Science Signaling 年发文量-刊鹿论文编译

TFEB drives PGC-1α expression in adipocytes to protect against diet-induced metabolic dysfunction

Abstract:

TFEB promotes the browning of white adipose tissue through mechanisms unrelated to autophagy. Browning fat with TFEB TFEB is a transcription factor best known for its role in transcriptionally activating genes encoding autophagy factors. Evans et al. found that mice overexpressing TFEB in adipocytes were protected from the adverse metabolic consequences of a high-fat diet. TFEB promoted adipose tissue browning, a process in which white adipose tissue acquires the energy-burning properties of brown adipose tissue, through the transcriptional coactivator PGC-1α, rather than the induction of autophagy genes. These results suggest that increasing TFEB expression in adipocytes could be a therapeutic strategy to stave the metabolic dysfunction caused by a high-fat diet. TFEB is a basic helix-loop-helix transcription factor that confers protection against metabolic diseases such as atherosclerosis by targeting a network of genes involved in autophagy-lysosomal biogenesis and lipid catabolism. In this study, we sought to characterize the role of TFEB in adipocyte and adipose tissue physiology and evaluate the therapeutic potential of adipocyte-specific TFEB overexpression in obesity. We demonstrated that mice with adipocyte-specific TFEB overexpression (Adipo-TFEB) were protected from diet-induced obesity, insulin resistance, and metabolic sequelae. Adipo-TFEB mice were lean primarily through increased metabolic rate, suggesting a role for adipose tissue browning and enhanced nonshivering thermogenesis in fat. Transcriptional characterization revealed that TFEB targeted genes involved in adipose tissue browning rather than those involved in autophagy. One such gene encoded PGC-1α, an established target of TFEB that promotes adipocyte browning. To dissect the role of PGC-1α in mediating the downstream effects of TFEB overexpression, we generated mice with adipocyte-specific PGC-1α deficiency and TFEB overexpression. Without PGC-1α, the ability of TFEB overexpression to brown adipose tissue and to elicit beneficial metabolic effects was blunted. Overall, these data implicate TFEB as a PGC-1α–dependent regulator of adipocyte browning and suggest its therapeutic potential in treating metabolic disease.

Author Listing： Trent D Evans;Xiangyu Zhang;Se-Jin Jeong;Anyuan He;Eric Song;Somashubhra Bhattacharya;Karyn B Holloway;Irfan J Lodhi;Babak Razani

Volume： 12

Pages： None

DOI： 10.1126/scisignal.aau2281

Language： English

Journal： Science Signaling

Science Signaling

SCI SIGNAL

影响因子：6.6

是否综述期刊：是

是否OA：否

是否预警：不在预警名单内

发行时间：-

ISSN：1945-0877

发刊频率：-

收录数据库：SCIE/Scopus收录

出版国家/地区：UNITED STATES

出版社：American Association for the Advancement of Science

期刊介绍

Uncovering mechanisms in biology, gaining insights into physiology and diseaseScience Signaling is a weekly, online multidisciplinary journal for the life sciences. The aim of the journal editors is to publish studies that uncover the basic mechanisms that underlie biological processes across all organisms. Particular emphasis is placed on studies that provide new insights into physiology; delineate aberrant mechanisms that cause disease; identify new potential therapeutic targets and strategies; and characterize the effects of drugs in vitro and in vivo.

揭示生物学机制，深入了解生理学和疾病科学信号是一个每周，在线多学科的生命科学杂志。期刊编辑的目标是发表研究，揭示所有生物体的生物过程的基本机制。特别强调提供生理学新见解的研究;描述引起疾病的异常机制;确定新的潜在治疗靶点和策略;并表征药物在体外和体内的作用。

年发文量	88
国人发稿量	15
国人发文占比	16.67%
自引率	0.0%
平均录取率	-
平均审稿周期	-
版面费	-
偏重研究方向	BIOCHEMISTRY & MOLECULAR BIOLOGY-CELL BIOLOGY
期刊官网	http://stke.sciencemag.org/
投稿链接	https://cts.sciencemag.org/scc/login.html

质量指标占比

研究类文章占比	OA被引用占比	撤稿占比	出版后修正文章占比
94.32%	1.73%	0.00%	0.00%

预警情况

时间	预警情况
2025年03月发布的2025版	不在预警名单中
2024年02月发布的2024版	不在预警名单中
2023年01月发布的2023版	不在预警名单中
2021年12月发布的2021版	不在预警名单中
2020年12月发布的2020版	不在预警名单中

JCR分区 WOS分区等级：Q1区

版本	按学科	分区
WOS期刊SCI分区（2021-2022年最新版）

中科院分区

版本	大类学科	小类学科	Top期刊	综述期刊
	生物学 1区	CELL BIOLOGY 细胞生物学 2区 BIOCHEMISTRY & MOLECULAR BIOLOGY 生化与分子生物学 1区	否	是
2021年12月基础版	生物 2区	CELL BIOLOGY 细胞生物学 2区 BIOCHEMISTRY & MOLECULAR BIOLOGY 生化与分子生物学 2区	否	否
2021年12月升级版	生物学 1区	CELL BIOLOGY 细胞生物学 2区 BIOCHEMISTRY & MOLECULAR BIOLOGY 生化与分子生物学 1区	否	是
2020年12月旧的升级版	生物学 1区	CELL BIOLOGY 细胞生物学 2区 BIOCHEMISTRY & MOLECULAR BIOLOGY 生化与分子生物学 2区	否	是
2022年12月最新升级版	生物学 1区	CELL BIOLOGY 细胞生物学 2区 BIOCHEMISTRY & MOLECULAR BIOLOGY 生化与分子生物学 2区	否	是