Suppr超能文献

LEAP2 对雄性小鼠和癌症相关性恶病质患者的反应。

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

机构信息

Center for Hypothalamic Research, Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, TX, 75390, USA.

Geriatric Research, Education and Clinical Center, Veterans Affairs Puget Sound Health Care System, Seattle, WA 98108, USA.

出版信息

Endocrinology. 2024 Sep 26;165(11). doi: 10.1210/endocr/bqae132.

Abstract

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.

摘要

激素 ghrelin 在癌症相关厌食-恶病质综合征(CACS)中发挥保护作用——在这种情况下,ghrelin 的血浆水平升高,其给药可减轻 CACS 的严重程度,而其受体(GHSR)的实验性信号减弱会导致脂肪丢失和厌食加重,并加速死亡。然而,相关激素肝表达抗菌肽-2(LEAP2)的作用在 CACS 中尚未得到探索,LEAP2 是一种内源性 GHSR 拮抗剂。在这里,我们发现Lewis 肺癌(LLC)和 RM-9 前列腺癌 CACS 小鼠模型中的血浆 LEAP2 和 LEAP2/ghrelin 比值较低。ghrelin 缺失会加剧无肿瘤体重和脂肪量的损失,减少食物摄入量,减少比目鱼肌重量和/或降低 LLC 或 RM-9 荷瘤小鼠的握力。LEAP2 缺失可减轻 LLC 或 RM-9 荷瘤小鼠无肿瘤体重和脂肪量的减少,并增加食物摄入量。在 55 例 CACS 或体重稳定癌症患者的队列中,血浆 LEAP2/总 ghrelin 比值与采血前 6 个月的体重变化呈负相关。这些数据表明,ghrelin 缺失会使 LLC 和 RM-9 荷瘤小鼠模型中的 CACS 恶化,而相反,LEAP2 缺失可减少这些荷瘤小鼠模型中的 CACS 指标。此外,它们表明较低的血浆 LEAP2/ghrelin 比值可预防 CACS 恶化。

相似文献

2
Ghrelin for the management of cachexia associated with cancer.胃饥饿素用于治疗与癌症相关的恶病质。
Cochrane Database Syst Rev. 2018 Feb 28;2(2):CD012229. doi: 10.1002/14651858.CD012229.pub2.
3
LEAP2: from feeding regulation to its implications in eating disorders.LEAP2:从进食调节到其在饮食失调中的影响
Physiol Behav. 2025 Oct 15;300:115013. doi: 10.1016/j.physbeh.2025.115013. Epub 2025 Jul 4.
10
Megestrol acetate for the treatment of anorexia-cachexia syndrome.醋酸甲地孕酮治疗恶病质综合征。
Cochrane Database Syst Rev. 2005 Apr 18(2):CD004310. doi: 10.1002/14651858.CD004310.pub2.

引用本文的文献

本文引用的文献

5
Involvement of POMC neurons in LEAP2 regulation of food intake and body weight.POMC 神经元参与 LEAP2 对摄食和体重的调节。
Front Endocrinol (Lausanne). 2022 Oct 28;13:932761. doi: 10.3389/fendo.2022.932761. eCollection 2022.
10

文献检索

告别复杂PubMed语法,用中文像聊天一样搜索,搜遍4000万医学文献。AI智能推荐,让科研检索更轻松。

立即免费搜索

文件翻译

保留排版,准确专业,支持PDF/Word/PPT等文件格式,支持 12+语言互译。

免费翻译文档

深度研究

AI帮你快速写综述,25分钟生成高质量综述,智能提取关键信息,辅助科研写作。

立即免费体验