Department of Lipid Chemistry, National Institute of Nutrition, Hyderabad, India.
Department of Pathology, National Institute of Nutrition, Hyderabad, India.
Eur J Nutr. 2018 Sep;57(6):2171-2187. doi: 10.1007/s00394-017-1492-1. Epub 2017 Jul 4.
Consumption of Western diet high in fat and fructose has been attributed to the recent epidemic of nonalcoholic fatty liver disease (NAFLD). However, the impact of specific fatty acids on the progression of NAFLD to nonalcoholic steatohepatitis (NASH) is poorly understood. In the present study, we investigated the chronic effects of consumption of fructose in combination with saturated fatty acids (SFA) or trans fatty acids (TFA) on the development of NAFLD.
Male Sprague-Dawley rats were randomly assigned to six isocaloric starch/high fructose (44% of calories), high fat (39% calories) diet containing either starch-peanut oil, fructose-peanut oil, fructose-palmolein, fructose-clarified butter, fructose-coconut oil or fructose-partially hydrogenated vegetable oil and fed for 24 weeks. Palmolein, clarified butter and coconut oil were used as the source of SFA whereas partially hydrogenated vegetable oil was used as the source of TFA. Peanut oil was used as the reference oil.
Long-term feeding of fructose in combination with SFA or TFA induced hepatic steatosis of similar extent associated with upregulation of stearoyl CoA desaturase-1. In contrast, fructose in combination with TFA induced NASH with fibrosis as evidenced by upregulation of hepatic proinflammatory cytokine and fibrogenic gene expression, increased hepatic oxidative stress and adipocytokine imbalance. Histopathological analysis revealed the presence of NASH with fibrosis. Further, peanut oil prevented the development of NAFLD in fructose-fed rats.
Fructose in combination with TFA caused NASH with fibrosis by inducing oxidative stress and inflammation, whereas, fructose in combination with SFA caused simple steatosis, suggesting that the type of fatty acid is more important for the progression of NAFLD.
高脂肪和果糖含量高的西方饮食的消费与非酒精性脂肪性肝病（NAFLD）的近期流行有关。然而，特定脂肪酸对 NAFLD 向非酒精性脂肪性肝炎（NASH）进展的影响尚不清楚。在本研究中，我们研究了果糖与饱和脂肪酸（SFA）或反式脂肪酸（TFA）结合消耗对 NAFLD 发展的慢性影响。
雄性 Sprague-Dawley 大鼠被随机分配到六种等热量淀粉/高果糖（44%卡路里）、高脂肪（39%卡路里）饮食中，其中含有淀粉-花生油、果糖-花生油、果糖-棕榈油、果糖-澄清黄油、果糖-椰子油或果糖-部分氢化植物油，并喂养 24 周。棕榈油、澄清黄油和椰子油被用作 SFA 的来源，而部分氢化植物油被用作 TFA 的来源。花生油被用作参比油。
长期摄入果糖与 SFA 或 TFA 结合会引起相似程度的肝脂肪变性，伴随着硬脂酰辅酶 A 去饱和酶-1 的上调。相比之下，果糖与 TFA 结合会引起 NASH，伴有纤维化，表现为肝前炎性细胞因子和纤维生成基因表达上调、肝氧化应激增加和脂肪细胞因子失衡。组织病理学分析显示存在伴有纤维化的 NASH。此外，花生油可预防果糖喂养大鼠的 NAFLD 发生。
果糖与 TFA 结合通过诱导氧化应激和炎症引起 NASH 伴纤维化，而果糖与 SFA 结合引起单纯性脂肪变性，表明脂肪酸的类型对 NAFLD 的进展更为重要。
