n-3 Fatty acids and rosiglitazone improve insulin sensitivity through additive stimulatory effects on muscle glycogen synthesis in mice fed a high-fat diet
n-3 Fatty acids and rosiglitazone improve insulin sensitivity through additive stimulatory effects on muscle glycogen synthesis in mice fed a high-fat diet
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DOI：
10.1007/s00125-009-1305-z
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发表时间：
2009-05-01
期刊：
影响因子：
8.2
通讯作者：
Kopecky, J.
中科院分区：
文献类型：
--
作者：
Kuda, O.;Jelenik, T.;Kopecky, J.
海洋来源的脂肪酸，即二十二碳六烯酸（DHA）和二十碳五烯酸（EPA）作为降血脂剂，但它们不能改善肥胖和糖尿病患者的血脂控制。噻唑烷二酮类如罗格列酮是过氧化物酶体增殖物激活受体γ的特异性激活剂，可改善全身胰岛素敏感性。我们假设，DHA和EPA浓缩物（DHA/EPA）和罗格列酮的联合治疗将纠正，通过互补的添加剂机制，脂质和葡萄糖的稳态在obesity.Male C57 BL/6小鼠喂养玉米油为基础的高脂肪饮食的损害。分析了DHA/EPA（替代15%的膳食脂质）、罗格列酮（10 mg/kg膳食）或两者组合对体重、肥胖、代谢标志物和血浆中脂联素以及肝脏和肌肉基因表达和代谢的影响。正常血-高胰岛素钳夹法测定胰岛素敏感性。DHA/EPA和罗格列酮在预防肥胖、脂肪细胞肥大、低度脂肪组织炎症、血脂异常和胰岛素抵抗方面具有相加作用，同时诱导脂联素、抑制肝脏脂肪生成和降低肌肉神经酰胺浓度。葡萄糖耐量的改善反映了联合治疗对肌糖原合成及其对胰岛素敏感性的协同刺激作用。DHA/EPA和罗格列酮可以作为补充疗法来对抗血脂异常和胰岛素抵抗。联合治疗可降低剂量需求，从而降低噻唑烷二酮治疗不良副作用的发生率。
Fatty acids of marine origin, i.e. docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) act as hypolipidaemics, but they do not improve glycaemic control in obese and diabetic patients. Thiazolidinediones like rosiglitazone are specific activators of peroxisome proliferator-activated receptor gamma, which improve whole-body insulin sensitivity. We hypothesised that a combined treatment with a DHA and EPA concentrate (DHA/EPA) and rosiglitazone would correct, by complementary additive mechanisms, impairments of lipid and glucose homeostasis in obesity.Male C57BL/6 mice were fed a corn oil-based high-fat diet. The effects of DHA/EPA (replacing 15% dietary lipids), rosiglitazone (10 mg/kg diet) or a combination of both on body weight, adiposity, metabolic markers and adiponectin in plasma, as well as on liver and muscle gene expression and metabolism were analysed. Euglycaemic-hyperinsulinaemic clamps were used to characterise the changes in insulin sensitivity. The effects of the treatments were also analysed in dietary obese mice with impaired glucose tolerance (IGT).DHA/EPA and rosiglitazone exerted additive effects in prevention of obesity, adipocyte hypertrophy, low-grade adipose tissue inflammation, dyslipidaemia and insulin resistance, while inducing adiponectin, suppressing hepatic lipogenesis and decreasing muscle ceramide concentration. The improvement in glucose tolerance reflected a synergistic stimulatory effect of the combined treatment on muscle glycogen synthesis and its sensitivity to insulin. The combination treatment also reversed dietary obesity, dyslipidaemia and IGT.DHA/EPA and rosiglitazone can be used as complementary therapies to counteract dyslipidaemia and insulin resistance. The combination treatment may reduce dose requirements and hence the incidence of adverse side effects of thiazolidinedione therapy.