Department of Internal Medicine A, Galilee Medical Center, Nahariya, Israel.
Nutrition and Diet Services, Hillel Yaffe, Hadera, Israel.
Adv Exp Med Biol. 2024;1460:869-882. doi: 10.1007/978-3-031-63657-8_29.
Dietary fatty acids play a role in the pathogenesis of obesity-associated nonalcoholic fatty liver disease. Lipotoxicity in obesity mediates insulin resistance, endothelial dysfunction, atherosclerosis, and gut microbiota dysbiosis. Cardiovascular complications are the main cause of morbidity and mortality in obese, insulin-resistant, and type 2 diabetes mellitus patients.Interventions targeting lipotoxicity are the main issue in preventing its multiple insults. Lifestyle modifications including healthy eating and regular exercise are the primary recommendations. Treatments also include drugs targeting energy intake, energy disposal, lipotoxic liver injury, and the resulting inflammation, fibrogenesis, and cirrhosis.Diet and nutrition have been linked to insulin resistance, an increased risk of developing type 2 diabetes, and impaired postprandial lipid metabolism. Low-fat diets are associated with higher survival. The Mediterranean diet includes an abundance of olive oil. Extra-virgin olive oil is the main source of monounsaturated fatty acids in Mediterranean diets. An olive oil-rich diet decreases triglyceride accumulation in the liver, improves postprandial triglyceride levels, improves glucose and insulin secretions, and upregulates GLUT-2 expression in the liver. The exact molecular mechanisms of olive oil's effects are unknown, but decreasing NF-kB activation, decreasing LDL oxidation, and improving insulin resistance by reducing the production of inflammatory cytokines (TNF-α and IL-6) and upregulating kinases and JNK-mediated phosphorylation of IRS-1 are possible principal mechanisms. Olive oil phenolic compounds also modulate gut microbiota diversity, which also affects lipotoxicity.In this review, we document lipotoxicity in obesity manifestations and the beneficial health effects of the Mediterranean diet derived from monounsaturated fatty acids, mainly from olive oil.
膳食脂肪酸在肥胖相关非酒精性脂肪性肝病的发病机制中起作用。肥胖中的脂毒性介导胰岛素抵抗、内皮功能障碍、动脉粥样硬化和肠道微生物失调。心血管并发症是肥胖、胰岛素抵抗和 2 型糖尿病患者发病率和死亡率的主要原因。针对脂毒性的干预措施是预防其多种损伤的主要问题。生活方式的改变，包括健康饮食和定期运动，是主要的建议。治疗还包括针对能量摄入、能量处置、脂毒性肝损伤以及由此产生的炎症、纤维化和肝硬化的药物。饮食和营养与胰岛素抵抗、2 型糖尿病风险增加和餐后脂质代谢受损有关。低脂饮食与更高的生存率相关。地中海饮食包括丰富的橄榄油。特级初榨橄榄油是地中海饮食中单不饱和脂肪酸的主要来源。富含橄榄油的饮食可减少肝脏中甘油三酯的积累，改善餐后甘油三酯水平，改善葡萄糖和胰岛素分泌，并上调肝脏中的 GLUT-2 表达。橄榄油作用的确切分子机制尚不清楚，但减少 NF-kB 激活、减少 LDL 氧化以及通过减少炎症细胞因子（TNF-α和 IL-6）的产生和上调 IRS-1 的激酶和 JNK 介导的磷酸化来改善胰岛素抵抗可能是主要机制。橄榄油酚类化合物还可调节肠道微生物群的多样性，这也会影响脂毒性。在这篇综述中，我们记录了肥胖表现中的脂毒性以及源自单不饱和脂肪酸（主要来自橄榄油）的地中海饮食对健康的有益影响。
