脂肪细胞中 Fas(CD95)的表达是饮食诱发肥胖的原因之一。

IF 4.2 2区 医学 Q1 ENDOCRINOLOGY & METABOLISM
Obesity Pub Date : 2024-07-17 DOI:10.1002/oby.24092
Stephan Wueest, Chiara Scaffidi, Pim P. van Krieken, Nils K. Konrad, Christian Koch, Michael S. F. Wiedemann, Anne Goergen, Marcela Borsigova, Ioannis G. Lempesis, Jonas Fullin, Konstantinos N. Manolopoulos, Steffen Böttcher, Gijs H. Goossens, Matthias Blüher, Daniel Konrad
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引用次数: 0

摘要

目的:诱导白脂肪组织(WAT)褐变可增加能量消耗,可能是治疗肥胖症的一个有吸引力的靶点。由于 Fas(CD95)的活化会诱导已知的阻碍解偶联蛋白 1(UCP1)表达的途径,我们假设脂肪细胞中 Fas 的表达会抑制白脂肪组织的褐变,从而导致肥胖症的发生:方法:对脂肪细胞特异性 Fas 基因敲除(FasΔadipo)小鼠和对照组同窝小鼠(FasF/F)喂食普通饲料或高脂饲料(HFD)20 周。能量消耗通过间接热量计进行评估,皮下脂肪褐变的测定也通过间接热量计进行。在体外,对使用或不使用 Fas 配体处理的小鼠皮下脂肪细胞中的 UCP1 进行了分析。此外,FAS在WAT中的表达与UCP1和人体脂肪百分比相关:结果:与对照组小鼠相比,以高密度脂蛋白饲料喂养的 FasΔadipo 小鼠体重增加减少,脂肪含量降低。同时,全身能量消耗和脂肪细胞褐变增加。在培养的脂肪细胞中,Fas 配体处理会减弱异丙肾上腺素诱导的 UCP1 蛋白水平。与啮齿类动物的这些发现相印证的是,FAS在WAT中的表达与UCP1呈负相关,但与人类的脂肪率呈正相关:结论:啮齿类动物脂肪细胞中的 Fas 激活导致了高氟酸脱硫相关性肥胖,可能是减少肥胖及相关疾病的治疗靶点。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

Fas (CD95) expression in adipocytes contributes to diet-induced obesity

Fas (CD95) expression in adipocytes contributes to diet-induced obesity

Objective

Induction of browning in white adipose tissue (WAT) increases energy expenditure and may be an attractive target for the treatment of obesity. Since activation of Fas (CD95) induces pathways known to blunt expression of uncoupling protein 1 (UCP1), we hypothesized that Fas expression in adipocytes inhibits WAT browning and thus contributes to the development of obesity.

Methods

Adipocyte-specific Fas knockout (FasΔadipo) and control littermate (FasF/F) mice were fed a regular chow diet or a high-fat diet (HFD) for 20 weeks. Energy expenditure was assessed by indirect calorimetry, and browning was determined in subcutaneous WAT. In vitro, UCP1 was analyzed in subcutaneous murine adipocytes treated with or without Fas ligand. Moreover, FAS expression in WAT was correlated to UCP1 and percentage of body fat in human individuals.

Results

HFD-fed FasΔadipo mice displayed reduced body weight gain and blunted adiposity compared to control littermates. Concomitantly, whole-body energy expenditure and WAT browning were elevated. In cultured adipocytes, Fas ligand treatment blunted isoproterenol-induced UCP1 protein levels. In support of these findings in rodents, FAS expression in WAT correlated negatively with UCP1 but positively with adiposity in human individuals.

Conclusions

Fas activation in adipocytes contributes to HFD-associated adiposity in rodents and may be a therapeutic target to reduce obesity and associated diseases.

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来源期刊
Obesity
Obesity 医学-内分泌学与代谢
CiteScore
11.70
自引率
1.40%
发文量
261
审稿时长
2-4 weeks
期刊介绍: Obesity is the official journal of The Obesity Society and is the premier source of information for increasing knowledge, fostering translational research from basic to population science, and promoting better treatment for people with obesity. Obesity publishes important peer-reviewed research and cutting-edge reviews, commentaries, and public health and medical developments.
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