肥胖是许多危及生命的疾病的主要危险因素。脂肪组织功能障碍正在成为从过度肥胖转变为代谢相关脂肪肝病、心血管疾病、2 型糖尿病和癌症等合并症的驱动因素。然而，人们对从健康的脂肪扩张到这些病症的发展的转变知之甚少。脂肪干细胞存在于皮下和内脏库的脉管系统和基质区域，负责器官功能的扩展和维持，现在被认为是病理转化的关键介质。组织扩张受损会导致炎症、内分泌功能失调以及肝脏、肌肉和重要器官周围的脂质沉积，而脂质在这些地方是有毒的。与之前的假设相反，促进健康脂肪组织的扩张和功能，而不是抑制脂肪生成，是代谢疾病治疗中最有吸引力的治疗策略。 AMP 激活蛋白激酶是能量稳态的主要调节因子，由于其在脂肪组织脂质代谢中的核心作用以及对脂肪生成的明显抑制作用，被认为是这样的靶标之一。然而，最近利用 AMP 激活蛋白激酶 (AMPK) 特异性化合物的研究强调了 AMPK 在脂肪生成过程中以及在先前未探索的瘦素抑制中的更微妙的、时间依赖性的作用，与脂肪细胞成熟度无关。在本文中，我讨论了 AMPK 介导的脂肪生成抑制的历史证据以及 AMPK 在脂肪组织中的多方面作用。© 2024 作者。

Obesity is a major risk factor for many life-threatening diseases. Adipose tissue dysfunction is emerging as a driving factor in the transition from excess adiposity to comorbidities such as metabolic-associated fatty liver disease, cardiovascular disease, Type 2 diabetes and cancer. However, the transition from healthy adipose expansion to the development of these conditions is poorly understood. Adipose stem cells, residing in the vasculature and stromal regions of subcutaneous and visceral depots, are responsible for the expansion and maintenance of organ function, and are now recognised as key mediators of pathological transformation. Impaired tissue expansion drives inflammation, dysregulation of endocrine function and the deposition of lipids in the liver, muscle and around vital organs, where it is toxic. Contrary to previous hypotheses, it is the promotion of healthy adipose tissue expansion and function, not inhibition of adipogenesis, that presents the most attractive therapeutic strategy in the treatment of metabolic disease. AMP-activated protein kinase, a master regulator of energy homeostasis, has been regarded as one such target, due to its central role in adipose tissue lipid metabolism, and its apparent inhibition of adipogenesis. However, recent studies utilising AMP-activated protein kinase (AMPK)-specific compounds highlight a more subtle, time-dependent role for AMPK in the process of adipogenesis, and in a previously unexplored repression of leptin, independent of adipocyte maturity. In this article, I discuss historic evidence for AMPK-mediated adipogenesis inhibition and the multi-faceted roles for AMPK in adipose tissue.© 2024 The Author(s).