title: Identification of novel GH-regulated pathway of lipid metabolism in adipose tissue: a gene expression study in hypopituitary men.
abstract: BACKGROUND
  Adipose tissue is a major target of GH action. GH stimulates lipolysis and reduces fat mass. The molecular mechanism underlying cellular and metabolic effects of GH in adipose tissue is not well understood.
  
  
  OBJECTIVE
  The aim of this study is to identify GH-responsive genes that regulate lipid metabolism in adipose tissue.
  
  
  METHODS
  Eight men with GH deficiency underwent measurement of plasma free fatty acid (FFA), whole-body lipid oxidation, and fat biopsies before and after 1 month of GH treatment (0.5 mg/d). Gene expression profiling was performed using Agilent 44K G4112F arrays using a two-color design. Differentially expressed genes were identified using an empirical Bayes, moderated t test, with a false discovery rate under 5%. Target genes were validated by quantitative RT-PCR.
  
  
  RESULTS
  GH increased circulating IGF-I and FFA and stimulated fat oxidation. A total of 246 genes were differentially expressed, of which 135 were up-regulated and 111 down-regulated. GH enhanced adipose tissue expression of IGF-I and SOCS3. GH increased expression of patatin-like phospholipase domain containing 3 (PNPLA3), a novel triglyceride (TG) hydrolase, but not hormone-sensitive lipase (HSL), a classical TG hydrolase. GH repressed cell death-inducing DFFA-like effector A (CIDEA), a novel lipid droplets-associated protein, promoting TG storage. GH differentially regulated genes promoting diacylglycerol synthesis. GH suppressed hydroxysteroid (11β) dehydrogenase 1, which activates local cortisol production and genes encoding components of extracellular matrix and TGF-β signaling pathway.
  
  
  CONCLUSIONS
  GH stimulates the TG/FFA cycle by regulating the expression of novel genes that enhance TG hydrolysis, reduce TG storage, and promote diacylglycerol synthesis. GH represses adipocyte growth, differentiation and inflammation.
authors.affiliation: Pituitary Research Unit, Garvan Institute of Medical Research, 384 Victoria Street, Darlinghurst, New South Wales 2010, Sydney, Australia.
authors.forename: Jing Ting
authors.initials: JT
authors.lastname: Zhao
authors.forename: Mark J
authors.initials: MJ
authors.lastname: Cowley
authors.forename: Paul
authors.initials: P
authors.lastname: Lee
authors.forename: Vita
authors.initials: V
authors.lastname: Birzniece
authors.forename: Warren
authors.initials: W
authors.lastname: Kaplan
authors.forename: Ken K Y
authors.initials: KK
authors.lastname: Ho
mesh_terms: D000273:Adipose Tissue / Q000378:metabolism*; D000328:Adult; D000368:Aged; D015870:Gene Expression; D020869:Gene Expression Profiling; D019382:Human Growth Hormone / Q000378:metabolism* / Q000627:therapeutic use; D006801:Humans; D007018:Hypopituitarism / Q000235:genetics* / Q000378:metabolism / Q000628:therapy; D050356:Lipid Metabolism / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D020411:Oligonucleotide Array Sequence Analysis
chemical_list: D019382:Human Growth Hormone