The effect of type 2 diabetes mellitus and obesity on muscle progenitor cell function

Abstract

In addition to its primary function to provide movement and maintain posture, the skeletal muscle plays important roles in energy and glucose metabolism. In healthy humans, skeletal muscle is the major site for postprandial glucose uptake and impairment of this process contributes to the pathogenesis of type 2 diabetes mellitus (T2DM). A key component to the maintenance of skeletal muscle integrity and plasticity is the presence of muscle progenitor cells, including satellite cells, fibroadipogenic progenitors, and some interstitial progenitor cells associated with vessels (myo-endothelial cells, pericytes, and mesoangioblasts). In this review, we aim to discuss the emerging concepts related to these progenitor cells, focusing on the identification and characterization of distinct progenitor cell populations, and the impact of obesity and T2DM on these cells. The recent advances in stem cell therapies by targeting diabetic and obese muscle are also discussed.

Keywords: Obesity; Satellite cell; T2DM; muscle progenitor cell.

Fig. 1

Illustration of the mechanisms for the adipogenic fate determination of FAP in skeletal muscle. Eosinophils infiltrate early during muscle injury, secrete IL-4/IL-13, and subsequently stimulate STAT6 to promote FAP proliferation, while inhibiting its adipogenic differentiation. Activation of Hh signaling also prevents the conversion of FAP to adipocyte. Meanwhile, the direct interaction of FAP with intact myofiber or myo-endothelial cell can prevent its differentiation into adipocyte at resting state. Upon muscle damage, FAPs proliferate dramatically to help debris clearance and induce myogenic cell differentiation. FAP, fibroadipogenic progenitor; STAT6, signal transducer and activator of transcription 6; Hh, hedgehog; TIMP3, tissue inhibitor of metalloproteinases 3; MMP14, matrix metallopeptidase 14