Toxalim (Research Center in Food Toxicology), INRAE, ENVT, INP- PURPAN, UMR 1331, UPS, Université de Toulouse, Toulouse, France.
Institute of Molecular Biosciences, NAWI Graz, University of Graz, Heinrichstraße 31/II, 8010 Graz, Austria; BioTechMed-Graz, Graz, Austria; Department of Pharmacology and Toxicology, University of Graz, Humboldtstraße 46/II, 8010 Graz, Austria.
Cell Rep. 2022 Jun 7;39(10):110910. doi: 10.1016/j.celrep.2022.110910.
In hepatocytes, peroxisome proliferator-activated receptor α (PPARα) orchestrates a genomic and metabolic response required for homeostasis during fasting. This includes the biosynthesis of ketone bodies and of fibroblast growth factor 21 (FGF21). Here we show that in the absence of adipose triglyceride lipase (ATGL) in adipocytes, ketone body and FGF21 production is impaired upon fasting. Liver gene expression analysis highlights a set of fasting-induced genes sensitive to both ATGL deletion in adipocytes and PPARα deletion in hepatocytes. Adipose tissue lipolysis induced by activation of the β-adrenergic receptor also triggers such PPARα-dependent responses not only in the liver but also in brown adipose tissue (BAT). Intact PPARα activity in hepatocytes is required for the cross-talk between adipose tissues and the liver during fat mobilization.
在肝细胞中，过氧化物酶体增殖物激活受体 α（PPARα）协调了禁食期间维持体内平衡所需的基因组和代谢反应。这包括酮体和成纤维细胞生长因子 21（FGF21）的生物合成。在这里，我们表明在脂肪细胞中缺乏脂肪甘油三酯酶（ATGL）的情况下，禁食时酮体和 FGF21 的产生受损。肝脏基因表达分析突出了一组受禁食诱导的基因，这些基因对脂肪细胞中 ATGL 的缺失和肝细胞中 PPARα 的缺失均敏感。β-肾上腺素能受体的激活诱导的脂肪组织脂肪分解也不仅在肝脏而且在棕色脂肪组织（BAT）中触发这种依赖于 PPARα 的反应。在脂肪动员期间，脂肪组织和肝脏之间的串扰需要肝细胞中完整的 PPARα 活性。
