title: Subcutaneous fat transplantation alleviates diet-induced glucose intolerance and inflammation in mice.
abstract: OBJECTIVE
  Adipose tissue (AT) distribution is a major determinant of mortality and morbidity in obesity. In mice, intra-abdominal transplantation of subcutaneous AT (SAT) protects against glucose intolerance and insulin resistance (IR), but the underlying mechanisms are not well understood.
  
  
  METHODS
  We investigated changes in adipokines, tissue-specific glucose uptake, gene expression and systemic inflammation in male C57BL6/J mice implanted intra-abdominally with either inguinal SAT or epididymal visceral AT (VAT) and fed a high-fat diet (HFD) for up to 17 weeks.
  
  
  RESULTS
  Glucose tolerance was improved in mice receiving SAT after 6 weeks, and this was not attributable to differences in adiposity, tissue-specific glucose uptake, or plasma leptin or adiponectin concentrations. Instead, SAT transplantation prevented HFD-induced hepatic triacylglycerol accumulation and normalised the expression of hepatic gluconeogenic enzymes. Grafted fat displayed a significant increase in glucose uptake and unexpectedly, an induction of skeletal muscle-specific gene expression. Mice receiving subcutaneous fat also displayed a marked reduction in the plasma concentrations of several proinflammatory cytokines (TNF-α, IL-17, IL-12p70, monocyte chemoattractant protein-1 [MCP-1] and macrophage inflammatory protein-1β [ΜIP-1β]), compared with sham-operated mice. Plasma IL-17 and MIP-1β concentrations were reduced from as early as 4 weeks after transplantation, and differences in plasma TNF-α and IL-17 concentrations predicted glucose tolerance and insulinaemia in the entire cohort of mice (n = 40). In contrast, mice receiving visceral fat transplants were glucose intolerant, with increased hepatic triacylglycerol content and elevated plasma IL-6 concentrations.
  
  
  CONCLUSIONS
  Intra-abdominal transplantation of subcutaneous fat reverses HFD-induced glucose intolerance, hepatic triacylglycerol accumulation and systemic inflammation in mice.
authors.affiliation: Diabetes and Metabolism Division, Garvan Institute of Medical Research, 384 Victoria Street, Darlinghurst, 2010, Sydney, NSW, Australia.
authors.forename: Samantha L
authors.initials: SL
authors.lastname: Hocking
authors.forename: Rebecca L
authors.initials: RL
authors.lastname: Stewart
authors.forename: Amanda E
authors.initials: AE
authors.lastname: Brandon
authors.forename: Eurwin
authors.initials: E
authors.lastname: Suryana
authors.forename: Ella
authors.initials: E
authors.lastname: Stuart
authors.forename: Emily M
authors.initials: EM
authors.lastname: Baldwin
authors.forename: Ganesh A
authors.initials: GA
authors.lastname: Kolumam
authors.forename: Zora
authors.initials: Z
authors.lastname: Modrusan
authors.forename: Jagath R
authors.initials: JR
authors.lastname: Junutula
authors.forename: Jenny E
authors.initials: JE
authors.lastname: Gunton
authors.forename: Michael
authors.initials: M
authors.lastname: Medynskyj
authors.forename: Sinead P
authors.initials: SP
authors.lastname: Blaber
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Karsten
authors.forename: Benjamin R
authors.initials: BR
authors.lastname: Herbert
authors.forename: David E
authors.initials: DE
authors.lastname: James
authors.forename: Gregory J
authors.initials: GJ
authors.lastname: Cooney
authors.forename: Michael M
authors.initials: MM
authors.lastname: Swarbrick
mesh_terms: D017667:Adipocytes / Q000378:metabolism / Q000648:ultrastructure; D052242:Adiponectin / Q000097:blood; D050154:Adiposity; D000818:Animals; D001823:Body Composition; D016207:Cytokines / Q000097:blood; D059305:Diet, High-Fat / Q000009:adverse effects; D004435:Eating; D005943:Gluconeogenesis; D005947:Glucose / Q000378:metabolism; D018149:Glucose Intolerance / Q000601:surgery*; D007249:Inflammation / Q000601:surgery*; D007328:Insulin / Q000097:blood; D020738:Leptin / Q000097:blood; D008099:Liver / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D050151:Subcutaneous Fat / Q000637:transplantation*; D014280:Triglycerides / Q000378:metabolism
chemical_list: D052242:Adiponectin; D016207:Cytokines; D007328:Insulin; D020738:Leptin; D014280:Triglycerides; D005947:Glucose