Decoding Immunometabolic Dynamics of Adipose Tissue in Obesity: Evolving Evidence and Way Forward

IF 3.7 Q1 CHEMISTRY, MEDICINAL

ACS Pharmacology and Translational Science Pub Date : 2026-08-14 Epub Date: 2026-07-25 DOI:10.1021/acsptsci.6c00071

Kajal Kumari, Kanika Verma, Richa Yadav, Jaya Dwivedi, Sarvesh Paliwal, Swapnil Sharma

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Abstract

Obesity is a prevalent global health condition associated with an increased risk of cardiovascular and metabolic diseases. Despite the transformative impact of GLP-1 receptor agonists and dual or triple incretin agonists in obesity management, a significant subset of patients develops therapeutic resistance, exhibits no weight loss, or experiences weight regain after treatment discontinuation. These limitations underscore critical gaps in understanding the biological mechanisms underlying the heterogeneity in drug responsiveness. Growing evidence indicates that adipose tissue is a dynamic immunometabolic organ in which chronic low-grade inflammation perturbs metabolic homeostasis and modulates the therapeutic responsiveness. This Review integrates emerging mechanistic, translational, and multiomics evidence on obesity-induced remodeling of adipose immune-cell niches. It also delineates the effects of these alterations, including impaired lipolysis, insulin resistance, defective thermogenesis, and resistance to weight loss. Overall, this Review highlights adipose tissue immunometabolism as a central yet often underappreciated contributor to therapeutic responsiveness and a promising target for future obesity therapies.

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解码肥胖中脂肪组织的免疫代谢动力学：进化的证据和前进的道路

肥胖是一种普遍的全球健康状况，与心血管和代谢疾病的风险增加有关。尽管GLP-1受体激动剂和双重或三重肠促胰岛素激动剂在肥胖管理中具有变革性影响，但仍有相当一部分患者出现治疗抵抗，没有表现出体重减轻，或在停止治疗后体重恢复。这些限制强调了在理解药物反应异质性的生物学机制方面的关键空白。越来越多的证据表明，脂肪组织是一个动态的免疫代谢器官，慢性炎症会扰乱代谢稳态并调节治疗反应。这篇综述整合了肥胖诱导脂肪免疫细胞龛重构的新机制、翻译和多组学证据。它还描述了这些改变的影响，包括脂肪分解受损、胰岛素抵抗、产热缺陷和减肥抵抗。总的来说，这篇综述强调了脂肪组织免疫代谢是治疗反应性的一个核心但经常被低估的因素，也是未来肥胖治疗的一个有希望的目标。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

ACS Pharmacology and Translational Science Medicine-Pharmacology (medical)

CiteScore

10.00

自引率

3.30%

发文量

133

期刊介绍： ACS Pharmacology & Translational Science publishes high quality, innovative, and impactful research across the broad spectrum of biological sciences, covering basic and molecular sciences through to translational preclinical studies. Clinical studies that address novel mechanisms of action, and methodological papers that provide innovation, and advance translation, will also be considered. We give priority to studies that fully integrate basic pharmacological and/or biochemical findings into physiological processes that have translational potential in a broad range of biomedical disciplines. Therefore, studies that employ a complementary blend of in vitro and in vivo systems are of particular interest to the journal. Nonetheless, all innovative and impactful research that has an articulated translational relevance will be considered. ACS Pharmacology & Translational Science does not publish research on biological extracts that have unknown concentration or unknown chemical composition. Authors are encouraged to use the pre-submission inquiry mechanism to ensure relevance and appropriateness of research.