{"title":"The role of oxidative stress, glucocorticoid receptor and ARMC5 in lipid metabolism.","authors":"Yosuke Okuno, Atsunori Fukuhara, Iichiro Shimomura","doi":"10.1507/endocrj.EJ24-0177","DOIUrl":null,"url":null,"abstract":"<p><p>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.</p>","PeriodicalId":11631,"journal":{"name":"Endocrine journal","volume":null,"pages":null},"PeriodicalIF":1.3000,"publicationDate":"2024-06-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Endocrine journal","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1507/endocrj.EJ24-0177","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q4","JCRName":"ENDOCRINOLOGY & METABOLISM","Score":null,"Total":0}
引用次数: 0
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.
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.