Abstract:
Dietary trans 10, cis 12-conjugated linoleic acid (t10c12-CLA) is a potential candidate in anti-obesity trials. A transgenic mouse was previously successfully established to determine the anti-obesity properties of t10c12-CLA in male mice that could produce endogenous t10c12-CLA. To test whether there is a different impact of t10c12-CLA on lipid metabolism in both sexes, this study investigated the adiposity and metabolic profiles of female Pai mice that exhibited a dose-dependent expression of foreign Pai gene and a shift of t10c12-CLA content in tested tissues. Compared to their gender-match wild-type littermates, Pai mice had no fat reduction but exhibited enhanced lipolysis and thermogenesis by phosphorylated hormone-sensitive lipase and up-regulating uncoupling proteins in brown adipose tissue. Simultaneously, Pai mice showed hepatic steatosis and hypertriglyceridemia by decreasing gene expression involved in lipid and glucose metabolism. Further investigations revealed that t10c10-CLA induced excessive prostaglandin E2, adrenaline, corticosterone, glucagon and inflammatory factors in a dose-dependent manner, resulting in less heat release and oxygen consumption in Pai mice. Moreover, fibroblast growth factor 21 overproduction only in monoallelic Pai/wt mice indicates that it was sensitive to low doses of t10c12-CLA. These results suggest that chronic t10c12-CLA has system-wide effects on female health via synergistic actions of various hormones.
摘要:
膳食反式10,顺式12-共轭亚油酸(t10c12-CLA)是抗肥胖试验的潜在候选者。先前成功地建立了转基因小鼠,以确定t10c12-CLA在雄性小鼠中的抗肥胖特性,其可以产生内源性t10c12-CLA。为了测试t10c12-CLA对两性脂质代谢是否有不同的影响,这项研究调查了雌性Pai小鼠的肥胖和代谢谱,这些小鼠表现出剂量依赖性的外源Pai基因表达和测试组织中t10c12-CLA含量的变化。与它们的性别匹配的野生型同窝相比,Pai小鼠没有脂肪减少,但通过磷酸化激素敏感脂肪酶和上调棕色脂肪组织中的解偶联蛋白,表现出增强的脂解作用和产热作用。同时,Pai小鼠通过降低与脂质和葡萄糖代谢有关的基因表达而表现出肝脂肪变性和高甘油三酯血症。进一步的调查显示,t10c10-CLA诱导过量的前列腺素E2,肾上腺素,皮质酮,胰高血糖素和炎症因子呈剂量依赖性,导致Pai小鼠的热量释放和氧气消耗减少。此外,成纤维细胞生长因子21仅在单等位基因Pai/wt小鼠中过量产生,表明它对低剂量的t10c12-CLA敏感。这些结果表明,慢性t10c12-CLA通过各种激素的协同作用对女性健康具有全系统影响。