Rezvani Reza, Shadmand Foumani Moghadam Mohammad Reza, Cianflone Katherine
Department of Nutrition, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran.
Department of Nutrition, Emam Reza Hospital, Mashhad University of Medical Sciences, Mashhad, Iran.
J Physiol. 2024 Mar;602(5):773-790. doi: 10.1113/JP285127. Epub 2024 Feb 2.
Adipose tissue, as an endocrine organ, secretes several adipocyte-derived hormones named 'adipokines' that are implicated in regulating energy haemostasis. Substantial evidence shows that white adipose tissue-derived adipokines mediate the link between obesity-related exogenous factors (like diet and lifestyle) and various biological events (such as pre- and postmenopausal status) that have obesity consequences (cardiometabolic disorders). One of the critical aetiological factors for obesity-related diseases is the dysfunction of adipokine pathways. Acylation-stimulating protein (ASP) is an adipokine that stimulates triglyceride synthesis and storage in adipose tissue by enhancing glucose and fatty acid uptake. ASP acts via its receptor C5L2. The primary objective of this review is to address the existing gap in the literature regarding ASP by investigating its diverse responses and receptor interactions across multiple determinants of obesity. These determinants include diet composition, metabolic disorders, organ involvement, sex and sex hormone levels. Furthermore, this article explores the broader paradigm shift from solely focusing on adipose tissue mass, which contributes to obesity, to considering the broader implications of adipose tissue function. Additionally, we raise a critical question concerning the clinical relevance of the insights gained from this review, both in terms of potential therapeutic interventions targeting ASP and in the context of preventing obesity-related conditions, highlighting the potential of the ASP-C5L2 interaction as a pharmacological target. In conclusion, these findings validate that obesity is a low-grade inflammatory status with multiorgan involvement and sex differences, demonstrating dynamic interactions between immune and metabolic response determinants.
脂肪组织作为一个内分泌器官，分泌几种由脂肪细胞产生的激素，即“脂肪因子”，它们参与调节能量稳态。大量证据表明，白色脂肪组织衍生的脂肪因子介导了肥胖相关的外源性因素（如饮食和生活方式）与各种具有肥胖后果（心脏代谢紊乱）的生物学事件（如绝经前后状态）之间的联系。肥胖相关疾病的关键病因之一是脂肪因子信号通路功能障碍。酰化刺激蛋白（ASP）是一种脂肪因子，它通过增强葡萄糖和脂肪酸摄取来刺激脂肪组织中甘油三酯的合成和储存。ASP通过其受体C5L2发挥作用。本综述的主要目的是通过研究ASP在肥胖的多个决定因素中的不同反应和受体相互作用，来填补文献中关于ASP的现有空白。这些决定因素包括饮食组成、代谢紊乱、器官受累、性别和性激素水平。此外，本文探讨了一个更广泛的范式转变，即从单纯关注导致肥胖的脂肪组织量，转向考虑脂肪组织功能的更广泛影响。此外，我们提出了一个关键问题，即从本综述中获得的见解在临床方面的相关性，无论是针对ASP的潜在治疗干预，还是在预防肥胖相关疾病的背景下，强调了ASP-C5L2相互作用作为药物靶点的潜力。总之，这些发现证实肥胖是一种伴有多器官受累和性别差异的低度炎症状态，表明免疫和代谢反应决定因素之间存在动态相互作用。
