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

Abstract

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.

Resveratrol exerts anti-obesity effects in high-fat diet obese mice and displays differential dosage effects on cytotoxicity, differentiation, and lipolysis in 3T3-L1 cells

“…While 3T3-L1 cells were grown to confluence, cells were stimulated by differentiation medium consisting of 10% FBS, 0.5 mM 3-isobutyl-1-methylxanthine (IBMX), and 1 μM dexamethasone (DEX) and incubation for 8 days and then insulin (10 μg/mL) was added at the last 2 days, at which time infiltration of macrophages in adipose tissue, releasing numerous pro-inflammatory cytokines, such as tumor necrosis factor alpha (TNF-α), and interleukins, which consequently contributed to progressive exacerbation of insulin resistance and eventually, metabolic syndrome [12,13].…”

Monocyte chemoattractant protein 1 and macrophage migration inhibitory factor in children with type 1 diabetes

“…MIF is released from cells through a nonconventional protein-secretion pathway [8]. It is involved in immunological and inflammatory diseases [9,10] such as chronic diseases including bowel disease [11], obesity [12,13], and diabetes [14]. More recently, MIF was proposed as a diagnostic biomarker for autoimmune diseases such as diabetes [15].…”

Association of Macrophage Migration Inhibitory Factor Polymorphisms with Gestational Diabetes Mellitus in Han Chinese Women

“…The most critical functions of MIF encompass the regulation of macrophage and lymphocyte activation in innate and adaptive immune responses, respectively [13], and its gene has been identified as a novel candidate gene for T2D. Several lines of evidence support a relationship between MIF and T2D [14,15]. Studies have demonstrated that MIF may play a key role in regulating glucose by altering insulin secretion [13].…”