title: Chronic leucine supplementation increases body weight and insulin sensitivity in rats on high-fat diet likely by promoting insulin signaling in insulin-target tissues.
abstract: METHODS
  This study investigated the effect of chronic leucine supplementation on insulin sensitivity and the associated mechanisms in rats on high-fat diet (HFD).
  
  
  RESULTS
  Male Sprague-Dawley rats were fed either normal chow diet or HFD supplemented with 0, 1.5, 3.0, and 4.5% leucine for 24 weeks. We found that chronic leucine supplementation increased insulin sensitivity together with increased body weight in rats on HFD, but had no effect on insulin sensitivity in rats on normal chow diet. The increased insulin sensitivity by leucine supplementation was not associated with altered ectopic fat accumulation in liver and muscle, plasma levels of lipids and cytokines, but is associated with reduced oxidative stress and improved insulin signaling. Chronic leucine supplementation did not enhance insulin receptor substract-1 (IRS-1) phosphorylation on serine 302, but elevated basal IRS-1 phosphorylation on tyrosine 632 and improved insulin-stimulated protein kinase B (Akt) and mammalian target of rapamycin (mTOR) phosphorylation in liver, skeletal muscle, and adipose tissue of rats on HFD rats, indicating leucine supplementation prevented HFD-induced insulin resistance in insulin-target tissues.
  
  
  CONCLUSIONS
  Chronic leucine supplementation can increase insulin sensitivity and body weight likely by reducing oxidative stress and improving insulin signaling pathway in rats on HFD.
authors: Department of Nutrition and Food Hygiene and MOE Key Laboratory of Environment and Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, P R China.
authors: Xiang
authors: X
authors: Li
authors: Xiaolei
authors: X
authors: Wang
authors: Rui
authors: R
authors: Liu
authors: Yan
authors: Y
authors: Ma
authors: Huailan
authors: H
authors: Guo
authors: Liping
authors: L
authors: Hao
authors: Ping
authors: P
authors: Yao
authors: Liegang
authors: L
authors: Liu
authors: Xiufa
authors: X
authors: Sun
authors: Ka
authors: K
authors: He
authors: Wenhong
authors: W
authors: Cao
authors: Xuefeng
authors: X
authors: Yang
mesh_terms: D000273:Adipose Tissue / Q000187:drug effects / Q000378:metabolism; D000818:Animals; D001835:Body Weight / Q000187:drug effects*; D016207:Cytokines / Q000097:blood / Q000378:metabolism; D059305:Diet, High-Fat / Q000009:adverse effects; D019587:Dietary Supplements; D002149:Energy Intake / Q000187:drug effects; D005943:Gluconeogenesis / Q000187:drug effects / Q000235:genetics; D007328:Insulin / Q000378:metabolism*; D055504:Insulin Receptor Substrate Proteins / Q000378:metabolism; D007333:Insulin Resistance; D007930:Leucine / Q000008:administration & dosage* / Q000494:pharmacology; D008099:Liver / Q000187:drug effects; D008297:Male; D018482:Muscle, Skeletal / Q000187:drug effects / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects; D010766:Phosphorylation / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction / Q000187:drug effects; D058570:TOR Serine-Threonine Kinases / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D014443:Tyrosine / Q000378:metabolism
chemical_list: D016207:Cytokines; D007328:Insulin; D055504:Insulin Receptor Substrate Proteins; C526296:Irs1 protein, rat; D014409:Tumor Necrosis Factor-alpha; D014443:Tyrosine; C546845:mTOR protein, rat; D058570:TOR Serine-Threonine Kinases; D007930:Leucine