Shifts in dietary carbohydrate-lipid exposure regulate expression of the non-alcoholic fatty liver disease-associated gene PNPLA3/adiponutrin in mouse liver and HepG2 human liver cells.
Shifts in dietary carbohydrate-lipid exposure regulate expression of the non-alcoholic fatty liver disease-associated gene PNPLA3/adiponutrin in mouse liver and HepG2 human liver cells.
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DOI：
10.1016/j.metabol.2014.06.016
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发表时间：
2014-10
影响因子：
9.8
通讯作者：
Ross, A. Catharine
中科院分区：
文献类型：
--
作者：
Hao, Lei;Ito, Kyoko;Huang, Kuan-Hsun;Sae-tan, Sudathip;Lambert, Joshua D.;Ross, A. Catharine
关键词：
Patatin 样磷脂酶结构域包含 3（PNPLA3，adiponutrin）已被确定为脂质代谢的调节剂。为了更好地了解 PNPLA3/adiponutrin 的生理作用，我们研究了其在各种营养/代谢条件下对完整小鼠和人肝细胞的调节作用。通过实时 PCR 测定饮食治疗后的 C57BL/6 小鼠肝脏中以及暴露于各种营养/代谢刺激的 HepG2 细胞中的 PNPLA3 基因表达。 siRNA 介导的 PNPLA3 敲低后，测定 HepG2 细胞中的细胞内脂质含量。在体内，与食物喂养的小鼠相比，高碳水化合物 (HC) 流质饮食喂养的小鼠肝脂质含量、PNPLA3 mRNA 和蛋白表达升高。通过向 HC 饮食中添加不饱和脂肪乳剂，升高的表达被完全消除。相比之下，在高脂饮食诱导的脂肪变性小鼠中，Pnpla3 表达与低脂喂养的小鼠没有差异。在 HepG2 细胞中，Pnpla3 表达因葡萄糖消耗而被可逆性抑制，并因葡萄糖补充而增加，但在添加胰岛素和胰高血糖素后没有变化。几种不饱和脂肪酸均显着降低 Pnpla3 mRNA，类似于体内脂肪乳剂。然而，HepG2 细胞中 Pnpla3 的敲低并没有改变高葡萄糖或油酸处理的细胞中的总脂质含量。我们的结果提供证据表明PNPLA3表达是碳水化合物诱导的脂肪生成的早期信号/特征，但其表达本身与脂肪变性无关。在高碳水化合物喂养导致的脂肪生成条件下，某些不饱和脂肪酸可以有效抑制体内和肝细胞系中的脂肪生成和PNPLA3表达。
Patatin-like phospholipase domain containing 3 (PNPLA3, adiponutrin) has been identified as a modifier of lipid metabolism. To better understand the physiological role of PNPLA3/adiponutrin, we have investigated its regulation in intact mice and human hepatocytes under various nutritional/metabolic conditions. PNPLA3 gene expression was determined by real-time PCR in liver of C57BL/6 mice after dietary treatments and in HepG2 cells exposed to various nutritional/metabolic stimuli. Intracellular lipid content was determined in HepG2 cells after siRNA-mediated knockdown of PNPLA3. In vivo, mice fed a high-carbohydrate (HC) liquid diet had elevated hepatic lipid content, and PNPLA3 mRNA and protein expression, compared to chow-fed mice. Elevated expression was completely abrogated by addition of unsaturated lipid emulsion to the HC diet. By contrast, in mice with high-fat diet-induced steatosis, Pnpla3 expression did not differ compared to low-fat fed mice. In HepG2 cells, Pnpla3 expression was reversibly suppressed by glucose depletion and increased by glucose refeeding, but unchanged by addition of insulin and glucagon. Several unsaturated fatty acids each significantly decreased Pnpla3 mRNA, similar to lipid emulsion in vivo. However, Pnpla3 knockdown in HepG2 cells did not alter total lipid content in high glucose- or oleic acid-treated cells. Our results provide evidence that PNPLA3 expression is an early signal/signature of carbohydrate-induced lipogenesis, but its expression is not associated with steatosis per se. Under lipogenic conditions due to high-carbohydrate feeding, certain unsaturated fatty acids can effectively suppress both lipogenesis and PNPLA3 expression, both in vivo and in a hepatocyte cell line.
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影响因子：
3.7
作者：
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通讯作者：
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影响因子：
25.7
作者：
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通讯作者：
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影响因子：
6.5
作者：
Lake, AC;Sun, Y;Gimeno, RE
通讯作者：
Gimeno, RE
影响因子：
13.5
作者：
Chen, Weiqin;Chang, Benny;Li, Lan;Chan, Lawrence
通讯作者：
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DOI：
10.1074/jbc.m109.064501
发表时间：
2010-02-26
期刊：
The Journal of biological chemistry
影响因子：
--
作者：
He S;McPhaul C;Li JZ;Garuti R;Kinch L;Grishin NV;Cohen JC;Hobbs HH
通讯作者：
Hobbs HH