The role of BCAA metabolism in metabolic health and disease.

It has long been postulated that dietary restriction is beneficial for ensuring longevity and extending the health span of mammals, including humans. In particular, a reduction in protein consumption has been shown to be specifically linked to the beneficial effect of dietary restriction on metabolic disorders, presumably by reducing the activity of the mechanistic target of rapamycin complex (mTORC) 1 and the reciprocal activation of AMP-activated protein kinase (AMPK) and sirtuin pathways. Although it is widely used as a dietary supplement to delay the aging process in humans, recent evidence suggests that branched-chain amino acids (BCAAs) might be a major cause of the deteriorating effect of a protein diet on aging and related disorders.

Impaired BCAA catabolism in adipose tissues promotes age-associated metabolic derangement.

Adipose tissues are central in controlling metabolic homeostasis and failure in their preservation is associated with age-related metabolic disorders. The exact role of mature adipocytes in this phenomenon remains elusive. Here we describe the role of adipose branched-chain amino acid (BCAA) catabolism in this process.

Hepatic Crtc2 controls whole body energy metabolism via a miR-34a-Fgf21 axis.

Liver plays a crucial role in controlling energy homeostasis in mammals, although the exact mechanism by which it influences other peripheral tissues has yet to be addressed. Here we show that Creb regulates transcriptional co-activator (Crtc) 2 is a major regulator of whole-body energy metabolism. Crtc2 liver-specific knockout lowers blood glucose levels with improved glucose and insulin tolerance.

Insulin-Inducible SMILE Inhibits Hepatic Gluconeogenesis.

The role of a glucagon/cAMP-dependent protein kinase-inducible coactivator PGC-1α signaling pathway is well characterized in hepatic gluconeogenesis. However, an opposing protein kinase B (PKB)/Akt-inducible corepressor signaling pathway is unknown. A previous report has demonstrated that small heterodimer partner-interacting leucine zipper protein (SMILE) regulates the nuclear receptors and transcriptional factors that control hepatic gluconeogenesis.