Pierce Andrew A, Duwaerts Caroline C, Soon Russell K, Siao Kevin, Grenert James P, Fitch Mark, Hellerstein Marc K, Beysen Carine, Turner Scott M, Maher Jacquelyn J
Liver Center, University of California San Francisco, San Francisco, CA 94143, USA; Department of Medicine, University of California San Francisco, San Francisco, CA 94143-0410, USA.
Liver Center, University of California San Francisco, San Francisco, CA 94143, USA; Department of Pathology, University of California San Francisco, San Francisco, CA 94143-0410, USA.
J Nutr Biochem. 2016 Mar;29:12-20. doi: 10.1016/j.jnutbio.2015.10.020. Epub 2015 Nov 17.
Diets containing excess carbohydrate and fat promote hepatic steatosis and steatohepatitis in mice. Little is known, however, about the impact of specific carbohydrate/fat combinations on liver outcome. This study was designed to determine whether high-energy diets with identical caloric density but different carbohydrate and fat composition have unique effects on the liver. Four experimental diets were formulated with 60%kcal carbohydrate and 20%kcal fat, each in nearly pure form from a single source: starch-oleate, starch-palmitate, sucrose-oleate and sucrose-palmitate. The diets were fed to mice for 3 or 12 weeks for analysis of lipid metabolism and liver injury. All mice developed hepatic steatosis over 12 weeks, but mice fed the sucrose-palmitate diet accumulated more hepatic lipid than those in the other three experimental groups. The exaggerated lipid accumulation in sucrose-palmitate-fed mice was attributable to a disproportionate rise in hepatic de novo lipogenesis. These mice accrued more hepatic palmitate and exhibited more evidence of liver injury than any of the other experimental groups. Interestingly, lipogenic gene expression in mice fed the custom diets did not correlate with actual de novo lipogenesis. In addition, de novo lipogenesis rose in all mice between 3 and 12 weeks, without feedback inhibition from hepatic steatosis. The pairing of simple sugar (sucrose) and saturated fat (palmitate) in a high-carbohydrate/moderate-fat diet induces more de novo lipogenesis and liver injury than other carbohydrate/fat combinations. Diet-induced liver injury correlates positively with hepatic de novo lipogenesis and is not predictable by isolated analysis of lipogenic gene expression.
含过量碳水化合物和脂肪的饮食会促进小鼠肝脏脂肪变性和脂肪性肝炎。然而，关于特定碳水化合物/脂肪组合对肝脏结局的影响却知之甚少。本研究旨在确定热量密度相同但碳水化合物和脂肪组成不同的高能量饮食对肝脏是否有独特影响。配制了四种实验性饮食，碳水化合物含量为60%千卡，脂肪含量为20%千卡，每种饮食几乎都来自单一来源的纯净形式：淀粉 - 油酸酯、淀粉 - 棕榈酸酯、蔗糖 - 油酸酯和蔗糖 - 棕榈酸酯。将这些饮食喂给小鼠3周或12周，以分析脂质代谢和肝脏损伤。所有小鼠在12周内均出现肝脏脂肪变性，但喂食蔗糖 - 棕榈酸酯饮食的小鼠肝脏脂质积累比其他三个实验组更多。蔗糖 - 棕榈酸酯喂养的小鼠中脂质积累过多归因于肝脏从头脂肪生成的不成比例增加。与其他任何实验组相比，这些小鼠肝脏中积累了更多的棕榈酸，并且表现出更多肝脏损伤的迹象。有趣的是，喂食定制饮食的小鼠中脂肪生成基因表达与实际的从头脂肪生成不相关。此外，所有小鼠在3至12周之间从头脂肪生成均增加，且没有受到肝脏脂肪变性的反馈抑制。在高碳水化合物/中等脂肪饮食中，简单糖（蔗糖）和饱和脂肪（棕榈酸酯）的组合比其他碳水化合物/脂肪组合诱导更多的从头脂肪生成和肝脏损伤。饮食诱导的肝脏损伤与肝脏从头脂肪生成呈正相关，并且通过单独分析脂肪生成基因表达无法预测。
