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

Clinical Signs ◽

Inhibitory Factor ◽

Macrophage Migration ◽

Deficient Mice

Macrophage migration inhibitory factor (MIF) is implicated in the pathogenesis of several inflammationrelated diseases, including obesity and type 2 diabetes (T2D). However, MIF deficiency itself promotes obesity and glucose intolerance in mice. Here we show that the introduction of a high-fat diet (HFD) further aggravates the parameters of obesity-associated T2D: weight gain and glucose intolerance. Furthermore, in contrast to MIF-KO mice on standard chow, HFD-fed MIF-KO mice develop insulin resistance. Although the clinical signs of obesity-associated T2D are upgraded, inflammation in MIF-deficient mice on HFD is significantly lower. These results imply that MIF possesses a complex role in glucose metabolism and the development of obesity-related T2D. However, the downregulation of inflammation upon MIF inhibition could be a useful tool in short-term T2D therapy for preventing pancreatic islet deterioration.

Oxidative stress-mediated (sex-specific) loss of protection against type-2 diabetes by macrophage migration inhibitory factor (MIF)−173G/C polymorphism

Clinica Chimica Acta ◽

10.1016/j.cca.2014.07.037 ◽

2015 ◽

Vol 438 ◽

pp. 1-6 ◽

Cited By ~ 14

Author(s):

Neslihan Coban ◽

Altan Onat ◽

Ozlem Yildirim ◽

Gunay Can ◽

Nihan Erginel-Unaltuna

Keyword(s):

Oxidative Stress ◽

Type 2 Diabetes ◽

Inhibitory Factor ◽

Macrophage Migration ◽

Specific Loss

Macrophage migration inhibitory factor is a novel structure component of centrioles and a novel transcriptional factor

10.21203/rs.3.rs-126373/v1 ◽

2020 ◽

Author(s):

Lu Zhang ◽

Hongbing Zhang ◽

Xiaoyan Li ◽

Ewud Agborbesong ◽

Xiaogang Li

Keyword(s):

Nuclear Translocation ◽

Transcriptional Factor ◽

Inhibitory Factor ◽

Human Diseases ◽

Macrophage Migration ◽

Novel Structure

Abstract Ciliopathies are a group of human diseases that affect the cellular cilia or the cilia anchoring structures, the bosal bodies, or ciliary function. Macrophage migration inhibitory factor (MIF) as an important inflammatory cytokine plays a prominent role in the pathogenesis of various human diseases. However, the role of MIF in ciliopathies remains elusive. In this study, we show that MIF is a structure protein of basal bodies, which forms a ring-like structure at proximal end of centrioles to regulate cilia assembly and elongation. Importantly, we identify MIF as a novel transcriptional factor, which regulates the expression of ciliary genes and genes associated with different signaling pathways. The phosphatidylinositol-5-phosphate 4-kinase type 2 alpha (PIP4K2a) mediated MIF phosphorylation at S91 is necessary for the nuclear translocation of MIF, a process that is regulated by 14-3-3ζ. This study suggests that MIF is a key player in cilia biogenesis and transcriptional regulation in homeostasis.

Insights into the role of macrophage migration inhibitory factor in obesity and insulin resistance

Proceedings of The Nutrition Society ◽

10.1017/s0029665112000730 ◽

2012 ◽

Vol 71 (4) ◽

pp. 622-633 ◽

Cited By ~ 41

Author(s):

Orla M. Finucane ◽

Clare M. Reynolds ◽

Fiona C. McGillicuddy ◽

Helen M. Roche

Keyword(s):

Insulin Resistance ◽

Adipose Tissue ◽

Metabolic Diseases ◽

Inhibitory Factor ◽

Low Grade ◽

Macrophage Migration ◽

Pharmacological Agents

High-fat diet (HFD)-induced obesity has emerged as a state of chronic low-grade inflammation characterised by a progressive infiltration of immune cells, particularly macrophages, into obese adipose tissue. Adipose tissue macrophages (ATM) present immense plasticity. In early obesity, M2 anti-inflammatory macrophages acquire an M1 pro-inflammatory phenotype. Pro-inflammatory cytokines including TNF-α, IL-6 and IL-1β produced by M1 ATM exacerbate local inflammation promoting insulin resistance (IR), which consequently, can lead to type-2 diabetes mellitus (T2DM). However, the triggers responsible for ATM recruitment and activation are not fully understood. Adipose tissue-derived chemokines are significant players in driving ATM recruitment during obesity. Macrophage migration inhibitory factor (MIF), a chemokine-like inflammatory regulator, is enhanced during obesity and is directly associated with the degree of peripheral IR. This review focuses on the functional role of macrophages in obesity-induced IR and highlights the importance of the unique inflammatory cytokine MIF in propagating obesity-induced inflammation and IR. Given MIF chemotactic properties, MIF may be a primary candidate promoting ATM recruitment during obesity. Manipulating MIF inflammatory activities in obesity, using pharmacological agents or functional foods, may be therapeutically beneficial for the treatment and prevention of obesity-related metabolic diseases.