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ghrelin 和 LEAP-2 在能量平衡中的作用受热中性、高脂肪饮食和衰老的调节。

The effects of ghrelin and LEAP-2 in energy homeostasis are modulated by thermoneutrality, high-fat diet and aging.

机构信息

Departamento de Fisioloxía and Centro de Investigación en Medicina Molecular (CIMUS), Universidade de Santiago de Compostela, Instituto de Investigaciones Sanitarias de Santiago de Compostela (IDIS), 15782, Santiago de Compostela, Spain.

CIBER Fisiopatología de la Obesidad y Nutrición (CIBERobn), 28029, Madrid, Spain.

出版信息

J Endocrinol Invest. 2024 Aug;47(8):2061-2074. doi: 10.1007/s40618-024-02307-4. Epub 2024 Feb 9.

DOI:10.1007/s40618-024-02307-4
PMID:38337094
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11266414/
Abstract

PURPOSE

Liver-expressed antimicrobial peptide 2 (LEAP-2) has been recently identified as the endogenous non-competitive allosteric antagonist of the growth hormone secretagogue receptor 1a (GHSR1a). In rodents, LEAP-2 blunts ghrelin-induced feeding and its plasma levels are modulated in response to nutritional status, being decreased upon fasting and increased in high-fat diet (HFD) fed mice. Clinical data support the regulation of circulating LEAP-2 by nutrient availability in humans. In this work, our primary objective was to examine the chronic effects of ghrelin and LEAP-2 administration on food intake, adiposity, and energy expenditure in young mice subjected to standard and HFD at both room temperature and at thermoneutrality. Furthermore, we aimed to assess the impact of these two hormones on aging mice.

RESULTS

Our results indicate that LEAP-2 produces a significant decrease of body weight and adiposity, an increase in energy expenditure, and activation of the thermogenic program in white and brown adipose tissue depots. However, this effect is not maintained under HFD or under thermoneutral conditions and is only partially observed in aging mice.

CONCLUSION

In summary our studies describe the central effects of LEAP-2 within distinct experimental contexts, and contribute to the comprehension of LEAP-2's role in energy metabolism.

摘要

目的

肝表达抗菌肽 2（LEAP-2）最近被鉴定为生长激素促分泌素受体 1a（GHSR1a）的内源性非竞争性变构拮抗剂。在啮齿动物中，LEAP-2 减弱了 ghrelin 诱导的进食，其血浆水平根据营养状况进行调节，禁食时降低，高脂肪饮食（HFD）喂养的小鼠中增加。临床数据支持人类循环 LEAP-2 受营养可用性的调节。在这项工作中，我们的主要目的是检查 ghrelin 和 LEAP-2 给药对标准和 HFD 喂养的年轻小鼠在室温下和热中性条件下的食物摄入、肥胖和能量消耗的慢性影响。此外，我们旨在评估这两种激素对衰老小鼠的影响。

结果

我们的结果表明，LEAP-2 显著降低体重和肥胖，增加能量消耗，并激活白色和棕色脂肪组织库中的产热程序。然而，这种效应在 HFD 或热中性条件下不能维持，并且仅在衰老小鼠中部分观察到。

结论

总之，我们的研究描述了 LEAP-2 在不同实验背景下的中枢作用，并有助于理解 LEAP-2 在能量代谢中的作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bc91/11266414/79ec43782aad/40618_2024_2307_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bc91/11266414/828298adcc34/40618_2024_2307_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bc91/11266414/ee7e32b6d02c/40618_2024_2307_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bc91/11266414/0c7bf53df443/40618_2024_2307_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bc91/11266414/f7fd409f5ca2/40618_2024_2307_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bc91/11266414/79ec43782aad/40618_2024_2307_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bc91/11266414/828298adcc34/40618_2024_2307_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bc91/11266414/ee7e32b6d02c/40618_2024_2307_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bc91/11266414/0c7bf53df443/40618_2024_2307_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bc91/11266414/f7fd409f5ca2/40618_2024_2307_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bc91/11266414/79ec43782aad/40618_2024_2307_Fig5_HTML.jpg

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