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Query: UMLS:C0028754 (obesity)
 124,988 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The aim of this study was to investigate the extent to which inflammation is linked with plasma endothelial lipase (EL) concentrations among healthy sedentary men. Plasma C-reactive protein (CRP) concentrations were measured with a highly sensitive commercial immunoassay, plasma interleukin-6 (IL-6) concentrations were measured using a commercial ELISA, and plasma secretory phospholipase A(2) type IIA (sPLA(2)-IIA) concentrations were measured using a commercial assay in a sample of 74 moderately obese men (mean body mass index, 29.8 +/- 5.2 kg/m(2)). Plasma EL concentrations were positively correlated with various indices of obesity, fasting plasma insulin, and plasma CRP, IL-6, and sPLA(2)-IIA concentrations. Multiple regression analyses revealed that plasma CRP concentrations explained 14.5% (P = 0.0008) of the variance in EL concentrations. When entered into the model, LPL activity accounted for 16.1% (P < 0.0001) and plasma CRP concentrations accounted for 20.9% (P < 0.0001) of the variance in EL concentrations. The combined impact of visceral adipose tissue (VAT) and of an inflammation score on EL concentrations was investigated. Among subjects with high or low VAT, those having a high inflammation score based on plasma CRP, IL-6, and sPLA(2)-IIA concentrations had increased plasma EL concentrations (P = 0.0005). In conclusion, our data reveal a strong association between proinflammatory cytokines and plasma EL concentrations among healthy people with low or high VAT levels.
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PMID:Endothelial lipase is associated with inflammation in humans. 1698 May 90

Lipoprotein lipase is a central enzyme in the lipid metabolism, which catalyses the hydrolysis of the triacylglycerol component of chylomicrons and very low density lipoproteins, thereby providing fatty acids and monoacylglycerol for tissue utilisation. LPL gene mutation may affect the activity of LPL, and results in lipid metabolism disorder. It is associated with type 2 diabetes, hypertension, atherosclerosis, obesity and coronary artery disease. Here we review the structure, function, expression regulation of the LPL gene along with its association with complex diseases.
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PMID:[Research progress of lipoprotein lipase gene]. 1728 17

Mice that overexpress human apolipoprotein C-I (apoC-I) homozygously (APOC1(+/+) mice) are protected against obesity and show cutaneous abnormalities. Although these effects can result from our previous observation that apoC-I inhibits FFA generation by LPL, we have also found that apoC-I impairs the uptake of a FFA analog in adipose tissue. In this study, we tested the hypothesis that apoC-I interferes with cellular FFA uptake independent of LPL activity. The cutaneous abnormalities of APOC1(+/+) mice were not affected after transplantation to wild-type mice, indicating that locally produced apoC-I prevents lipid entry into the skin. Subsequent in vitro studies with apoC-I-deficient versus wild-type macrophages revealed that apoC-I reduced the cell association and subsequent esterification of [(3)H]oleic acid by approximately 35% (P < 0.05). We speculated that apoC-I binds FFA extracellularly, thereby preventing cell association of FFA. We showed that apoC-I was indeed able to mediate the binding of oleic acid to otherwise protein-free VLDL-like emulsion particles involving electrostatic interaction. We conclude that apoC-I binds FFA in the circulation, thereby reducing the availability of FFA for uptake by cells. This mechanism can serve as an additional mechanism behind the resistance to obesity and the cutaneous abnormalities of APOC1(+/+) mice.
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PMID:Apolipoprotein C-I binds free fatty acids and reduces their intracellular esterification. 1733 54

The growing population of overweight humans threatens both industrialized and developing countries and has been accompanied by obesity-related disorders, including type II diabetes, hypertension, cardiovascular pathology and nonalcoholic fatty liver disease. Recent researches have demonstrated that intestinal microbiota may be associated with the host's obesity. There were researches on the interaction between Bacteroides thetaiotaomicron and the energy metabolism of the host. Methanobrevibacer smithii had been improved to impact the host's energy metabolism through modulating the gene transcription of B. thetaiotaomicron. The microbiota can direct the host to increase hepatic production of triglycerides, promote storage of triglycerides in adipocytes through suppression of intestinal expression of a circulating LPL inhibitor, and have an effect on the host's energy deposition through the interaction with host's hormones (eg. Leptin) . Some metabolic products of the microbiota like SCFAs, other organic acids, alcohols and gases can be used by the host directly. Researches mentioned above are just started. According to the results above, some key points remain unknown. For example, the underlying mechanism of the interaction between microbiota or some unique microbes and the host, the procedure of dietary polysaccharides degradation of the microbes, and the relationship between the microbiota and the host's hormones. In this paper, the corresponding research results of author' s lab has also been reviewed and the future research prospect s have been summarized.
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PMID:[The intestinal microbiota and obesity of the host]. 1827 Dec 77

A number of human and animal studies using conjugated linoleic acids (CLA) or diacylglycerol (DAG) oil have shown positive physiological effects on abdominal adiposity, plasma triglycerides, plasma glucose, and insulin sensitivity. A novel DAG composition containing CLA called CLA diacylglyceride (CLA-DAG) may offer potential as a therapeutic agent in reducing some of the symptoms associated with the diabetic phenotype and metabolic syndrome. This study was designed to investigate the effect of CLA-DAG oil on the diabetic phenotype in male Zucker diabetic fatty rats. Animals were assigned to one of four groups: control (C), rosiglitazone (ROS), CLA-DAG, or CLA as free fatty acid (CLA-FFA). After 11 weeks, body weight was higher and kidney weight was lower in the CLA-DAG and ROS groups compared with the C group. The ROS treatment increased the percentage of body fat as compared with all other groups. Final fasting blood glucose was lower in the CLA-DAG and ROS groups than in the C group. Plasma cholesterol was lower in the CLA-DAG group, and plasma triglycerides were lower in the ROS group compared with the C group. We also observed changes in transcript abundance of PPAR-gamma, PPAR-alpha, FAS, LPL, UCP2, UCP3, CPT1, RxR, ObRb, ApoAII, ApoD, and IRS1 in liver, muscle, and adipose tissue, suggesting treatment-induced effects on these genes. Collectively, these data suggest the need for further research on the therapeutic relevance of CLA-DAG oil in obesity and diabetes. Future research should also differentiate between CLA alone and DAG alone compared with the combination.
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PMID:A combination of CLA-DAG oil modifies the diabetic phenotype in male Zucker diabetic fatty rats. 1854 85

Recent genome-wide association (GWA) studies have identified new genetic determinants of complex quantitative traits, including plasma triglyceride (TG). We hypothesized that common variants associated with mild TG variation identified in GWA studies would also be associated with severe hypertriglyceridemia (HTG). We studied 132 patients of European ancestry with severe HTG (fasting plasma TG > 10 mmol/l), who had no mutations found by resequencing of candidate genes, and 351 matched normolipidemic controls. We determined genotypes for: GALNT2 rs4846914, TBL2/MLXIPL rs17145738, TRIB1 rs17321515, ANGPTL3 rs12130333, GCKR rs780094, APOA5 rs3135506 (S19W), APOA5 rs662799 (-1131T > C), APOE (isoforms) and LPL rs328 (S447X). We found that: (i) genotypes, including those of APOA5 S19W, APOA5 -1131T > C, APOE, GCKR, TRIB1 and TBL2/MLXIPL, were significantly associated with severe HTG; (ii) odds ratios for these genetic variables were significant in both univariate and multivariate regression analyses, irrespective of the presence or absence of diabetes or obesity; (iii) a significant fraction-about one-quarter-of the explained variation in disease status was associated with these genotypes. Therefore, common SNPs (single nucleotide polymorphisms) that are associated with mild TG variation in GWA studies of normolipidemic subjects are also associated with severe HTG. Our findings are consistent with the emerging model of a complex genetic trait. At the extremes of a quantitative trait, such as severe HTG, are found the cumulative contributions of both multiple rare alleles with large genetic effects and common alleles with small effects.
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PMID:Polygenic determinants of severe hypertriglyceridemia. 1859 51

Resveratrol, a phytoallexin, has recently been reported to slow aging by acting as a sirtuin activator. Resveratrol also has a wide range of pharmacological effects on adipocytes. In this study, we investigated the effects of resveratrol on adipogenesis and apoptosis using 3T3-L1 cells. In mature adipocytes, 100 and 200 microM resveratrol decreased cell viability dose-dependently by 23 +/- 2.7%, and 75.3 +/- 2.8% (p < 0.0001), respectively, after 48 h treatment, and 100 microM resveratrol increased apoptosis by 76 +/- 8.7% (p < 0.0001). Resveratrol at 25 and 50 microM decreased lipid accumulation in maturing preadipocytes significantly by 43 +/- 1.27% and 94.3 +/- 0.3% (p < 0.0001) and decreased cell viability by 25 +/- 1.3% and 70.4 +/- 1.6% (p < 0.0001), respectively. In order to understand the anti-adipogenic effects of resveratrol, maturing 3T3-L1 preadipocytes were treated with 25 microM resveratrol and the change in the expression of several adipogenic transcription factors and enzymes was investigated using real-time RT-PCR. Resveratrol down-regulated the expression of PPAR gamma, C/EBP alpha, SREBP-1c, FAS, HSL, LPL and up-regulated the expression of genes regulating mitochondrial activity (SIRT3, UCP1 and Mfn2). These results indicate that resveratrol may alter fat mass by directly affecting cell viability and adipogenesis in maturing preadipocytes and inducing apoptosis in adipocytes and thus may have applications for the treatment of obesity.
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PMID:Resveratrol induces apoptosis and inhibits adipogenesis in 3T3-L1 adipocytes. 1868 88

Increased circulating free fatty acid (FFA) concentrations have been demonstrated to potentially link obesity, insulin resistance and cardiovascular diseases. Astragaloside IV (AS-IV) is a saponin which is widely used in traditional Chinese medicine to treat type 2 diabetes and cardiovascular diseases. The purpose of the present study was to examine the effects of AS-IV on the lipolysis and insulin resistance induced by tumor necrosis factor-alpha (TNFalpha) in cultured 3T3-L1 adipocytes. TNFalpha promotes lipolysis in mammal adipocytes via the mitogen activated protein kinase (MAPK) family resulting in reduced expression/function of perilipin. Application of AS-IV inhibited TNFalpha-induced accelerated lipolysis in a dose-dependent manner, which was compatible with suppressed phosphorylation of ERK1/2 and reversed the downregulation of perilipin. Moreover, TNFalpha induced downregulation of key enzymes in lipogenesis, including LPL, FAS and GPAT, were also attenuated by AS-IV. Further studies showed that AS-IV improved TNFalpha-induced insulin resistance in 3T3-L1 adipocytes. This study provides the first direct evidence of the antilipolytic action of AS-IV in adipocytes, which may allow this agent to decrease the circulating FFA levels, thus increase insulin sensitivity and treat cardiovascular diseases.
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PMID:Astragaloside IV attenuates lipolysis and improves insulin resistance induced by TNFalpha in 3T3-L1 adipocytes. 1897 82

Peroxisome proliferator-activated receptors (PPARs) are transcriptional factors involved in the regulation of insulin resistance and adipogenesis. Cinnamon, a widely used spice in food preparation and traditional antidiabetic remedy, is found to activate PPARgamma and alpha, resulting in improved insulin resistance, reduced fasted glucose, FFA, LDL-c, and AST levels in high-caloric diet-induced obesity (DIO) and db/db mice in its water extract form. In vitro studies demonstrate that cinnamon increases the expression of peroxisome proliferator-activated receptors gamma and alpha (PPARgamma/alpha) and their target genes such as LPL, CD36, GLUT4, and ACO in 3T3-L1 adipocyte. The transactivities of both full length and ligand-binding domain (LBD) of PPARgamma and PPARalpha are activated by cinnamon as evidenced by reporter gene assays. These data suggest that cinnamon in its water extract form can act as a dual activator of PPARgamma and alpha, and may be an alternative to PPARgamma activator in managing obesity-related diabetes and hyperlipidemia.
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PMID:Improved Insulin Resistance and Lipid Metabolism by Cinnamon Extract through Activation of Peroxisome Proliferator-Activated Receptors. 1909 9

Excessive weight gain arises from the interactions among environmental factors, genetic predisposition and the individual behavior. However, it is becoming evident that interindividual differences in obesity susceptibility depend also on epigenetic factors. Epigenetics studies the heritable changes in gene expression that do not involve changes to the underlying DNA sequence. These processes include DNA methylation, covalent histone modifications, chromatin folding and, more recently described, the regulatory action of miRNAs and polycomb group complexes. In this review, we focus on experimental evidences concerning dietary factors influencing obesity development by epigenetic mechanisms, reporting treatment doses and durations. Moreover, we present a bioinformatic analysis of promoter regions for the search of future epigenetic biomarkers of obesity, including methylation pattern analyses of several obesity-related genes (epiobesigenes), such as FGF2, PTEN, CDKN1A and ESR1, implicated in adipogenesis, SOCS1/SOCS3, in inflammation, and COX7A1 LPL, CAV1, and IGFBP3, in intermediate metabolism and insulin signalling. The identification of those individuals that at an early age could present changes in the methylation profiles of specific genes could help to predict their susceptibility to later develop obesity, which may allow to prevent and follow-up its progress, as well as to research and develop newer therapeutic approaches.
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PMID:Individuality and epigenetics in obesity. 1941


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