Department of Biochemistry and Biotechnology, Vasyl Stefanyk Precarpathian National University, 57 Shevchenko Str., Ivano-Frankivsk 76018, Ukraine.
Department of Biochemistry and Biotechnology, Vasyl Stefanyk Precarpathian National University, 57 Shevchenko Str., Ivano-Frankivsk 76018, Ukraine.
Biochim Biophys Acta Gen Subj. 2022 Dec;1866(12):130226. doi: 10.1016/j.bbagen.2022.130226. Epub 2022 Aug 17.
Diets rich in fats and/or carbohydrates are used to study obesity and related metabolic complications. We studied the effects of a high fat high fructose diet (HFFD) on intermediary metabolism and the development of oxidative stress in mouse liver and tested the ability of alpha-ketoglutarate to prevent HFFD-induced changes.
Male mice were fed a standard diet (10% kcal fat) or HFFD (45% kcal fat, 15% kcal fructose) with or without addition of 1% alpha-ketoglutarate (AKG) in drinking water for 8 weeks.
The HFFD had no effect on body mass but activated fructolysis and glycolysis and induced inflammation and oxidative stress with a concomitant increase in activity of antioxidant enzymes in the mouse liver. HFFD-fed mice also showed lower mRNA levels of pyruvate dehydrogenase kinase 4 (PDK4) and slightly increased intensity of mitochondrial respiration in liver compared to mice on the standard diet. No significant effects of HFFD on transcription of PDK2 and PGC1α, a peroxisome proliferator-activated receptor co-activator-1α, or protein levels of p-AMPK, an active form of AMP-activated protein kinase, were found. The addition of AKG to HFFD decreased oxidized glutathione levels, did not affect levels of lipid peroxides and PDK4 transcripts but increased activities of hexokinase and phosphofructokinase in mouse liver.
Supplementation with AKG had weak modulating effects on HFFD-induced oxidative stress and changes in energetics in mouse liver.
Our research expands the understanding of diet-induced metabolic switching and elucidates further roles of alpha-ketoglutarate as a metabolic regulator.
富含脂肪和/或碳水化合物的饮食被用于研究肥胖症和相关代谢并发症。我们研究了高脂肪高果糖饮食（HFFD）对小鼠肝脏中间代谢和氧化应激发展的影响，并测试了α-酮戊二酸（AKG）预防 HFFD 诱导变化的能力。
雄性小鼠喂食标准饮食（10%卡路里脂肪）或 HFFD（45%卡路里脂肪，15%卡路里果糖），同时或不添加 1%α-酮戊二酸（AKG）于饮用水中 8 周。
HFFD 对体重没有影响，但激活了果糖分解和糖酵解，并诱导了炎症和氧化应激，同时抗氧化酶的活性增加。与标准饮食组相比，HFFD 喂养的小鼠的丙酮酸脱氢酶激酶 4（PDK4）mRNA 水平较低，肝线粒体呼吸强度略有增加。HFFD 对 PDK2 和 PGC1α（过氧化物酶体增殖物激活受体共激活因子 1α）的转录或 p-AMPK（一种活性形式的 AMP 激活蛋白激酶）的蛋白水平没有显著影响。向 HFFD 添加 AKG 降低了氧化型谷胱甘肽水平，对脂质过氧化物水平和 PDK4 转录物没有影响，但增加了小鼠肝中己糖激酶和磷酸果糖激酶的活性。
AKG 的补充对 HFFD 诱导的氧化应激和小鼠肝能量代谢变化具有较弱的调节作用。
我们的研究扩展了对饮食诱导的代谢转换的理解，并进一步阐明了α-酮戊二酸作为代谢调节剂的作用。
