Different action of glucocorticoid receptor in adipose tissue remodelling to modulate energy homeostasis by chronic restraint stress.

IF 3.9 2区 医学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY
Yinghua Luo, Qinyu Liu, Yaqian Mao, Junping Wen, Gang Chen
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引用次数: 0

Abstract

Background: Chronic stress in daily life is a well-known trigger for various health issues. Despite advancements in obesity research, the mechanisms governing lipid metabolism in adipose tissue during cachexia remain poorly understood.

Methods: A chronic restraint stress (CRS) model was used to induce significant physiological and psychological stress in mice. Mice were subjected to 6 h of restraint daily in 50 mL plastic tubes for seven consecutive days. A fasting control group was included for comparison. Post-stress assessments included behavioural tests, glucose and insulin tolerance tests and indirect calorimetry. Blood and adipose tissue samples were collected for mRNA and protein analyses.

Results: CRS induced significant psychological and physiological changes in mice, including depression-like behaviours, weight loss and reduced insulin sensitivity. Notably, CRS caused extensive adipose tissue remodelling. White adipose tissue (WAT) underwent significant 'browning' accompanied by an increase in the expression of thermogenic proteins. This counteracted the stress-induced 'whitening' of brown adipose tissue (BAT), which exhibited impaired thermogenesis and functionality, thereby maintaining energy balance systematically. The glucocorticoid receptor (GR) plays a crucial role in lipid metabolism regulation during these changes. GR expression levels were inversely correlated in BAT and WAT, but aligned with the expression patterns of thermogenic proteins across adipose tissues. These findings suggest that under chronic metabolic stress, GR mediates tissue-specific responses in adipose tissues, driving functional and phenotypic transitions in BAT and WAT to maintain energy homeostasis.

Conclusions: This study provides novel insights into the contrasting thermogenic phenotypes of BAT and WAT under emaciation and highlights the critical role of GRs in adipose tissue remodelling during CRS and its potential as a therapeutic target. Addressing GR-mediated changes in adipose tissues may help alleviate BAT dysfunction in cachexia and promote WAT browning, enhancing metabolic stress resistance.

糖皮质激素受体在脂肪组织重构中对慢性约束应激下能量稳态调节的不同作用。
背景:众所周知,日常生活中的慢性压力会引发各种健康问题。尽管肥胖研究取得了进展,但对恶病质期间脂肪组织脂质代谢的调控机制仍然知之甚少。方法:采用慢性约束应激(CRS)模型诱导小鼠明显的生理和心理应激。将小鼠置于50 mL塑料管中,每天约束6 h,连续7天。另设禁食对照组进行比较。应激后评估包括行为测试、葡萄糖和胰岛素耐量测试以及间接量热法。采集血液和脂肪组织样本进行mRNA和蛋白分析。结果:CRS引起小鼠明显的心理和生理变化,包括抑郁样行为、体重减轻和胰岛素敏感性降低。值得注意的是,CRS引起了广泛的脂肪组织重塑。白色脂肪组织(WAT)经历了显著的“褐变”,并伴有产热蛋白表达的增加。这抵消了应激诱导的棕色脂肪组织(BAT)的“变白”,棕色脂肪组织表现出受损的产热和功能,从而系统地维持了能量平衡。糖皮质激素受体(GR)在脂质代谢调节中起着至关重要的作用。GR在BAT和WAT中的表达水平呈负相关,但与脂肪组织中产热蛋白的表达模式一致。这些发现表明,在慢性代谢应激下,GR介导脂肪组织的组织特异性反应,驱动BAT和WAT的功能和表型转变,以维持能量稳态。结论:本研究为瘦化状态下BAT和WAT的热源表型对比提供了新的见解,并强调了GRs在CRS期间脂肪组织重塑中的关键作用及其作为治疗靶点的潜力。解决gr介导的脂肪组织变化可能有助于缓解恶病质中BAT功能障碍,促进WAT褐变,增强代谢应激抵抗能力。
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来源期刊
Lipids in Health and Disease
Lipids in Health and Disease 生物-生化与分子生物学
CiteScore
7.70
自引率
2.20%
发文量
122
审稿时长
3-8 weeks
期刊介绍: Lipids in Health and Disease is an open access, peer-reviewed, journal that publishes articles on all aspects of lipids: their biochemistry, pharmacology, toxicology, role in health and disease, and the synthesis of new lipid compounds. Lipids in Health and Disease is aimed at all scientists, health professionals and physicians interested in the area of lipids. Lipids are defined here in their broadest sense, to include: cholesterol, essential fatty acids, saturated fatty acids, phospholipids, inositol lipids, second messenger lipids, enzymes and synthetic machinery that is involved in the metabolism of various lipids in the cells and tissues, and also various aspects of lipid transport, etc. In addition, the journal also publishes research that investigates and defines the role of lipids in various physiological processes, pathology and disease. In particular, the journal aims to bridge the gap between the bench and the clinic by publishing articles that are particularly relevant to human diseases and the role of lipids in the management of various diseases.
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