Zheng Jia-Lang, Luo Zhi, Hu Wei, Pan Ya-Xiong, Zhuo Mei-Qing
Key Laboratory of Freshwater Animal Breeding, Ministry of Agriculture of PRC, Fishery College, Huazhong Agricultural University, Wuhan, 430070, China.
Lipids. 2015 Apr;50(4):417-26. doi: 10.1007/s11745-015-3999-7. Epub 2015 Mar 11.
Fenofibrate is known to possess lipid-lowering effects by regulation of gene transcription involved in lipid metabolism. Waterborne Zn exposure induces lipid deposition in yellow catfish Pelteobagrus fulvidraco. Thus, the present working hypothesis is that dietary fenofibrate addition will reduce hepatic lipids in yellow catfish exposed to waterborne Zn. To this end, juvenile yellow catfish were exposed to 0.04 (control), 0.35 mg/L waterborne Zn, 0.15% dietary fenofibrate, and 0.35 mg Zn/l + 0.15% dietary fenofibrate for 8 weeks. Growth performance, lipid deposition and metabolism in the liver were determined. Dietary fenofibrate promoted growth performance and reduced hepatic lipid content of yellow catfish exposed to waterborne Zn. However, these effects did not appear in fish in normal water. The lipid-lowering effect of fenofibrate on fish exposed to waterborne Zn was associated with increased lipolysis, as indicated by increased CPT I activities and expression of lipolytic genes PPARα, CPT IA, ATGL and HSL, and with reduced lipogenesis as indicated by reduced activities of G6PD, 6PGD, ME and ICDH. Dietary fenofibrate significantly increased mRNA levels of FAS, LPL and ACCα, but reduced mRNA levels of ACCβ and PPARγ in fish exposed to waterborne Zn. Pearson correlations between transcriptional factors expression, and activities and expression of several enzymes were observed, indicating that changes at the molecular and enzymatic levels may underlie the patterns of lipid metabolism and accordingly affect hepatic fat storage. Taken together, our results suggest that the lipid-lowering effect of fenofibrate was attributed, in part, to the down-regulation of lipogenesis and up-regulation of fatty acid oxidation.
已知非诺贝特通过调节参与脂质代谢的基因转录发挥降脂作用。水体锌暴露会诱导黄颡鱼（Pelteobagrus fulvidraco）体内脂质沉积。因此，本研究的工作假设是，添加非诺贝特的饲料将减少暴露于水体锌的黄颡鱼肝脏中的脂质。为此，将幼年黄颡鱼暴露于0.04（对照）、0.35 mg/L水体锌、0.15%饲料非诺贝特以及0.35 mg Zn/l + 0.15%饲料非诺贝特环境中8周。测定生长性能、肝脏中的脂质沉积和代谢情况。饲料中的非诺贝特促进了暴露于水体锌的黄颡鱼的生长性能并降低了其肝脏脂质含量。然而，在正常水体中的鱼未出现这些效应。非诺贝特对暴露于水体锌的鱼的降脂作用与脂肪分解增加有关，表现为肉碱棕榈酰转移酶I（CPT I）活性增加以及脂解基因PPARα、CPT IA、脂肪甘油三酯脂酶（ATGL）和激素敏感性脂肪酶（HSL）的表达增加，同时与脂肪生成减少有关，表现为葡萄糖-6-磷酸脱氢酶（G6PD）、6-磷酸葡萄糖酸脱氢酶（6PGD）、苹果酸酶（ME）和异柠檬酸脱氢酶（ICDH）的活性降低。饲料非诺贝特显著增加了暴露于水体锌的鱼中脂肪酸合成酶（FAS）、脂蛋白脂肪酶（LPL）和乙酰辅酶A羧化酶α（ACCα）的mRNA水平，但降低了乙酰辅酶A羧化酶β（ACCβ）和过氧化物酶体增殖物激活受体γ（PPARγ）的mRNA水平。观察到转录因子表达与几种酶的活性和表达之间存在皮尔逊相关性，表明分子和酶水平的变化可能是脂质代谢模式的基础，并相应地影响肝脏脂肪储存。综上所述，我们的结果表明，非诺贝特的降脂作用部分归因于脂肪生成的下调和脂肪酸氧化的上调。
