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 β-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 β-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 β-3 adrenergic receptors, iWAT of GHR-391 mice did not beige in response to administration of the β-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.

中文翻译：

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在体内诱导米色脂肪需要生长激素激活的STAT5。

目的

生长激素（GH）的抗肥胖作用使我们研究了GH信号是否能够调节白色脂肪组织（WAT）的米色/棕褐色脂肪发育。

方法

我们在GHR-391小鼠中研究了WAT，这些小鼠被设计为无法响应GH激活STAT5，在GHR脂肪特异性缺失的小鼠中，在GHR-/-小鼠和bGH转基因小鼠中研究了WAT。QPCR，免疫印迹和免疫组织化学被用来表征WAT。还研究了CL-316,243对β-3肾上腺素能激活的体内作用以及FGF21输注的体内作用。

结果

GHR-391小鼠的体表温度比WT低，β-氧化和包括Ucp1在内的beig转录本均缺乏。氧化磷酸化复合亚基蛋白在GHR-391腹股沟白脂肪组织（iWAT）中显着降低，但在bGH iWAT中升高，在米色/棕色标记中也是如此。由于缺乏β-3肾上腺素能受体，与WT小鼠相比，GHR-391小鼠的iWAT对β-3特异性激动剂CL-316,243的给药没有米色。GHR-391小鼠缺乏FGF21，但与WT不同，输注纯化的蛋白质对加糖程度没有影响。最终，GHR的脂肪特异性删除复制了开始的相关转录本的丢失。

结论

除了促进脂肪分解外，我们的研究还表明GH能够通过激活STAT5和诱导Adrb3来促进米色脂肪组织的形成。这会使WAT对肾上腺素输入敏感，并且可能有助于GH的抗肥胖作用。