Department of Biomedical Engineering, Mokwon University, Daejeon 35349, Korea.
Department of Formula Sciences, College of Korean Medicine, Dongeui University, Busan 47340, Korea.
Int J Mol Sci. 2021 Apr 1;22(7):3675. doi: 10.3390/ijms22073675.
Fibrates, including fenofibrate, are a class of hypolipidemic drugs that activate peroxisome proliferator-activated receptor α (PPARα), which in-turn regulates the expression of lipid and lipoprotein metabolism genes. We investigated whether fenofibrate can reduce visceral obesity and nonalcoholic fatty liver disease via adipose tissue PPARα activation in female ovariectomized (OVX) C57BL/6J mice fed a high-fat diet (HFD), a mouse model of obese postmenopausal women. Fenofibrate reduced body weight gain (-38%, < 0.05), visceral adipose tissue mass (-46%, < 0.05), and visceral adipocyte size (-20%, < 0.05) in HFD-fed obese OVX mice. In addition, plasma levels of alanine aminotransferase and aspartate aminotransferase, as well as free fatty acids, triglycerides, and total cholesterol, were decreased. Fenofibrate also inhibited hepatic lipid accumulation (-69%, < 0.05) and infiltration of macrophages (-72%, < 0.05), while concomitantly upregulating the expression of fatty acid β-oxidation genes targeted by PPARα and decreasing macrophage infiltration and mRNA expression of inflammatory factors in visceral adipose tissue. These results suggest that fenofibrate inhibits visceral obesity, as well as hepatic steatosis and inflammation, in part through visceral adipose tissue PPARα activation in obese female OVX mice.
贝特类药物，包括非诺贝特，是一类降脂药物，可激活过氧化物酶体增殖物激活受体α（PPARα），进而调节脂质和脂蛋白代谢基因的表达。我们研究了非诺贝特是否可以通过激活脂肪组织中的 PPARα，减少肥胖去卵巢（OVX）C57BL/6J 雌性小鼠高脂饮食（HFD）喂养引起的内脏肥胖和非酒精性脂肪性肝病，该模型模拟了肥胖绝经后女性。非诺贝特可降低 HFD 喂养肥胖 OVX 小鼠的体重增加（-38%，<0.05）、内脏脂肪组织质量（-46%，<0.05）和内脏脂肪细胞大小（-20%，<0.05）。此外，血浆丙氨酸转氨酶和天冬氨酸转氨酶水平、游离脂肪酸、甘油三酯和总胆固醇水平降低。非诺贝特还抑制肝脂质积累（-69%，<0.05）和巨噬细胞浸润（-72%，<0.05），同时上调 PPARα 靶向的脂肪酸β氧化基因的表达，并减少内脏脂肪组织中巨噬细胞浸润和炎症因子的 mRNA 表达。这些结果表明，非诺贝特通过激活肥胖雌性 OVX 小鼠的内脏脂肪组织中的 PPARα，抑制内脏肥胖以及肝脂肪变性和炎症。
