PPARδ attenuates hepatic steatosis through autophagy-mediated fatty acid oxidation
PPARδ attenuates hepatic steatosis through autophagy-mediated fatty acid oxidation
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PPAR δ 通过自噬介导的脂肪酸氧化减轻肝脏脂肪变性
DOI：
10.1038/s41419-019-1458-8
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发表时间：
2019-02-27
影响因子：
9
通讯作者：
Zhang, Zhiguo
中科院分区：
文献类型：
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作者：
Tong, Lei;Wang, Long;Zhang, Zhiguo
过氧化物酶体增殖体激活受体δ (PPAR δ)属于核受体家族，参与代谢性疾病。虽然已知PPARd可以减轻肝脏脂质沉积，但其机制尚不清楚。在这里，我们发现PPAR δ是肝自噬通量的有效刺激物。肥胖和衰老小鼠肝组织中PPAR δ和自噬相关蛋白的表达水平降低。在肥胖的转基因db/db和高脂饲料喂养的小鼠中，PPAR δ的表达和活性在药理学和腺病毒介导下增加。利用遗传、药理学和代谢方法，我们证明PPAR δ降低肝内脂质含量，并通过涉及AMPK/mTOR信号的自噬-溶酶体途径刺激肝脏和肝细胞的β -氧化。这些结果为PPAR δ通过肝脏自噬的脂溶作用提供了新的见解，并强调了其在NAFLD中的潜在有益作用。
Peroxisome proliferator-activated receptor delta (PPAR delta) belongs to the nuclear receptor family and is involved in metabolic diseases. Although PPARd is known to attenuate hepatic lipid deposition, its mechanism remains unclear. Here, we show that PPAR delta is a potent stimulator of hepatic autophagic flux. The expression levels of PPAR delta and autophagy-related proteins were decreased in liver tissues from obese and ageing mice. Pharmacological and adenovirus-mediated increases in PPAR delta expression and activity were achieved in obese transgenic db/db and high fat diet-fed mice. Using genetic, pharmacological and metabolic approaches, we demonstrate that PPAR delta reduces intrahepatic lipid content and stimulates beta-oxidation in liver and hepatic cells by an autophagy-lysosomal pathway involving AMPK/mTOR signalling. These results provide novel insight into the lipolytic actions of PPAR delta through autophagy in the liver and highlight its potential beneficial effects in NAFLD.