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Suppression of uric acid and lactate production by sodium acetate ameliorates hepatic triglyceride accumulation in fructose-insulin resistant pregnant rats.
Environmental Toxicology and Pharmacology ( IF 4.3 ) Pub Date : 2020-06-28 , DOI: 10.1016/j.etap.2020.103452
Adewumi O Oyabambi 1 , Kehinde S Olaniyi 2 , Ayodele O Soladoye 3 , Lawrence A Olatunji 1
Affiliation  

High fructose intake has been associated with perturbed lipid, uric acid and lactate homeostasis. However, consumption of fructose-sweetened beverages is not usually regulated during pregnancy. The effect of short-chain fatty acid (acetate) on the metabolic effects of high fructose intake during pregnancy is not known. We hypothesized that acetate prevents gestational fructose-induced hepatic triglyceride (TG) accumulation by suppressing uric acid and lactate production. Pregnant Wistar rats were randomly separated into three groups (n = 6/group) receiving drinking water (CON), 10 % (w/v) fructose drink (FRU) and 10 % (w/v) fructose with 200 mg/kg (w/w; p.o.) sodium acetate (FRU + ACE) daily for nineteen days. Fructose intake resulted in increased body weight gain, liver weight, fluid intake, visceral fat, insulin resistance, fasting blood glucose, insulin, plasma and hepatic TG, total cholesterol, free fatty acid, lipid peroxidation, adenosine deaminase, xanthine oxidase, uric acid, lactate, lactate dehydrogenase, and liver injury marker enzymes. However, gestational high fructose intake led to depressed plasma and hepatic glucose-6-phosphate dehydrogenase (G6PD)-dependent antioxidant barrier, adenosine and food intake. All these effects except water intake and food intake were abated by sodium acetate. These results demonstrate that maternal fructose-enriched drink would cause hepatic TG accumulation that is associated with perturbed glucose, uric acid, lactate homeostasis, and G6PD-dependent antioxidant barrier. These results also demonstrate that acetate protects the liver against gestational fructose-induced TG accumulation by inhibiting uric acid and lactate production. Thus, acetate may be useful in the treatment of hyperuricemia- and hyperlactatemia-related disorders.



中文翻译:

乙酸钠抑制尿酸和乳酸的产生可改善果糖-胰岛素抵抗的妊娠大鼠肝中甘油三酸酯的积累。

果糖摄入高与脂质,尿酸和乳酸稳态紊乱有关。但是,怀孕期间通常不限制使用果糖加糖的饮料。短链脂肪酸(乙酸盐)对怀孕期间高果糖摄入的代谢作用的影响尚不清楚。我们假设乙酸盐通过抑制尿酸和乳酸的产生来防止妊娠果糖诱导的肝甘油三酸酯(TG)积累。将Wistar怀孕大鼠随机分为三组(n = 6 /组),分别接受饮用水(CON),10%(w / v)果糖饮料(FRU)和10%(w / v)果糖(200 mg / kg, w / w; po)乙酸钠(FRU + ACE),每天持续19天。果糖摄入导致体重增加,肝脏重量,液体摄入,内脏脂肪,胰岛素抵抗,空腹血糖,胰岛素,血浆和肝甘油三酯,总胆固醇,游离脂肪酸,脂质过氧化,腺苷脱氨酶,黄嘌呤氧化酶,尿酸增加,乳酸,乳酸脱氢酶和肝损伤标记酶。然而,妊娠期果糖摄入过多会导致血浆和肝6磷酸葡萄糖磷酸脱氢酶(G6PD)依赖的抗氧化屏障,腺苷和食物摄入降低。除水分和食物摄入外,所有这些作用均由乙酸钠减轻。这些结果表明,孕妇富含果糖的饮料会引起肝脏TG蓄积,这与葡萄糖,尿酸,乳酸稳态,和依赖G6PD的抗氧化剂屏障。这些结果还表明乙酸盐通过抑制尿酸和乳酸盐的产生来保护肝脏免受果糖诱导的TG积累。因此,乙酸盐可用于治疗高尿酸血症和高脂血症相关疾病。

更新日期:2020-06-28
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