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糖皮质激素与棕色脂肪组织:糖皮质激素真的会抑制产热吗?

Glucocorticoids and Brown Adipose Tissue: Do glucocorticoids really inhibit thermogenesis?

机构信息

Department of Molecular Biosciences, The Wenner-Gren Institute, Stockholm University, Stockholm, Sweden.

Department of Molecular Biosciences, The Wenner-Gren Institute, Stockholm University, Stockholm, Sweden.

出版信息

Mol Aspects Med. 2019 Aug;68:42-59. doi: 10.1016/j.mam.2019.07.002. Epub 2019 Jul 27.

Abstract

A reduction in the thermogenic activity of brown adipose tissue (BAT) is presently discussed as a possible determinant for the development of obesity in humans. One group of endogenous factors that could potentially affect BAT activity is the glucocorticoids (e.g. cortisol). We analyse here studies examining the effects of alterations in glucocorticoid signaling on BAT recruitment and thermogenic capacity. We find that irrespective of which manipulation of glucocorticoid signaling is examined, a seemingly homogeneous picture of lowered thermogenic capacity due to glucocorticoid stimulation is apparently obtained: e.g. lowered uncoupling protein 1 (UCP1) protein levels per mg protein, and an increased lipid accumulation in BAT. However, further analyses generally indicate that these effects result from a dilution effect rather than a true decrease in total capacity; the tissue may thus be said to be in a state of pseudo-atrophy. However, under conditions of very low physiological stimulation of BAT, glucocorticoids may truly inhibit Ucp1 gene expression and consequently lower total UCP1 protein levels, but the metabolic effects of this reduction are probably minor. It is thus unlikely that glucocorticoids affect organismal metabolism and induce the development of obesity through alterations of BAT activity.

摘要

目前认为棕色脂肪组织(BAT)产热活性降低是人类肥胖发生的一个可能决定因素。内源性因素中可能影响 BAT 活性的一类是糖皮质激素(如皮质醇)。我们分析了研究糖皮质激素信号转导改变对 BAT 募集和产热能力的影响。我们发现,无论检测到哪种糖皮质激素信号转导的改变,由于糖皮质激素刺激而导致的产热能力降低的情况似乎是一致的:例如,每毫克蛋白的解偶联蛋白 1(UCP1)蛋白水平降低,BAT 中的脂质积累增加。然而,进一步的分析通常表明,这些效应是由于稀释效应而不是总产热能力的真正下降所致;因此,可以说组织处于假性萎缩状态。然而,在 BAT 受到极低生理刺激的情况下,糖皮质激素可能真正抑制 Ucp1 基因表达,从而降低总 UCP1 蛋白水平,但这种减少的代谢效应可能较小。因此,糖皮质激素不太可能通过改变 BAT 活性影响机体代谢并导致肥胖的发生。

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