共查询到20条相似文献，搜索用时 15 毫秒
1.
Ruige JB Mertens IL Bartholomeeusen E Dirinck E Ferrannini E Van Gaal LF 《Obesity (Silver Spring, Md.)》2006,14(7):1250-1256
Objective: To identify simple methods to estimate the degree of insulin resistance. Research Methods and Procedures: The performance of a wide range of fasting‐based index estimates of insulin sensitivity was compared by receiver operating characteristic analysis (area under curves and their 95% confidence intervals) against the M value from euglycemic insulin clamp studies collected in the San Antonio (non‐Hispanic whites and Hispanic residents of San Antonio, TX) and European Group for the Study of Insulin Resistance (non‐diabetic white Europeans) databases (n = 638). Results: Insulin resistance differed substantially between lean (BMI < 25 kg/m2), overweight or obese (BMI ≥ 25 kg/m2), and type 2 diabetic individuals. Estimates of insulin resistance were, therefore, assessed in each group separately. In the overweight and obese subgroup (n = 302), the receiver operating characteristic performance of fasting‐based indices varied from 0.72 (0.62 to 0.82), in the case of the insulin/glucose ratio, to 0.80 (0.72 to 0.88) in the case of Belfiore free fatty acids. One superior method could not be identified; the confidence intervals overlapped, and no statistically significant differences emerged. All indices performed better when using the whole study population, with fasting plasma insulin, homeostatic model assessment, insulin/glucose ratio, quantitative insulin sensitivity check index, glucose/insulin ratio, Belfiore glycemia, revised quantitative insulin sensitivity check index, McAuley index, and Belfiore free fatty acids showing area under curves of 0.83, 0.90, 0.66, 0.90, 0.66, 0.90, 0.85, 0.83, and 0.86, respectively, because of the inclusion of very insulin sensitive (lean) and very insulin resistant cases (diabetic subjects). Discussion: In conclusion, a superior fasting‐based index estimate to distinguish between the presence and absence of insulin resistance in overweight and obesity could not be identified despite the use of the large datasets. 相似文献
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Kavanagh K Fairbanks LA Bailey JN Jorgensen MJ Wilson M Zhang L Rudel LL Wagner JD 《Obesity (Silver Spring, Md.)》2007,15(7):1666-1674
Objective: The objective was to determine the prevalence and heritability of obesity and risk factors associated with metabolic syndrome (MS) in a pedigreed colony of vervet monkeys. Design: A cross‐sectional study of plasma lipid and lipoprotein concentrations, glycemic indices, and morphometric measures with heritability calculated from pedigree analysis. A selected population of females was additionally assessed for insulin sensitivity and glucose tolerance. Subjects: All mature male (n = 98), pregnant (n = 40) and non‐pregnant female (n = 157) vervet monkeys were included in the study. Seven non‐pregnant females were selected on the basis of high or average glycated hemoglobin (GHb) for further characterization of carbohydrate metabolism. Measurements: Morphometric measurements included body weight, length, waist circumference, and calculated BMI. Plasma lipids [total cholesterol (TC), triglycerides (TG), high‐density lipoprotein cholesterol (HDL‐C)] and glycemic measures (fasting blood glucose, insulin, and GHb) were measured. A homeostasis model assessment index was further reported. Glucose tolerance testing and hyperinsulinemic‐euglycemic clamps were performed on 7 selected females. Conclusion: Vervet monkeys demonstrate obesity, insulin resistance, and associated changes in plasma lipids even while consuming a low‐fat (chow) diet. Furthermore, these parameters are heritable. Females are at particular risk for central obesity and an unfavorable lipid profile (higher TG, TC, and no estrogen‐related increase in HDL‐C). Selection of females by elevated GHb indicated impaired glucose tolerance and was associated with central obesity. This colony provides a unique opportunity to study the development of obesity‐related disorders, including both genetic and environmental influences, across all life stages. 相似文献
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Bodles AM Varma V Yao-Borengasser A Phanavanh B Peterson CA McGehee RE Rasouli N Wabitsch M Kern PA 《Journal of lipid research》2006,47(9):2080-2088
Metabolic syndrome and type 2 diabetes mellitus are associated with an increased number of macrophage cells that infiltrate white adipose tissue (WAT). Previously, we demonstrated that the treatment of subjects with impaired glucose tolerance (IGT) with the peroxisome proliferator-activated receptor gamma (PPARgamma) agonist pioglitazone resulted in a decrease in macrophage number in adipose tissue. Here, adipose tissue samples from IGT subjects treated with pioglitazone were examined for apoptosis with terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling (TUNEL) staining. TUNEL-positive cells were identified, and there was a significant 42% increase in TUNEL-positive cells following pioglitazone treatment. Overlay experiments with anti-CD68 antibody demonstrated that most of the TUNEL-positive cells were macrophages. To determine whether macrophage apoptosis was a direct or indirect effect of pioglitazone treatment, human THP1 cells were treated with pioglitazone in vitro, demonstrating increased TUNEL staining in a dose- and time-dependent manner. Furthermore, the appearance of the active proteolytic subunits of caspase-3 and caspase-9 were detected in cell lysate from THP1 cells and also increased in a dose- and time-dependent manner following pioglitazone treatment. Pretreatment with a PPARgamma inhibitor, GW9662, prevented pioglitazone induction of the apoptotic pathway in THP1 cells. Differentiated human adipocytes did not show any significant increase in apoptosis after treatment in vitro with piolgitazone. These findings indicate that PPARgamma has distinct functions in different cell types in WAT, such that pioglitazone reduces macrophage infiltration by inducing apoptotic cell death specifically in macrophages through PPARgamma activation. 相似文献
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LIU, JIANMEI, HASAN ASKARI, AND SAMUEL DAGOGO-JACK. Basal and stimulated plasma leptin in diabetic subjects. Obes Res. Objective: To determine whether leptin secretion is impaired in diabetes, we compared basal and stimulated plasma leptin levels in diabetic subjects and healthy controls. Research Methods and Procedures: Blood samples for assay of leptin and other hormones were obtained at baseline in 54 diabetic patients and 65 controls, and 8 hours, 16 hours, and 40 hours following ingestion of dexamethasone (4 mg) in 6 healthy and 12 controls. C-peptide status was defined as “negative” if ≤0.1 ng/mL or “positive” if ≥0.3 ng/mL, in fasting plasma. Results: Basal plasma leptin levels were 19. 7±2. 2 ng/mL in nondiabetic subjects, 13. 4±1. 5 ng/ml in C-peptide negative (n = 28) and 26. 1±23. 7 ng/mL in C-peptide positive (n = 26, p = 0. 001) diabetic patients. Dexamethasone increased leptin levels of controls (n = 6) to 145±17% of baseline values at 8 hours (p = O. O3), 224±18% at 16 hours (p = 0. 01), and 134218% at 40 hours (p = 0. 05). The corresponding changes were 108±13%, 126±23%, and 98±16% in C-peptide negative (n = 6), and 121±10%, 144±16% (p = 0. 03), and 147±23% (p = 0. 11) in C-peptide positive (n = 6) diabetic patients, respectively. The peak stimulated leptin levels were lower in the diabetic patients, compared with controls. Plasma insulin increased (p = 0. 02) in controls, but not in the diabetic patients, following dexamethasone. Discussion: Although diabetic patients have normal plasma leptin levels under basal conditions, their leptin responses to glucocorticoid are impaired, probably because of the concomitant insulin secretory defect. A subnormal leptin secretory response could worsen obesity and insulin resistance in diabetes. 相似文献
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Wei-Shiung Yang Wei-Jei Lee Tohru Funahashi Sachiyo Tanaka Yuji Matsuzawa Chia-Ling Chao Chi-Ling Chen Tong-Yuan Tai Lee-Ming Chuang M.D. Ph.D. 《Obesity (Silver Spring, Md.)》2002,10(11):1104-1110
Objective: Hypoadiponectin has been documented in subjects with obesity, diabetes mellitus, or coronary heart disease, suggesting a potential use of plasma adiponectin in following the clinical progress in subjects with metabolic syndrome (MS). In this study, we investigated the plasma adiponectin levels in relation to the variables of MS among overweight/obese Asian subjects. Research Methods and Procedures: The plasma adiponectin, anthropometric and biochemical measurements, oral glucose tolerance tests (OGTT), and modified insulin suppression tests were performed on 180 overweight/obese Asian subjects [body mass index (BMI) ≥ 23 kg/m2], including 47 subjects with morbid obesity (BMI ≥ 40 kg/m2). Results: The plasma adiponectin levels negatively correlated with BMI, waist-to-hip ratio, fasting plasma glucose, insulin, triglyceride, uric acid levels, hyperinsulinemia, and glucose intolerance in OGTT, but positively with high-density lipoprotein-cholesterol. In contrast, they were not related to blood pressure and total cholesterol. Moreover, insulin sensitivity, measured by quantitative insulin sensitivity check index (QUICKI) or in insulin suppression tests, significantly correlated with the plasma adiponectin levels. Among morbidly obese subjects, only the waist-to-hip ratio correlated with the plasma adiponectin levels. Using multivariate linear regression models, the area under curve of plasma glucose in OGTT and high-density lipoprotein-cholesterol among the overweight/obese subjects and WHR among the morbidly obese subjects were significantly related to the plasma adiponectin levels after adjustment for other variables. Discussion: In overweight/obese Asians, the plasma adiponectin levels significantly correlated with various indices of MS except hypertension. Whether the plasma adiponectin level could be a suitable biomarker for following the clinical progress of MS warrants further investigation. 相似文献
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《Critical reviews in biochemistry and molecular biology》2013,48(4):379-390
The renin-angiotensin system (RAS) is classically known for its role in regulation of blood pressure, fluid and electrolyte balance. In this system, angiotensinogen (Agt), the obligate precursor of all bioactive angiotensin peptides, undergoes two enzymatic cleavages by renin and angiotensin converting enzyme (ACE) to produce angiotensin I (Ang I) and angiotensin II (Ang II), respectively. The contemporary view of RAS has become more complex with the discovery of additional angiotensin degradation pathways such as ACE2. All components of the RAS are expressed in and have independent regulation of adipose tissue. This local adipose RAS exerts important auto/paracrine functions in modulating lipogenesis, lipolysis, adipogenesis as well as systemic and adipose tissue inflammation. Mice with adipose-specific Agt overproduction have a 30% increase in plasma Agt levels and develop hypertension and insulin resistance, while mice with adipose-specific Agt knockout have a 25% reduction in Agt plasma levels, demonstrating endocrine actions of adipose RAS. Emerging evidence also points towards a role of RAS in regulation of energy balance. Because adipose RAS is overactivated in many obesity conditions, it is considered a potential candidate linking obesity to hypertension, insulin resistance and other metabolic derangements. 相似文献
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Xiuqing Han Chunhua Liu Yong Xue Jingfeng Wang Changhu Xue Teruyoshi Yanagita 《Bioscience, biotechnology, and biochemistry》2016,80(4):735-743
We investigated whether fatty liver preceded insulin resistance or vice versa using a long-term orotic acid (OA)-induced nonalcoholic fatty liver disease (NAFLD) model without the confounding effects of obesity and hyperlipidemia and explored the role of the liver in insulin resistance. Male Wistar rats were fed with or without OA supplementation for 30, 60, and 90 days. The NAFLD group showed increased liver lipid at 30, 60, and 90 days; glucose intolerance was noted at 60 and 90 days. Furthermore, partial liver proteins and gene expressions related to upstream signaling of insulin were decreased. However, the liver glycogen content was elevated, and gluconeogenesis genes expressions were obviously decreased at 90 days. The occurrence of fatty liver preceded insulin resistance in OA-induced NAFLD without the interference of obesity and hyperlipidemia, and hepatic insulin resistance may not play a conclusive role in insulin resistance in this model. 相似文献
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Beneficial effect of oral administration of Lactobacillus casei strain Shirota on insulin resistance in diet-induced obesity mice 总被引：2，自引：0，他引：2
Naito E Yoshida Y Makino K Kounoshi Y Kunihiro S Takahashi R Matsuzaki T Miyazaki K Ishikawa F 《Journal of applied microbiology》2011,110(3):650-657
Aims: This study aimed at determining whether oral administration of a probiotic strain, Lactobacillus casei strain Shirota (LcS), can improve insulin resistance, which is the underlying cause of obesity‐associated metabolic abnormalities, in diet‐induced obesity (DIO) mice. Methods and Results: DIO mice were fed a high‐fat diet without or with 0·05% LcS for 4 weeks and then subjected to an insulin tolerance test (ITT) or oral glucose tolerance test (OGTT). Oral administration of LcS not only accelerated the reduction in plasma glucose levels during the ITT, but also reduced the elevation of plasma glucose levels during the OGTT. In addition, plasma levels of lipopolysaccharide‐binding protein (LBP), which is a marker of endotoxaemia, were augmented in the murine models of obese DIO, ob/ob, db/db and KK‐Ay and compared to those of lean mice. LcS treatment suppressed the elevation of plasma LBP levels in DIO mice, but did not affect intra‐abdominal fat weight. Conclusions: LcS improves insulin resistance and glucose intolerance in DIO mice. The reduction in endotoxaemia, but not intra‐abdominal fat, may contribute to the beneficial effects of LcS. Significance and Impact of the Study: This study suggests that LcS has the potential to prevent obesity‐associated metabolic abnormalities by improving insulin resistance. 相似文献
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Bhumsoo Kim Claudia Figueroa-Romero Crystal Pacut Carey Backus Eva L. Feldman 《The Journal of biological chemistry》2015,290(31):19146-19157
Metabolic syndrome (MetS) is a cluster of cardiovascular risk factors including obesity, diabetes, and dyslipidemia, and insulin resistance (IR) is the central feature of MetS. Recent studies suggest that MetS is a risk factor for Alzheimer disease (AD). AMP-activated kinase (AMPK) is an evolutionarily conserved fuel-sensing enzyme and a key player in regulating energy metabolism. In this report, we examined the role of IR on the regulation of AMPK phosphorylation and AMPK-mediated Tau phosphorylation. We found that AMPKSer-485, but not AMPKThr-172, phosphorylation is increased in the cortex of db/db and high fat diet-fed obese mice, two mouse models of IR. In vitro, treatment of human cortical stem cell line (HK-5320) and primary mouse embryonic cortical neurons with the AMPK activator, 5-aminoimidazole-4-carboxamide 1-β-d-ribofuranoside (AICAR), induced AMPK phosphorylation at both Thr-172 and Ser-485. AMPK activation also triggered Tau dephosphorylation. When IR was mimicked in vitro by chronically treating the cells with insulin, AICAR specifically induced AMPKSer-485, but not AMPKThr-172, hyperphosphorylation whereas AICAR-induced Tau dephosphorylation was inhibited. IR also resulted in the overactivation of Akt by AICAR treatment; however, preventing Akt overactivation during IR prevented AMPKSer-485 hyperphosphorylation and restored AMPK-mediated Tau dephosphorylation. Transfection of AMPKS485A mutant caused similar results. Therefore, our results suggest the following mechanism for the adverse effect of IR on AD pathology: IR → chronic overactivation of Akt → AMPKSer-485 hyperphosphorylation → inhibition of AMPK-mediated Tau dephosphorylation. Together, our results show for the first time a possible contribution of IR-induced AMPKSer-485 phosphorylation to the increased risk of AD in obesity and diabetes. 相似文献
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Anton Sandhofer Markus Laimer Christoph F. Ebenbichler Susanne Kaser Bernhard Paulweber Josef R. Patsch 《Obesity (Silver Spring, Md.)》2003,11(6):760-768
Objective: In obesity, plasma leptin is high and soluble leptin receptor (sOb‐R) levels are low, resulting in a low fraction of bound leptin. The aim of this study was to investigate the influence of insulin resistance (IR) and the metabolic syndrome (MS) on sOb‐R concentration and the bound‐free ratio of leptin. Research Methods and Procedures: sOb‐R, leptin levels, and homeostasis model assessment (HOMA) index for IR were determined in 76 middle‐aged obese or overweight men. Results: Concentration of sOb‐R and soluble receptor‐bound fraction of leptin were lowest in the highest tertile of HOMA‐IR. sOb‐R and the bound‐free ratio of leptin correlated with HOMA‐IR, leptin concentration, and waist‐to‐hip ratio independently of age, BMI, and fat mass. Leptin and waist‐to‐hip ratio were the sole independent determinants of sOb‐R concentration, and BMI, HOMA‐IR, and visceral adipose tissue were independent determinants of the bound fractin of leptin. sOb‐R concentration and the bound fraction of leptin decreased with increasing numbers of components of the MS, resulting in lower sOb‐R concentration and a lower fraction of bound leptin in men with the MS. Discussion: IR and abdominal obesity are associated with low sOb‐R concentration and low bound‐free ratio of leptin independent of fat mass. Low sOb‐R concentration and low bound‐free ratio of leptin segregate with components of the MS. We suggest that low sOb‐R levels and a low fraction of specifically bound leptin are markers of leptin resistance, which is independently associated with IR and abdominal obesity and may constitute an additional component of the MS. 相似文献
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Silver RJ Mehta S Soeldner JS Martin BC Warram JH Goldfine AB 《Obesity (Silver Spring, Md.)》2006,14(1):67-72
Objective: We sought to determine the role of the acute insulin secretory response to glucose (AIRg) in predicting weight gain in normoglycemic persons with no family history of diabetes, who are at low risk for development of disease. Research Methods and Procedures: One hundred five individuals (64 men and 41 women) who underwent measures of weight and AIRg and insulin sensitivity index (SI) by intravenous glucose tolerance test between 1963 and 1983 were surveyed again for weight between 1994 and 1999, with a mean follow‐up of 26 ± 4 years. Results: Mean change in weight was 8 ± 10 kg. Annualized weight change was calculated as change in kilograms divided by change in year and averaged 0.27 ± 0.04 kg/yr. Dividing the cohort by either median AIRg or median SI demonstrated no association of either AIRg or SI with total or annualized weight gain. Subgroup analysis by ideal body weight or gender did not alter the association. Furthermore, no association between AIRg and weight gain rate was seen within insulin‐sensitive or ‐resistant subgroups, although younger age at entry was associated with greater rates of weight gain. Discussion: Our data suggest that neither AIRg nor SI plays a role in predicting weight gain in normoglycemic individuals with no family history of diabetes. 相似文献
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Coletta DK Schneider J Stern MP Blangero J DeFronzo RA Duggirala R Jenkinson CP 《Obesity (Silver Spring, Md.)》2007,15(4):809-815
We examined the genetic association of neuropeptide Y receptor Y5 (NPY5R) single nucleotide polymorphisms (SNPs) with measures of the insulin resistance (metabolic) syndrome. We genotyped 10 NPY5R SNPs in 439 Mexican American individuals (age=43.3+/-17.3 years and BMI=30.0+/-6.7 kg/m2) distributed across 27 pedigrees from the San Antonio Family Diabetes Study and performed association analyses using the measured genotype approach as implemented in Sequential Oligogenic Linkage Analysis Routines (SOLAR). Minor alleles for five (rs11100493, rs12501691, P1, rs11100494, rs12512687) of the NPY5R SNPs were found to be significantly (p<0.05) associated with fasting plasma triglyceride concentrations and decreased high-density lipoprotein concentrations. In addition, the minor allele for SNP P2 was significantly associated (p=0.031) with a decreased homeostasis model assessment of beta-cell function (HOMA-%beta). Linkage disequilibrium between SNP pairs indicated one haplotype block of five SNPs (rs11100493, rs12501691, P1, rs11100494, rs12512687) that were highly correlated (r2>0.98). These preliminary results provide evidence for association of SNPs in the NPY5R gene with dyslipidemia (elevated triglyceride concentrations and reduced high-density lipoprotein levels) in our Mexican American population. 相似文献
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G. Neil Thomas Sai‐Yin Ho Karen S.L. Lam Edward D. Janus Anthony J. Hedley Tai Hing Lam 《Obesity (Silver Spring, Md.)》2004,12(11):1805-1813
Objective: Body fat distribution has been reported to differentially contribute to the development of cardiovascular risk. We report the relative associations between general and central obesity and risk factors in 2893 Chinese subjects recruited from the Hong Kong population. Research Methods and Procedures: Anthropometric parameters [waist circumference (WC) and BMI], surrogate measures of insulin resistance (fasting plasma glucose and insulin, oral glucose tolerance test, 2 hours glucose and insulin), fasting lipids (total, low‐density lipoprotein‐cholesterol, high‐density lipoprotein‐cholesterol, and triglycerides) and systolic and diastolic blood pressure were measured. General obesity was classified as BMI ≥25.0 kg/m2 and central obesity as a WC ≥80 or ≥90 cm in women and men, respectively. Results: A total of 39.2% of the population was found to be obese. Obesity per se increased the levels of the risk factors, but central adiposity contributed to a greater extent to adverse high‐density lipoprotein‐cholesterol, triglyceride, and insulin resistance levels. There was a continuous relationship between increasing obesity, both general and central, and cardiovascular risk, with lowest risk associated with the lowest indices of obesity. In the 1759 nonobese subjects divided into quartiles of BMI or WC, the levels of the cardiovascular risk factors still significantly increased with increasing quartiles of adiposity. Discussion: Central adiposity appears to contribute to a greater extent than general adiposity to the development of cardiovascular risk in this population. The relationship between obesity parameters and risk is a continuum, with risk factors significantly increasing even at levels usually considered nonobese. These observations support the proposed redefinition of overweight and obesity in Asian populations using lower cut‐off points. 相似文献
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Objective: To compare the prevalence of metabolic syndrome (MS) defined according to the American Heart Association (AHA)/National Heart Lung and Blood Institute (NHLBI) and the International Diabetes Federation (IDF) and to determine the effect of the presence of central obesity on the phenotype (insulin resistance and other cardiovascular risk factors) associated with MS. Research Methods and Procedures: We studied 4723 Chinese, Malays, and Asian Indians living in Singapore. Each individual was categorized according to the five criteria for MS as defined by the AHA/NHLBI and the IDF. The population was categorized according to the presence of three or more criteria and then further subcategorized according to the presence or absence of central obesity. Characteristics of each group were compared using ANOVA and the χ2 test. Results: MS was present in 20.2% (IDF) and 26.9% (AHA/NHLBI) of the population. Of the population, 6.7% exhibited three or more features of MS without central obesity. Use of the IDF definition, which requires central obesity, is associated with greater insulin resistance but similar levels of other cardiovascular disease risk factors than the use of the AHA/NHLBI definition, which does not require central obesity. Discussion: In this Southeast Asian population, the IDF and the AHA/NHLBI definitions of MS identify different segments of the MS population. The IDF definition may be more appropriate for the identification of those with insulin resistance and increased risk of type 2 diabetes. In contrast, the AHA/NHLBI definition may better identify those at increased risk of cardiovascular disease. 相似文献
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Objective: The aim of this study was to examine the association between the clinical and biochemical features of the metabolic syndrome and quantity and type of alcohol intake in the severely obese. Research Methods and Procedures: A cross‐sectional study was performed in 486 consecutive severely obese subjects. Data on alcohol consumption was collected by serial clinical interviews and a questionnaire. The relationship between alcohol intake and the clinical and serum chemistry features of the metabolic syndrome was analyzed by multiple statistical techniques. Laboratory measures included lipid profile, fasting blood glucose, hemoglobin A1c, and fasting serum insulin. An indirect index of insulin resistance was calculated using the log‐transformed fasting insulin and glucose product. Results: There were 486 subjects, 84% women, with a mean age of 40.6 ± 10 years (range, 16 to 71 years) and a body mass index of 45.3 ± 7 kg/m2 (range, 34 to 77 kg/m2). Alcohol consumers (N = 276) showed a marked reduction in the adjusted odds ratio of type 2 diabetes (odds ratio = 0.29; 95% confidence interval, 0.16 to 0.55) compared with rare or nonconsumers (N = 210). There was a U‐shaped relationship between the amount and frequency of alcohol consumption and fasting triglyceride, fasting glucose, hemoglobin A1c, and index of insulin resistance measurements. Consumers of <100 g/wk had more favorable measures. The effect was attenuated when diabetics were excluded from the analysis. Timing of alcohol consumption did not influence outcome measures. Discussion: Light‐to‐moderate alcohol consumption is associated with a lower prevalence of type 2 diabetes, reduced insulin resistance, and more favorable vascular risk profile in the severely obese. We would propose that light to moderate alcohol consumption should not be discouraged in the severely obese. 相似文献
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Goto T Lee JY Teraminami A Kim YI Hirai S Uemura T Inoue H Takahashi N Kawada T 《Journal of lipid research》2011,52(5):873-884
Peroxisome proliferator-activated receptor-α (PPARα) is a dietary lipid sensor, whose activation results in hypolipidemic effects. In this study, we investigated whether PPARα activation affects energy metabolism in white adipose tissue (WAT). Activation of PPARα by its agonist (bezafibrate) markedly reduced adiposity in KK mice fed a high-fat diet. In 3T3-L1 adipocytes, addition of GW7647, a highly specific PPARα agonist, during adipocyte differentiation enhanced glycerol-3-phosphate dehydrogenase activity, insulin-stimulated glucose uptake, and adipogenic gene expression. However, triglyceride accumulation was not increased by PPARα activation. PPARα activation induced expression of target genes involved in FA oxidation and stimulated FA oxidation. In WAT of KK mice treated with bezafibrate, both adipogenic and FA oxidation-related genes were significantly upregulated. These changes in mRNA expression were not observed in PPARα-deficient mice. Bezafibrate treatment enhanced FA oxidation in isolated adipocytes, suppressing adipocyte hypertrophy. Chromatin immunoprecipitation (ChIP) assay revealed that PPARα was recruited to promoter regions of both adipogenic and FA oxidation-related genes in the presence of GW7647 in 3T3-L1 adipocytes. These findings indicate that the activation of PPARα affects energy metabolism in adipocytes, and PPARα activation in WAT may contribute to the clinical effects of fibrate drugs. 相似文献
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Sairam MR Wang M Danilovich N Javeshghani D Maysinger D 《Obesity (Silver Spring, Md.)》2006,14(7):1142-1154
Objective: To investigate the relationship of early obesity to metabolic syndrome during sex hormonal imbalances in mutant female mice at different ages. Research Methods and Procedures: Hormonal imbalances, accumulation and nature of adipose tissue, food intake, glucose tolerance, and expression of candidate genes and markers of inflammation were studied by comparing wild‐type, null, and haploinsufficient follitropin receptor knockout female mice at different ages. Results: Follitropin receptor deletion in mice produced null females that are infertile and haploinsufficient mice that undergo accelerated biological aging. Both types of mutants with sex hormonal imbalances have central obesity without hyperphagia, but circulating leptin is elevated. Adipocyte hyperplasia and hypertrophy is attributed to elevated peroxisome proliferator‐activated receptor γ expression. Adiponectin protein levels increase in fat tissue and plasma. Only mutants but not controls acquire age‐dependent decline in glucose tolerance with high insulin and altered pancreatic β cells. Changes in inflammation markers, decreased muscle insulin receptor phosphorylation, and increase of the enzyme protein tyrosine phosphatase 1B indicate insulin resistance. Discussion: In this animal model, the chronological appearance of early obesity induced by hormonal imbalances culminates in characteristics that are attributable to metabolic syndrome, including cardiovascular abnormalities. Dissection of the depot‐specific alterations and defining molecular interrelationships could help in developing targeted remedies and resolving complications and controversies related to health benefits and adversities of current hormone replacement therapy. 相似文献