title: Leucine supplementation improves acquired growth hormone resistance in rats with protein-energy malnutrition.
abstract: BACKGROUND
  Protein-energy malnutrition (PEM) can lead to growth hormone (GH) resistance. Leucine supplementation diets have been shown to increase protein synthesis in muscles. Our study aimed at investigating if long-term leucine supplementation could modulate GH-insulin-like growth factor (IGF)-1 system function and mammalian target of rapamycin (mTOR)-related signal transduction in skeletal muscles in a rat model of severe malnutrition.
  
  
  RESULTS
  Male Sprague-Dawley rats (n = 50; weight, 302 ± 5 g) were divided into 5 treatment groups, including 2 control groups (a normal control group that was fed chow and ad libitum water [CON, n = 10] and a malnourished control group [MC, n = 10] that was fed a 50% chow diet). After undergoing a weight loss stage for 4 weeks, rats received either the chow diet (MC-CON, n = 10), the chow diet supplemented with low-dose leucine (MC-L, n = 10), or the chow diet supplemented with high-dose leucine (MC-H, n = 10) for 2 weeks. The muscle masses of the gastrocnemius, soleus, and extensor digitorum longus were significantly reduced in the MC group. Re-feeding increased muscle mass, especially in the MC-L and MC-H groups. In the MC group, serum IGF-1, IGF-binding protein (IGFBP)-3, and hepatic growth hormone receptor (GHR) levels were significantly decreased and phosphorylation of the downstream anabolic signaling effectors protein kinase B (Akt), mTOR, and ribosomal protein S6 kinase 1 (S6K1) were significantly lower than in other groups. However, serum IGF-1 and IGF binding protein (IGFBP)-3 concentrations and hepatic growth hormone receptor (GHR) levels were significantly higher in the MC-L and MC-H groups than in the MC-CON group, and serum IGFBP-1 levels was significantly reduced in the MC-L and MC-H groups. These changes were consistent with those observed for hepatic mRNA expression levels. Phosphorylation of the downstream anabolic signaling effectors Akt, mTOR, and S6K1 were also significantly higher in the MC-L and MC-H groups than in the MC-CON group.
  
  
  CONCLUSIONS
  Our data are the first to demonstrate that long-term supplementation with leucine improved acquired growth hormone resistance in rats with protein-energy malnutrition. Leucine might promote skeletal muscle protein synthesis by regulating downstream anabolic signaling transduction.
authors.affiliation: Research Institute of General Surgery, Jinling Hospital, Southern Medical University, Guangzhou, Guangdong Province, China.
authors.forename: Xuejin
authors.initials: X
authors.lastname: Gao
authors.affiliation: Research Institute of General Surgery, Jinling Hospital, Medical School of Nanjing University, Nanjing, Jiangsu Province, China.
authors.forename: Feng
authors.initials: F
authors.lastname: Tian
authors.affiliation: Research Institute of General Surgery, Jinling Hospital, Southern Medical University, Guangzhou, Guangdong Province, China; Research Institute of General Surgery, Jinling Hospital, Medical School of Nanjing University, Nanjing, Jiangsu Province, China.
authors.forename: Xinying
authors.initials: X
authors.lastname: Wang
authors.affiliation: Department of Neurosurgery, Jinling Hospital, Medical School of Nanjing University, Nanjing, Jiangsu Province, China.
authors.forename: Jie
authors.initials: J
authors.lastname: Zhao
authors.affiliation: Research Institute of General Surgery, Jinling Hospital, Medical School of Nanjing University, Nanjing, Jiangsu Province, China.
authors.forename: Xiao
authors.initials: X
authors.lastname: Wan
authors.affiliation: Research Institute of General Surgery, Jinling Hospital, Medical School of Nanjing University, Nanjing, Jiangsu Province, China.
authors.forename: Li
authors.initials: L
authors.lastname: Zhang
authors.affiliation: Research Institute of General Surgery, Jinling Hospital, Medical School of Nanjing University, Nanjing, Jiangsu Province, China.
authors.forename: Chao
authors.initials: C
authors.lastname: Wu
authors.affiliation: Research Institute of General Surgery, Jinling Hospital, Medical School of Nanjing University, Nanjing, Jiangsu Province, China.
authors.forename: Ning
authors.initials: N
authors.lastname: Li
authors.affiliation: Research Institute of General Surgery, Jinling Hospital, Medical School of Nanjing University, Nanjing, Jiangsu Province, China.
authors.forename: Jieshou
authors.initials: J
authors.lastname: Li
mesh_terms: D000818:Animals; D019587:Dietary Supplements; D004195:Disease Models, Animal; D013006:Growth Hormone / Q000097:blood / Q000378:metabolism*; D018970:Insulin-Like Growth Factor Binding Protein 1 / Q000097:blood / Q000235:genetics; D018972:Insulin-Like Growth Factor Binding Protein 3 / Q000097:blood / Q000235:genetics; D007334:Insulin-Like Growth Factor I / Q000235:genetics / Q000378:metabolism; D007930:Leucine / Q000008:administration & dosage*; D008099:Liver / Q000378:metabolism; D008297:Male; D018482:Muscle, Skeletal / Q000378:metabolism / Q000473:pathology; D011502:Protein-Energy Malnutrition / Q000178:diet therapy / Q000378:metabolism / Q000473:pathology; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D011986:Receptors, Somatotropin / Q000235:genetics; D015398:Signal Transduction; D058570:TOR Serine-Threonine Kinases / Q000378:metabolism
chemical_list: D018970:Insulin-Like Growth Factor Binding Protein 1; D018972:Insulin-Like Growth Factor Binding Protein 3; D012333:RNA, Messenger; D011986:Receptors, Somatotropin; D007334:Insulin-Like Growth Factor I; D013006:Growth Hormone; C546845:mTOR protein, rat; D058570:TOR Serine-Threonine Kinases; D007930:Leucine