Department of Medicine I, Medical University of Innsbruck, Innsbruck, Austria; Christan Doppler Laboratory for Metabolic Crosstalk, Department of Medicine I, Medical University of Innsbruck, Innsbruck, Austria.
Institut Pasteur de Lille, CHU Lille, Univ. Lille - EGID, Lille, France.
Nutr Metab Cardiovasc Dis. 2021 Mar 10;31(3):972-978. doi: 10.1016/j.numecd.2020.11.008. Epub 2020 Nov 17.
Western dietary habits are partially characterized by increased uptake of fructose, which contributes to metabolic dysregulation and associated liver diseases. For example, a diet enriched with fructose drives insulin resistance and non-alcoholic fatty liver disease (NAFLD). The molecular hubs that control fructose-induced metabolic dysregulation are poorly understood. Apolipoprotein A5 (apoA5) controls triglyceride metabolism with a putative role in hepatic lipid deposition. We explored apoA5 as a rheostat for fructose-induced hepatic and metabolic disease in mammals.
ApoA5 knock out (-/-) and wildtype (wt) mice were fed with high fructose diet or standard diet for 10 weeks. Afterwards, we conducted a metabolic characterization by insulin tolerance test as well as oral glucose tolerance test. Additionally, hepatic lipid content as well as transcription patterns of key enzymes and transcription factors in glucose and lipid metabolism were evaluated. Despite comparable body weight, insulin sensitivity was significantly improved in high fructose diet fed apoA5 (-/-) when compared to wildtype mice on the same diet. In parallel, hepatic triglyceride content was significantly lower in apoA5 (-/-) mice than in wt mice. No difference was seen between apoA5 (-/-) and wt mice on a standard diet.
ApoA5 is involved in fructose-induced metabolic dysregulation and associated hepatic steatosis suggesting that apoA5 may be a novel target to treat metabolic diseases.
西方饮食习惯的特点之一是果糖摄取量增加，这导致了代谢失调和相关的肝脏疾病。例如，富含果糖的饮食会导致胰岛素抵抗和非酒精性脂肪性肝病（NAFLD）。控制果糖诱导的代谢失调的分子枢纽尚未得到充分理解。载脂蛋白 A5（apoA5）控制甘油三酯代谢，在肝脏脂质沉积中可能具有作用。我们探讨了 apoA5 作为哺乳动物果糖诱导的肝脏和代谢疾病的变阻器。
apoA5 敲除（-/-）和野生型（wt）小鼠分别用高果糖饮食或标准饮食喂养 10 周。然后，我们通过胰岛素耐量试验和口服葡萄糖耐量试验进行代谢特征分析。此外，评估了肝脂质含量以及葡萄糖和脂质代谢关键酶和转录因子的转录模式。尽管体重相当，但与同饮食的野生型小鼠相比，高果糖饮食喂养的 apoA5（-/-）小鼠的胰岛素敏感性显著改善。与此同时，apoA5（-/-）小鼠的肝甘油三酯含量明显低于 wt 小鼠。在标准饮食下，apoA5（-/-）和 wt 小鼠之间没有差异。
apoA5 参与果糖诱导的代谢失调和相关的肝脂肪变性，表明 apoA5 可能是治疗代谢疾病的新靶点。
