Exercise and Adipose Tissue Macrophages: New Frontiers in Obesity Research?

Abstract

Obesity is a major public health problem in the twenty-first century. Mutations in genes that regulate substrate metabolism, subsequent dysfunction in their protein products, and other factors, such as increased adipose tissue inflammation, are some underlying etiologies of this disease. Increased inflammation in the adipose tissue microenvironment is partly mediated by the presence of cells from the innate and adaptive immune system. A subset of the innate immune population in adipose tissue include macrophages, termed adipose tissue macrophages (ATMs), which are central players in adipose tissue inflammation. Being extremely plastic, their responses to diverse molecular signals in the microenvironment dictate their identity and functional properties, where they become either pro-inflammatory (M1) or anti-inflammatory (M2). Endurance exercise training exerts global anti-inflammatory responses in multiple organs, including skeletal muscle, liver, and adipose tissue. The purpose of this review is to discuss the different mechanisms that drive ATM-mediated inflammation in obesity and present current evidence of how exercise training, specifically endurance exercise training, modulates the polarization of ATMs from an M1 to an M2 anti-inflammatory phenotype.

Effects of long-term exercise on plasma adipokine levels and inflammation-related gene expression in subcutaneous adipose tissue in sedentary dysglycaemic, overweight men and sedentary normoglycaemic men of healthy weight

“…Our pathway analysis and assessment of high-specificity transcript markers of scWAT cell populations [45] indicated less immune cell infiltration, especially of leucocytes and macrophages, after 12 weeks of the exercise intervention in men with dysglycaemia. This is in line with previous studies suggesting that exercise may reduce immune cell infiltration in the stromal vascular fraction of adipose tissue and positively influence adipose tissue macrophage phenotypes [17,18,23]. However, these studies focused on visceral adipose tissue [17,18,23], not scWAT.…”

“…Mediators of these effects may involve extensive adaptations in adipokine expression [4,16]. Numerous studies have focused on the effect of different types of exercise on circulating levels of adipose tissuederived factors [3,[17][18][19]. However, the main body of literature on adipokines and exercise is limited to plasma analyses of one or a few targets and the effects of acute exercise [3,[19][20][21][22] confounded by weight loss [23] or focused on only visceral adipose tissue [3,17,18].…”

“…Numerous studies have focused on the effect of different types of exercise on circulating levels of adipose tissuederived factors [3,[17][18][19]. However, the main body of literature on adipokines and exercise is limited to plasma analyses of one or a few targets and the effects of acute exercise [3,[19][20][21][22] confounded by weight loss [23] or focused on only visceral adipose tissue [3,17,18]. Few studies have addressed long-term exercise-induced alterations in scWAT expression of such factors [22,24], and these studies have only been performed in insulin-sensitive women [22,24].…”

Macrophage functions in lean and obese adipose tissue

“…Endurance exercise exerts global anti-inflammatory effects including skeletal muscle and adipose tissue and modulates polarization of ATM towards a M2 phenotype 229 . The anti-inflammatory effects of exercise on systemic inflammation and ATM infiltration have been reviewed elsewhere 230 .…”

Itaconate itinerary changed: Now it’s a potential metabolite to switch-off inflammation!

“…Current evidence also emphasizes on how exercise training, more precisely the endurance exercise training, could mediate the polarization state of tissue macrophages from an M1 to an M2 anti-inflammatory phenotype. 10 Future studies should investigate whether these health benefits of exercise could occur through the expanding molecular actions of itaconate and its effector functions.…”