title: Adipocyte death, adipose tissue remodeling, and obesity complications.
abstract: OBJECTIVE
  We sought to determine the role of adipocyte death in obesity-induced adipose tissue (AT) inflammation and obesity complications.
  
  
  METHODS
  Male C57BL/6 mice were fed a high-fat diet for 20 weeks to induce obesity. Every 4 weeks, insulin resistance was assessed by intraperitoneal insulin tolerance tests, and epididymal (eAT) and inguinal subcutaneous AT (iAT) and livers were harvested for histological, immunohistochemical, and gene expression analyses.
  
  
  RESULTS
  Frequency of adipocyte death in eAT increased from <0.1% at baseline to 16% at week 12, coincident with increases in 1) depot weight; 2) AT macrophages (ATM Phi s) expressing F4/80 and CD11c; 3) mRNA for tumor necrosis factor (TNF)-alpha, monocyte chemotactic protein (MCP)-1, and interleukin (IL)-10; and 4) insulin resistance. ATM Phi s in crown-like structures surrounding dead adipocytes expressed TNF-alpha and IL-6 proteins. Adipocyte number began to decline at week 12. At week 16, adipocyte death reached approximately 80%, coincident with maximal expression of CD11c and inflammatory genes, loss (40%) of eAT mass, widespread collagen deposition, and accelerated hepatic macrosteatosis. By week 20, adipocyte number was restored with small adipocytes, coincident with reduced adipocyte death (fourfold), CD11c and MCP-1 gene expression (twofold), and insulin resistance (35%). eAT weight did not increase at week 20 and was inversely correlated with liver weight after week 12 (r = -0. 85, P < 0.001). In iAT, adipocyte death was first detected at week 12 and remained <or=3%.
  
  
  CONCLUSIONS
  These results implicate depot-selective adipocyte death and M Phi-mediated AT remodeling in inflammatory and metabolic complications of murine obesity.
authors.affiliation: Obesity and Metabolism Laboratory, Jean Mayer-U.S. Department of Agriculture Human Nutrition Research Center on Aging (JM-USDA HNRCA) at Tufts University, Boston, MA, USA.
authors.forename: Katherine J
authors.initials: KJ
authors.lastname: Strissel
authors.forename: Zlatina
authors.initials: Z
authors.lastname: Stancheva
authors.forename: Hideaki
authors.initials: H
authors.lastname: Miyoshi
authors.forename: James W
authors.initials: JW
authors.lastname: Perfield
authors.forename: Jason
authors.initials: J
authors.lastname: DeFuria
authors.forename: Zoe
authors.initials: Z
authors.lastname: Jick
authors.forename: Andrew S
authors.initials: AS
authors.lastname: Greenberg
authors.forename: Martin S
authors.initials: MS
authors.lastname: Obin
mesh_terms: D017667:Adipocytes / Q000473:pathology*; D000273:Adipose Tissue / Q000473:pathology / Q000503:physiopathology*; D000818:Animals; D016923:Cell Death; D004195:Disease Models, Animal; D007249:Inflammation / Q000503:physiopathology; D008264:Macrophages / Q000166:cytology / Q000473:pathology / Q000502:physiology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D009765:Obesity / Q000150:complications* / Q000473:pathology / Q000503:physiopathology*