Unit of Endocrinology and Metabolic Diseases, Department of Systems Medicine, CTO A. Alesini Hospital, ASL Roma 2, University Tor Vergata, Rome, Italy.
Laboratory of Cardiovascular Endocrinology, IRCCS San Raffaele Pisana, Rome, Italy.
Compr Physiol. 2017 Sep 12;7(4):1425-1447. doi: 10.1002/cphy.c160037.
Corticosteroids are secreted by the adrenal glands and control the functions of adipose tissue via the activation of mineralocorticoid receptor (MR) and glucocorticoid receptor (GR). In turn, adipocytes release a large variety of adipokines into the bloodstream, regulating the function of several organs and tissues, including the adrenal glands, hereby controlling corticosteroid production. In adipose tissue, the activation of the MR by glucocorticoids (GC) and aldosterone affects important processes such as adipocyte differentiation, oxidative stress, autophagic flux, adipokine expression as well as local production of GC through upregulation of the enzyme 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1). Notably, the proinflammatory responses induced by the MR are counteracted by activation of the GR, whose activity inhibits the expression of inflammatory adipokines. Both GR and MR are deeply involved in adipogenesis and adipose expansion; hence pharmacological blockade of these two receptors has proven effective against adipose tissue dysfunction in experimental models of obesity and metabolic syndrome (MetS), suggesting a potential use for MR and GR antagonists in these clinical settings. Importantly, obesity and Cushing's syndrome (CS) share metabolic similarities and are characterized by high levels of circulating corticosteroids, which in turn are able to deeply affect adipose tissue. In addition, pharmacological approaches aimed at reducing aldosterone and GC levels, by means of the inhibition of CYP11B2 (aldosterone synthase) or 11β-HSD1, represent alternative strategies to counter the detrimental effects of excessive levels of corticosteroids, which are often observed in obesity and, more general, in MetS. © 2017 American Physiological Society. Compr Physiol 7:1425-1447, 2017.
皮质类固醇由肾上腺分泌，通过激活盐皮质激素受体 (MR) 和糖皮质激素受体 (GR) 控制脂肪组织的功能。反过来，脂肪细胞将大量的脂肪细胞因子释放到血液中，调节包括肾上腺在内的多个器官和组织的功能，从而控制皮质类固醇的产生。在脂肪组织中，糖皮质激素 (GC) 和醛固酮对 MR 的激活影响重要过程，如脂肪细胞分化、氧化应激、自噬流、脂肪细胞因子表达以及通过上调酶 11β-羟类固醇脱氢酶 1 型 (11β-HSD1) 产生局部 GC。值得注意的是，MR 引起的促炎反应被 GR 的激活所抵消，GR 的活性抑制了炎症性脂肪细胞因子的表达。GR 和 MR 都深深参与了脂肪生成和脂肪扩张；因此，这两种受体的药理学阻断已被证明在肥胖和代谢综合征 (MetS) 的实验模型中对脂肪组织功能障碍有效，这表明 MR 和 GR 拮抗剂在这些临床环境中具有潜在用途。重要的是，肥胖和库欣综合征 (CS) 具有代谢相似性，其特征是循环皮质类固醇水平升高，而皮质类固醇反过来又能深刻影响脂肪组织。此外，通过抑制 CYP11B2（醛固酮合酶）或 11β-HSD1 来降低醛固酮和 GC 水平的药理学方法是对抗皮质类固醇水平过高的有害影响的替代策略，这种情况在肥胖症中经常观察到，更普遍地说，在 MetS 中也是如此。美国生理学会。综合生理学 7:1425-1447, 2017。
