These findings reveal a novel link between methylation and expression of inhibin. Knockdown of the inhibin a-subunit during ACC formation through methylation might predispose to unopposed paracrine TGF-b or activin action on adrenocortical proliferation or steroidogenesis. Restoring inhibin and also follistatin levels in ACC by demethylating agents might contribute to the antiproliferative and steroidogenic effects seen with DNA methylation inhibitor 5-aza-29-deoxycytidine in adrenocortical cells. Conversely, methylation of the inhibin promoter might also be a common regulatory mechanism of inhibin expression in gonadal, adrenal and placental tissue and treatment with demethylating agents could be speculated to affect inhibin production in these organs. Obesity and type 2 diabetes constitute a significant health care concern in the United States and other developing and developed nations, especially since their incidence is on the rise in children and young adults. Sarcopenic obesity, the co-existence of sarcopenia and obesity, is seen in 5�C10% of healthy, ambulatory, community-dwelling Americans in their sixties, rising to over 50% in those over age eighty. Studies indicate that up to 50% of muscle may be lost by the age of 90 years. Since muscle is the primary tissue contributing to whole-body insulinmediated glucose disposal, sarcopenia may be an important causal factor in age-induced insulin resistance and type 2 diabetes susceptibility. Inflammation is a central underpinning in the pathogenesis of insulin resistance and is also seen in both obesity and sarcopenia. Inflammation may be an important mediator in restraining myogenesis and/or accelerating muscle GDC-0994 protein degradation. In addition, intramyocellular lipid accumulation, seen in obesity, results in the formation of bioactive lipid intermediates and lipid peroxides, which are known to activate pro-inflammatory cascades.Recent studies in rodents suggest a strong GS-9451 inverse association between muscle mass and disease risk. Even a modest increase in muscle mass can prevent diet-induced obesity and insulin resistance as well as atherogenesis in prone mice.