小鼠褐色脂肪细胞中PPARα的缺失增加了其从头脂肪生成。

IF 6.6 2区医学 Q1 ENDOCRINOLOGY & METABOLISM

Molecular Metabolism Pub Date : 2025-06-10 DOI:10.1016/j.molmet.2025.102184

Pierre-Louis Batrow , Sylvie Caspar-Bauguil , Nathalie Rochet , Nadine Gautier , Anne-Sophie Rousseau , Marielle Maret , Samah Rekima , Etienne Mouisel , Emmanuel Van Obberghen , Christian H. Roux , Hervé Guillou , Catherine Postic , Christian Wolfrum , Dominique Langin , Ez-Zoubir Amri , Isabelle Mothe-Satney

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引用次数: 0

摘要

目的：过氧化物酶体增殖物激活受体（PPARs）是参与脂质代谢控制的核受体。PPARα亚型在棕色脂肪组织（BAT）中高度表达。然而，它在BAT中的确切作用仍不清楚。在此，我们旨在研究PPARα在热中性环境下高脂肪饮食诱导的肥胖小鼠BAT中的作用。方法：我们使用他莫昔芬诱导的BAT特异性PPARα敲除小鼠（PPARα batko），将其置于热中性环境以最小化BAT基础激活，喂食高脂肪饮食20周，并在最后一周使用β3-肾上腺素能激动剂（CL316,243）。研究人员对雄性和雌性小鼠进行了研究。结果：体重和糖耐量试验在两性和基因型中相似。然而，PPARαBATKO小鼠的BAT形态发生了改变，与对照小鼠相比，其单眼脂滴更多，脂滴更大，表明BAT功能受损。事实上，当用CL316,243处理时，雄性和雌性小鼠都增加了新生脂肪生成（DNL），这反映在ChREBPβ和脂肪生成酶ACLY， ACC1， FASN和SCD1的表达增加。这些变化伴随着甘油三酯中脂肪酸的增加，因此脂质储存增加。此外，磷脂的脂质谱不同，表明膜含量随着棕榈油酸盐的增加而改变。结论：总之，我们的研究结果揭示了PPARα在BAT的DNL和hfd诱导肥胖的脂质代谢调节中的关键作用。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

Deletion of PPARα in mouse brown adipocytes increases their De Novo Lipogenesis

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Deletion of PPARα in mouse brown adipocytes increases their De Novo Lipogenesis

Objective

Peroxisome Proliferator-Activated Receptors (PPARs) are nuclear receptors involved in the control of lipid metabolism. The PPARα isoform is highly expressed in brown adipose tissue (BAT). However, its precise role in BAT remains unclear. Here, we aimed to investigate the role of PPARα in BAT of high fat diet-induced obese mice in a thermoneutral environment.

Methods

We used tamoxifen-inducible-BAT specific PPARα knockout mice (PPARαBATKO) that were housed at thermoneutrality to minimize BAT basal activation, fed a high-fat diet for 20 weeks and challenged with a β₃-adrenergic agonist (CL316,243) during the last week. Both male and female mice were studied.

Results

Body weight and glucose tolerance tests were similar in both sexes and genotypes. However, BAT morphology was altered in PPARαBATKO mice, with more unilocular and larger lipid droplets compared to control mice, suggesting BAT impaired function. Indeed, when treated with CL316,243, both male and female mice had increased De Novo Lipogenesis (DNL), reflected by an increased expression of ChREBPβ and lipogenic enzymes ACLY, ACC1, FASN and SCD1. These changes were accompanied by an increase in fatty acids in triglycerides, and thus an increase in lipid storage. Moreover, lipid profiles in phospholipids were different, suggesting a modification in the membrane content with an increase of palmitoleate.

Conclusions

Altogether, our results reveal a key role for PPARα in DNL in BAT and in the regulation of lipid metabolism in HFD-induced obesity.

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来源期刊

Molecular Metabolism ENDOCRINOLOGY & METABOLISM-

CiteScore

14.50

自引率

2.50%

发文量

219

审稿时长

43 days

期刊介绍： Molecular Metabolism is a leading journal dedicated to sharing groundbreaking discoveries in the field of energy homeostasis and the underlying factors of metabolic disorders. These disorders include obesity, diabetes, cardiovascular disease, and cancer. Our journal focuses on publishing research driven by hypotheses and conducted to the highest standards, aiming to provide a mechanistic understanding of energy homeostasis-related behavior, physiology, and dysfunction. We promote interdisciplinary science, covering a broad range of approaches from molecules to humans throughout the lifespan. Our goal is to contribute to transformative research in metabolism, which has the potential to revolutionize the field. By enabling progress in the prognosis, prevention, and ultimately the cure of metabolic disorders and their long-term complications, our journal seeks to better the future of health and well-being.