Regulatory role of CD40 in obesity-induced insulin resistance

Zuoan Yi; Gail A Bishop

doi:10.4161/adip.32214

Back

Regulatory role of CD40 in obesity-induced insulin resistance

Journal article

Open access

Peer reviewed

Regulatory role of CD40 in obesity-induced insulin resistance

Zuoan Yi and Gail A Bishop

Adipocyte, Vol.4(1), pp.65-69

01/02/2015

DOI: 10.4161/adip.32214

PMCID: PMC4497298

PMID: 26167405

Files and links (1)

url

https://doi.org/10.4161/adip.32214View

Published (Version of record) Open Access

Abstract

Excessive nutrient intake in obesity triggers the accumulation of various types of immune cells in adipose tissue, particularly visceral adipose tissue (VAT). This can result in chronic inflammation which disrupts insulin effects on adipocytes and muscle cells and culminates in development of insulin resistance. The interplay between immune cells and adipose tissue is a key event for the development of insulin resistance that precedes type 2 diabetes. CD40, a well-documented costimulatory receptor, is required for efficient systemic adaptive immune responses. However, we and other groups recently showed that CD40 unexpectedly ameliorates inflammation in VAT and accordingly attenuates obesity-induced insulin resistance. Specifically, although CD40 is typically considered to play its principal immune roles on B lymphocytes and myeloid cells, we found that CD40 + CD8 + T lymphocytes were major contributors to the protective effect. This unexpected inhibitory role of CD40 on CD8 + T cell activation in VAT may reflect unique features of this microenvironment. Additional knowledge gaps include whether CD40 also plays roles in mucosal immunity that control the homeostasis of gut microbiota, and human metabolic diseases. Potential therapeutic approaches, including stimulating CD40 signaling and/or manipulating specific CD40 signaling pathways in the VAT microenvironment, may open new avenues for treatment of obesity-induced insulin resistance, and prevention of type 2 diabetes.

Ab, antibody

CD40

CD40KO, CD40 deficiency

DIO, diet induced obesity

gut microbiota

HFD, high fat diet

HIGM, Hyper-IgM syndrome

Ig, immunoglobulin

IL-1β, interleukin-1β

IL-6, interleukin-6

insulin resistance

IR, insulin resistance

LFD, low fat diet

MCP-1, Monocyte Chemoattractant Protein-1

mucosal immunity

Mϕ, macrophage

obesity

PPAR-γ, peroxisome proliferator-activated receptor-γ

Rag1, recombination activating gene 1

T cell

TNF-α, tumor necrosis factor-α

Treg, regulatory T cells

UPR, unfolded protein response

VAT, visceral adipose tissue

Details

Title: Subtitle: Regulatory role of CD40 in obesity-induced insulin resistance
Creators: Zuoan Yi - University of Iowa
Gail A Bishop - University of Iowa
Resource Type: Journal article
Publication Details: Adipocyte, Vol.4(1), pp.65-69
Publisher: Taylor & Francis
DOI: 10.4161/adip.32214
PMID: 26167405
PMCID: PMC4497298
ISSN: 2162-3945
eISSN: 2162-397X
Language: English
Date published: 01/02/2015
Academic Unit: Microbiology and Immunology; President; Fraternal Order of Eagles Diabetes Research Center
Record Identifier: 9984297435902771

Metrics

14 Record Views

14 Times Cited - Web of Science

See more details