生长激素释放激素缺乏症可延长寿命,并在中后期高脂肪喂养期间提高代谢恢复能力。

IF 7.8 1区 医学 Q1 Biochemistry, Genetics and Molecular Biology
Aging Cell Pub Date : 2024-06-12 DOI:10.1111/acel.14238
Joseph Adkins-Jablonsky, Alexander Tate Lasher, Amit Patki, Akash Nagarajan, Liou Y. Sun
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引用次数: 0

摘要

生长激素释放激素缺乏(GHRH-KO)小鼠以前的特点是体重较轻、体内脂肪积累过多、脂质代谢优于碳水化合物代谢、胰岛素敏感性提高以及寿命延长。这些小鼠寿命长且对胰岛素敏感,这与脂肪组织堆积会导致与肥胖相关的健康损害(如糖尿病)的观点相冲突,并表明 GH 信号传导可能是与肥胖相关的不良影响发展所必需的。这促使我们研究饮食诱导肥胖对这些长寿小鼠寿命的最终影响。为此,我们在 GHRH-KO 和野生型(WT)小鼠的生命中期和晚期开始进行高脂肪喂养。我们进行了广泛的寿命分析,并结合葡萄糖/胰岛素耐受性测试和间接热量测定法来评估高脂饮食压力对这些小鼠成年期的代谢影响。我们发现,在高脂饮食(HFD)条件下,GHRH-KO 小鼠的寿命比 WT 对照组要长。我们还发现,与 WT 小鼠相比,GHRH-KO 小鼠对胰岛素更敏感,新陈代谢的变化也更小,喂食高脂饮食的 GHRH-KO 小鼠的呼吸交换比和葡萄糖氧化率与喂食对照饮食的 GHRH-KO 小鼠相当,而喂食高脂饮食的 WT 小鼠的这些参数显著降低。我们的研究结果表明,GH 缺乏可防止饮食诱发的肥胖对后代的不利影响。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

Growth hormone-releasing hormone deficiency confers extended lifespan and metabolic resilience during high-fat feeding in mid and late life

Growth hormone-releasing hormone deficiency confers extended lifespan and metabolic resilience during high-fat feeding in mid and late life

Growth hormone-releasing hormone deficiency confers extended lifespan and metabolic resilience during high-fat feeding in mid and late life

Growth hormone-releasing hormone-deficient (GHRH-KO) mice have previously been characterized by lower body weight, disproportionately high body fat accumulation, preferential metabolism of lipids compared to carbohydrates, improved insulin sensitivity, and an extended lifespan. That these mice are long-lived and insulin-sensitive conflicts with the notion that adipose tissue accumulation drives the health detriments associated with obesity (i.e., diabetes), and indicates that GH signaling may be necessary for the development of adverse effects linked to obesity. This prompts investigation into the ultimate effect of diet-induced obesity on the lifespan of these long-lived mice. To this end, we initiated high-fat feeding in mid and late-life in GHRH-KO and wild-type (WT) mice. We carried out extensive lifespan analysis coupled with glucose/insulin tolerance testing and indirect calorimetry to gauge the metabolic effect of high-fat dietary stress through adulthood on these mice. We show that under high-fat diet (HFD) conditions, GHRH-KO mice display extended lifespans relative to WT controls. We also show that GHRH-KO mice are more insulin-sensitive and display less dramatic changes in their metabolism relative to WT mice, with GHRH-KO mice fed HFD displaying respiratory exchange ratios and glucose oxidation rates comparable to control-diet fed GHRH-KO mice, while WT mice fed HFD showed significant reductions in these parameters. Our results indicate that GH deficiency protects against the adverse effects of diet-induced obesity in later life.

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来源期刊
Aging Cell
Aging Cell 生物-老年医学
CiteScore
14.40
自引率
2.60%
发文量
212
审稿时长
8 weeks
期刊介绍: Aging Cell, an Open Access journal, delves into fundamental aspects of aging biology. It comprehensively explores geroscience, emphasizing research on the mechanisms underlying the aging process and the connections between aging and age-related diseases.
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