Testosterone or 17{beta}-estradiol exposure reveals sex-specific effects on glucose and lipid metabolism in human myotubes.

Changes in sex hormone levels with aging or illness may lead to metabolic disorders. Moreover, the ratio changes in men versus women may have distinct pathological responses. Since little is known about sex hormone action on muscle metabolism, we examined the role of testosterone or 17β-estradiol (E(2)) in metabolism and investigated whether either hormone may mediate a sex-specific effect.

Non-CpG methylation of the PGC-1alpha promoter through DNMT3B controls mitochondrial density.

Epigenetic modification through DNA methylation is implicated in metabolic disease. Using whole-genome promoter methylation analysis of skeletal muscle from normal glucose-tolerant and type 2 diabetic subjects, we identified cytosine hypermethylation of peroxisome proliferator-activated receptor gamma (PPARgamma) coactivator-1 alpha (PGC-1alpha) in diabetic subjects. Methylation levels were negatively correlated with PGC-1alpha mRNA and mitochondrial DNA (mtDNA).

Regulation of skeletal muscle sucrose, non-fermenting 1/AMP-activated protein kinase-related kinase (SNARK) by metabolic stress and diabetes.

Aims/hypothesis: Sucrose, non-fermenting 1/AMP-activated protein kinase-related kinase (SNARK) is involved in cellular stress responses linked to obesity and type 2 diabetes. We determined the role of SNARK in response to metabolic stress and insulin action on glucose and lipid metabolism in skeletal muscle.

Methods: Vastus lateralis skeletal muscle biopsies were obtained from normal glucose tolerant (n = 35) and type 2 diabetic (n = 31) men and women for SNARK expression studies.

Evidence against a sexual dimorphism in glucose and fatty acid metabolism in skeletal muscle cultures from age-matched men and post-menopausal women.

Aim: In vivo whole body differences in glucose/lipid metabolism exist between men and women. Thus, we tested the hypothesis that intrinsic sex differences exist in skeletal muscle gene expression and glucose/lipid metabolism using cultured myotubes.

Methods: Myotube cultures were prepared for gene expression and metabolic studies from vastus lateralis skeletal muscle biopsies obtained from age-matched men (n = 11; 59 +/- 2 years) and post-menopausal women (n = 10; 60 +/- 1 years).

siRNA-mediated reduction of inhibitor of nuclear factor-kappaB kinase prevents tumor necrosis factor-alpha-induced insulin resistance in human skeletal muscle.

Objective: Proinflammatory cytokines contribute to systemic low-grade inflammation and insulin resistance. Tumor necrosis factor (TNF)-alpha impedes insulin signaling in insulin target tissues. We determined the role of inhibitor of nuclear factor-kappaB kinase (IKK)beta in TNF-alpha-induced impairments in insulin signaling and glucose metabolism in skeletal muscle.

Malonyl CoenzymeA decarboxylase regulates lipid and glucose metabolism in human skeletal muscle.

Objective: Malonyl coenzyme A (CoA) decarboxylase (MCD) is a key enzyme responsible for malonyl-CoA turnover and functions in the control of the balance between lipid and glucose metabolism. We utilized RNA interference (siRNA)-based gene silencing to determine the direct role of MCD on metabolic responses in primary human skeletal muscle.

Research Design And Methods: We used siRNA to silence MCD gene expression in cultured human myotubes from healthy volunteers (seven male and seven female) with no known metabolic disorders.