EFFECTS OF INDIVIDUAL BRANCHED-CHAIN AMINO ACIDS DEPRIVATION ON INSULIN SENSITIVITY AND GLUCOSE METABOLISM IN MICE
F. Xiao Ann Nutr Metab 2013;63(suppl 1):1390
We have previously shown that serum insulin levels decrease threefold and fed blood glucose levels remain normal in mice fed a leucine-deficient diet, suggesting increased insulin sensitivity. The goal of the present study was to investigate the effect of branched chain amino
acids (BCAAs) deficiency on insulin sensitivity and underlying mechanisms.
Methods: Changes in metabolic parameters and expression of genes and proteins involved in regulation of insulin sensitivity and glucose metabolism were analyzed in mice, human HepG2 cells, primary hepatocytes and C2C12, a mouse myoblast cell line under different BCAAs deprivation.
Results: We showed that all three BCAAs deprivation for 7 days improves hepatic insulin sensitivity via General Control Nondepressible 2/mammalian Target of Rapamycin and AMPactivated protein kinase pathways. Different from leucine, valine or isoleucine deprivation for 7 days significantly decreased fed blood glucose levels, possibly by decreasing expression of a key gluconeogenesis gene glucose-6-phosphatase. Finally, we
showed that insulin sensitivity is rapidly improved in mice 1 day following maintenance on a diet deficient for any individual BCAAs.
Conclusions: Our results showed that the effect of leucine deprivation represents a general effect of BCAAs on regulation of insulin sensitivity, but not glucose levels, suggesting that each individual BCAA has unique feature in metabolism regulation. These observations are also important for understanding the molecular mechanisms underlying regulation of insulin sensitivity during different BCAAs deprivation and provide a rationale for short-term dietary deprivation or restriction of BCAAs for the treatment of insulin resistance and associated metabolic diseases. The effect of other individual amino acids will be investigated in the future.