| First Author | Nwadozi E | Year | 2019 |
| Journal | Angiogenesis | Volume | 22 |
| Issue | 1 | Pages | 103-115 |
| PubMed ID | 30121753 | Mgi Jnum | J:317334 |
| Mgi Id | MGI:6850901 | Doi | 10.1007/s10456-018-9641-6 |
| Citation | Nwadozi E, et al. (2019) Leptin is a physiological regulator of skeletal muscle angiogenesis and is locally produced by PDGFRalpha and PDGFRbeta expressing perivascular cells. Angiogenesis 22(1):103-115 |
| abstractText | Skeletal muscle capillarity is characteristically reduced in mature leptin receptor-deficient (Lepr(db)) mice, which has been attributed to the capillary loss that occurs secondary to metabolic dysfunction. Despite wide recognition of leptin as a pro-angiogenic molecule, the contribution of this adipokine has largely been overlooked in peripheral tissues. Moreover, prior documentation of leptin production within skeletal muscle indicates a potential paracrine role in maintaining local tissue homeostasis. Thus, we hypothesized that leptin is a physiological local paracrine regulator of skeletal muscle angiogenesis and that its production may be modulated by nutrient availability. Lepr(db) mice exhibited impaired angiogenesis during normal developmental maturation of skeletal myocytes, corresponding with an inability to increase vascular endothelial growth factor-A (VEGFA) mRNA and protein levels between 4 and 13 weeks. In cultured murine and human skeletal myocytes, recombinant leptin increased VEGFA mRNA levels. Leptin mRNA was detectable in skeletal muscle, increasing with prolonged high-fat feeding in mice, and with adiposity in human subjects. Platelet-derived growth factor receptor (PDGFR)alpha- and PDGFRbeta- expressing perivascular cell populations were identified as leptin producing within skeletal muscle of mice and humans. Furthermore, in response to 2 weeks of high-fat feeding, PDGFRbeta+ but not PDGFRalpha+ cells increased leptin production. We conclude that leptin is a physiological regulator of the capillary network in skeletal muscle and stimulates VEGFA production by skeletal myocytes. PDGFRbeta expressing perivascular cells exhibit the capacity to act as local "nutrient-sensors" that couple nutrient status to leptin production in skeletal muscle. |
