Cross-talk between adipokines and myokines in fat browning
Rodríguez A (1,2,3), Becerril S (1,2,3), Ezquerro S (1), Méndez-Giménez L (1,2,3), Frühbeck G (1,2,3,4).
(1) Metabolic Research Laboratory, Clínica Universidad de Navarra, Pamplona, Spain.
(2) CIBER Fisiopatología de la Obesidad y Nutrición (CIBEROBN), Instituto de Salud Carlos III, Madrid, Spain.
(3) Obesity & Adipobiology Group, Instituto de Investigación Sanitario de Navarra (IdiSNA), Pamplona, Spain.
(4) Department of Endocrinology & Nutrition, Clínica Universidad de Navarra, Pamplona, Spain.
Skeletal muscle is the largest organ determining whole-body insulin sensitivity and metabolic homeostasis. 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, 6, 7 and 15, myonectin, follistatin-like 1 or LIF.
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 cross-talk 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 (FGF-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 cross-talk between skeletal muscle and adipose tissue in order to regulate thermogenesis and energy expenditure.
CITATION Acta Physiol (Oxf). 2016 Apr 4. doi: 10.1111/apha.12686