title: Leucine alters hepatic glucose/lipid homeostasis via the myostatin-AMP-activated protein kinase pathway - potential implications for nonalcoholic fatty liver disease.
abstract: BACKGROUND
  Elevated plasma levels of the branched-chain amino acid (BCAA) leucine are associated with obesity and insulin resistance (IR), and thus the propensity for type 2 diabetes mellitus development. However, other clinical studies suggest the contradictory view that leucine may in fact offer a degree of protection against metabolic syndrome. Aiming to resolve this apparent paradox, we assessed the effect of leucine supplementation on the metabolism of human hepatic HepG2 cells.
  
  
  RESULTS
  We demonstrate that pathophysiological leucine appears to be antagonistic to insulin, promotes glucose uptake (and not glycogen synthesis), but results in hepatic cell triglyceride (TG) accumulation. Further, we provide evidence that myostatin (MSTN) regulation of AMP-activated protein kinase (AMPK) is a key pathway in the metabolic effects elicited by excess leucine. Finally, we report associated changes in miRNA expression (some species previously linked to metabolic disease etiology), suggesting that epigenetic processes may contribute to these effects.
  
  
  CONCLUSIONS
  Collectively, our observations suggest leucine may be both 'friend' and 'foe' in the context of metabolic syndrome, promoting glucose sequestration and driving lipid accumulation in liver cells. These observations provide insight into the clinical consequences of excess plasma leucine, particularly for hyperglycemia, IR and nonalcoholic fatty liver disease (NAFLD).
authors: Developmental Epigenetics Group, Liggins Institute, The University of Auckland, 85 Park Road, Grafton Auckland, 1023 New Zealand.
authors: Aida
authors: A
authors: Zarfeshani
authors: Developmental Epigenetics Group, Liggins Institute, The University of Auckland, 85 Park Road, Grafton Auckland, 1023 New Zealand.
authors: Sherry
authors: S
authors: Ngo
authors: Developmental Epigenetics Group, Liggins Institute, The University of Auckland, 85 Park Road, Grafton Auckland, 1023 New Zealand.
authors: Allan M
authors: AM
authors: Sheppard
keywords: AMP-activated protein kinase; fatty liver; leucine; miRNAs; myostatin