Adipocyte death, adipose tissue remodeling, and obesity complications

作者：Strissel Katherine J; Stancheva Zlatina; Miyoshi Hideaki; Perfield James W II; DeFuria Jason; Jick Zoe; Greenberg Andrew S; Obin Martin S^*

来源：Diabetes, 2007, 56(12): 2910-2918.

DOI：10.2337/db07-0767

OBJECTIVE-We sought to determine the role of adipocyte death in obesity-induced adipose tissue (AT) inflammation and obesity complications.
RESEARCH DESIGN AND 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 I 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)-l, 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 similar to 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 <= 3%.
CONCLUSIONS-These results implicate depot-selective adipocyte death and M Phi-mediated AT remodeling in inflammatory and metabolic complications of murine obesity.

• 出版日期2007-12