EZMADP-60K MilliporeMouse Adiponectin ELISA

Fibroblast growth factor-21 (FGF21) is a hormone secreted by the liver during fasting that elicits diverse aspects of the adaptive starvation response. Among its effects, FGF21 induces hepatic fatty acid oxidation and ketogenesis, increases insulin sensitivity, blocks somatic growth and causes bone loss. Here we show that transgenic overexpression of FGF21 markedly extends lifespan in mice without reducing food intake or affecting markers of NAD+ metabolism or AMP kinase and mTOR signaling. Transcriptomic analysis suggests that FGF21 acts primarily by blunting the growth hormone/insulin-like growth factor-1 signaling pathway in liver. These findings raise the possibility that FGF21 can be used to extend lifespan in other species.DOI:http://dx.doi.org/10.7554/eLife.00065.001.

In the present study, resveratrol, a polyphenolic SIRT1 activator was evaluated for its SIRT1 activation in an in vitro fluorescent based assay (EC(50) : 7 μM). The efficacy of resveratrol was also evaluated in ob/ob mice for its antidiabetic and associated metabolic effects. Mice aged 5-8 weeks were included in four groups; control and resveratrol at 5, 15, 50 mg/kg, b.i.d. and were dosed orally. After 4 weeks of drug treatment, body weights were noted and random blood glucose and insulin was estimated for the antidiabetic effect. Animals were also subjected to the oral glucose tolerance test to observe any improvement in the glucose excursion. Triglycerides, total cholesterol, adiponectin and free fatty acid levels were also estimated. The results showed that resveratrol exhibited significant antihyperglycemic activity with an improvement in the insulin levels compared with the control mice. There was also a significant improvement observed in the glucose excursion in the oral glucose tolerance test performed for 120 min; although an insignificant improvement in the triglycerides, total cholesterol, adiponectin and free fatty acid levels was observed at different doses of resveratrol tested. The present findings suggest that resveratrol is an antihyperglycemic agent and drugs similar to resveratrol can be considered as an effective therapeutic adjuvant for the current treatment of diabetes mellitus.Copyright © 2010 John Wiley & Sons, Ltd.

The study aimed to investigate the effect of swimming training in reducing the nonalcoholic fatty liver disease (NAFLD) and associated comorbidities, including the hepatic expression of fatty acid synthesis and peroxisome proliferator receptor activity-alpha. Male C57BL/6 mice were separated into two major groups according to their nutrition and studied during 22 weeks: standard chow (10% fat, SC) or high-fat chow (60% fat, HF), characterizing the sedentary groups SC-Sed and HF-Sed. In the last 10 weeks of the experiment, half of the sedentary groups were submitted to a swimming training with a progressive increase in duration, characterizing the exercised groups: SC-Ex and HF-Ex. At the end of the experiment, considering the findings in the SC-Sed group, HF-Sed group had significantly higher body mass, hyperglycemia, hyperinsulinemia with insulin resistance, hypertrophy of the adipocytes (with inflammatory infiltrate), hypertrophy of the pancreatic islets, dyslipidemia, altered liver enzymes and inflammatory cytokines, and NAFLD with changes in gene expression of hepatic lipogenic and oxidative proteins. The swimming program, even concomitant with the high-fat diet, reduced overweight and all the other worst findings, especially NAFLD. In conclusion, the swimming training can attenuate the morbid effects of a high-fat diet combined with sedentary lifestyle in mice. These data reinforce the notion that swimming exercise can be considered an efficient nonpharmacologic therapy in the treatment of NAFLD, obesity and insulin resistance.

The incidence of nonalcoholic fatty liver disease (NAFLD) has risen along with the ongoing obesity epidemic. Green tea extract (GTE) inhibits intestinal lipid absorption and may regulate hepatic lipid accumulation. The objective of this study was to determine whether GTE protects against hepatic lipid accumulation during the development of NAFLD in an obese mouse model. Five-wk-old ob/ob (obese) mice and their lean littermates (8 mice x genotype(-1) x dietary treatment(-1)) were fed GTE at 0, 1, or 2% (wt:wt) for 6 wk. The body weights of obese mice and lean littermates fed diets containing GTE were 23-25% and 11-20% lower (P 0.05) than their respective controls fed no GTE. Histologic evaluation showed a significant reduction in hepatic steatosis in GTE-fed obese mice only and histologic scores were correlated with hepatic lipid concentration (r = 0.84; P 0.05), which was reduced dose dependently by GTE. GTE protected against hepatic injury as suggested by 30-41% and 22-33% lower serum alanine aminotransferase and aspartate aminotransferase activities, respectively. Hepatic alpha-tocopherol was 36% higher in obese mice than lean mice. GTE tended (P = 0.06) to lower hepatic alpha-tocopherol, which was not fully explained by the GTE-mediated reduction in hepatic lipid. Hepatic ascorbic acid was lower in obese mice than in lean mice (P 0.05) and was unaltered by GTE. Obese mice had lower serum adiponectin than lean mice and this was not affected by GTE. The results suggest that GTE protects against NAFLD by limiting hepatic lipid accumulation and injury without affecting hepatic antioxidant status and adiponectin-mediated lipid metabolism. Further study is underway to define the events by which GTE protects against obesity-triggered NAFLD.

Dietary supplementation with conjugated linoleic acid (CLA) has been shown, in several animal models, to decrease the development of atherosclerosis. The mechanism behind the anti-atherogenic properties of CLA is not clear. The objectives of this study were to determine the effect of CLA on atherosclerosis, lipoprotein and liver lipid metabolism, and plasma adiponectin and insulin in apoE(-/-) mice fed an atherogenic (16%, w/w fat; 1.25%, w/w cholesterol) diet. Mice were fed the diet with or without supplementation of linoleic acid (LA), c-9,t-11 CLA, t-10,c-12 CLA, or a 1:1 mixture of the two CLA isomers, at a concentration of 0.5% (w/w), for 12 weeks. Relative to the LA group, CLA supplementation had no significant effect on the lesion area in either en face preparations of the aorta or in aortic root cross-sections. Plasma triacylglycerol and cholesterol concentrations were higher in the t-10,c-12 CLA group than all other treatment groups and liver weight was also increased in this group due to a three-fold increase in liver triacylglycerol. Supplementation with t-10,c-12 CLA or mixed CLA reduced plasma adiponectin levels, whereas t-10,c-12 CLA increased plasma insulin levels. Liver triglycerides correlated directly with blood glucose and plasma insulin and inversely with plasma adiponectin. We conclude that dietary supplementation with CLA does not affect atherosclerosis of the apoE(-/-) mouse on a high-cholesterol diet. Furthermore, t-10,c-12 CLA causes adverse changes in adipocyte function and plasma and liver lipid metabolism, which are partially ameliorated by the inclusion of the c-9,t-11 CLA isomer.

An inverse correlation between the pro-inflammatory cytokine interleukin-18 and the anti-atherogenic adipokine adiponectin has been reported in the chronic pathological conditions obesity, insulin resistance, coronary artery disease, and metabolic syndrome. We investigated whether this relationship is coincidental or has a causal basis. Here we show that interleukin-18 (IL-18) suppresses adiponectin transcription, mRNA expression, and secretion by 3T3-L1 adipocytes. IL-18 suppresses adiponectin promoter-reporter activity, an effect reversed by deletion or mutation of the NFATc4 core DNA-binding site. IL-18 induces NFATc4 phosphorylation (Ser(676)), nuclear translocation, and in vivo DNA binding. IL-18 induces ERK1/2 phosphorylation and enzyme activity, and pretreatment with the MEK inhibitor U0126, ERK1/2 inhibitor PD98059, or small interference RNA targeted to ERK1/2 attenuates ERK1/2 activation and NFATc4 phosphorylation. Finally, inhibition of ERK1/2 or NFATc4 knockdown reverses IL-18-mediated adiponectin suppression. In contrast to its inhibitory effects on adiponectin expression, IL-18 potently stimulates PAI-1 secretion. These data demonstrate for the first time that IL-18 selectively suppresses adiponectin expression via ERK1/2-dependent NFATc4 activation and suggest that the inverse relationship observed between IL-18 and adiponectin in various chronic pathological conditions is causally related. Thus, targeting IL-18 expression may enhance adiponectin expression and mitigate disease progression.

OBJECTIVE AND DESIGN: Elevated blood pressure and insulin resistance are strongly associated in patients. We explored the potential for the anti-hypertensive angiotensin II type 1-receptor (ATR(1)) antagonists to improve insulin sensitivity through modulation of the nuclear receptor PPARgamma, in vitro and in vivo compared to the potent insulin sensitizer, rosiglitazone. METHODS: PPARgamma modulation by ATR(1) antagonists was measured first by direct recruitment of PGC-1, followed by trans-activation reporter assays in cells, and promotion of adipogenesis in fibroblast and pre-adipocyte cell lines. Improvement of insulin sensitivity was measured as changes in levels of glucose, insulin, and adiponectin in ob/ob mice. RESULTS: Telmisartan, candesartan, irbesartan, and losartan (but not valsartan or olmesartan) each served as bona fide PPARgamma ligands in vitro, with EC(50) values between 3 and 5 micro mol/l. However, only telmisartan, and to a lesser extent candesartan, resulted in significant PPARgamma agonism in cells. In vivo, although rosiglitazone significantly lowered both glucose (33%, p0.01) and insulin (61%, p0.01) levels and increased expression of adiponectin (74%, p0.001), sartan treatment had no effect. CONCLUSIONS: Many members of the sartan family of ATR(1) antagonists are PPARgamma ligands in cell-free assays but their modulation of PPARgamma in cells is relatively weak. Furthermore, none appear to improve insulin sensitivity in a rodent model under conditions where other insulin sensitizers, including rosiglitazone, do. These results question whether reported effects of sartans on insulin sensitivity may be through other means, and should guide further efforts to develop dual agents to treat hypertension and insulin resistance.