and larger insulin area under the curve following glucose tolerances test than rats fed a low-fat (10% fat en) diet. Exercising (12 weeks at 5 times per week in a motorized wheel) of obese rats normalized IR indices, an effect not modified by vitamin E and vitamin C. Vitamin E and vitamin C supplementation with exercise elevated mtDNA content in adipose and skeletal muscle to a greater extent (20%) than exercise alone in a depot-specific manner. On the other hand, vitamin C and vitamin E decreased exercise-induced increases in mitochondrial protein content for complex I (40%) and nicotinamide nucleotide transhydrogenase (35%) in a muscle-dependent manner. These data indicate that vitamin E and vitamin C supplementation in obese rodents does not modify exercise-induced improvements in insulin sensitivity but that changes in mitochondrial biogenesis and mitochondrial protein expression may be modified by antioxidant supplementation. PMID:25761734

A randomized trial of high-dairy-protein, variable-carbohydrate diets and exercise on body composition in adults with obesity.

PubMed

Parr, Evelyn B; Coffey, Vernon G; Cato, Louise E; Phillips, Stuart M; Burke, Louise M; Hawley, John A

2016-05-01

This study determined the effects of 16-week high-dairy-protein, variable-carbohydrate (CHO) diets and exercise training (EXT) on body composition in men and women with overweight/obesity. One hundred and eleven participants (age 47 ± 6 years, body mass 90.9 ± 11.7 kg, BMI 33 ± 4 kg/m(2) , values mean ± SD) were randomly stratified to diets with either: high dairy protein, moderate CHO (40% CHO: 30% protein: 30% fat; ∼4 dairy servings); high dairy protein, high CHO (55%: 30%: 15%; ∼4 dairy servings); or control (55%: 15%: 30%; ∼1 dairy serving). Energy restriction (500 kcal/day) was achieved through diet (∼250 kcal/day) and EXT (∼250 kcal/day). Body composition was measured using dual-energy X-ray absorptiometry before, midway, and upon completion of the intervention. Eighty-nine (25 M/64 F) of 115 participants completed the 16-week intervention, losing 7.7 ± 3.2 kg fat mass (P < 0.001) and gaining 0.50 ± 1.75 kg lean mass (P < 0.01). There was no difference in the changes in body composition (fat mass or lean mass) between groups. Compared to a healthy control diet, energy-restricted high-protein diets containing different proportions of fat and CHO confer no advantage to weight loss or change in body composition in the presence of an appropriate exercise stimulus. © 2016 The Obesity Society.

Applications of geographic information systems (GIS) data and methods in obesity-related research.

PubMed

Jia, P; Cheng, X; Xue, H; Wang, Y

2017-04-01

Geographic information systems (GIS) data/methods offer good promise for public health programs including obesity-related research. This study systematically examined their applications and identified gaps and limitations in current obesity-related research. A systematic search of PubMed for studies published before 20 May 2016, utilizing synonyms for GIS in combination with synonyms for obesity as search terms, identified 121 studies that met our inclusion criteria. We found primary applications of GIS data/methods in obesity-related research included (i) visualization of spatial distribution of obesity and obesity-related phenomena, and basic obesogenic environmental features, and (ii) construction of advanced obesogenic environmental indicators. We found high spatial heterogeneity in obesity prevalence/risk and obesogenic environmental factors. Also, study design and characteristics varied considerably across studies because of lack of established guidance and protocols in the field, which may also have contributed to the mixed findings about environmental impacts on obesity. Existing findings regarding built environment are more robust than those regarding food environment. Applications of GIS data/methods in obesity research are still limited, and related research faces many challenges. More and better GIS data and more friendly analysis methods are needed to expand future GIS applications in obesity-related research. © 2017 World Obesity Federation.

[Relation of variant rs180077 of gen cholesterol ester transfer protein variant, with fat mass, HDL-cholesterol in obese subjects with diabetes mellitus type 2].

PubMed

De Luis, Daniel Antonio; Izaola, Olatz; Primo, David; García Calvo, Susana; Gómez Hoyos, Emilia; López Gómez, Juan José; Ortola, Ana; Serrano, Cristina; Delgado, Esther; Torres Torres, Beatriz

2017-11-14

There is few evidence of cholesterol ester transfer protein (CETP) in subjects with obesity and diabetes mellitus. We examined the association of the polymorphism (rs1800777) of CETP gene on anthropometric parameters, lipid profile and adipokines in subjects with obesity and diabetes mellitus type 2. A population of 229 obese subjects with diabetes mellitus type 2 was enrolled. An electrical bioimpedance, blood pressure, dietary intake, exercise and biochemical analyses were recorded. Two hundred and seventeen subjects (94.8%) had genotype GG and 12 GA (5.2%) (genotype AA was not detected). Weight (delta: 14.4 ± 2.1 kg, p = 0.01), body mass index (delta: 2.2 ± 1.1 kg/m2, p = 0.01), fat mass (delta: 11.2 ± 3.1 kg, p = 0.02), waist circumference (delta: 3.9 ± 2.0 cm, p = 0.02), waist to hip ratio (delta: 0.04 ± 0.02 cm; p = 0.01), tryglicerides (delta: 48.6 ± 9.1 mg / dl, p = 0.03) and leptin levels (delta: 58.6 ± 15.9 mg/dl, p = 0.02) were higher in A allele carriers than non A allele carriers. Levels of HDL-cholesterol were lower in A allele carriers than non-carriers (delta: 5.6 ± 1.1 mg/dl, p = 0.03). In regression analysis, HDl cholesterol, weight and fat mass remained in the model with the SNP. Our results show an association of this CETP variant at position +82 on HDL cholesterol, levels and adiposity parameters in obese subjects with diabetes mellitus type 2.

GLUT4 translocation is not impaired after acute exercise in skeletal muscle of women with obesity and polycystic ovary syndrome.

PubMed

Dantas, Wagner Silva; Marcondes, José Antonio Miguel; Shinjo, Samuel Katsuyuki; Perandini, Luiz Augusto; Zambelli, Vanessa Olzon; Neves, Willian Das; Barcellos, Cristiano Roberto Grimaldi; Rocha, Michele Patrocínio; Yance, Viviane Dos Reis Vieira; Pereira, Renato Tavares Dos Santos; Murai, Igor Hisashi; Pinto, Ana Lucia De Sá; Roschel, Hamilton; Gualano, Bruno

2015-11-01

The aim of this study was to examine the effects of acute exercise on insulin signaling in skeletal muscle of women with polycystic ovary syndrome (PCOS) and controls (CTRL). Fifteen women with obesity and PCOS and 12 body mass index-matched CTRL participated in this study. Subjects performed a 40-min single bout of exercise. Muscle biopsies were performed before and 60 min after exercise. Selected proteins were assessed by Western blotting. CTRL, but not PCOS, showed a significant increase in PI3-k p85 and AS160 Thr 642 after a single bout of exercise (P = 0.018 and P = 0.018, respectively). Only PCOS showed an increase in Akt Thr 308 and AMPK phosphorylation after exercise (P = 0.018 and P = 0.018, respectively). Total GLUT4 expression was comparable between groups (P > 0.05). GLUT4 translocation tended to be significantly higher in both groups after exercise (PCOS: P = 0.093; CTRL: P = 0.091), with no significant difference between them (P > 0.05). A single bout of exercise elicited similar GLUT4 translocation in skeletal muscle of PCOS and CTRL, despite a slightly differential pattern of protein phosphorylation. The absence of impairment in GLUT4 translocation suggests that PCOS patients with obesity and insulin resistance may benefit from exercise training. © 2015 The Obesity Society.

Pharmacological inhibition of protein tyrosine phosphatase 1B: a promising strategy for the treatment of obesity and type 2 diabetes mellitus.

PubMed

Panzhinskiy, E; Ren, J; Nair, S

2013-01-01

Obesity and metabolic syndrome represent major public health problems, and are the biggest preventable causes of death worldwide. Obesity is the leading risk factor for type 2 diabetes mellitus (T2DM), cardiovascular diseases and non-alcoholic fatty liver disease. Obesity-associated insulin resistance, which is characterized by reduced uptake and utilization of glucose in muscle, adipose and liver tissues, is a key predictor of metabolic syndrome and T2DM. With increasing prevalence of obesity in adults and children, the need to identify and characterize potential targets for treating metabolic syndrome is imminent. Emerging evidence from animal models, clinical studies and cell lines studies suggest that protein tyrosine phosphatase 1B (PTP1B), an enzyme that negatively regulates insulin signaling, is likely to be involved in the pathways leading to insulin resistance. PTP1B is tethered to the cytosolic surface of endoplasmic reticulum (ER), an organelle that is responsible for folding, modification, and trafficking of proteins. Recent evidence links the disruption of ER homeostasis, referred to as ER stress, to the pathogenesis of obesity and T2DM. PTP1B has been recognized as an important player linking ER stress and insulin resistance in obese subjects. This review highlights recent advances in the research related to the role of PTP1B in signal transduction processes implicated in pathophysiology of obesity and type 2 diabetes, and focuses on the potential therapeutic exploitation of PTP1B inhibitors for the management of these conditions.

Role of anti-inflammatory adipokines in obesity-related diseases.

PubMed

Ohashi, Koji; Shibata, Rei; Murohara, Toyoaki; Ouchi, Noriyuki

2014-07-01

Obesity results in many health complications. Accumulating evidence indicates that the obese state is characterized by chronic low-grade inflammation, thereby leading to the initiation and progression of obesity-related disorders such as type 2 diabetes, hypertension, cardiovascular disease, and atherosclerosis. Fat tissue releases numerous bioactive molecules, called adipokines, which affect whole-body homeostasis. Most adipokines are proinflammatory, whereas a small number of anti-inflammatory adipokines including adiponectin exert beneficial actions on obese complications. The dysregulated production of adipokines seen in obesity is linked to the pathogenesis of various disease processes. In this review we focus on the role of the anti-inflammatory adipokines that are of current interest in the setting of obesity-linked metabolic and cardiovascular diseases. Copyright © 2014 Elsevier Ltd. All rights reserved.

Obesity-hypertension and its relation to other diseases in dogs.

PubMed

Pérez-Sánchez, Alicia Pamela; Del-Angel-Caraza, Javier; Quijano-Hernández, Israel Alejandro; Barbosa-Mireles, Marco Antonio

2015-03-01

Obesity is a chronic disease in which adipose tissue accumulates in such a way that it affects the health of the patient and is associated with a myriad of alterations such as systemic hypertension (HTN). The mechanisms by which obesity causes HTN are complex and involve several organic mechanisms. The objective of this study was to determine the correlation between obesity to HTN in dogs in accordance with recent international protocols (systolic blood pressure >160 mmHg) relating to age, genre, gonadal status, breed and other diseases commonly associated with HTN. A total of 244 dogs were studied, 105 non-obese controls and 139 in the obese group. For both groups, healthy and a variety of diseased dogs were observed; the correlations between pathologies and obesity were studied, paying special attention to diseases whose pathophysiologies could lead to HTN. We conclude that obesity is not a risk factor for dogs to develop HTN, and that HTN present in these patients was related to comorbidities such as chronic kidney disease, cardiopathies and endocrinopathies.

Obesity-Related Genomic Loci Are Associated with Type 2 Diabetes in a Han Chinese Population

PubMed Central

Zhao, Qi; He, Jiang; Chen, Li; Zhao, Zhigang; Li, Qiang; Ge, Jiapu; Chen, Gang; Guo, Xiaohui; Lu, Juming; Weng, Jianping; Jia, Weiping; Ji, Linong; Xiao, Jianzhong; Shan, Zhongyan; Liu, Jie; Tian, Haoming; Ji, Qiuhe; Zhu, Dalong; Zhou, Zhiguang; Shan, Guangliang; Yang, Wenying

2014-01-01

Background and Aims Obesity is a well-known risk factor for type 2 diabetes. Genome-wide association studies have identified a number of genetic loci associated with obesity. The aim of this study is to examine the contribution of obesity-related genomic loci to type 2 diabetes in a Chinese population. Methods We successfully genotyped 18 obesity-related single nucleotide polymorphisms among 5338 type 2 diabetic patients and 4663 controls. Both individual and joint effects of these single nucleotide polymorphisms on type 2 diabetes and quantitative glycemic traits (assessing β-cell function and insulin resistance) were analyzed using logistic and linear regression models, respectively. Results Two single nucleotide polymorphisms near MC4R and GNPDA2 genes were significantly associated with type 2 diabetes before adjusting for body mass index and waist circumference (OR (95% CI) = 1.14 (1.06, 1.22) for the A allele of rs12970134, P = 4.75×10−4; OR (95% CI) = 1.10 (1.03, 1.17) for the G allele of rs10938397, P = 4.54×10−3). When body mass index and waist circumference were further adjusted, the association of MC4R with type 2 diabetes remained significant (P = 1.81×10−2) and that of GNPDA2 was attenuated (P = 1.26×10−1), suggesting the effect of the locus including GNPDA2 on type 2 diabetes may be mediated through obesity. Single nucleotide polymorphism rs2260000 within BAT2 was significantly associated with type 2 diabetes after adjusting for body mass index and waist circumference (P = 1.04×10−2). In addition, four single nucleotide polymorphisms (near or within SEC16B, BDNF, MAF and PRL genes) showed significant associations with quantitative glycemic traits in controls even after adjusting for body mass index and waist circumference (all P values<0.05). Conclusions This study indicates that obesity-related genomic loci were associated with type 2 diabetes and glycemic traits in the Han Chinese population. PMID:25093408

Recovery of insulin sensitivity and optimal body composition after rapid weight loss in obese dogs fed a high-protein medium-carbohydrate diet.

PubMed

André, A; Leriche, I; Chaix, G; Thorin, C; Burger, M; Nguyen, P

2017-06-01

This study investigated the effects of an experimental high-protein medium-carbohydrate diet (protein level, 46% metabolizable energy, ME). First, postprandial plasma glucose and insulin kinetics were determined in steady-state overweight/obese Beagle dogs (28%-41% excess body weight) for an experimental high-protein medium-carbohydrate diet (protein level, 46% ME) and a commercial high-carbohydrate medium-protein diet (protein level, 24%ME) in obese dogs. Secondly, all the dogs were included in a weight loss programme. They were fed the high-protein medium-carbohydrate diet, and the energy allocation was gradually reduced until they reached their optimal body weight. Insulin sensitivity and body composition were evaluated before and after weight loss using a euglycaemic-hyperinsulinaemic clamp and the deuterium oxide dilution technique respectively. For statistical analysis, linear mixed effect models were used with a significance level of 5%. Postprandial plasma glucose and insulin concentrations were substantially lower with the high-protein medium-carbohydrate diet than the high-carbohydrate medium-protein diet. These differences can be explained mainly by the difference in carbohydrate content between the two diets. Energy restriction (35% lower energy intake than in the obese state) resulted in a 2.23 ± 0.05% loss in body weight/week, and the dogs reached their optimal body weight in 12-16 weeks. Weight loss was associated with a significant increase in insulin sensitivity. The high-protein medium-carbohydrate diet allowed fat-free mass preservation despite a relatively high rate of weekly weight loss. The increase in insulin sensitivity indicated improved control of carbohydrate metabolism, possible due to weight loss and to the nature of the diet. Thus, a high-protein medium-carbohydrate diet is a good nutritional solution for managing the weight of overweight dogs. This diet may improve glycaemic control, which could be beneficial for preventing or

Beta-arrestin-1 protein represses diet-induced obesity.

PubMed

Zhuang, Le-nan; Hu, Wen-xiang; Zhang, Ming-liang; Xin, Shun-mei; Jia, Wei-ping; Zhao, Jian; Pei, Gang

2011-08-12

Diet-related obesity is a major metabolic disorder. Excessive fat mass is associated with type 2 diabetes, hepatic steatosis, and arteriosclerosis. Dysregulation of lipid metabolism and adipose tissue function contributes to diet-induced obesity. Here, we report that β-arrestin-1 knock-out mice are susceptible to diet-induced obesity. Knock-out of the gene encoding β-arrestin-1 caused increased fat mass accumulation and decreased whole-body insulin sensitivity in mice fed a high-fat diet. In β-arrestin-1 knock-out mice, we observed disrupted food intake and energy expenditure and increased macrophage infiltration in white adipose tissue. At the molecular level, β-arrestin-1 deficiency affected the expression of many lipid metabolic genes and inflammatory genes in adipose tissue. Consistently, transgenic overexpression of β-arrestin-1 repressed diet-induced obesity and improved glucose tolerance and systemic insulin sensitivity. Thus, our findings reveal that β-arrestin-1 plays a role in metabolism regulation.

[Role of infection in the pathogenesis of obesity].

PubMed

Hainer, Vojtěch; Hainerová, Irena Aldhoon; Zamrazilová, Hana

2012-01-01

Current global epidemic of obesity is mainly related to increased consumption of high energy density foods and sedentary lifestyle that leads to a positive energy balance with subsequent accumulation of fat stores, primarily in genetically predisposed individuals. However, additional pathogenetic factors should be considered, including an infection. Several viruses causing obesity have been described in mice, chicken, rats, hamsters and monkeys. In humans, a significant positive association between being overweight and IgG antibodies was found for Helicobacter pylori and Chlamydia pneumoniae. This association of bacterial infections with increased BMI might not represent a causal relationship but could be a marker for greater susceptibility of obese individuals to infection. Crucial role in the development of "infectious obesity" in humans may be played by adenovirus infection, particularly AD-36 type that is also capable of inducing obesity in experimental animals as chicken, mice and monkeys. AD-36-induced obesity is paradoxically associated with lower levels of serum cholesterol and triglycerides both in humans and in experimental animals. Moreover, AD-36 enhances insulin sensitivity and improves hepatic steatosis. AD-36 effects in target organs as adipose tissue, liver and skeletal muscle are mediated through the viral protein E4orf1. This way AD-36 improves metabolic profile, as indicated by a greater glucose uptake by adipose tissue and skeletal muscle, reduced glucose output by hepatocytes, increased adiponectin levels and increased expression of adipogenic genes as peroxisome proliferator-activated receptor gamma. If E4orf1 improves glycemic control without reducing dietary fat intake and body fat stores, this viral protein would be highly valuable to develop novel anti-diabetic agents that mimic its effects.Key words: obesity, infection, adenovirus AD-36, diabetes mellitus, lipid profile, insulin sensitivity.

A Novel Melanocortin-4 Receptor Mutation MC4R-P272L Associated with Severe Obesity Has Increased Propensity To Be Ubiquitinated in the ER in the Face of Correct Folding

PubMed Central

Granell, Susana; Serra-Juhé, Clara; Martos-Moreno, Gabriel Á.; Díaz, Francisca; Pérez-Jurado, Luis A.; Baldini, Giulia; Argente, Jesús

2012-01-01

Heterozygous mutations in the melanocortin-4 receptor (MC4R) gene represent the most frequent cause of monogenic obesity in humans. MC4R mutation analysis in a cohort of 77 children with morbid obesity identified previously unreported heterozygous mutations (P272L, N74I) in two patients inherited from their obese mothers. A rare polymorphism (I251L, allelic frequency: 1/100) reported to protect against obesity was found in another obese patient. When expressed in neuronal cells, the cell surface abundance of wild-type MC4R and of the N74I and I251L variants and the cAMP generated by these receptors in response to exposure to the agonist, α-MSH, were not different. Conversely, MC4R P272L was retained in the endoplasmic reticulum and had reduced cell surface expression and signaling (by ≈3-fold). The chemical chaperone PBA, which promotes protein folding of wild-type MC4R, had minimal effects on the distribution and signaling of the P272L variant. In contrast, incubation with UBE-41, a specific inhibitor of ubiquitin activating enzyme E1, inhibited ubiquitination of MC4R P272L and increased its cell surface expression and signaling to similar levels as wild-type MC4R. UBE41 had much less profound effects on MC4R I316S, another obesity-linked MC4R variant trapped in the ER. These data suggest that P272L is retained in the ER by a propensity to be ubiquitinated in the face of correct folding, which is only minimally shared by MC4R I316S. Thus, studies that combine clinical screening of obese patients and investigation of the functional defects of the obesity-linked MC4R variants can identify specific ways to correct these defects and are the first steps towards personalized medicine. PMID:23251400

Prevalence of overweight and obesity in The Netherlands in relation to sociodemographic variables, lifestyle and eating behavior: starting points for the prevention and treatment of obesity.

PubMed

Deurenberg, P; Hautvast, J G

1989-01-01

The prevalence and incidence of overweight and obesity has been studied in a young adult population aged 19-35 years. Special attention was given to the relation with psychosociological variables and life-style. The prevalence of overweight and obesity was also studied in a representative population for The Netherlands, in which population also the relation with self-reported illness and subjective health was studied. In the patient population of four general practices the relation of overweight and obesity with disease was investigated in a retrospective design. Also the influence of the body fat distribution was studied. The prevalence of overweight (BMI greater than 25 kg/m2) in the Dutch adult population was 34% in men and 24% in women. The prevalence of obesity (BMI greater than 30 kg/m2) was 4 and 6% in men and women, respectively. The prevalence of overweight and obesity was negatively related with social class and increased with age. Also, life-style variables such as coffee consumption, alcohol consumption, smoking and amount of hours sleep (CASS behavior), physical activity during leisure time, slimming behavior and health-conscious behavior were correlated with the prevalence of overweight. Life events caused an increase in body weight, but in women (not in men) this gain was suppressed by following slimming periods. Thus, emotional eating seems to be an important factor in the etiology of obesity. The results of our studies on the relation of overweight and obesity with morbidity aspects show a clear relation of some diseases and subjective health with overweight, especially in men and women with an abdominal fat distribution. From the results of this study starting points for the prevention and treatment of obesity are proposed.

Gene-gene interactions among genetic variants from obesity candidate genes for nonobese and obese populations in type 2 diabetes.

PubMed

Lin, Eugene; Pei, Dee; Huang, Yi-Jen; Hsieh, Chang-Hsun; Wu, Lawrence Shih-Hsin

2009-08-01

Recent studies indicate that obesity may play a key role in modulating genetic predispositions to type 2 diabetes (T2D). This study examines the main effects of both single-locus and multilocus interactions among genetic variants in Taiwanese obese and nonobese individuals to test the hypothesis that obesity-related genes may contribute to the etiology of T2D independently and/or through such complex interactions. We genotyped 11 single nucleotide polymorphisms for 10 obesity candidate genes including adrenergic beta-2-receptor surface, adrenergic beta-3-receptor surface, angiotensinogen, fat mass and obesity associated gene, guanine nucleotide binding protein beta polypeptide 3 (GNB3), interleukin 6 receptor, proprotein convertase subtilisin/kexin type 1 (PCSK1), uncoupling protein 1, uncoupling protein 2, and uncoupling protein 3. There were 389 patients diagnosed with T2D and 186 age- and sex-matched controls. Single-locus analyses showed significant main effects of the GNB3 and PCSK1 genes on the risk of T2D among the nonobese group (p = 0.002 and 0.047, respectively). Further, interactions involving GNB3 and PCSK1 were suggested among the nonobese population using the generalized multifactor dimensionality reduction method (p = 0.001). In addition, interactions among angiotensinogen, fat mass and obesity associated gene, GNB3, and uncoupling protein 3 genes were found in a significant four-locus generalized multifactor dimensionality reduction model among the obese population (p = 0.001). The results suggest that the single nucleotide polymorphisms from the obesity candidate genes may contribute to the risk of T2D independently and/or in an interactive manner according to the presence or absence of obesity.

Targeting the S1P Axis and Development of a Novel Therapy for Obesity-Related Triple-Negative Breast Cancer

DTIC Science & Technology

2016-09-01

1 AWARD NUMBER: W81XWH-14-1-0086 TITLE: Targeting the S1P Axis and Development of a Novel Therapy for Obesity -Related Triple- Negative Breast...Sep 2015 - 31Aug2016 4. TITLE AND SUBTITLE Targeting the S1P Axis and Development of a Novel Therapy for Obesity -Related Triple-Negative Breast...hormonal therapies and have limited treatment options. Epidemiological and clinical studies indicate that obesity , which is now endemic, increases

Partly replacing meat protein with soy protein alters insulin resistance and blood lipids in postmenopausal women with abdominal obesity.

PubMed

van Nielen, Monique; Feskens, Edith J M; Rietman, Annemarie; Siebelink, Els; Mensink, Marco

2014-09-01

Increasing protein intake and soy consumption appear to be promising approaches to prevent metabolic syndrome (MetS). However, the effect of soy consumption on insulin resistance, glucose homeostasis, and other characteristics of MetS is not frequently studied in humans. We aimed to investigate the effects of a 4-wk, strictly controlled, weight-maintaining, moderately high-protein diet rich in soy on insulin sensitivity and other cardiometabolic risk factors. We performed a randomized crossover trial of 2 4-wk diet periods in 15 postmenopausal women with abdominal obesity to test diets with 22 energy percent (En%) protein, 27 En% fat, and 50 En% carbohydrate. One diet contained protein of mixed origin (mainly meat, dairy, and bread), and the other diet partly replaced meat with soy meat analogues and soy nuts containing 30 g/d soy protein. For our primary outcome, a frequently sampled intravenous glucose tolerance test (FSIGT) was performed at the end of both periods. Plasma total, LDL, and HDL cholesterol, triglycerides, glucose, insulin, and C-reactive protein were assessed, and blood pressure, arterial stiffness, and intrahepatic lipid content were measured at the start and end of both periods. Compared with the mixed-protein diet, the soy-protein diet resulted in greater insulin sensitivity [FSIGT: insulin sensitivity, 34 ± 29 vs. 22 ± 17 (mU/L)(-1) · min(-1), P = 0.048; disposition index, 4974 ± 2543 vs. 2899 ± 1878, P = 0.038; n = 11]. Total cholesterol was 4% lower after the soy-protein diet than after the mixed-protein diet (4.9 ± 0.7 vs. 5.1 ± 0.6 mmol/L, P = 0.001), and LDL cholesterol was 9% lower (2.9 ± 0.7 vs. 3.2 ± 0.6 mmol/L, P = 0.004; n = 15). Thus, partly replacing meat with soy in a moderately high-protein diet has clear advantages regarding insulin sensitivity and total and LDL cholesterol. Therefore, partly replacing meat products with soy products could be important in preventing MetS. This trial was registered at clinicaltrials

Relationship of oxidative stress in skeletal muscle with obesity and obesity-associated hyperinsulinemia in horses.

PubMed

Banse, Heidi E; Frank, Nicholas; Kwong, Grace P S; McFarlane, Dianne

2015-10-01

In horses, hyperinsulinemia and insulin resistance (insulin dysregulation) are associated with the development of laminitis. Although obesity is associated with insulin dysregulation, the mechanism of obesity-associated insulin dysregulation remains to be established. We hypothesized that oxidative stress in skeletal muscle is associated with obesity-associated hyperinsulinemia in horses. Thirty-five light breed horses with body condition scores (BCS) of 3/9 to 9/9 were studied, including 7 obese, normoinsulinemic (BCS ≥ 7, resting serum insulin < 30 μIU/mL) and 6 obese, hyperinsulinemic (resting serum insulin ≥ 30 μIU/mL) horses. Markers of oxidative stress (oxidative damage, mitochondrial function, and antioxidant capacity) were evaluated in skeletal muscle biopsies. A Spearman's rank correlation coefficient was used to determine relationships between markers of oxidative stress and BCS. Furthermore, to assess the role of oxidative stress in obesity-related hyperinsulinemia, markers of antioxidant capacity and oxidative damage were compared among lean, normoinsulinemic (L-NI); obese, normoinsulinemic (O-NI); and obese, hyperinsulinemic (O-HI) horses. Increasing BCS was associated with an increase in gene expression of a mitochondrial protein responsible for mitochondrial biogenesis (estrogen-related receptor alpha, ERRα) and with increased antioxidant enzyme total superoxide dismutase (TotSOD) activity. When groups (L-NI, O-NI, and O-HI) were compared, TotSOD activity was increased and protein carbonyls, a marker of oxidative damage, decreased in the O-HI compared to the L-NI horses. These findings suggest that a protective antioxidant response occurred in the muscle of obese animals and that obesity-associated oxidative damage in skeletal muscle is not central to the pathogenesis of equine hyperinsulinemia.

Impact of canine overweight and obesity on health-related quality of life.

PubMed

Yam, P S; Butowski, C F; Chitty, J L; Naughton, G; Wiseman-Orr, M L; Parkin, T; Reid, J

2016-05-01

Canine obesity is increasing in prevalence in the UK and raises concerns about dog welfare. This study compares the health-related quality of life (HRQL) of dogs of varying body condition: overweight and obese (BCS 4 and 5) versus non-overweight dogs (BCS 2 and 3), obese (BCS 5) versus non-overweight (BCS 2 and 3) and an overall comparison between all four BCS (BCS 2, 3, 4 and 5) using a novel, validated HRQL instrument which is both web and mobile tablet/phone app based. Of 271 dog owners who were approached, 174 completed a web-based instrument (2013) or a mobile tablet app instrument (2014) during the summers of 2013 and 2014. Automatically generated scores in four domains of HRQL (energetic/enthusiastic, happy/content, active/comfortable, calm/relaxed) were compared for dogs with each of the body condition scores (BCS 2-5). For all body condition scores a statistically significant difference was found between the HRQL scores in two of the domains: energetic/enthusiastic (p=0.02) and active comfortable (p=0.004). When BCS 2 and 3 were compared to BCS 4 and 5, statistical significance was found in the same two domains - energetic/enthusiastic (p=0.01) and active comfortable (p=0.001) - as it was in comparison of non-overweight (BCS 2 and 3) compared to obese dogs (BCS 5): energetic/enthusiastic (p=0.012) and active comfortable (p=0.004). These results suggest that overweight and obese dogs have a reduced HRQL in two of the domains compared to non-overweight dogs, and that differences in HRQL are detectable between BCS scores 2, 3, 4 and 5. Copyright © 2016 Elsevier B.V. All rights reserved.

Comparative proteomics of umbilical vein blood plasma from normal and gestational diabetes mellitus patients reveals differentially expressed proteins associated with childhood obesity.

PubMed

Miao, Zhijing; Wang, Jianqing; Wang, Fuqiang; Liu, Lan; Ding, Hongjuan; Shi, Zhonghua

2016-11-01

Offspring obesity is one of long-term complications of gestational diabetes mellitus (GDM). The aim of this study is to identify proteins differentially expressed in the umbilical vein blood plasma, which could become markers for early diagnosis of childhood obesity. Umbilical vein plasma samples were collected from 30 control and 30 GDM patients in 2007-2008 whose offspring were suffering from obesity at 6-7 years old. Multiplexed isobaric tandem mass tag labeling combined with LC-MS/MS was used to identify differentially expressed proteins. Ingenuity pathway analysis was performed to identify canonical pathways, biological functions, and networks of interacting proteins. Western blotting was used to verify the expression of three selected proteins. A total of 318 proteins were identified, of which 12 proteins were upregulated in GDM group while 24 downregulated. Lipid metabolism was the top category identified by ingenuity pathway analysis. Three randomly chosen proteins were validated by Western blotting, which were consistent with LC-MS. There are significant differences of protein profile in the umbilical vein blood plasma between normal and GDM patients with obese offspring. The results indicate that a variety of proteins and biological mechanisms may contribute to childhood obesity. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

[Obesity studies in candidate genes].

PubMed

Ochoa, María del Carmen; Martí, Amelia; Martínez, J Alfredo

2004-04-17

There are more than 430 chromosomic regions with gene variants involved in body weight regulation and obesity development. Polymorphisms in genes related to energy expenditure--uncoupling proteins (UCPs), related to adipogenesis and insulin resistance--hormone-sensitive lipase (HLS), peroxisome proliferator-activated receptor gamma (PPAR gamma), beta adrenergic receptors (ADRB2,3), and alfa tumor necrosis factor (TNF-alpha), and related to food intake--ghrelin (GHRL)--appear to be associated with obesity phenotypes. Obesity risk depends on two factors: a) genetic variants in candidate genes, and b) biographical exposure to environmental risk factors. It is necessary to perform new studies, with appropriate control groups and designs, in order to reach relevant conclusions with regard to gene/environmental (diet, lifestyle) interactions.

The social patterning of relative body weight and obesity in Denmark and Finland.

PubMed

Sarlio-Lähteenkorva, Sirpa; Lissau, Inge; Lahelma, Eero

2006-02-01

Relative body weight is typically inversely associated with social status in affluent societies but studies comparing the social patterning of relative body weight and obesity in different countries have only seldom been conducted. The aim of this study was to analyse and compare the social patterning of relative weight and obesity by occupational status, educational attainment and marital status between Danish and Finnish women and men. Data from the Finnish Survey on Living Conditions and the Danish Health and Morbidity Survey, both collected in 1994, were compared. Relative weight was studied by using body mass index (BMI), and those with BMI > or =30 kg/m(2) were regarded as obese. Logistic regression analysis was used to examine the social patterning of obesity in the pooled dataset. Two-variable interaction effects were tested separately. Compared with their Danish counterparts, Finnish women and men had higher average relative weight and they were more often obese. There were no country differences in the socio-economic patterning of obesity by educational attainment, but a stronger patterning of obesity by occupational status was found among Danish women. Moreover, non-married women in Denmark were more likely to be obese than their married counterparts. Finns have higher relative weight and they are more often obese than Danes. The social patterning of obesity was similar in both studied countries but stronger in Denmark.

Obesity and Sleep-Related Breathing Disorders in Middle East and UAE.

PubMed

Vats, Mayank G; Mahboub, Bassam H; Al Hariri, Hassan; Al Zaabi, Ashraf; Vats, Deepa

2016-01-01

A pandemic of obesity is sweeping all across the globe and the Middle East region also does not remain untouched by this prevailing pandemic. In fact, as per WHO report, Kuwait has the second highest obesity prevalence followed closely by other Middle East (ME) countries, namely, Qatar, Saudi Arabia, and United Arab Emirates (UAE). Apart from direct medical, psychological, and quality of life related adverse effects of obesity, many indirect medical comorbidities, namely, obstructive sleep apnea (OSA), obesity hypoventilation syndrome (OHS), diabetes mellitus (DM), hypertension (HTN), and metabolic syndrome, imposes a significant health burden on the individual and community with consequent morbidity and mortality. The purpose of this review is to shed light on the very high prevalence of obesity, undiagnosed sleep apnea, and other obesity related disorders with discussion of the contributing factors specific to the region including the fair insight into the current status of sleep medicine services in Middle East and UAE despite huge number of patients having undiagnosed sleep disorders. We will also suggest to control this epidemic of obesity and OSA so that the corrective measure could be taken at health ministry level to help people of this region to fight against obesity and related disorders, primarily OSA.

Obesity and Sleep-Related Breathing Disorders in Middle East and UAE

PubMed Central

Mahboub, Bassam H.; Al Hariri, Hassan; Al Zaabi, Ashraf; Vats, Deepa

2016-01-01

A pandemic of obesity is sweeping all across the globe and the Middle East region also does not remain untouched by this prevailing pandemic. In fact, as per WHO report, Kuwait has the second highest obesity prevalence followed closely by other Middle East (ME) countries, namely, Qatar, Saudi Arabia, and United Arab Emirates (UAE). Apart from direct medical, psychological, and quality of life related adverse effects of obesity, many indirect medical comorbidities, namely, obstructive sleep apnea (OSA), obesity hypoventilation syndrome (OHS), diabetes mellitus (DM), hypertension (HTN), and metabolic syndrome, imposes a significant health burden on the individual and community with consequent morbidity and mortality. The purpose of this review is to shed light on the very high prevalence of obesity, undiagnosed sleep apnea, and other obesity related disorders with discussion of the contributing factors specific to the region including the fair insight into the current status of sleep medicine services in Middle East and UAE despite huge number of patients having undiagnosed sleep disorders. We will also suggest to control this epidemic of obesity and OSA so that the corrective measure could be taken at health ministry level to help people of this region to fight against obesity and related disorders, primarily OSA. PMID:28070158

Factors affecting subspecialty referrals by pediatric primary care providers for children with obesity-related comorbidities.

PubMed

Walsh, Carolyn O; Milliren, Carly E; Feldman, Henry A; Taveras, Elsie M

2013-08-01

To determine referral patterns from pediatric primary care to subspecialists for overweight/obesity and related comorbidities. We used the National Ambulatory Medical Care Survey and National Hospital Ambulatory Medical Care Survey to identify overweight/obesity and 5 related comorbidities in primary care visits between 2005 and 2009 by children 6 to 18 years. The primary outcome was whether the visit ended in referral. We used multivariable analysis to examine factors associated with referral. We identified 34,225 database visits. A total of 17.1% were with overweight (body mass index=85th to 94th percentile) or obese (body mass index≥95th percentile) patients. A total of 7.1% of primary care visits with overweight/obese children ended in referral. Referral was more likely when obesity was the reason for visit (odds ratio=2.83; 95% confidence interval=1.61-4.97) but was not associated with presence of a comorbidity (odds ratio=1.35; 95% confidence interval=0.75-2.44). Most overweight or obese children are not referred, regardless of comorbidity status. One reason may be low levels of appropriate diagnosis.

Overweight, obesity and related conditions: a cross-sectional study of adult inpatients at a Norwegian Hospital

PubMed Central

2014-01-01

Background Overweight, obesity and associated conditions are major public health concerns in Norway. The prevalence of overweight and obesity in the general population in Norway is increasing, but there are limited data on how the situation is in hospitals. This study aimed to find the prevalence of overweight and obesity, and explore the associations of overweight, obesity and its related medical conditions in an adult in-patient sample at specified somatic and psychiatric departments at St. Olavs Hospital, Trondheim. Results A total of 497 patients participated. The mean BMI for the total sample at screening was 25.4 kg/m2. The prevalence of overweight and obesity was 45.1%. There was a higher association of overweight and obesity among patients aged 40–59 years (OR: 1.7) compared to those being younger. There was no significant difference between the somatic and the psychiatric samples. In the somatic sample overweight and obesity was associated with obesity-related conditions for both genders (OR: 2.0 and 2.1, respectively), when adjusted for age. Conclusion The substantial prevalence of overweight and obese patients may pose a threat to future hospital services. To further address the burden of overweight and obesity in hospitals, we need more knowledge about consequences of length of stay, use of resources and overall cost. PMID:24571809

A role for whey-derived lactoferrin and immunoglobulins in the attenuation of obesity-related inflammation and disease.

PubMed

Brimelow, Rachel E; West, Nicholas P; Williams, Lauren T; Cripps, Allan W; Cox, Amanda J

2017-05-24

Obesity is a strong predictive factor in the development of chronic disease and has now superseded undernutrition as a major public health issue. Chronic inflammation is one mechanism thought to link excess body weight with disease. Increasingly, the gut and its extensive population of commensal microflora are recognized as playing an important role in the development of obesity-related chronic inflammation. Obesity and a high fat diet are associated with altered commensal microbial communities and increased intestinal permeability which contributes to systemic inflammation as a result of the translocation of lipopolysaccharide into the circulation and metabolic endotoxemia. Various milk proteins are showing promise in the prevention and treatment of obesity and chronic low-grade inflammation via reductions in visceral fat, neutralization of bacteria at the mucosa and reduced intestinal permeability. In this review, we focus on evidence supporting the potential antiobesogenic and anti-inflammatory effects of bovine whey-derived lactoferrin and immunoglobulins.

Excessive endoplasmic reticulum stress and decreased neuroplasticity-associated proteins in prefrontal cortex of obese rats and the regulatory effects of aerobic exercise.

PubMed

Li, Feng; Liu, Bei Bei; Cai, Ming; Li, Jing Jing; Lou, Shu-Jie

2018-04-06

Studies have shown high fat diet induced obesity may cause cognition impairment and down-regulation of neuroplasticity-associated proteins, while aerobic exercise could improve that damage. Endoplasmic reticulum stress (ERS) has been reported to play a key role in regulating neuroplasticity-associated proteins expression, folding and post-translational modification in hippocampus of obese rodent models, however, the effects of ERS on neuroplasticity-associated proteins and possible underlying mechanisms in prefrontal cortex are not fully clear. In order to clarify changes of neuroplasticity-associated proteins and ERS in the prefrontal cortex of obese rats, male SD rats were fed on high fat diet for 8 weeks to establish the obese model. Then, 8 weeks of aerobic exercise treadmill intervention was arranged for the obese rats. Results showed that high fat diet induced obesity caused hyperlipidemia, and significantly promoted FATP1 expression in the prefrontal cortex, meanwhile, we found up-regulation of GRP78, p-PERK, p-eIF2α, caspase-12, CHOP, and Bax/Bcl-2, reflecting the activation of ERS and ERS-mediated apoptosis. Moreover, reduced BDNF and SYN was found in obese rats. However, FATP1, GRP78, p-PERK, p-eIF2α, caspase-12, CHOP, and Bax/Bcl-2 expressions were obviously reversed by aerobic exercise intervention. These results suggested that dietary obesity could induce Prefrontal ERS in SD rats and excessive ERS may play a critical role in decreasing the levels of neuroplasticity-associated proteins. Moreover, aerobic exercise could relieve ERS, thus promoted the expression of neuroplasticity-associated proteins. Copyright © 2018. Published by Elsevier Inc.

Recombinant HT{sub m4} gene, protein and assays

DOEpatents

Lim, B.; Adra, C.N.; Lelias, J.M.

1996-09-03

The invention relates to a recombinant DNA molecule which encodes a HT{sub m4} protein, a transformed host cell which has been stably transfected with a DNA molecule which encodes a HT{sub m4} protein and a recombinant HT{sub m4} protein. The invention also relates to a method for detecting the presence of a hereditary atopy. 2 figs.

Recombinant HT.sub.m4 gene, protein and assays

DOEpatents

Lim, Bing; Adra, Chaker N.; Lelias, Jean-Michel

1996-01-01

The invention relates to a recombinant DNA molecule which encodes a HT.sub.m4 protein, a transformed host cell which has been stably transfected with a DNA molecule which encodes a HT.sub.m4 protein and a recombinant HT.sub.m4 protein. The invention also relates to a method for detecting the presence of a hereditary atopy.

Astrocytes and endoplasmic reticulum stress: A bridge between obesity and neurodegenerative diseases.

PubMed

Martin-Jiménez, Cynthia A; García-Vega, Ángela; Cabezas, Ricardo; Aliev, Gjumrakch; Echeverria, Valentina; González, Janneth; Barreto, George E

2017-11-01

Endoplasmic reticulum (ER) is a subcellular organelle involved in protein folding and processing. ER stress constitutes a cellular process characterized by accumulation of misfolded proteins, impaired lipid metabolism and induction of inflammatory responses. ER stress has been suggested to be involved in several human pathologies, including neurodegenerative diseases and obesity. Different studies have shown that both neurodegenerative diseases and obesity trigger similar cellular responses to ER stress. Moreover, both diseases are assessed in astrocytes as evidences suggest these cells as key regulators of brain homeostasis. However, the exact contributions to the effects of ER stress in astrocytes in the various neurodegenerative diseases and its relation with obesity are not well known. Here, we discuss recent advances in the understanding of molecular mechanisms that regulate ER stress-related disorders in astrocytes such as obesity and neurodegeneration. Moreover, we outline the correlation between the activated proteins of the unfolded protein response (UPR) in these pathological conditions in order to identify possible therapeutic targets for ER stress in astrocytes. We show that ER stress in astrocytes shares UPR activation pathways during both obesity and neurodegenerative diseases, demonstrating that UPR related proteins like ER chaperone GRP 78/Bip, PERK pathway and other exogenous molecules ameliorate UPR response and promote neuroprotection. Copyright © 2017 Elsevier Ltd. All rights reserved.

Small for gestational age and obesity related comorbidities

PubMed Central

Hong, Yong Hee

2018-01-01

Infant born small for gestational age (SGA) are at increased risk of perinatal morbidity, persistent short stature and metabolic alterations in later life. The result of SGA followed by rapid weight gain during early postnatal life has been associated with increased long-term risks for central obesity, insulin resistance, impaired glucose tolerance, type 2 diabetes, hypertension, increased fat mass, and cardiovascular disease. We should carefully monitor their weight during infancy and childhood to prevent excessive rates of weight gain. ‘Healthy catch up growth’ may decreased the risk of obesity-related comorbidities in SGA. Establishing the optimal growth patterns in SGA to minimize short- and long-term risks is important, and further studies will be needed. This review discusses recent studies concentrating on obesity-related morbidities in SGA infants that may provide insight into growth monitoring. PMID:29609443

Anti-obesity effects of boiled tuna extract in mice with obesity induced by a high-fat diet.

PubMed

Kim, Youngmin; Kwon, Mi-Jin; Choi, Jeong-Wook; Lee, Min-Kyeong; Kim, Chorong; Jung, Jaehun; Aprianita, Heny; Nam, Heesop; Nam, Taek-Jeong

2016-10-01

The aim of this study was to examine the anti-obesity effects of boiled tuna extract in C57BL/6N mice with obesity induced by a high-fat diet (HFD). We determined the anti-obesity effects of boiled tuna extract (100, 200, or 400 mg/kg) on the progression of HFD-induced obesity for 10 weeks. The mice were divided into 5 groups as follows: the normal diet (ND) group (n=10); the HFD group (n=10); the mice fed HFD and 100 mg/kg boiled tuna extract group (n=10); those fed a HFD and 200 mg/kg boiled tuna extract group (n=10); and those fed a HFD and 400 mg/kg boiled tuna extract group (n=10). Changes in body weight, fat content, serum lipid levels and lipogenic enzyme levels were measured. The consumption of boiled tuna extract lowered epididymal tissue weight and exerted anti-obesity effects, as reflected by the serum glucose, triglyceride (TG), total cholesterol (TC), high-density lipoprotein cholesterol (HDL‑C), low-density lipoprotein cholesterol (LDL-C), insulin and leptin levels. In addition, we demonstrated changes in liver adipogenic- and lipogenic-related protein expression by western blot analysis. Boiled tuna extract downregulated the levels of the CCAAT/enhancer-binding protein α, β and δ (C/EBPα, β, δ), and peroxisome proliferator-activated receptor-γ (PPAR-γ) adipocyte marker genes. Boiled tuna extract also attenuated adipogenic and lipogenic gene expression, namely the levels of fatty acid synthase (FAS), lipoprotein lipase (LPL), acetyl-CoA carboxylase (ACC), glucose transporter type 4 (Glut4) and phosphorylated adenosine monophosphate-activated protein kinase α and β (AMPKα, β) in a dose-dependent manner. Moreover, the consumption of boiled tuna extract restored the levels of superoxide dismutase (SOD), catalase (CAT), glutamic oxaloacetic transaminase (GOT), glutamic-pyruvate transaminase (GPT), aspartate transaminase (AST) and alanine transaminase (ALT) to those of the control group. These results

Urinary leukotriene E4, obesity, and adenotonsillar hypertrophy in Chinese children with sleep disordered breathing.

PubMed

Shen, Yuelin; Xu, Zhifei; Shen, Kunling

2011-08-01

Sleep disordered breathing (SDB) has been associated with increased inflammatory responses. Changes in the level of pro-inflammatory leukotrienes (LTs) may initiate or exacerbate pediatric SDB and may play a major role in end-organ morbidity. The objective of the study was to investigate the relationship of LT productions with severity of SDB, obesity, and adenotonsillar hypertrophy in children. Prospective, observational study that included standard questionnaires, physical examinations, overnight polysomnography (PSG), and urinary leukotriene E(4) (LTE(4)) assay. Sleep Center and Laboratory of Nutriology. 282 children with SDB and 94 healthy control subjects were recruited. Urinary LTE(4) levels were elevated in children with SDB compared to the controls, and LTE(4) productions emerged disease severity- and obesity-dependent increases. In stepwise multiple regression analysis, the independent predictors of the apnea-hypopnea index (AHI) included LTE(4) level and adenotonsillar-size sum score (P < 0.001 respectively; adjusted R(2)=0.318). A positive relationship between LTE(4) urinary level and adenotonsillar-size sum scores was present in the underweight/normal weight SDB subjects (r=0.276; P < 0.001), but not in the overweight/obese children (P > 0.05). Systemic inflammation mediated by LTs participates in the pathophysiological mechanisms of SDB in children. The magnitude of inflammation as reflected by urinary LTE(4) is significantly related to the severity of SDB and obesity. However, a correlation between LTE(4) concentration and adenotonsillar size is present only among nonobese children.

Parental Predictions and Perceptions Regarding Long-Term Childhood Obesity-Related Health Risks

PubMed Central

Wright, Davene R.; Lozano, Paula; Dawson-Hahn, Elizabeth; Christakis, Dimitri A.; Haaland, Wren; Basu, Anirban

2016-01-01

Objectives To assess how parents perceive long-term risks for developing obesity-related chronic health conditions. Methods A web-based nationally representative survey was administered to 502 U.S. parents with a 5–12 year old child. Parents reported whether their child was most likely to be at a healthy weight or overweight, and the probability that their child would develop hypertension, heart disease, depression, or type 2 diabetes in adulthood. Responses of parents of children with overweight and obesity were compared to those of healthy weight children using multivariate models. Results The survey had an overall response rate of 39.2%. The mean (SD) unadjusted parent predicted health risks were 15.4% (17.7%), 11.2% (14.7%), 12.5% (16.2%), and 12.1% (16.1%) for hypertension, heart disease, depression, and diabetes, respectively. Despite under-perceiving their child’s current BMI class, parents of children with obesity estimate their children to be at greater risk for obesity-related health conditions than parents of healthy weight children by 5–6 percentage points. Having a family history of a chronic disease, higher quality of care, and older parent age were also significant predictors of estimating higher risk probabilities. Conclusions Despite evidence that parents of overweight children may not perceive these children as being overweight, parents unexpectedly estimate greater future risk of weight-related health conditions for these children. Focusing communication about weight on screening for and reducing the risk of weight-related diseases may prove useful in engaging parents and children in weight management PMID:26875508

Lower protein content in infant formula reduces BMI and obesity risk at school age: follow-up of a randomized trial.

PubMed

Weber, Martina; Grote, Veit; Closa-Monasterolo, Ricardo; Escribano, Joaquín; Langhendries, Jean-Paul; Dain, Elena; Giovannini, Marcello; Verduci, Elvira; Gruszfeld, Dariusz; Socha, Piotr; Koletzko, Berthold

2014-05-01

Early nutrition is recognized as a target for the effective prevention of childhood obesity. Protein intake was associated with more rapid weight gain during infancy-a known risk factor for later obesity. We tested whether the reduction of protein in infant formula reduces body mass index (BMI; in kg/m(2)) and the prevalence of obesity at 6 y of age. The Childhood Obesity Project was conducted as a European multicenter, double-blind, randomized clinical trial that enrolled healthy infants born between October 2002 and July 2004. Formula-fed infants (n = 1090) were randomly assigned to receive higher protein (HP)- or lower protein (LP)-content formula (within recommended amounts) in the first year of life; breastfed infants (n = 588) were enrolled as an observational reference group. We measured the weight and height of 448 (41%) formula-fed children at 6 y of age. BMI was the primary outcome. HP children had a significantly higher BMI (by 0.51; 95% CI: 0.13, 0.90; P = 0.009) at 6 y of age. The risk of becoming obese in the HP group was 2.43 (95% CI: 1.12, 5.27; P = 0.024) times that in the LP group. There was a tendency for a higher weight in HP children (0.67 kg; 95% CI: -0.04, 1.39 kg; P = 0.064) but no difference in height between the intervention groups. Anthropometric measurements were similar in the LP and breastfed groups. Infant formula with a lower protein content reduces BMI and obesity risk at school age. Avoidance of infant foods that provide excessive protein intakes could contribute to a reduction in childhood obesity. This trial was registered at clinicaltrials.gov as NCT00338689.

Hypolipidemic, antioxidant and antiatherogenic property of sardine by-products proteins in high-fat diet induced obese rats.

PubMed

Affane, Fouad; Louala, Sabrine; El Imane Harrat, Nour; Bensalah, Fatima; Chekkal, Hadjera; Allaoui, Amine; Lamri-Senhadji, Myriem

2018-04-15

Fish by-products valorization on account of their richness in bioactive compounds may represent a better alternative to marine products with a view to economic profitability and sustainable development. In this study, we compared the effect of sardine by-product proteins (SBy-P), with those of the fillets (SF-P) or casein (Cas), on growth parameters, serum leptin level, lipids disorders, lipid peroxidation and reverse cholesterol transport, in diet-induced obese rats. Obesity was induced by feeding rats a high-fat diet (20% sheep fat), during 12 weeks. At body weight (BW) of 400 ± 20 g, eighteen obese rats were divided into three homogenous groups and continue to consume the high-fat diet for 4 weeks containing either, 20% SBy-P, SF-P or Cas. The results showed that SBy-P, compared to SF-P and Cas, efficiently reduced food intake (FI), BW gain and serum leptin level, and improved blood lipids levels and reverse cholesterol transport by reducing total cholesterol (TC), triacylglycerols (TG) and low-density lipoprotein cholesterol (LDL-HDL 1 -C) serum levels, increasing the level of high-density lipoprotein cholesterol (HDL 2 -C and HDL 3 -C), and enhancing lecithin: cholesterol acyltransferase (LCAT) activity. Furthermore, they attenuated lipid peroxidation by increasing atheroprotective activity of the paraoxonase-1 (PON-1). Sardine by-product proteins due to their richness in certain essential amino acids, highlight weight-loss, lipid-lowering, antioxidant and anti-atherogenic potentials, contributing to the improvement of the complications associated with obesity. Copyright © 2018 Elsevier Inc. All rights reserved.

Whey protein preloads are more beneficial than soy protein preloads in regulating appetite, calorie intake, anthropometry, and body composition of overweight and obese men.

PubMed

Tahavorgar, Atefeh; Vafa, Mohammadreza; Shidfar, Farzad; Gohari, Mahmoodreza; Heydari, Iraj

2014-10-01

High-protein diets exert beneficial effects on appetite, anthropometry, and body composition; however, the effects of protein preloads depend on the amount, type, and time of consumption. Therefore, we hypothesized that long-term supplemental preloads of whey protein concentrate (WPC) and soy protein isolate (SPI) consumed 30 minutes before the largest meal would decrease appetite, calorie intake (CI), and anthropometry and improve body composition in overweight and obese men in free-living conditions. The subjects included 45 men with a body mass index between 25 and 40 kg/m(2) and who were randomly allocated to either the WPC (n = 26) or SPI (n = 19) groups. For 12 weeks, the subjects consumed 65 g WPC or 60 g SPI that was dissolved in 500 mL water 30 minutes before their ad libitum lunch. Appetite, CI, anthropometry, and body composition were assessed before and after the study and biweekly throughout. After 12 weeks, mean changes between the groups were significant for appetite (P = .032), CI (P = .045), anthropometry (body weight [P = .008], body mass index [P = .006], and waist circumference), and body composition (body fat mass and lean muscle [P < .001]). Relative to baseline, within-group mean changes from WPC were significant for appetite, CI, anthropometry, and body composition (P < .001). In the SPI group, mean changes were significant, relative to baseline, for all variables except lean muscle (P = .37). According to this 12-week study, WPC preloads conducted 30 minutes prior to the ad libitum main meal exerted stronger beneficial effects than did SPI preloads on appetite, CI, anthropometry, and body composition of free-living overweight and obese men. Copyright © 2014 Elsevier Inc. All rights reserved.

Weight-Related Correlates of Psychological Dysregulation in Adolescent and Young Adult (AYA) Females with Severe Obesity

PubMed Central

Gowey, Marissa A.; Reiter-Purtill, Jennifer; Becnel, Jennifer; Peugh, James; Mitchell, James E.; Zeller, Meg H.

2016-01-01

Objective Severe obesity is the fastest growing pediatric subgroup of excess weight levels. Psychological dysregulation (i.e., impairments in regulating cognitive, emotional, and/or behavioral processes) has been associated with obesity and poorer weight loss outcomes. The present study explored associations of dysregulation with weight-related variables among adolescent and young adult (AYA) females with severe obesity. Methods Fifty-four AYA females with severe obesity (MBMI=48.71 kg/m2; Mage=18.29, R=15–21 years; 59.3% White) completed self-report measures of psychological dysregulation and weight-related constructs including meal patterns, problematic eating behaviors, and body and weight dissatisfaction, as non-surgical comparison participants in a multi-site study of adolescent bariatric surgery outcomes. Pearson and bivariate correlations were conducted and stratified by age group to analyze associations between dysregulation subscales (affective, behavioral, cognitive) and weight-related variables. Results Breakfast was the most frequently skipped meal (consumed 3–4 times/week). Eating out was common (4–5 times/week) and mostly occurred at fast-food restaurants. Evening hyperphagia (61.11%) and eating in the absence of hunger (37.04%) were commonly endorsed, while unplanned eating (29.63%), a sense of loss of control over eating (22.22%), eating beyond satiety (22.22%), night eating (12.96%), and binge eating (11.11%) were less common. Almost half of the sample endorsed extreme weight dissatisfaction. Dysregulation was associated with most weight-related attitudes and behaviors of interest in young adults but select patterns emerged for adolescents. Conclusions Higher levels of psychological dysregulation are associated with greater BMI, problematic eating patterns and behaviors, and body dissatisfaction in AYA females with severe obesity. These findings have implications for developing novel intervention strategies for severe obesity in AYAs that may

The Interaction of Obstructive Sleep Apnea and Obesity on the Inflammatory Markers C-Reactive Protein and Interleukin-6: The Icelandic Sleep Apnea Cohort

PubMed Central

Arnardottir, Erna S.; Maislin, Greg; Schwab, Richard J.; Staley, Bethany; Benediktsdottir, Bryndis; Olafsson, Isleifur; Juliusson, Sigurdur; Romer, Micah; Gislason, Thorarinn; Pack, Allan I.

2012-01-01

Study Objectives: To assess the relative roles and interaction of obstructive sleep apnea (OSA) severity and obesity on interleukin-6 (IL-6) and C-reactive protein (CRP) levels. Design: Cross-sectional cohort. Setting: The Icelandic Sleep Apnea Cohort. Participants: 454 untreated OSA patients (380 males and 74 females), mean ± standard deviation age 54.4 ± 10.6 yr. Interventions: N/A. Measurements and Results: Participants underwent a sleep study, abdominal magnetic resonance imaging to measure total abdominal and visceral fat volume, and had fasting morning IL-6 and CRP levels measured in serum. A significantly higher correlation was found for BMI than visceral fat volume with CRP and IL-6 levels. Oxygen desaturation index, hypoxia time, and minimum oxygen saturation (SaO2) significantly correlated with IL-6 and CRP levels, but apnea-hypopnea index did not. When stratified by body mass index (BMI) category, OSA severity was associated with IL-6 levels in obese participants only (BMI > 30 kg/m2). A multiple linear regression model with interaction terms showed an independent association of OSA severity with IL-6 levels and an interaction between OSA severity and BMI, i.e., degree of obesity altered the relationship between OSA and IL-6 levels. An independent association of OSA severity with CRP levels was found for minimum SaO2 only. A similar interaction of OSA severity and BMI on CRP levels was found for males and postmenopausal women. Conclusions: OSA severity is an independent predictor of levels of IL-6 and CRP but interacts with obesity such that this association is found only in obese patients. Citation: Arnardottir ES; Maislin G; Schwab RJ; Staley B; Benediktsdottir B; Olafsson I; Juliusson S; Romer M; Gislason T; Pack AI. The interaction of obstructive sleep apnea and obesity on the inflammatory markers c-reactive protein and interleukin-6: the Icelandic Sleep Apnea Cohort. SLEEP 2012;35(7):921-932. PMID:22754038

Prmt7 Deficiency Causes Reduced Skeletal Muscle Oxidative Metabolism and Age-Related Obesity.

PubMed

Jeong, Hyeon-Ju; Lee, Hye-Jin; Vuong, Tuan Anh; Choi, Kyu-Sil; Choi, Dahee; Koo, Sung-Hoi; Cho, Sung Chun; Cho, Hana; Kang, Jong-Sun

2016-07-01

Maintenance of skeletal muscle function is critical for metabolic health and the disruption of which exacerbates many chronic diseases such as obesity and diabetes. Skeletal muscle responds to exercise or metabolic demands by a fiber-type switch regulated by signaling-transcription networks that remains to be fully defined. Here, we report that protein arginine methyltransferase 7 (Prmt7) is a key regulator for skeletal muscle oxidative metabolism. Prmt7 is expressed at the highest levels in skeletal muscle and decreased in skeletal muscles with age or obesity. Prmt7(-/-) muscles exhibit decreased oxidative metabolism with decreased expression of genes involved in muscle oxidative metabolism, including PGC-1α. Consistently, Prmt7(-/-) mice exhibited significantly reduced endurance exercise capacities. Furthermore, Prmt7(-/-) mice exhibit decreased energy expenditure, which might contribute to the exacerbated age-related obesity of Prmt7(-/-) mice. Similarly to Prmt7(-/-) muscles, Prmt7 depletion in myoblasts also reduces PGC-1α expression and PGC-1α-promoter driven reporter activities. Prmt7 regulates PGC-1α expression through interaction with and activation of p38 mitogen-activated protein kinase (p38MAPK), which in turn activates ATF2, an upstream transcriptional activator for PGC-1α. Taken together, Prmt7 is a novel regulator for muscle oxidative metabolism via activation of p38MAPK/ATF2/PGC-1α. © 2016 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered.

Increased Levels of Calprotectin in Obesity Are Related to Macrophage Content: Impact on Inflammation and Effect of Weight Loss

PubMed Central

Catalán, Victoria; Gómez-Ambrosi, Javier; Rodríguez, Amaia; Ramírez, Beatriz; Rotellar, Fernando; Valentí, Victor; Silva, Camilo; Gil, María J; Fernández-Real, José Manuel; Salvador, Javier; Frühbeck, Gema

2011-01-01

Calprotectin has been recently described as a novel marker of obesity. The aim of this study was to determine the circulating concentrations and expression levels of calprotectin subunits (S100A8 and S100A9) in visceral adipose tissue (VAT), exploring its impact on insulin resistance and inflammation and the effect of weight loss. We included 53 subjects in the study. Gene expression levels of the S100A8/A9 complex were analyzed in VAT as well as in both adipocytes and stromovascular fraction cells (SVFCs). In addition, circulating calprotectin and soluble receptor for the advanced glycation end product (sRAGE) concentrations were measured before and after weight loss achieved by Roux-en-Y gastric bypass (RYGB) (n = 26). Circulating concentrations and VAT expression of S100A8/A9 complex were increased in normoglycemic and type 2 diabetic obese patients (P < 0.01) and associated with markers of inflammation (P < 0.01). Oppositely, concentrations of sRAGE were significantly lower (P < 0.001) in both obese groups compared to lean volunteers. Elevated calprotectin levels in obese patients decreased (P < 0.00001) after RYGB, whereas sRAGE concentrations tended to increase. Calprotectin was mainly expressed by SVFCs, and its expression was significantly correlated (P < 0.01) with mRNA levels of the monocyte-macrophage–related molecules macrophage-specific antigen CD68 (CD68), monocyte chemotactic protein 1 (MCP1), integrin α-M (CD11B), and NADPH oxidase 2 (NOX2). Tumor necrosis factor-α treatment significantly enhanced (P < 0.05) the mRNA levels of S100 calcium-binding protein A8 (S100A8) of human visceral adipocytes. The increased levels of calprotectin in obesity and obesity-associated type 2 diabetes, its positive association with inflammation as well as the higher expression levels in the SVFCs in VAT suggests a potential role of this protein as a chemotactic factor in the recruitment of macrophages to VAT, increasing inflammation and the development of obesity

Increased urinary leukotriene E4 excretion in obstructive sleep apnea: effects of obesity and hypoxia.

PubMed

Stanke-Labesque, Françoise; Bäck, Magnus; Lefebvre, Blandine; Tamisier, Renaud; Baguet, Jean-Philippe; Arnol, Nathalie; Lévy, Patrick; Pépin, Jean-Louis

2009-08-01

Low-grade inflammation may potentially explain the relationship between obstructive sleep apnea syndrome (OSA) and cardiovascular events. However, the respective contribution of intermittent hypoxia and confounders, such as obesity, is still debated. To monitor urinary leukotriene E(4) (U-LTE(4)), a validated marker of proinflammatory cysteinyl leukotriene production, in OSA; to determine the influence of obesity and other confounders on U-LTE(4) concentrations; to examine the mechanisms involved through transcriptional profiling of the leukotriene pathway in peripheral blood mononuclear cells (PBMCs); and to investigate the effect of continuous positive air pressure (CPAP) on U-LTE(4) concentrations. We measured U-LTE(4) by liquid chromatography-tandem mass spectrometry. The U-LTE(4) concentrations were increased (P = .019) in 40 nonobese patients with OSA carefully matched for age, sex, and body mass index (BMI) to 25 control subjects, and correlated (r = 0.0312; P = .017) to the percentage of time spent with mean oxygen saturation (SaO(2)) less than 90%. In a larger cohort of patients with OSA (n = 72), U-LTE(4) increased as a function of BMI (r = 0.445; P = .0002). In those patients, the expression levels of 5-lipoxygenase activating protein mRNA in mononuclear cells exhibited a similar pattern. A stepwise multiple linear regression analysis performed in this cohort identified BMI (P = .001; regression coefficient, 3.33) and percentage of time spent with SaO(2) <90% (P = .001; regression coefficient, 1.01) as independent predictors of U-LTE(4) concentrations. Compared with baseline, CPAP reduced by 22% (P = .006) U-LTE(4) concentrations only in patients with OSA with normal BMI. Obesity, and to a lesser extent hypoxia severity, are determinant of U-LTE(4) production in patients with OSA.

Association of obesity susceptibility gene variants with metabolic syndrome and related traits in 1,443 Czech adolescents.

PubMed

Dušátková, L; Zamrazilová, H; Sedláčková, B; Včelák, J; Hlavatý, P; Aldhoon Hainerová, I; Korenková, V; Bradnová, O; Bendlová, B; Kunešová, M; Hainer, V

2013-01-01

Genome-wide association studies have revealed several gene variants associated with obesity; however, only a few studies have further investigated their association with metabolic syndrome. We performed a study of eleven variants in/near genes TMEM18, SH2B1, KCTD15, PCSK1, BDNF, SEC16B, MC4R, and FTO in Czech adolescents and analysed their association with obesity, metabolic syndrome and related traits. Genotyping was performed in 1,443 adolescents aged 13.0-17.9 years. Anthropometric parameters, biochemical parameters and blood pressure were assessed. Metabolic syndrome was defined according to the International Diabetes Federation. The FTO rs9939609 variant was associated with overweight/obesity (OR 1.40, 95% CI 1.21-1.63, P < 0.001). The minor allele of TMEM18 rs7561317 was related to underweight (OR 1.78, 95% CI 1.14-2.79, P = 0.015). BDNF rs925946 and MC4R rs17782313 were associated with metabolic syndrome (OR 1.53, 95% CI 1.14-2.04, P = 0.005; 1.51, 95% CI 1.12-2.04, P = 0.009). The PCSK1 rs6235 variant was negatively related to increased blood glucose (OR 0.69, 95% CI 0.49-0.97, P = 0.040). In conclusion, the FTO variant was associated with overweight/obesity in Czech adolescents. Moreover, MC4R and BDNF variants increased the risk of metabolic syndrome, probably through their effect on abdominal obesity. The PCSK1 variant may have a protective role in the development of type 2 diabetes.

Effects of Dietary Fibre (Pectin) and/or Increased Protein (Casein or Pea) on Satiety, Body Weight, Adiposity and Caecal Fermentation in High Fat Diet-Induced Obese Rats.

PubMed

Adam, Clare L; Gratz, Silvia W; Peinado, Diana I; Thomson, Lynn M; Garden, Karen E; Williams, Patricia A; Richardson, Anthony J; Ross, Alexander W

2016-01-01

Dietary constituents that suppress appetite, such as dietary fibre and protein, may aid weight loss in obesity. The soluble fermentable dietary fibre pectin promotes satiety and decreases adiposity in diet-induced obese rats but effects of increased protein are unknown. Adult diet-induced obese rats reared on high fat diet (45% energy from fat) were given experimental diets ad libitum for 4 weeks (n = 8/group): high fat control, high fat with high protein (40% energy) as casein or pea protein, or these diets with added 10% w/w pectin. Dietary pectin, but not high protein, decreased food intake by 23% and induced 23% body fat loss, leading to 12% lower final body weight and 44% lower total body fat mass than controls. Plasma concentrations of satiety hormones PYY and total GLP-1 were increased by dietary pectin (168% and 151%, respectively) but not by high protein. Plasma leptin was decreased by 62% on pectin diets and 38% on high pea (but not casein) protein, while plasma insulin was decreased by 44% on pectin, 38% on high pea and 18% on high casein protein diets. Caecal weight and short-chain fatty acid concentrations in the caecum were increased in pectin-fed and high pea protein groups: caecal succinate was increased by pectin (900%), acetate and propionate by pectin (123% and 118%, respectively) and pea protein (147% and 144%, respectively), and butyrate only by pea protein (309%). Caecal branched-chain fatty acid concentrations were decreased by pectin (down 78%) but increased by pea protein (164%). Therefore, the soluble fermentable fibre pectin appeared more effective than high protein for increasing satiety and decreasing caloric intake and adiposity while on high fat diet, and produced a fermentation environment more likely to promote hindgut health. Altogether these data indicate that high fibre may be better than high protein for weight (fat) loss in obesity.

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

Uncoupling protein 2 gene polymorphisms are associated with obesity

PubMed Central

2012-01-01

Background Uncoupling protein 2 (UCP2) gene polymorphisms have been reported as genetic risk factors for obesity and type 2 diabetes mellitus (T2DM). We examined the association of commonly observed UCP2 G(−866)A (rs659366) and Ala55Val (C > T) (rs660339) single nucleotide polymorphisms (SNPs) with obesity, high fasting plasma glucose, and serum lipids in a Balinese population. Methods A total of 603 participants (278 urban and 325 rural subjects) were recruited from Bali Island, Indonesia. Fasting plasma glucose (FPG), triglyceride (TG), high density lipoprotein cholesterol (HDL-C), low density lipoprotein cholesterol (LDL-C) and total cholesterol (TC) were measured. Obesity was determined based on WHO classifications for adult Asians. Participants were genotyped for G(−866)A and Ala55Val polymorphisms of the UCP2 gene. Results Obesity prevalence was higher in urban subjects (51%) as compared to rural subjects (23%). The genotype, minor allele (MAF), and heterozygosity frequencies were similar between urban and rural subjects for both SNPs. All genotype frequencies were in Hardy-Weinberg equilibrium. A combined analysis of genotypes and environment revealed that the urban subjects carrying the A/A genotype of the G(−866)A SNP have higher BMI than the rural subjects with the same genotype. Since the two SNPs showed strong linkage disequilibrium (D’ = 0.946, r2 = 0.657), a haplotype analysis was performed. We found that the AT haplotype was associated with high BMI only when the urban environment was taken into account. Conclusions We have demonstrated the importance of environmental settings in studying the influence of the common UCP2 gene polymorphisms in the development of obesity in a Balinese population. PMID:22533685

Prevalence of Obesity and Related Factors among Bouyei and Han Peoples in Guizhou Province, Southwest China.

PubMed

Wang, Ke; Wang, Dingming; Pan, Li; Yu, Yangwen; Dong, Fen; Li, Ling; Wang, Li; Liu, Tao; Zeng, Xianjia; Sun, Liangxian; Zhu, Guangjin; Feng, Kui; Jonasson, Junmei Miao; Wu, Zhenglai; Xu, Ke; Pang, Xinglong; Chen, Ting; Pan, Hui; Ma, Jin; Zhong, Yong; Ping, Bo; Shan, Guangliang

2015-01-01

To investigate the prevalence of general and abdominal obesity and associated factors in Bouyei and Han peoples. A cross-sectional study was carried out in Guizhou province, southwest China in 2012, with multi-stage sampling to enroll 4551 participants aged 20 to 80 years. General and abdominal obesity were defined by World Health Organization (WHO) for Chinese. A design-based analysis was performed to evaluate prevalence of obesity and its related factors. Bouyei people had a significantly lower prevalence of general obesity (4.8% vs. 10.9%, p < 0.05) and abdominal obesity (13.6% vs. 26.8%, p < 0.05) than that in Han people. Prevalence of obesity increased with age until middle-age period and declined thereafter. Men aged 40-49 years group and women aged 50-59 years group have the highest prevalence of general obesity. Prevalence of abdominal obesity was higher than that of general obesity. Middle-age, Higher income, Han people were significantly associated with an increased risk of General/abdominal obesity. Bouyei people had a lower prevalence of general and abdominal obesity than the Han people. Etiological studies should be conducted to determine underlying genetic factors and dietary factors.

Multidimensional Assessment of Impulsivity in Relation to Obesity and Food Addiction

PubMed Central

VanderBroek-Stice, Lauren; Stojek, Monika K.; Beach, Steven R. H.; vanDellen, Michelle R.; MacKillop, James

2017-01-01

Based on similarities between overconsumption of food and addictive drugs, there is increasing interest in “food addiction,” a compulsive eating pattern defined using symptoms parallel to substance use disorders. Impulsivity, a multidimensional construct robustly linked to drug addiction, has been increasingly examined as an obesity determinant, but with mixed findings. This study sought to clarify relations between three major domains of impulsivity (i.e., impulsive personality traits, discounting of delayed rewards, and behavioral inhibition) in both obesity and food addiction. Based on the association between impulsivity and compulsive drug use, the general hypothesis was that the impulsivity-food addiction relation would be stronger than and responsible for the impulsivity-obesity relation. Using a cross-sectional dimensional design, participants (N = 181; 32% obese) completed a biometric assessment, the Yale Food Addiction Scale (YFAS), the UPPS-P Impulsive Behavior Scales, a Go/NoGo task, and measures of monetary delay discounting. Results revealed significantly higher prevalence of food addiction among obese participants and stronger zero-order associations between impulsivity indices and YFAS compared to obesity. Two aspects of impulsivity were independently significantly associated with food addiction: (a) a composite of Positive and Negative Urgency, reflecting proneness to act impulsively during intense mood states, and (b) steep discounting of delayed rewards. Furthermore, the results supported food addiction as a mediator connecting both urgency and delay discounting with obesity. These findings provide further evidence linking impulsivity to food addiction and obesity, and suggest that food addiction may be a candidate etiological pathway to obesity for individuals exhibiting elevations in these domains. PMID:28087369

Health-equity issues related to childhood obesity: a scoping review.

PubMed

Vargas, Clemencia M; Stines, Elsie M; Granado, Herta S

2017-06-01

The purpose of this scoping review was to determine the health-equity issues that relate to childhood obesity. Health-equity issues related to childhood obesity were identified by analyzing food environment, natural and built environment, and social environment. The authors searched Medline, PubMed, and Web of Science, using the keywords "children" and "obesity." Specific terms for each environment were added: "food desert," "advertising," "insecurity," "price," "processing," "trade," and "school" for food environment; "urban design," "land use," "transportation mode," "public facilities," and "market access" for natural and built environment; and "financial capacity/poverty," "living conditions," "transport access," "remoteness," "social support," "social cohesion," "working practices," "eating habits," "time," and "social norms" for social environment. Inclusion criteria were studies or reports with populations under age 12, conducted in the United States, and published in English in 2005 or later. The final search yielded 39 references (16 for food environment, 11 for built environment, and 12 for social environment). Most food-environment elements were associated with obesity, except food insecurity and food deserts. A natural and built environment that hinders access to physical activity resources and access to healthy foods increased the risk of childhood obesity. Similarly, a negative social environment was associated with childhood obesity. More research is needed on the effects of food production, living conditions, time for shopping, and exercise, as related to childhood obesity. Most elements of food, natural and built, and social-environments were associated with weight in children under age 12, except food insecurity and food deserts. © 2017 American Association of Public Health Dentistry.

Evidence of a novel quantitative-trait locus for obesity on chromosome 4p in Mexican Americans.

PubMed

Arya, Rector; Duggirala, Ravindranath; Jenkinson, Christopher P; Almasy, Laura; Blangero, John; O'Connell, Peter; Stern, Michael P

2004-02-01

Although several genomewide scans have identified quantitative-trait loci influencing several obesity-related traits in humans, genes influencing normal variation in obesity phenotypes have not yet been identified. We therefore performed a genome scan of body mass index (BMI) on Mexican Americans, a population prone to obesity and diabetes, using a variance-components linkage analysis to identify loci that influence BMI. We used phenotypic data from 430 individuals (26% diabetics, 59% females, mean age +/- SD = 43 +/- 17 years, mean BMI +/- SD = 30.0 +/- 6.7, mean leptin (ng/ml) +/- SD = 22.1 +/- 17.1) distributed across 27 low-income Mexican American pedigrees who participated in the San Antonio Family Diabetes Study (SAFDS) for whom a 10-15-cM map is available. In this genomewide search, after accounting for the covariate effects of age, sex, diabetes, and leptin, we identified a genetic region exhibiting the most highly significant evidence for linkage (LOD 4.5) with BMI on chromosome 4p (4p15.1) at 42 cM, near marker D4S2912. This linkage result has been confirmed in an independent linkage study of severe obesity in Utah pedigrees. Two strong positional candidates, the human peroxisome proliferator-activated receptor gamma coactivator 1 (PPARGC1) and cholecystokinin A receptor (CCKAR) with major roles in the development of obesity, are located in this region. In conclusion, we identified a major genetic locus influencing BMI on chromosome 4p in Mexican Americans.

Parents' obesity-related behavior and confidence to support behavioral change in their obese child: data from the STAR study.

PubMed

Arsenault, Lisa N; Xu, Kathleen; Taveras, Elsie M; Hacker, Karen A

2014-01-01

Successful childhood obesity interventions frequently focus on behavioral modification and involve parents or family members. Parental confidence in supporting behavior change may be an element of successful family-based prevention efforts. We aimed to determine whether parents' own obesity-related behaviors were related to their confidence in supporting their child's achievement of obesity-related behavioral goals. Cross-sectional analyses of data collected at baseline of a randomized control trial testing a treatment intervention for obese children (n = 787) in primary care settings (n = 14). Five obesity-related behaviors (physical activity, screen time, sugar-sweetened beverage, sleep duration, fast food) were self-reported by parents for themselves and their child. Behaviors were dichotomized on the basis of achievement of behavioral goals. Five confidence questions asked how confident the parent was in helping their child achieve each goal. Logistic regression modeling high confidence was conducted with goal achievement and demographics as independent variables. Parents achieving physical activity or sleep duration goals were significantly more likely to be highly confident in supporting their child's achievement of those goals (physical activity, odds ratio 1.76; 95% confidence interval 1.19-2.60; sleep, odds ratio 1.74; 95% confidence interval 1.09-2.79) independent of sociodemographic variables and child's current behavior. Parental achievements of TV watching and fast food goals were also associated with confidence, but significance was attenuated after child's behavior was included in models. Parents' own obesity-related behaviors are factors that may affect their confidence to support their child's behavior change. Providers seeking to prevent childhood obesity should address parent/family behaviors as part of their obesity prevention strategies. Copyright © 2014 Academic Pediatric Association. Published by Elsevier Inc. All rights reserved.

Soya protein attenuates abnormalities of the renin-angiotensin system in adipose tissue from obese rats.

PubMed

Frigolet, María E; Torres, Nimbe; Tovar, Armando R

2012-01-01

Several metabolic disturbances during obesity are associated with adipose tissue-altered functions. Adipocytes contain the renin-angiotensin system (RAS), which regulates signalling pathways that control angiogenesis via Akt in an autocrine fashion. Soya protein (Soy) consumption modifies the gene expression pattern in adipose tissue, resulting in an improved adipocyte function. Therefore, the aim of the present work is to study whether dietary Soy regulates the expression of RAS and angiogenesis-related genes and its association with the phosphorylated state of Akt in the adipose tissue of obese rats. Animals were fed a 30 % Soy or casein (Cas) diet containing 5 or 25 % fat for 160 d. mRNA abundance was studied in the adipose tissue, and Akt phosphorylation and hormone release were measured in the primary adipocyte culture. The present results show that Soy treatment in comparison with Cas consumption induces lower angiotensin release and increased insulin-stimulated Akt activation in adipocytes. Furthermore, Soy consumption varies the expression of RAS and angiogenesis-related genes, which maintain cell size and vascularity in the adipose tissue of rats fed a high-fat diet. Thus, adipocyte hypertrophy and impaired angiogenesis, which are frequently observed in dysfunctional adipose tissue, were avoided by consuming dietary Soy. Taken together, these findings suggest that Soy can be used as a dietary strategy to preserve adipocyte functionality and to prevent obesity abnormalities.

Patterns of dietary habits in relation to obesity in Iranian adults.

PubMed

Saneei, Parvane; Esmaillzadeh, Ahmad; Keshteli, Ammar Hassanzadeh; Feizi, Awat; Feinle-Bisset, Christine; Adibi, Peyman

2016-03-01

Findings from few studies that investigated the relation between dietary behaviors and obesity are inconsistent. We aimed to assess the relation between patterns of dietary habits, identified by latent class analysis (LCA), and obesity in a large sample of Iranian adults. In a cross-sectional study on 7958 adults, dietary behaviors were assessed in five domains (meal patterns, eating rate, intra-meal fluid intake, meal-to-sleep interval, and fatty foods intake) using a pretested questionnaire. LCA was applied to identify classes of diet-related practices. Anthropometric measures were assessed through the use of a validated self-reported questionnaire. General and abdominal obesity were defined as a body mass index ≥ 30 kg/m(2), and a waist circumference ≥ 88 cm for women and ≥ 102 cm for men. General and abdominal obesity were prevalent in 9.7 and 27.7 % of the study population, respectively. We identified three distinct classes of eating rates (moderate, moderate to slow, and moderate to fast), two classes of meal patterns (regular and irregular), two classes of intra-meal fluid intake (moderate and more intra-meal drinking), three classes of meal-to-sleep interval (short, moderate, and long meal-to-sleep interval), and three classes of fatty food intake (low to moderate, moderate to high, and low intake of fatty foods). After adjustment for potential confounders, individuals with 'irregular meal pattern' were 21, 24, and 22 % more likely to be overweight/obese, abdominally overweight/obese, and abdominally obese, compared with those who had a 'regular meal pattern.' Individuals with 'more intra-meal drinking' had greater odds of overweight (OR 1.37; 1.19-1.458) and obesity (OR 1.51; 1.16-1.97) than those with 'moderate intra-meal drinking.' Moderate-to-high intake of fatty foods was inversely associated with abdominally overweight/obese (OR 0.85; 0.73-1.00) and abdominally obesity (OR 0.80; 0.68-0.96) compared with 'low-to-moderate intake of fatty foods

Dietary Aloe Improves Insulin Sensitivity via the Suppression of Obesity-induced Inflammation in Obese Mice.

PubMed

Shin, Eunju; Shim, Kyu-Suk; Kong, Hyunseok; Lee, Sungwon; Shin, Seulmee; Kwon, Jeunghak; Jo, Tae Hyung; Park, Young-In; Lee, Chong-Kil; Kim, Kyungjae