过表达增强 表达 。
Overexpression Enhances Expression .
机构信息
Department of Endocrine and Metabolic Diseases, Shanghai Institute of Endocrine and Metabolic Diseases, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Shanghai National Clinical Research Center for Metabolic Diseases, Key Laboratory for Endocrine and Metabolic Diseases of the National Health Commission of the PR China, Shanghai National Center for Translational Medicine, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
出版信息
Front Endocrinol (Lausanne). 2021 Mar 10;12:634191. doi: 10.3389/fendo.2021.634191. eCollection 2021.
OBJECTIVE
The Iroquois homeobox 3 () gene was recently reported to be a functional downstream target of a common polymorphism in the gene, which encodes an obesity-associated protein; however, the role of in energy expenditure remains unclear. Studies have revealed that the overexpression of a dominant-negative form of IRX3 in the mouse hypothalamus and adipose tissue promoted energy expenditure by enhancing brown/browning activities. Meanwhile, we and others recently demonstrated that knockdown impaired the browning program of primary preadipocytes . In this study, we aimed to further clarify the effects of overexpressing human (h) on brown/beige adipose tissues .
METHODS
Brown/beige adipocyte-specific h-overexpressing mice were generated and the browning program of white adipose tissues was induced by both chronic cold stimulation and CL316,243 injection. Body weight, fat mass, lean mass, and energy expenditure were measured, while morphological changes and the expression of thermogenesis-related genes in adipose tissue were analyzed. Moreover, the browning capacity of primary preadipocytes derived from h-overexpressing mice was assessed. RNA sequencing was also employed to investigate the effect of h on the expression of thermogenesis-related genes.
RESULTS
h overexpression in embryonic brown/beige adipose tissues ( ;Cre) led to increased energy expenditure, decreased fat mass, and a lean body phenotype. After acute cold exposure or CL316,243 stimulation, brown/beige tissue h-overexpressing mice showed an increase in expression. Consistent with this, induced h overexpression in adult mice ( ;Cre) also promoted a moderate increase in expression. experiments further revealed that h overexpression induced by -driven Cre recombinase activity upregulated brown/beige adipocytes expression and oxygen consumption rate (OCR). RNA sequencing analyses indicated that h overexpression in brown adipocytes enhanced brown fat cell differentiation, glycolysis, and gluconeogenesis.
CONCLUSION
Consistent with the findings, brown/beige adipocyte-specific overexpression of h promoted expression and thermogenesis, while reducing fat mass.
目的
最近有研究报道，一种常见的肥胖相关蛋白基因（编码产物）的多态性可作为同源盒基因 3（）的一个功能性下游靶标；然而，在能量消耗方面，的作用仍不清楚。研究表明，在小鼠下丘脑和脂肪组织中过表达一种显性负形式的 IRX3，可通过增强棕色/米色活动来促进能量消耗。同时，我们和其他人最近的研究表明，敲低会损害原代前体脂肪细胞的成棕色程序。在这项研究中，我们旨在进一步阐明过表达人（h）对棕色/米色脂肪组织的影响。
方法
生成了棕色/米色脂肪细胞特异性 h 过表达小鼠，并通过慢性冷刺激和 CL316,243 注射诱导白色脂肪组织的成棕色程序。测量体重、脂肪量、瘦体重和能量消耗，分析脂肪组织形态变化和产热相关基因的表达。此外，还评估了源自 h 过表达小鼠的原代前体脂肪细胞的成棕色能力。还进行了 RNA 测序以研究 h 对产热相关基因表达的影响。
结果
胚胎棕色/米色脂肪组织（；Cre）中的 h 过表达导致能量消耗增加、脂肪量减少和瘦体重表型。急性冷暴露或 CL316,243 刺激后，棕色/米色组织 h 过表达小鼠中表达增加。与此一致，成年小鼠（；Cre）中诱导的 h 过表达也促进了适度增加。实验进一步表明，由 Cre 重组酶活性驱动的 h 过表达上调了棕色/米色脂肪细胞的表达和耗氧量（OCR）。RNA 测序分析表明，棕色脂肪细胞中 h 的过表达增强了棕色脂肪细胞的分化、糖酵解和糖异生。
结论
与发现一致，棕色/米色脂肪细胞特异性过表达 h 促进了的表达和产热，同时减少了脂肪量。
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