title: NAG-1/GDF-15 prevents obesity by increasing thermogenesis, lipolysis and oxidative metabolism.
abstract: OBJECTIVE
  Obesity is a major health problem associated with high morbidity and mortality. NSAID-activated gene (NAG-1) is a TGF-β superfamily member reported to alter adipose tissue levels in mice. We investigated whether hNAG-1 acts as a regulator of adiposity and energy metabolism.
  
  
  METHODS
  hNAG-1 mice, ubiquitously expressing hNAG-1, were placed on a control or high-fat diet for 12 weeks. hNAG-1-expressing B16/F10 melanoma cells were used in a xenograft model to deliver hNAG-1 to obese C57BL/6 mice.
  
  
  RESULTS
  As compared with wild-type littermates, transgenic hNAG-1 mice have less white fat and brown fat despite equivalent food intake, improved glucose tolerance, lower insulin levels and are resistant to dietary- and genetic-induced obesity. hNAG-1 mice are more metabolically active with higher energy expenditure. Obese C57BL/6 mice treated with hNAG-1-expressing xenografts show decreases in adipose tissue and serum insulin levels. hNAG-1 mice and obese mice treated with hNAG-1-expressing xenografts show increased thermogenic gene expression (UCP1, PGC1α, ECH1, Cox8b, Dio2, Cyc1, PGC1β, PPARα, Elvol3) in brown adipose tissue (BAT) and increased expression of lipolytic genes (Adrb3, ATGL, HSL) in both white adipose tissue (WAT) and BAT, consistent with higher energy metabolism.
  
  
  CONCLUSIONS
  hNAG-1 modulates metabolic activity by increasing the expression of key thermogenic and lipolytic genes in BAT and WAT. hNAG-1 appears to be a novel therapeutic target in preventing and treating obesity and insulin resistance.
authors: Laboratory of Molecular Carcinogenesis, NIEHS, NIH, Research Triangle Park, NC, USA.
authors: K
authors: K
authors: Chrysovergis
authors: Laboratory of Molecular Carcinogenesis, NIEHS, NIH, Research Triangle Park, NC, USA.
authors: X
authors: X
authors: Wang
authors: Laboratory of Molecular Carcinogenesis, NIEHS, NIH, Research Triangle Park, NC, USA.
authors: J
authors: J
authors: Kosak
authors: Department of Biomedical and Diagnostic Sciences, College of Veterinary Medicine, University of Tennessee, Knoxville, TN, USA.
authors: S-H
authors: SH
authors: Lee
authors: 1] Laboratory of Molecular Carcinogenesis, NIEHS, NIH, Research Triangle Park, NC, USA [2] Department of Biological Sciences, Andong National University, Andong, South Korea.
authors: J S
authors: JS
authors: Kim
authors: Cellular and Molecular Pathology Branch, NIEHS, NIH, Research Triangle Park, NC, USA.
authors: J F
authors: JF
authors: Foley
authors: Cellular and Molecular Pathology Branch, NIEHS, NIH, Research Triangle Park, NC, USA.
authors: G
authors: G
authors: Travlos
authors: Laboratory of Molecular Carcinogenesis, NIEHS, NIH, Research Triangle Park, NC, USA.
authors: S
authors: S
authors: Singh
authors: Department of Biomedical and Diagnostic Sciences, College of Veterinary Medicine, University of Tennessee, Knoxville, TN, USA.
authors: S J
authors: SJ
authors: Baek
authors: Laboratory of Molecular Carcinogenesis, NIEHS, NIH, Research Triangle Park, NC, USA.
authors: T E
authors: TE
authors: Eling
mesh_terms: D000273:Adipose Tissue / Q000378:metabolism* / Q000473:pathology; D000818:Animals; D015153:Blotting, Western; D059305:Diet, High-Fat; D004435:Eating; D004734:Energy Metabolism; D004797:Enzyme-Linked Immunosorbent Assay; D055436:Growth Differentiation Factor 15 / Q000378:metabolism*; D006801:Humans; D007333:Insulin Resistance; D008066:Lipolysis; D051379:Mice; D008810:Mice, Inbred C57BL; D008820:Mice, Obese; D009765:Obesity / Q000517:prevention & control*; D018384:Oxidative Stress / Q000187:drug effects; D060888:Real-Time Polymerase Chain Reaction; D022722:Thermogenesis
chemical_list: C526140:GDF15 protein, human; D055436:Growth Differentiation Factor 15