Crosstalk between adipokines and myokines in fat browning

Abstract

Skeletal muscle is the largest organ determining whole-body insulin sensitivity and metabolic homoeostasis. Adaptive changes of skeletal muscle in response to physical activity include adjustments in the production and secretion of muscle-derived bioactive factors, known as myokines, such as myostatin, IL-4, IL-6, IL-7 and IL-15, myonectin, follistatin-like 1 or leukaemia inhibitory factor. These myokines not only act locally in the muscle in an autocrine/paracrine manner, but also are released to the bloodstream as endocrine factors to regulate physiological processes in other tissues. Irisin, derived from the cleavage of FNDC5 protein, constitutes a myokine that induces myogenesis and fat browning (switch of white adipocytes to brown fat-like cells) together with a concomitant increase in energy expenditure. Besides being a target for irisin actions, the adipose tissue also constitutes a production site of FNDC5. Interestingly, irisin secretion from subcutaneous and visceral fat depots is decreased by long-term exercise training and fasting, suggesting a discordant regulation of FNDC5/irisin in skeletal muscle and adipose tissue. Accordingly, our group has recently reported that the adipokine leptin differentially regulates FNDC5/irisin expression in skeletal muscle and fat, confirming the crosstalk between both tissues. Moreover, irisin secretion and function are regulated by other myokines, such as follistatin or myostatin, as well as by other adipokines, including fibroblast growth factor 21 and leptin. Taken together, myokines have emerged as novel molecular mediators of fat browning and their activity can be modulated by adipokines, confirming the crosstalk between skeletal muscle and adipose tissue to regulate thermogenesis and energy expenditure.

Is Brown Adipose Tissue-Mediated Adaptive Thermogenesis the Missing Component of the Constrained Total Energy Expenditure Model?

“…Interestingly, both sympathetic and non-sympathetic pathways (e.g. irisin, BAIBA, IL-6, FGF21, cardiac natriuretic peptides, myostatin, meteorin-like, lactate, and leptin) are sensitive to exercise [6,7]. It was therefore suggested that exercise could be an activator of BAT [6,7,8,9,10,11,12,13].…”

“…It was therefore suggested that exercise could be an activator of BAT [6,7,8,9,10,11,12,13]. Several studies reported that exercise induces beige activation and recruitment in murine models [6,10,11]. In contrast, although available results are not yet conclusive, murine classical BAT seems to be inhibited in response to long-term exercise [10].…”

“…The exercise-induced sympathetic nervous system, myokines and adipokines responses related to BAT physiology observed in animals are also present in humans [6,13]; it is therefore biologically plausible that exercise also stimulates human's BAT activity [7]. Dinas et al [8] reported, in a cross-sectional study, a positive association between PA and BAT activity in cancer patients who were unfit and inactive.…”

“…In summary, there is epidemiological evidence [8] and biological base [6,7] to believe that human BAT activation takes place in response to exercise at low training status or PA level. However, based also on observational data [9,10] and animals studies [11], it is plausible that human BAT activity is reduced in response to exercise in fit or very active individuals, which might be explained by a decrease in classic brown adipocytes activity not completely compensated by an increase in beige adipocytes activity [11].…”

Modulation of transforming growth factor-β/follistatin signaling and white adipose browning: therapeutic implications for obesity related disorders

“…Both brown and beige adipocytes have the potential to be metabolically beneficial due to their unique ability to burn excess stored energy and alter the balance between energy intake and energy expenditure. As several excellent reviews have highlighted the importance of white adipose browning in regulating key metabolic aspects that has the potential to combat obesity and related diseases [11], [17], [18], [19], [20], we will briefly examine the emerging role of two key members of the transforming growth factor-β (TGF-β) superfamily, namely myostatin (Mst) and follistatin (Fst).…”