The LEAP2 Response to Cancer-Related Anorexia-Cachexia Syndrome in Male Mice and Patients.

Autor:	Varshney S; Center for Hypothalamic Research, Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, TX, 75390, USA., Shankar K; Center for Hypothalamic Research, Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, TX, 75390, USA., Kerr HL; Geriatric Research, Education and Clinical Center, Veterans Affairs Puget Sound Health Care System, Seattle, WA 98108, USA.; Gerontology and Geriatric Medicine, Department of Medicine, University of Washington, Seattle, WA 98195, USA., Anderson LJ; Geriatric Research, Education and Clinical Center, Veterans Affairs Puget Sound Health Care System, Seattle, WA 98108, USA.; Gerontology and Geriatric Medicine, Department of Medicine, University of Washington, Seattle, WA 98195, USA., Gupta D; Center for Hypothalamic Research, Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, TX, 75390, USA., Metzger NP; Center for Hypothalamic Research, Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, TX, 75390, USA., Singh O; Center for Hypothalamic Research, Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, TX, 75390, USA., Ogden SB; Center for Hypothalamic Research, Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, TX, 75390, USA., Paul S; Center for Hypothalamic Research, Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, TX, 75390, USA., Piñon F; Center for Hypothalamic Research, Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, TX, 75390, USA., Osborne-Lawrence S; Center for Hypothalamic Research, Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, TX, 75390, USA., Richard CP; Center for Hypothalamic Research, Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, TX, 75390, USA., Lawrence C; Center for Hypothalamic Research, Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, TX, 75390, USA., Mani BK; Center for Hypothalamic Research, Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, TX, 75390, USA., Garcia JM; Geriatric Research, Education and Clinical Center, Veterans Affairs Puget Sound Health Care System, Seattle, WA 98108, USA.; Gerontology and Geriatric Medicine, Department of Medicine, University of Washington, Seattle, WA 98195, USA., Zigman JM; Center for Hypothalamic Research, Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, TX, 75390, USA.; Division of Endocrinology & Metabolism, Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, TX, 75390, USA.; Department of Psychiatry, University of Texas Southwestern Medical Center, Dallas, TX, 75390, USA.
Jazyk:	angličtina
Zdroj:	Endocrinology [Endocrinology] 2024 Sep 26; Vol. 165 (11).
DOI:	10.1210/endocr/bqae132
Abstrakt:	The hormone ghrelin serves a protective role in cancer-related anorexia-cachexia syndrome (CACS)-a condition in which plasma levels of ghrelin rise, its administration lessens CACS severity, and experimentally reduced signaling by its receptor (GHSR) worsens fat loss and anorexia and accelerates death. Yet, actions for the related hormone liver-expressed antimicrobial peptide-2 (LEAP2), which is an endogenous GHSR antagonist, are unexplored in CACS. Here, we found that plasma LEAP2 and LEAP2/ghrelin ratio were lower in Lewis lung carcinoma (LLC) and RM-9 prostate cancer CACS mouse models. Ghrelin deletion exaggerated losses of tumor-free body weight and fat mass, reduced food intake, reduced soleus muscle weight, and/or lowered grip strength in LLC or RM-9 tumor-bearing mice. LEAP2 deletion lessened reductions in tumor-free body weight and fat mass and increased food intake in LLC or RM-9 tumor-bearing mice. In a 55-subject cohort of patients with CACS or weight-stable cancer, the plasma LEAP2/total ghrelin ratio was negatively correlated with 6-month weight change preceding blood collection. These data demonstrate that ghrelin deletion exacerbates CACS in the LLC and RM-9 tumor-bearing mouse models while contrastingly, LEAP2 deletion reduces measures of CACS in these tumor-bearing mouse models. Further, they suggest that lower plasma LEAP2/ghrelin ratio protects against worsened CACS. (© The Author(s) 2024. Published by Oxford University Press on behalf of the Endocrine Society. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com. See the journal About page for additional terms.)
Databáze:	MEDLINE
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