Connecting Myokines and Metabolism

Abstract

Skeletal muscle is the largest organ of the body in non-obese individuals and is now considered to be an endocrine organ. Hormones (myokines) secreted by skeletal muscle mediate communications between muscle and liver, adipose tissue, brain, and other organs. Myokines affect muscle mass and myofiber switching, and have profound effects on glucose and lipid metabolism and inflammation, thus contributing to energy homeostasis and the pathogenesis of obesity, diabetes, and other diseases. In this review, we summarize recent findings on the biology of myokines and provide an assessment of their potential as therapeutic targets.

Keywords: Diabetes; Exercise; Metabolism; Muscle, skeletal; Myokine; Obesity.

Fig. 1. Positive and negative regulators of skeletal muscle mass. Myokines are produced and secreted by skeletal muscle and act via autocrine, paracrine and endocrine mechanisms to regulate skeletal muscle mass and metabolism. IGF-1, insulin-like growth factor 1; IL, interleukin; BDNF, brain-derived neurotrophic factor; FGF-21, fibroblast growth factor 21; LIF, leukemia inhibitory factor.

Fig. 2. Magnetic resonance imaging scans comparing the distributions of abdominal and thigh fat and muscle in (A) lean, (B, C) overweight, and (D) obese women. As in (B) and (D), increased visceral adiposity and sarcopenia are associated with diabetes mellitus (DM), hypertension (HT), dyslipidemia, and cardiovascular disease (CVD). BMI, body mass index.

Fig. 3. Myostatin and insulin-like growth factor 1 (IGF-1) signaling pathways in skeletal muscle. Myostatin and other transforming growth factor β family members signal via activin receptor II (ActRII), Smad2, and Smad3, which blocks muscle differentiation and leads to muscle atrophy. Inhibition of regulatory-associated protein of mammalian target of rapamycin (mTOR) and mTOR complex 1 (mTORC1) has an additive effect on myostatin signaling. The IGF-1/Akt pathway induces skeletal muscle hypertrophy. ALK, activin receptor-like kinase; GDF11, growth differentiation factor 11; IGFR, IGF receptor; FoxO1, forkhead box protein O1; PI3K, phosphatidylinositol 3-kinase; GSK-3β, glycogen synthase kinase 3β; MuRF, muscle ring finger; p70S6K, p70 S6 kinase.