Format

Send to

Choose Destination
Diabetes. 2007 Dec;56(12):2910-8. Epub 2007 Sep 11.

Adipocyte death, adipose tissue remodeling, and obesity complications.

Author information

1
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.

Abstract

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, 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.

PMID:
17848624
DOI:
10.2337/db07-0767
[Indexed for MEDLINE]
Free full text

Supplemental Content

Full text links

Icon for HighWire
Loading ...
Support Center