Adipocyte Death, Adipose Tissue Remodeling, and Obesity Complications

  1. Katherine J. Strissel,
  2. Zlatina Stancheva,
  3. Hideaki Miyoshi,
  4. James W. Perfield II,
  5. Jason DeFuria,
  6. Zoe Jick,
  7. Andrew S. Greenberg and
  8. Martin S. Obin
  1. From the Obesity and Metabolism Laboratory, Jean Mayer-U.S. Department of Agriculture Human Nutrition Research Center on Aging (JM-USDA HNRCA) at Tufts University, Boston, Massachusetts
  1. Address correspondence and reprint requests to Martin S. Obin or Andrew S. Greenberg, USDA, HNRCA at Tufts University, Boston, MA 02111. E-mail: martin.obin{at} or andrew.greenberg{at}


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 (ATMΦs) expressing F4/80 and CD11c; 3) mRNA for tumor necrosis factor (TNF)-α, monocyte chemotactic protein (MCP)-1, and interleukin (IL)-10; and 4) insulin resistance. ATMΦs in crown-like structures surrounding dead adipocytes expressed TNF-α and IL-6 proteins. Adipocyte number began to decline at week 12. At week 16, adipocyte death reached ∼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 MΦ-mediated AT remodeling in inflammatory and metabolic complications of murine obesity.


  • Published ahead of print at on 11 September 2007. DOI: 10.2337/db07-0767.

    Additional information for this article can be found in an online appendix at

    The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked “advertisement” in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

    • Accepted August 27, 2007.
    • Received June 5, 2007.
| Table of Contents