Title
Role of Macrophage Migration Inhibitory Factor in Obesity, Insulin Resistance, Type 2 Diabetes, and Associated Hepatic Co-Morbidities: A Comprehensive Review of Human and Rodent Studies
Author
Morrison, M.C.
Kleemann, R.
Publication year
2015
Abstract
Obesity is associated with a chronic low-grade inflammatory state that drives the -development of obesity-related co-morbidities such as insulin resistance/type 2 diabetes, non-alcoholic fatty liver disease (NAFLD), and cardiovascular disease. This metabolic inflammation is thought to originate in the adipose tissue, which becomes inflamed and insulin resistant when it is no longer able to expand in response to excess caloric and nutrient intake. The production of inflammatory mediators by dysfunctional adipose tissue is thought to drive the development of more complex forms of disease such as type 2 diabetes and NAFLD. An important factor that may contribute to metabolic inflammation is the cytokine macrophage migration inhibitory factor (MIF). Increasing evidence suggests that MIF is released by adipose tissue in obesity and that it is also involved in metabolic and inflammatory processes that underlie the development of obesity-related pathologies. This review provides a comprehensive summary of our current knowledge on the role of MIF in obesity, its production by adipose tissue, and its involvement in the development of insulin resistance, type 2 diabetes, and NAFLD. We discuss the main findings from recent clinical studies in obese subjects and weight-loss intervention studies as well as results from clinical studies in patients with insulin resistance and type 2 diabetes. Furthermore, we summarize findings from experimental disease models studying the contribution of MIF in obesity and insulin resistance, type 2 diabetes, and hepatic lipid accumulation and fibrosis. Although many of the findings support a pro-inflammatory role of MIF in disease development, recent reports also provide indications that MIF may exert protective effects under certain conditions.
Subject
ELSS - Earth, Life and Social Sciences
Life
Healthy Living
Biomedical Innovation
MIF
Adipose tissue
Insulin resistance
Non-alcoholic fatty liver disease
Obesity
Type 2 diabetes
Macrophage migration inhibition factor
Comorbidity
Correlation analysis
Fatty liver
Glucose homeostasis
Human
Lipid storage
Liver fibrosis
Non insulin dependent diabetes mellitus
Nonalcoholic fatty liver
Nonhuman
Review
Weight reduction
MHR - Metabolic Health Research
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http://resolver.tudelft.nl/uuid:6f454b2a-5c75-47e0-bca0-3fff0d0a2790
DOI
https://doi.org/10.3389/fimmu.2015.00308
TNO identifier
526305
Source
Frontiers in Immunology, 6 (6)
Document type
article