基于活动的厌食症诱导脂肪组织棕色化,与下丘脑 AMPK 无关。

Activity-Based Anorexia Induces Browning of Adipose Tissue Independent of Hypothalamic AMPK.

机构信息

Department of Physiology, Center for Research in Molecular Medicine and Chronic Diseases (CiMUS), University of Santiago de Compostela-Instituto de Investigación Sanitaria, Santiago de Compostela, Spain.

CIBER Fisiopatología de la Obesidad y Nutrición (CIBERobn), Santiago de Compostela, Spain.

出版信息

Front Endocrinol (Lausanne). 2021 Jun 2;12:669980. doi: 10.3389/fendo.2021.669980. eCollection 2021.

Abstract

Anorexia nervosa (AN) is an eating disorder leading to malnutrition and, ultimately, to energy wasting and cachexia. Rodents develop activity-based anorexia (ABA) when simultaneously exposed to a restricted feeding schedule and allowed free access to running wheels. These conditions lead to a life-threatening reduction in body weight, resembling AN in human patients. Here, we investigate the effect of ABA on whole body energy homeostasis at different housing temperatures. Our data show that ABA rats develop hyperactivity and hypophagia, which account for a massive body weight loss and muscle cachexia, as well as reduced uncoupling protein 1 (UCP1) expression in brown adipose tissue (BAT), but increased browning of white adipose tissue (WAT). Increased housing temperature reverses not only the hyperactivity and weight loss of animals exposed to the ABA model, but also hypothermia and loss of body and muscle mass. Notably, despite the major metabolic impact of ABA, none of the changes observed are associated to changes in key hypothalamic pathways modulating energy metabolism, such as AMP-activated protein kinase (AMPK) or endoplasmic reticulum (ER) stress. Overall, this evidence indicates that although temperature control may account for an improvement of AN, key hypothalamic pathways regulating thermogenesis, such as AMPK and ER stress, are unlikely involved in later stages of the pathophysiology of this devastating disease.

摘要

神经性厌食症(AN)是一种导致营养不良的饮食失调症,最终会导致能量消耗和恶病质。当同时暴露于限制喂养时间表和允许自由使用跑步轮的条件下时,啮齿动物会发展出基于活动的厌食症(ABA)。这些条件导致危及生命的体重减轻,类似于人类患者的 AN。在这里,我们研究了 ABA 在不同住房温度下对全身能量稳态的影响。我们的数据表明,ABA 大鼠表现出过度活跃和摄食减少,这导致大量体重减轻和肌肉恶病质,以及棕色脂肪组织(BAT)中解偶联蛋白 1(UCP1)表达减少,但白色脂肪组织(WAT)的褐色化增加。增加住房温度不仅可以逆转暴露于 ABA 模型的动物的过度活跃和体重减轻,还可以逆转体温过低和身体和肌肉质量的损失。值得注意的是,尽管 ABA 具有重大的代谢影响,但观察到的变化都与调节能量代谢的关键下丘脑途径(如 AMP 激活蛋白激酶(AMPK)或内质网(ER)应激)的变化无关。总体而言,这一证据表明,尽管体温控制可能是 AN 改善的原因,但调节产热的关键下丘脑途径,如 AMPK 和 ER 应激,不太可能参与这种破坏性疾病病理生理学的后期阶段。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/542f/8206787/942083a3496b/fendo-12-669980-g001.jpg

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