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转基因雌性小鼠产生反式 10、顺式 12-共轭亚油酸,表现出过多的前列腺素 E2、肾上腺素、皮质酮、胰高血糖素和 FGF21。

Transgenic female mice producing trans 10, cis 12-conjugated linoleic acid present excessive prostaglandin E2, adrenaline, corticosterone, glucagon, and FGF21.

机构信息

Institute of Comparative Medicine, College of Veterinary Medicine, Yangzhou University, Yangzhou, 225009, China.

Jiangsu Co-innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonoses, Department of Experimental Zoology, College of Veterinary Medicine, Yangzhou University, Yangzhou, 225009, China.

出版信息

Sci Rep. 2024 May 30;14(1):12430. doi: 10.1038/s41598-024-63282-7.

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

反式 10、顺式 12-共轭亚油酸(t10c12-CLA)是抗肥胖试验的潜在候选物。先前成功建立了转基因小鼠,以确定 t10c12-CLA 在能够产生内源性 t10c12-CLA 的雄性小鼠中的抗肥胖特性。为了测试 t10c12-CLA 对两性脂质代谢是否有不同的影响,本研究调查了表现出外源性 Pai 基因剂量依赖性表达和测试组织中 t10c12-CLA 含量转移的雌性 Pai 小鼠的肥胖和代谢特征。与它们的性别匹配的野生型同窝仔相比,Pai 小鼠没有减少脂肪,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,表现出增强的脂肪分解和产热作用。同时,Pai 小鼠通过降低参与脂质和葡萄糖代谢的基因表达表现出肝脂肪变性和高甘油三酯血症。进一步的研究表明,t10c10-CLA 以剂量依赖性方式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,导致 Pai 小鼠的热量释放和耗氧量减少。此外,仅在单等位基因 Pai/wt 小鼠中过度产生成纤维细胞生长因子 21 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产生全身性影响。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fa52/11139873/6fbbd13c8877/41598_2024_63282_Fig1_HTML.jpg

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