The role of oxidative stress, glucocorticoid receptor and ARMC5 in lipid metabolism.

IF 1.3 4区 医学 Q4 ENDOCRINOLOGY & METABOLISM Endocrine journal Pub Date : 2024-06-26 DOI:10.1507/endocrj.EJ24-0177
Yosuke Okuno, Atsunori Fukuhara, Iichiro Shimomura
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Abstract

Lipid metabolism includes lipogenesis, lipolysis, and cholesterol metabolism and it exerts a wide range of biological effects. We previously found novel roles of adipocyte oxidative stress in diet-induced obesity, adipocyte glucocorticoid receptor in Cushing syndrome, and ARMC5 in adrenocortical cells. Using genetically modified mice in which oxidative stress was eliminated or augmented specifically in adipose tissues, we have been able to elucidate that obesity-induced oxidative stress inhibited healthy adipose expansion and ameliorated insulin sensitivity. Using adipocyte-specific glucocorticoid receptor knockout mice, we found that glucocorticoids also inhibited healthy adipose expansion and decreased insulin sensitivity. This was partly due to the transcriptional upregulation of ATGL. We identified ARMC5 as a novel ubiquitin E3 ligase of full-length SREBF, a master regulator of lipid metabolism. In adrenocortical cells, ARMC5 suppresses SREBF2 activity, and loss of ARMC5 may lead to cholesterol accumulation and the development of primary bilateral macronodular adrenal hyperplasia.

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氧化应激、糖皮质激素受体和 ARMC5 在脂质代谢中的作用
脂质代谢包括脂肪生成、脂肪分解和胆固醇代谢,具有广泛的生物效应。我们以前曾发现脂肪细胞氧化应激在饮食诱发肥胖中的新作用、脂肪细胞糖皮质激素受体在库欣综合征中的作用以及 ARMC5 在肾上腺皮质细胞中的作用。我们利用转基因小鼠消除或增加脂肪组织中的氧化应激,阐明了肥胖诱导的氧化应激抑制了健康脂肪组织的扩张,并改善了胰岛素敏感性。通过使用脂肪细胞特异性糖皮质激素受体基因敲除小鼠,我们发现糖皮质激素也会抑制健康脂肪的扩张并降低胰岛素敏感性。其部分原因是 ATGL 的转录上调。我们发现 ARMC5 是全长 SREBF 的新型泛素 E3 连接酶,而 SREBF 是脂质代谢的主调节因子。在肾上腺皮质细胞中,ARMC5抑制SREBF2的活性,而ARMC5的缺失可能导致胆固醇积累和原发性双侧巨肾上腺增生症的发生。
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来源期刊
Endocrine journal
Endocrine journal 医学-内分泌学与代谢
CiteScore
4.30
自引率
5.00%
发文量
224
审稿时长
1.5 months
期刊介绍: Endocrine Journal is an open access, peer-reviewed online journal with a long history. This journal publishes peer-reviewed research articles in multifaceted fields of basic, translational and clinical endocrinology. Endocrine Journal provides a chance to exchange your ideas, concepts and scientific observations in any area of recent endocrinology. Manuscripts may be submitted as Original Articles, Notes, Rapid Communications or Review Articles. We have a rapid reviewing and editorial decision system and pay a special attention to our quick, truly scientific and frequently-citable publication. Please go through the link for author guideline.
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