title: Leucine deprivation decreases fat mass by stimulation of lipolysis in white adipose tissue and upregulation of uncoupling protein 1 (UCP1) in brown adipose tissue.
abstract: OBJECTIVE
  White adipose tissue (WAT) and brown adipose tissue (BAT) play distinct roles in adaptation to changes in nutrient availability, with WAT serving as an energy store and BAT regulating thermogenesis. We previously showed that mice maintained on a leucine-deficient diet unexpectedly experienced a dramatic reduction in abdominal fat mass. The cellular mechanisms responsible for this loss, however, are unclear. The goal of current study is to investigate possible mechanisms.
  
  
  METHODS
  Male C57BL/6J mice were fed either control, leucine-deficient, or pair-fed diets for 7 days. Changes in metabolic parameters and expression of genes and proteins related to lipid metabolism were analyzed in WAT and BAT.
  
  
  RESULTS
  We found that leucine deprivation for 7 days increases oxygen consumption, suggesting increased energy expenditure. We also observed increases in lipolysis and expression of beta-oxidation genes and decreases in expression of lipogenic genes and activity of fatty acid synthase in WAT, consistent with increased use and decreased synthesis of fatty acids, respectively. Furthermore, we observed that leucine deprivation increases expression of uncoupling protein (UCP)-1 in BAT, suggesting increased thermogenesis.
  
  
  CONCLUSIONS
  We show for the first time that elimination of dietary leucine produces significant metabolic changes in WAT and BAT. The effect of leucine deprivation on UCP1 expression is a novel and unexpected observation and suggests that the observed increase in energy expenditure may reflect an increase in thermogenesis in BAT. Further investigation will be required to determine the relative contribution of UCP1 upregulation and thermogenesis in BAT to leucine deprivation-stimulated fat loss.
authors.affiliation: Key Laboratory of Nutrition and Metabolism, Institute for Nutritional Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, the Graduate School of the Chinese Academy of Sciences, Shanghai, China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Cheng
authors.forename: Qingshu
authors.initials: Q
authors.lastname: Meng
authors.forename: Chunxia
authors.initials: C
authors.lastname: Wang
authors.forename: Houkai
authors.initials: H
authors.lastname: Li
authors.forename: Zhiying
authors.initials: Z
authors.lastname: Huang
authors.forename: Shanghai
authors.initials: S
authors.lastname: Chen
authors.forename: Fei
authors.initials: F
authors.lastname: Xiao
authors.forename: Feifan
authors.initials: F
authors.lastname: Guo
mesh_terms: D000273:Adipose Tissue / Q000033:anatomy & histology* / Q000502:physiology*; D002001:Adipose Tissue, Brown / Q000378:metabolism*; D000818:Animals; D002153:Calorimetry, Indirect; D004247:DNA / Q000235:genetics / Q000378:metabolism; D004837:Epinephrine / Q000097:blood; D064429:Fatty Acid Synthases / Q000378:metabolism; D005230:Fatty Acids, Nonesterified / Q000097:blood; D005938:Glucocorticoids / Q000097:blood; D005990:Glycerol / Q000378:metabolism; D007473:Ion Channels / Q000235:genetics*; D007930:Leucine / Q000172:deficiency*; D008066:Lipolysis; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D024101:Mitochondrial Proteins / Q000235:genetics*; D010101:Oxygen Consumption / Q000502:physiology; D012313:RNA / Q000235:genetics / Q000302:isolation & purification; D020133:Reverse Transcriptase Polymerase Chain Reaction; D000071256:Uncoupling Protein 1; D015854:Up-Regulation
chemical_list: D005230:Fatty Acids, Nonesterified; D005938:Glucocorticoids; D007473:Ion Channels; D024101:Mitochondrial Proteins; C000604372:Ucp1 protein, mouse; D000071256:Uncoupling Protein 1; D012313:RNA; D004247:DNA; D064429:Fatty Acid Synthases; D007930:Leucine; D005990:Glycerol; D004837:Epinephrine