University of Cambridge Metabolic Research Laboratories, Wellcome Trust-MRC Institute of Metabolic Science, University of Cambridge, Cambridge, UK.
Centro de Investigación Principe Felipe, Valencia, Spain.
Adv Exp Med Biol. 2024;1460:231-272. doi: 10.1007/978-3-031-63657-8_8.
The adipose tissue organ is organised as distinct anatomical depots located all along the body axis, and it is constituted of three different types of adipocytes: white, beige and brown, which are integrated with vascular, immune, neural, and extracellular stroma cells. These distinct adipocytes serve different specialised functions. The main function of white adipocytes is to ensure healthy storage of excess nutrients/energy and its rapid mobilisation to supply the demand of energy imposed by physiological cues in other organs, whereas brown and beige adipocytes are designed for heat production through uncoupling lipid oxidation from energy production. The concerted action of the three types of adipocytes/tissues ensures an optimal metabolic status. However, when one or several of these adipose depots become dysfunctional because of sustained lipid/nutrient overload, then insulin resistance and associated metabolic complications ensue. These metabolic alterations close a vicious cycle that negatively affects the adipose tissue functionality and compromises global metabolic homeostasis. Optimising white adipose tissue expandability and ensuring its functional metabolic flexibility and/or promoting brown/beige mediated thermogenic activity are complementary strategies that counteract obesity and its associated lipotoxic metabolic effects. However, the development of these therapeutic approaches requires a deep understanding of adipose tissue in all broad aspects. In this chapter, we will discuss the characteristics of the different adipose tissue depots with respect to origins and precursors recruitment, plasticity, cellular composition, and expandability capacity potential as well as molecular and metabolic characteristic signatures in both physiological and pathophysiological conditions. Current antilipotoxic strategies for future clinical application are also discussed in this chapter.
脂肪组织器官组织化为分布在整个体轴上的不同解剖脂肪库，由三种不同类型的脂肪细胞组成：白色、米色和棕色，它们与血管、免疫、神经和细胞外基质细胞整合在一起。这些不同类型的脂肪细胞具有不同的特殊功能。白色脂肪细胞的主要功能是确保过量营养物质/能量的健康储存，并迅速动员这些能量以满足其他器官生理信号所要求的能量供应，而棕色和米色脂肪细胞则设计用于通过将脂质氧化与能量产生解偶联来产生热量。三种脂肪细胞/组织的协同作用确保了最佳的代谢状态。然而，当由于持续的脂质/营养超负荷而导致一个或多个这些脂肪库功能失调时，胰岛素抵抗和相关的代谢并发症就会随之而来。这些代谢改变形成了一个恶性循环，会对脂肪组织功能产生负面影响，并损害整体代谢平衡。优化白色脂肪组织的扩展性，并确保其功能性代谢灵活性，或者促进棕色/米色介导的产热活性，是对抗肥胖及其相关脂毒性代谢作用的互补策略。然而，这些治疗方法的发展需要深入了解脂肪组织在各个方面的特征。在本章中，我们将讨论不同脂肪组织库的特征，包括其起源和前体细胞募集、可塑性、细胞组成以及在生理和病理生理条件下的扩展性潜力，以及分子和代谢特征签名。本章还讨论了针对未来临床应用的抗脂毒性策略。
