Insights into the role of macrophage migration inhibitory factor in obesity and insulin resistance.
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.
Insitiute of Molecular Medicine, School of Medicine, Trinity Centre for Health Sciences, St James Hospital, Dublin 8, Republic of Ireland.
Orla M
OM
Finucane
Clare M
CM
Reynolds
Fiona C
FC
McGillicuddy
Helen M
HM
Roche
D000273:Adipose Tissue / Q000276:immunology / Q000378:metabolism*; D002633:Chemotaxis; D059305:Diet, High-Fat / Q000009:adverse effects; D006801:Humans; D007249:Inflammation / Q000209:etiology / Q000276:immunology / Q000378:metabolism*; D007333:Insulin Resistance / Q000276:immunology*; D008263:Macrophage Migration-Inhibitory Factors / Q000378:metabolism*; D008264:Macrophages / Q000378:metabolism*; D009765:Obesity / Q000150:complications / Q000276:immunology / Q000378:metabolism*
D008263:Macrophage Migration-Inhibitory Factors