Metformin mitigates the impaired development of skeletal muscle in the offspring of obese mice

Background: Maternal obesity is linked with offspring obesity and type 2 diabetes. Skeletal muscle (SM) insulin resistance is central to the development of diabetes. Adenosine monophosphate (AMP)-activated protein kinase (AMPK) is inhibited in SM of fetuses born to obese mothers

ReishiMax, mushroom based dietary supplement, inhibits adipocyte differentiation, stimulates glucose uptake and activates AMPK

<p>Abstract</p> <p>Background</p> <p>Obesity is a health hazard which is closely associated with various complications including insulin resistance, hypertension, dyslipidemia, atherosclerosis, type 2 diabetes and cancer. In spite of numerous preclinical and clinical interventions, the prevalence of obesity and its related disorders are on the rise demanding an urgent need for exploring novel therapeutic agents that can regulate adipogenesis. In the present study, we evaluated whether a dietary supplement ReishiMax (RM), containing triterpenes and polysaccharides extracted from medicinal mushroom <it>Ganoderma lucidum</it>, affects adipocyte differentiation and glucose uptake in 3T3-L1 cells.</p> <p>Methods</p> <p>3T3-L1 pre-adipocytes were differentiated into adipocytes and treated with RM (0-300 μg/ml). Adipocyte differentiation/lipid uptake was evaluated by oil red O staining and triglyceride and glycerol concentrations were determined. Gene expression was evaluated by semi-quantitative RT-PCR and Western blot analysis. Glucose uptake was determined with [³H]-glucose.</p> <p>Results</p> <p>RM inhibited adipocyte differentiation through the suppresion of expression of adipogenic transcription factors peroxisome proliferator-activated receptor-γ (PPAR-γ), sterol regulatory element binding element protein-1c (SREBP-1c) and CCAAT/enhancer binding protein-α (C/EBP-α). RM also suppressed expression of enzymes and proteins responsible for lipid synthesis, transport and storage: fatty acid synthase (FAS), acyl-CoA synthetase-1 (ACS1), fatty acid binding protein-4 (FABP4), fatty acid transport protein-1 (FATP1) and perilipin. RM induced AMP-activated protein kinase (AMPK) and increased glucose uptake by adipocytes.</p> <p>Conclusion</p> <p>Our study suggests that RM can control adipocyte differentiation and glucose uptake. The health benefits of ReishiMax warrant further clinical studies.</p

AMP-activated protein kinase is activated in adipose tissue of individuals with type 2 diabetes treated with metformin:a randomised glycaemia-controlled crossover study

The hypoglycaemic actions of metformin have been proposed to be mediated by hepatic AMP-activated protein kinase (AMPK). As the effects of metformin and the role of AMPK in adipose tissue remain poorly characterised, we examined the effect of metformin on AMPK activity in adipose tissue of individuals with type 2 diabetes in a randomised glycaemia-controlled crossover study. Twenty men with type 2 diabetes (aged 50-70 years) treated with diet, metformin or sulfonylurea alone were recruited from North Glasgow University National Health Service Trusts' diabetes clinics and randomised to either metformin or gliclazide for 10 weeks. Randomisation codes, generated by computer, were put into sealed envelopes and stored by the hospital pharmacist. Medication bottles were numbered, and allocation was done in sequence. The participants and investigators were blinded to group assignment. At the end of each phase of therapy adipose biopsy, AMPK activity (primary endpoint) and levels of lipid metabolism and signalling proteins were assessed. In parallel, the effect of metformin on AMPK and insulin-signalling pathways was investigated in 3T3-L1 adipocytes. Ten participants were initially randomised to metformin and subsequently crossed over to gliclazide, while ten participants were initially randomised to gliclazide and subsequently crossed over to metformin. No participants discontinued the intervention and the adipose tissue AMPK activity was analysed in all 20 participants. There were no adverse events or side effects in the study group. Adipose AMPK activity was increased following metformin compared with gliclazide therapy (0.057 +/- 0.007 vs 0.030 +/- 0.005 [mean +/- SEM] nmol min(-1) [mg lysate](-1); p &lt; 0.005), independent of AMPK level, glycaemia or plasma adiponectin concentrations. The increase was associated with reduced levels of acetyl-CoA carboxylase (ACC) protein and increased ACC Ser80 phosphorylation. In 3T3-L1 adipocytes, metformin reduced levels of ACC protein and stimulated phosphorylation of AMPK Thr172 and hormone-sensitive lipase Ser565. These results provide the first evidence that metformin activates AMPK and reduces ACC protein levels in human adipose tissue in vivo. Future studies are required to assess the role of adipose AMPK activation in the pharmacological effects of metformin