Department of Structural and Functional Biology, Institute of Biology, University of Campinas, Campinas, SP, Brazil.
Obesity and Comorbidities Research Center, University of Campinas, Campinas, SP, Brazil.
Front Endocrinol (Lausanne). 2023 Feb 21;14:1090039. doi: 10.3389/fendo.2023.1090039. eCollection 2023.
Adipose tissue is an organ with metabolic and endocrine activity. White, brown and ectopic adipose tissues have different structure, location, and function. Adipose tissue regulates energy homeostasis, providing energy in nutrient-deficient conditions and storing it in high-supply conditions. To attend to the high demand for energy storage during obesity, the adipose tissue undergoes morphological, functional and molecular changes. Endoplasmic reticulum (ER) stress has been evidenced as a molecular hallmark of metabolic disorders. In this sense, the ER stress inhibitor tauroursodeoxycholic acid (TUDCA), a bile acid conjugated to taurine with chemical chaperone activity, has emerged as a therapeutic strategy to minimize adipose tissue dysfunction and metabolic alterations associated with obesity. In this review, we highlight the effects of TUDCA and receptors TGR5 and FXR on adipose tissue in the setting of obesity. TUDCA has been demonstrated to limit metabolic disturbs associated to obesity by inhibiting ER stress, inflammation, and apoptosis in adipocytes. The beneficial effect of TUDCA on perivascular adipose tissue (PVAT) function and adiponectin release may be related to cardiovascular protection in obesity, although more studies are needed to clarify the mechanisms. Therefore, TUDCA has emerged as a potential therapeutic strategy for obesity and comorbidities.
脂肪组织是具有代谢和内分泌活性的器官。白色、棕色和异位脂肪组织具有不同的结构、位置和功能。脂肪组织调节能量稳态，在营养缺乏的情况下提供能量，在供应充足的情况下储存能量。为了满足肥胖期间对能量储存的高需求，脂肪组织发生形态、功能和分子变化。内质网（ER）应激已被证明是代谢紊乱的分子标志。在这种意义上，ER 应激抑制剂牛磺熊脱氧胆酸（TUDCA），一种与牛磺酸结合的胆酸，具有化学伴侣活性，已成为一种治疗策略，以最小化与肥胖相关的脂肪组织功能障碍和代谢改变。在这篇综述中，我们强调了 TUDCA 及其受体 TGR5 和 FXR 在肥胖背景下对脂肪组织的影响。TUDCA 通过抑制脂肪细胞中的 ER 应激、炎症和细胞凋亡，限制与肥胖相关的代谢紊乱。TUDCA 对血管周脂肪组织（PVAT）功能和脂联素释放的有益作用可能与肥胖中的心血管保护有关，尽管还需要更多的研究来阐明机制。因此，TUDCA 已成为肥胖及其合并症的一种潜在治疗策略。
