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在小鼠中,整个成年早期脉冲式 GH 分泌的下降因饮食引起的体重增加而加剧。

The decline in pulsatile GH secretion throughout early adulthood in mice is exacerbated by dietary-induced weight gain.

机构信息

School of Biomedical Sciences, University of Queensland, St. Lucia, Queensland 4072, Australia.

出版信息

Endocrinology. 2012 Sep;153(9):4380-8. doi: 10.1210/en.2012-1178. Epub 2012 Jul 16.

DOI:10.1210/en.2012-1178
PMID:22802464
Abstract

The transition between puberty and adulthood is accompanied by a slowing in linear growth. Although GH is a key factor that drives somatic development into adulthood, early adulthood coincides with a reduction in circulating levels of GH. To this extent, a pathological decline in postpubertal GH secretion is detrimental to attainment of peak lean muscle mass and bone mass and promotes adiposity and increases susceptibility to the development of obesity in adulthood. Here we characterized pulsatile GH secretion in C57BL/6J mice at 12 and 16 wk of age. Deconvolution analysis of these measures reveals a reduction in pulsatile GH secretion between 12 and 16 wk of age. Dietary intervention with high-fat feeding at 8 wk of age results in a significant increase in adiposity, the development of glucose intolerance, and hyperinsulinemia. We show the exacerbation of the age-associated decline in pulsatile GH secretion in high-fat-fed mice after 4 wk of dietary intervention (at 12 wk of age), and a further suppression of pulsatile GH secretion by 8 wk of dietary intervention (at 16 wk of age). Suppressed pulsatile secretion of GH did not coincide with an elevation in circulating free fatty acids. Rather, we observed increased hepatic triglyceride content and an eventual decrease in circulating levels of IGF-I. Given the established role of GH in maintaining healthy aging, we anticipate that an advancing of the age-associated decline in pulsatile GH secretion as a consequence of dietary-induced weight gain may have long-term ramifications on adult health.

摘要

青春期到成年的过渡伴随着线性生长的减缓。虽然 GH 是驱动躯体发育到成年的关键因素,但成年早期恰逢循环 GH 水平的降低。在这种程度上,青春期后 GH 分泌的病理性下降不利于获得最大瘦肌肉量和骨量,并促进肥胖和增加成年后肥胖症发展的易感性。在这里,我们描述了 12 周和 16 周龄 C57BL/6J 小鼠的脉冲 GH 分泌。对这些测量值的去卷积分析表明,12 至 16 周龄之间脉冲 GH 分泌减少。8 周龄时高脂肪饮食的饮食干预导致肥胖、葡萄糖不耐受和高胰岛素血症的发展。我们显示了高脂肪喂养小鼠在 4 周饮食干预后(在 12 周龄时),与年龄相关的脉冲 GH 分泌下降加剧,并且在 8 周饮食干预时(在 16 周龄时)进一步抑制了脉冲 GH 分泌。GH 的脉冲分泌抑制与循环游离脂肪酸的升高不一致。相反,我们观察到肝甘油三酯含量增加,最终循环 IGF-I 水平降低。鉴于 GH 在维持健康衰老中的既定作用,我们预计由于饮食诱导的体重增加而导致与年龄相关的脉冲 GH 分泌下降的提前可能对成年健康产生长期影响。

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