GSBS Student Publications

Title

CD40 Deficiency in Mice Exacerbates Obesity-induced Adipose Tissue Inflammation, Hepatic Steatosis and Insulin Resistance

Student Author(s)

Chang-An Guo; Sophia Kogan; Shinya U. Amano; Mengxi Wang; Sezin Dagdeviren

GSBS Program

Interdisciplinary Graduate Program

Publication Date

2013-03-12

UMMS Affiliation

Program in Molecular Medicine

Document Type

Article

Disciplines

Cellular and Molecular Physiology | Endocrinology

Abstract

The pathophysiology of obesity and type 2 diabetes in rodents and humans is characterized by low-grade inflammation in adipose tissue and liver. The CD40 receptor and its ligand, CD40L, initiate immune cell signaling promoting inflammation, but conflicting data on CD40L null mice confound its role in obesity-associated insulin resistance. Here we demonstrate that CD40 receptor deficient mice on a high fat diet display the expected decrease in hepatic cytokine levels, but paradoxically exhibit liver steatosis, insulin resistance and glucose intolerance compared to their age-matched wild type controls. Hyperinsulinemic-euglycemic clamp studies also demonstrated insulin resistance in glucose utilization by the CD40 null mice compared to wild type mice. In contrast to liver, adipose tissue in CD40 deficient animals harbors elevated cytokine levels and infiltration of inflammatory cells, particularly macrophages and CD8+ effector T-cells. In addition, ex vivo explants of epididymal adipose tissue from CD40(-/-) mice display elevated basal and isoproterenol-stimulated lipolysis, suggesting a potential increase of lipid efflux from visceral fat to the liver. These findings reveal that, 1) CD40 null mice represent an unusual model of hepatic steatosis with reduced hepatic inflammation, and 2) CD40 unexpectedly functions in adipose tissue to attenuate its inflammation in obesity, thereby protecting against hepatic steatosis.

DOI of Published Version

10.​1152/​ajpendo.​00514.​2012

Source

Am J Physiol Endocrinol Metab. 2013 Mar 12. DOI 10.​1152/​ajpendo.​00514.​2012

Journal/Book/Conference Title

American journal of physiology. Endocrinology and metabolism

Related Resources

Link to article in PubMed

PubMed ID

23482447

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