| First Author | Nelson CN | Year | 2018 |
| Journal | Growth Horm IGF Res | Volume | 42-43 |
| Pages | 40-51 | PubMed ID | 30193158 |
| Mgi Jnum | J:310282 | Mgi Id | MGI:6761651 |
| Doi | 10.1016/j.ghir.2018.08.004 | Citation | Nelson CN, et al. (2018) Growth hormone activated STAT5 is required for induction of beige fat in vivo. Growth Horm IGF Res 42-43:40-51 |
| abstractText | OBJECTIVE: The anti-obesity actions of growth hormone (GH) led us to investigate if GH signaling is able to regulate beige/brite fat development of white adipose tissue (WAT). METHODS: We studied WAT in GHR-391 mice engineered to be unable to activate STAT5 in response to GH, in mice with adipose specific deletion of GHR, in GHR-/- mice and in bGH transgenic mice. QPCR, immunoblots and immunohistochemistry were used to characterize WAT. The in vivo effects of beta-3 adrenergic activation with CL-316,243 and that of FGF21 infusion were also studied. RESULTS: GHR-391 mice had lower surface temperature than WT, with deficiency in beta-oxidation and beiging transcripts including Ucp1. Oxidative phosphorylation complex subunit proteins were decreased dramatically in GHR-391 inguinal white adipose tissue (iWAT), but increased in bGH iWAT, as were proteins for beige/brown markers. In accord with its lack of beta-3 adrenergic receptors, iWAT of GHR-391 mice did not beige in response to administration of the beta-3 specific agonist CL-316,243 in contrast to WT mice. GHR-391 mice are deficient in FGF21, but unlike WT, infusion of the purified protein was without effect on extent of beiging. Finally, fat-specific deletion of the GHR replicated the loss of beiging associated transcripts. CONCLUSION: In addition to promoting lipolysis, our study suggests that GH is able to promote formation of beige adipose tissue through activation of STAT5 and induction of Adrb3. This sensitizes WAT to adrenergic input, and may contribute to the anti-obesity actions of GH. |
