Department of Physiology and Biophysics, Institute of Biomedical Sciences, University of São Paulo, São Paulo, 05508-000, Brazil.
Department of Biochemistry, Institute of Chemistry, University of Sao Paulo, Sao Paulo, 05508-000, Brazil.
Mol Nutr Food Res. 2019 Apr;63(7):e1800813. doi: 10.1002/mnfr.201800813. Epub 2019 Jan 17.
The mechanisms and involvement of uncoupling protein 1 (UCP1) in the protection from obesity and insulin resistance induced by intake of a high-fat diet rich in omega-3 (n-3) fatty acids are investigated.
C57BL/6J mice are fed either a low-fat (control group) or one of two isocaloric high-fat diets containing either lard (HFD) or fish oil (HFN3) as fat source and evaluated for body weight, adiposity, energy expenditure, glucose homeostasis, and inguinal white and interscapular brown adipose tissue (iWAT and iBAT, respectively) gene expression, lipidome, and mitochondrial bioenergetics. HFN3 intake protected from obesity, glucose and insulin intolerances, and hyperinsulinemia. This is associated with increased energy expenditure, iWAT UCP1 expression, and incorporation of n-3 eicosapentaenoic and docosahexaenoic fatty acids in iWAT and iBAT triacylglycerol. Importantly, HFN3 is equally effective in reducing body weight gain, adiposity, and glucose intolerance and increasing energy expenditure in wild-type and UCP1-deficient mice without recruiting other thermogenic processes in iWAT and iBAT, such as mitochondrial uncoupling and SERCA-mediated calcium and creatine-driven substrate cyclings.
Intake of a high-fat diet rich in omega-3 fatty acids protects both wild-type and UCP1-deficient mice from obesity and insulin resistance by increasing energy expenditure through unknown mechanisms.
探究解偶联蛋白 1（UCP1）在保护机体免受高脂肪饮食诱导的肥胖和胰岛素抵抗中的作用机制和参与情况，这种高脂肪饮食富含 ω-3（n-3）脂肪酸。
C57BL/6J 小鼠分别喂食低脂肪（对照组）或两种等热量高脂肪饮食中的一种，这两种高脂肪饮食的脂肪来源分别为猪油（HFD）或鱼油（HFN3），并评估其体重、肥胖程度、能量消耗、葡萄糖稳态以及腹股沟白色和肩胛间棕色脂肪组织（iWAT 和 iBAT，分别）的基因表达、脂质组学和线粒体生物能学。HFN3 的摄入可防止肥胖、葡萄糖和胰岛素不耐受以及高胰岛素血症。这与能量消耗增加、iWAT UCP1 表达增加以及 iWAT 和 iBAT 三酰甘油中 n-3 二十碳五烯酸和二十二碳六烯酸的掺入有关。重要的是，HFN3 同样有效地减少体重增加、肥胖和葡萄糖不耐受，并增加野生型和 UCP1 缺陷型小鼠的能量消耗，而不会招募 iWAT 和 iBAT 中的其他产热过程，如线粒体解偶联和 SERCA 介导的钙和肌酸驱动的底物循环。
富含 ω-3 脂肪酸的高脂肪饮食可通过未知机制增加能量消耗，从而保护野生型和 UCP1 缺陷型小鼠免受肥胖和胰岛素抵抗。
