Wang Shari, Goodspeed Leela, Turk Katherine E, Houston Barbara, den Hartigh Laura J
Department of Medicine, Division of Metabolism, Endocrinology, and Nutrition, University of Washington, Seattle, Washington 98109.
Endocrinology. 2017 Sep 1;158(9):2848-2859. doi: 10.1210/en.2017-00213.
Trans-10, cis-12 conjugated linoleic acid (10,12 CLA) is a dietary fatty acid that promotes weight loss and disproportionate fat loss. Obese mice fed a high-fat, high-sucrose (HFHS) diet containing 10,12 CLA are resistant to weight gain and contain markedly reduced subcutaneous fat and adiponectin, with a concurrent lack of improvement in insulin sensitivity despite significant weight loss. Taken together, 10,12 CLA promotes a phenotype resembling peroxisome proliferator-activated receptor (PPAR)γ antagonism. Because thiazolidinediones such as rosiglitazone (Rosi) are used clinically to improve insulin sensitivity by activating PPARγ, with particular efficacy in subcutaneous white adipose tissue, we hypothesized that Rosi would improve glucose metabolism in mice losing weight with 10,12 CLA. Obese low-density lipoprotein receptor-deficient mice were fed a HFHS control diet, or supplemented with 1% 10,12 CLA with or without Rosi (10 mg/kg) for 8 weeks. Body composition, glucose and insulin tolerance tests, tissue gene expression, and plasma lipid analyses were performed. Mice consuming 10,12 CLA with Rosi lost weight and body fat compared with control groups, but with a healthier redistribution of body fat toward more subcutaneous adipose tissue than with 10,12 CLA alone. Further, Rosi improved 10,12 CLA-mediated insulin resistance parameters and increased plasma and subcutaneous adipose tissue adiponectin levels without adverse effects on plasma or hepatic lipids. We conclude that cotreatment of mice with 10,12 CLA and Rosi promotes fat loss with a healthier fat distribution that leads to improved insulin sensitivity, suggesting that the combination treatment strategy of 10,12 CLA with Rosi could have therapeutic potential for obesity treatment.
反式-10，顺式-12共轭亚油酸（10,12 CLA）是一种膳食脂肪酸，可促进体重减轻和不成比例的脂肪减少。喂食含10,12 CLA的高脂肪、高蔗糖（HFHS）饮食的肥胖小鼠对体重增加具有抵抗力，皮下脂肪和脂联素明显减少，尽管体重显著减轻，但胰岛素敏感性并未同时得到改善。综上所述，10,12 CLA促进了一种类似于过氧化物酶体增殖物激活受体（PPAR）γ拮抗作用的表型。由于罗格列酮（Rosi）等噻唑烷二酮类药物在临床上用于通过激活PPARγ来改善胰岛素敏感性，在皮下白色脂肪组织中具有特殊疗效，我们推测Rosi会改善食用10,12 CLA减肥的小鼠的葡萄糖代谢。给肥胖的低密度脂蛋白受体缺陷小鼠喂食HFHS对照饮食，或补充1%的10,12 CLA，同时添加或不添加Rosi（10 mg/kg），持续8周。进行了身体成分、葡萄糖和胰岛素耐受性测试、组织基因表达以及血浆脂质分析。与对照组相比，同时摄入10,12 CLA和Rosi的小鼠体重和体脂减少，但与单独使用10,12 CLA相比，体脂向更多皮下脂肪组织的重新分布更健康。此外，Rosi改善了10,12 CLA介导的胰岛素抵抗参数，并提高了血浆和皮下脂肪组织中的脂联素水平，而对血浆或肝脏脂质没有不良影响。我们得出结论，10,12 CLA和Rosi联合治疗小鼠可促进脂肪减少，并使脂肪分布更健康，从而改善胰岛素敏感性，这表明10,12 CLA与Rosi的联合治疗策略可能对肥胖治疗具有治疗潜力。
