美国哈佛医学院的C. Ronald Kahn和Samir Softic等研究人员发现，膳食糖通过线粒体蛋白的转录和翻译后修饰来改变肝脏脂肪酸的氧化。2019年10月刊的《细胞—代谢》发表了这一成果。

研究人员发现果糖和葡萄糖补充的高脂饮食（HFD）对肝线粒体功能和脂肪酸氧化产生不同的影响。这是通过三个不同的调控节点介导的，包括对丙二酰辅酶A水平的不同影响、对线粒体大小/蛋白质丰度的影响以及线粒体蛋白质的乙酰化。HFD和HFD加果糖喂养的小鼠出现CTP1a（脂肪酸氧化的限速酶）活性的降低，而果糖代谢的抑制增加了CPT1a及其酰基肉碱产物的含量。

此外，果糖补充的HFD导致ACADL蛋白和CPT1a的乙酰化增加，这与脂肪代谢减少有关。

总之，膳食果糖而不是葡萄糖补充HFD会损害线粒体的大小、功能和蛋白质乙酰化，从而导致脂肪酸氧化减少和代谢失调的发展。

据介绍，膳食糖、果糖和葡萄糖可促进肝脏新生脂肪形成，并改善HFD对胰岛素抵抗发展的影响。

附：英文原文

Title: Dietary Sugars Alter Hepatic Fatty Acid Oxidation via Transcriptional and Post-translational Modifications of Mitochondrial Proteins

Author: Samir Softic, Jesse G. Meyer, Guo-Xiao Wang, Manoj K. Gupta, Thiago M. Batista, Hans P.M.M. Lauritzen, Shiho Fujisaka, Dolors Serra, Laura Herrero, Jennifer Willoughby, Kevin Fitzgerald, Olga Ilkayeva, Christopher B. Newgard, Bradford W. Gibson, Birgit Schilling, David E. Cohen, C. Ronald Kahn

Issue&Volume: VOLUME 30, ISSUE 4

Abstract: 

Dietary sugars, fructose and glucose, promote hepatic de novo lipogenesis and modify the effects of a high-fat diet (HFD) on the development of insulin resistance. Here, we show that fructose and glucose supplementation of an HFD exert divergent effects on hepatic mitochondrial function and fatty acid oxidation. This is mediated via three different nodes of regulation, including differential effects on malonyl-CoA levels, effects on mitochondrial size/protein abundance, and acetylation of mitochondrial proteins. HFD- and HFD plus fructose-fed mice have decreased CTP1a activity, the rate-limiting enzyme of fatty acid oxidation, whereas knockdown of fructose metabolism increases CPT1a and its acylcarnitine products. Furthermore, fructose-supplemented HFD leads to increased acetylation of ACADL and CPT1a, which is associated with decreased fat metabolism. In summary, dietary fructose, but not glucose, supplementation of HFD impairs mitochondrial size, function, and protein acetylation, resulting in decreased fatty acid oxidation and development of metabolic dysregulation.

DOI: 10.1016/j.cmet.2019.09.003

Source: https://www.cell.com/cell-metabolism/fulltext/S1550-4131(19)30504-2