Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0028754 (obesity)
 124,988 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Variants in the TCF7L2 gene (transcription factor 7-like 2) have shown strong association with type 2 diabetes with two defined risk haplotypes, HapA and HapB(T2D). TCF7L2 may play a role in both glucose homeostasis and adipogenesis. Our aim was to characterize the TCF7L2 mRNA expression and regulation in human adipose tissue. We quantified TCF7L2 mRNA levels in cultured human adipocytes and in biopsies from visceral (VAT) and subcutaneous (SAT) adipose tissue from 38 obese non-diabetic subjects, using real-time PCR. The influence of haplotype and clinical traits on TCF7L2 mRNA levels were investigated. In vitro, insulin decreased TCF7L2 mRNA expression. This effect was attenuated in cells incubated with the free fatty acids palmitate or oleate. In vivo, we found significantly higher expression in SAT from more insulin resistant subjects. No correlations between TCF7L2 mRNA expression and obesity measures were observed. TCF7L2 expression was higher in VAT than in SAT and when stratifying for haplotype, this difference was seen in HapA carriers but not in non-HapA carriers. In conclusion, TCF7L2 mRNA levels in adipocytes are decreased by insulin and seem to increase in insulin resistant subjects and in HapA carriers.
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PMID:Expression of the transcription factor 7-like 2 gene (TCF7L2) in human adipocytes is down regulated by insulin. 1834 27

The aim of the present study was to evaluate the expression profile of genes potentially related to metabolic complications of obesity in the whole adipose tissue and isolated adipocytes from subcutaneous (SAT) and visceral adipose tissue (VAT) from 12 non-diabetic obese women and 12 lean women. Real-time polymerase chain reaction was used for expression analysis of 41 genes of interest and two housekeeping genes. We found increased expression of specific proinflammatory and adipogenic genes and reduced expression of specific lipogenic and insulin signaling pathway genes in obese relative to lean women with no preferable localization in SAT or VAT depot. The gene expression significantly differed between adipocytes and adipose tissue but both contributed to the proinflammatory profile in obesity. We conclude that both SAT and VAT exhibit alterations in the expression of specific genes possibly contributing to proinflammatory and insulin resistance state and consequently to metabolic complications of obesity.
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PMID:The endocrine profile of subcutaneous and visceral adipose tissue of obese patients. 1856 43

The optical device LIPOMETER enables the non-invasive, quick, and save determination of the thickness of subcutaneous adipose tissue layers at any given site of the human body. The specification of 15 evenly distributed body sites allows the precise measurement of subcutaneous body fat distribution, so-called subcutaneous adipose tissue topography (SAT-Top). In the present paper we focus on SAT-Top of male type-2 diabetes patients (N=21), describing very precisely their special SAT development and their SAT-Top deviation from a healthy control group (N=111), applying factor analysis and ROC curves. Factor analysis revealed three independent subcutaneous body fat compartments, which can be summarised as "upper body", "lower trunks" and "legs". The upper body SAT-Top is much more pronounced in diabetic men compared to their healthy controls (p<0.001). Furthermore, high diagnostic power by ROC curve analysis was achieved by different measurement sites of the upper body and summary measures of upper body obesity (sum2, which is the sum of neck and biceps, provides: area index =0.86, sensitivity =81%, specificity =90.1%, at an optimal cutoff value of 18.8 mm), ascribing a higher diabetes probability to subjects with a more upper body SAT-Top pattern. Calculating new ROC curves for diabetic patients with HBA1C values >8 (N=17) and their healthy controls (N=111) we received improved discrimination power for several SAT-Top body sites, especially for sum2, showing an area index of 0.91, a sensitivity of 94.1%, and a specificity of 90.1% at the optimal cutoff value of 18.8 mm. Concluding, the exact and complete description of the especial type 2 diabetic SAT pattern, which differs strongly from the SAT-Top of healthy controls, suggests the LIPOMETER technique combined with advanced statistical methods such as factor analysis and ROC curve analysis as a possible detecting tool for this disease.
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PMID:Subcutaneous fat patterns in type-2 diabetic men and healthy controls. 1875 18

The newly discovered adipokine visfatin has been hypothesized to be related to obesity and insulin resistance. In this study, we investigate if the 2 single nucleotide polymorphisms rs4730153 and G-948T are associated with obesity and/or related traits and whether they influence the messenger RNA (mRNA) levels of PBEF1 (originally the abbreviation for pre-B-cell colony-enhancing factor 1) in visceral and subcutaneous adipose tissue (VAT and SAT). We found that obese carriers of the PBEF1 G-948T variant allele had significantly higher levels of high-density lipoprotein cholesterol (GG, 1.1 [0.97-1.3] mmol/L; GT + TT, 1.3 [1.0-1.5] mmol/L; P = .02). Other than that, neither rs4730153 nor G-948T had any major impact on any of the obesity-related phenotypes. There was no difference in mRNA expression between VAT and SAT (2.08 +/- 0.17 and 2.09 +/- 0.14, respectively; P = .26), but there was a nonsignificant trend toward higher PBEF1 mRNA levels in the variant allele carriers concerning both VAT and SAT for both single nucleotide polymorphisms. A significant correlation was observed between body mass index and PBEF1 mRNA expression in SAT (R = 0.37, P = .03) but not in VAT (R = 0.26, P = .12). In conclusion, PBEF1 G-948T is associated with increased high-density lipoprotein cholesterol; but genetic variation in PBEF1 does not seem to have a major impact on the development of obesity or on the expression of the gene.
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PMID:The visfatin (PBEF1) G-948T gene polymorphism is associated with increased high-density lipoprotein cholesterol in obese subjects. 1894 Mar 94

We examined mechanisms by which L-4F reduces obesity and diabetes in obese (ob) diabetic mice. We hypothesized that L-4F reduces adiposity via increased pAMPK, pAKT, HO-1, and increased insulin receptor phosphorylation in ob mice. Obese and lean mice were divided into five groups: lean, lean-L-4F-treated, ob, ob-L-4F-treated, and ob-L-4F-LY294002. Food intake, insulin, glucose adipocyte stem cells, pAMPK, pAKT, CB1, and insulin receptor phosphorylation were determined. Subcutaneous (SAT) and visceral adipose tissue (VAT) were determined by MRI and hepatic lipid content by magnetic resonance spectroscopy. SAT and VAT volumes decreased in ob-L-4F-treated animals compared with control. L-4F treatment decreased hepatic lipid content and increased the numbers of small adipocytes (P < 0.05) and phosphorylation of insulin receptors. L-4F decreased CB1 in SAT and VAT and increased pAKT and pAMPK in endothelium. L-4F-mediated improvement in endothelium was prevented by LY294002. Inhibition of pAKT and pAMPK by LY294002 was associated with an increase in glucose levels. Upregulation of HO-1 by L-4F produced adipose remodeling and increased the number of small differentiated adipocytes. The anti-obesity effects of L-4F are manifested by a decrease in visceral fat content with reciprocal increases in adiponectin, pAMPK, pAKT, and phosphorylation of insulin receptors with improved insulin sensitivity.
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PMID:The L-4F mimetic peptide prevents insulin resistance through increased levels of HO-1, pAMPK, and pAKT in obese mice. 1922 72

The objective of the study was to examine the association between a functional 4 bp proinsulin gene insertion polymorphism (IVS-69), fasting insulin concentrations, and body composition in black South African women. Body composition, body fat distribution, fasting glucose and insulin concentrations, and IVS-69 genotype were measured in 115 normal-weight (BMI<25 kg/m2) and 138 obese (BMI>or=30 kg/m2) premenopausal women. The frequency of the insertion allele was significantly higher in the class 2 obese (BMI>or=35 kg/m2) compared with the normal-weight group (P=0.029). Obese subjects with the insertion allele had greater fat mass (42.3+/-0.9 vs. 38.9+/-0.9 kg, P=0.034) and fat-free soft tissue mass (47.4+/-0.6 vs. 45.1+/-0.6 kg, P=0.014), and more abdominal subcutaneous adipose tissue (SAT, 595+/-17 vs. 531+/-17 cm2, P=0.025) but not visceral fat (P=0.739), than obese homozygotes for the wild-type allele. Only SAT was greater in normal-weight subjects with the insertion allele (P=0.048). There were no differences in fasting insulin or glucose levels between subjects with the insertion allele or homozygotes for the wild-type allele in the normal-weight or obese groups. In conclusion, the 4 bp proinsulin gene insertion allele is associated with extreme obesity, reflected by greater fat-free soft tissue mass and fat mass, particularly SAT, in obese black South African women.
Obesity (Silver Spring) 2009 Jun
PMID:Association between the 4 bp proinsulin gene insertion polymorphism (IVS-69) and body composition in black South African women. 1924 82

Increased circulating adhesion molecules in patients with obesity play an important role in the development of endothelial dysfunction/atherosclerosis. The aim of this study was to assess the contribution of various fat depots to the production of adhesion molecules in obesity. 12 women with first and second degree of obesity, 13 women with third degree of obesity and 14 lean age-matched women were included into study. Circulating levels of vascular cell adhesion molecule-1 (VCAM-1), intercellular adhesion molecule-1 (ICAM-1), and E-selectin were measured by Luminex kits. mRNA expression of ICAM-1, VCAM-1, E-selectin, monocyte chemoattractant protein-1 (MCP-1), and CD68 in subcutaneous (SAT) and visceral adipose tissue (VAT) was measured by RT-PCR; ICAM-1 and VCAM-1 protein levels by Luminex kits, normalized to protein content. Obesity increased ICAM-1 and VCAM-1 mRNA expression and protein levels and CD68 mRNA expression in VAT. Expression of E-selectin and MCP-1 did not significantly differ between groups. Expression of ICAM-1 and VCAM-1 positively correlated with expression of CD68 in both adipose depots. In VAT, ICAM-1 and VCAM-1 expression and protein levels positively correlated with BMI. Obesity was associated with increased adhesion molecules mRNA expression and protein levels in VAT, but not in SAT. Increased adhesion molecules production in visceral fat may provide a novel direct link between visceral adiposity and increased risk of cardiovascular complications.
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PMID:The influence of obesity and different fat depots on adipose tissue gene expression and protein levels of cell adhesion molecules. 1924 17

Multiple studies have identified FTO gene variants associated with measures of adiposity in European-derived populations. The objective of the study was to determine whether FTO variants were associated with adiposity, including visceral and subcutaneous adipose tissue (VAT, SAT), and glucose homeostasis measures in the Insulin Resistance Atherosclerosis Family Study (IRASFS). A total of 27 SNPs in FTO intron 1, including SNPs prominent in the literature (rs9939609, rs8050136, rs1121980, rs17817449, rs1421085, and rs3751812), were genotyped in 1,424 Hispanic Americans and 604 African Americans. Multiple SNPs were associated with BMI and SAT (P values ranging from 0.001 to 0.033), and trending or associated with waist circumference (P values ranging from 0.008 to 0.099) in the Hispanic Americans. No association was observed with VAT, illustrating that FTO variants are associated with overall fat mass instead of specific fat depots. For the glucose homeostasis measures, variants were associated with fasting insulin but, consistent with other studies, after BMI adjustment, no evidence of association remained. The lack of association of FTO SNPs with insulin sensitivity is consistent with the lack of association with VAT, since these traits are strongly correlated. In the African Americans, only rs8050136 and rs9939609 were associated with BMI and WAIST (P values of 0.011 and 0.034), and associated or trending towards association with SAT (P values of 0.038 and 0.058). These results confirm that FTO variants are associated with adiposity measures, predisposing individuals to obesity by increasing overall fat mass in Hispanic Americans and to a lesser degree in African Americans.
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PMID:Analysis of FTO gene variants with measures of obesity and glucose homeostasis in the IRAS Family Study. 1932 89

Our previous work in cynomolgus monkeys demonstrated significant relationships between (i) social reorganization stress and visceral fat deposition, and (ii) central fat deposition and coronary artery atherosclerosis (CAA). Nevertheless, direct relationships between CAA and visceral fat have not been demonstrated in people or animals, nor have relationships among stress, visceral obesity, and CAA been observed within a single study. Here, we examine the hypothesis that visceral obesity provides a link between social stress and CAA. Subjects were 41 socially housed females that consumed an atherogenic diet for 32 months. Social behavior and ovarian function were continuously recorded; dexamethasone suppression tests, telemetered overnight heart rate, BMI, visceral (VAT) and subcutaneous abdominal (SAT) adipose tissue were measured before necropsy. Females with high VAT:SAT were relatively subordinate, socially isolated, received more aggression and less grooming, desensitized to circulating glucocorticoids, had impaired ovarian function, higher heart rates late in the day, and more CAA than low VAT:SAT females. High-BMI females had higher heart rates than low-BMI females. Poor ovarian function in high VAT:SAT females is a novel observation suggesting the need for studies of fat distribution and ovarian function in women. The results of this study are the first to demonstrate a relationship between CAA and visceral obesity, and suggest that social stress may exacerbate CAA in part by increasing the ratio of visceral:subcutaneous fat mass in selected individuals susceptible to diet-induced CAA. Further studies are needed to understand the complex and multifactorial temporal relationship among relative visceral obesity, physiological stress responses, and CAA.
Obesity (Silver Spring) 2009 Aug
PMID:Social stress, visceral obesity, and coronary artery atherosclerosis in female primates. 1932 45

To analyze in severely obese women the circadian expression of the clock genes hPer2, hBmal1, and hCry1 in explants from subcutaneous (SAT) and visceral (VAT) adipose tissue (AT), in order to elucidate whether this circadian clockwork can oscillate accurately and independently of the suprachiasmatic nucleus (SCN) and if glucocorticoid metabolism-related genes such as glucocorticoid receptor (hGr) and 11beta-hydroxysteroid dehydrogenase 1 (h11 beta Hsd1) and the transcription factor peroxisome proliferator activated receptor gamma (hPPAR gamma) are part of the clock controlled genes. AT biopsies were obtained from morbid obese patients (BMI > or =40 kg/m(2)) (n = 7). Anthropometric variables were measured and fasting plasma lipids and lipoprotein concentrations were analyzed. In order to carry out rhythmic expression analysis, AT explants were cultured during 24 h and gene expression was performed at the following times (T): 0, 6, 12, and 18 h, with quantitative real-time PCR. Clock genes oscillated accurately and independently of the SCN in AT explants. Their intrinsic oscillatory mechanism regulated the timing of other genes such as hPPAR gamma and glucocorticoid-related genes. Circadian patterns differed between VAT and SAT. Correlation analyses between the genetic circadian oscillation and components of the metabolic syndrome (MetS) revealed that subjects with a higher sagittal diameter showed an increased circadian variability in hPer2 expression (r = 0.91; P = 0.031) and hBmal1 (r = 0.90; P = 0.040). Data demonstrate the presence of peripheral circadian oscillators in human AT independently of the central circadian control mechanism. This knowledge paves the way for a better understanding of the circadian contribution to medical conditions such as obesity and MetS.
Obesity (Silver Spring) 2009 Aug
PMID:Circadian rhythm of clock genes in human adipose explants. 1947 85


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