Gender-specific impact of trans 10, cis 12-conjugated linoleic acid on pai transgenic female mice

Trans 10, cis 12-conjugated linoleic acid (t10c12-CLA) has been shown to induce body fat loss in mammals. In this study, we analysed female pai transgenic mice that produced t10c12-CLA to determine the long-term impact of this substance on the lipid metabolism of lean mammals. Phenotype profiling showed that the effects of t10c12-CLA were genotype-specific in biallelic pai/pai or monoallelic pai/wt mice compared to their wild-type littermates. In both pai genotypes, white fat was not reduced, but heat release was decreased. Specifically, pai/wt mice exhibited increased chronic FGF21 and adrenaline possibly to regulate energy homeostasis and reduce physical activities. Contrarily, pai/pai mice showed hypothermia which may be related to the overproduction of prostaglandins and adrenaline, as well as an inflammatory response. Analysis of brown adipose tissue indicated that hypothermia might conversely promote thermogenesis and lipolysis by up-regulating UCP1/2, pHSL, CPT1B, and AMPK, and down-regulating pAMPK in pai/pai mice. Moreover, pai/pai mice also showed hypertriglyceridemia and fatty liver which is associated with long-term excesses of corticosterone and glucagon. Further analysis of pai/pai livers revealed that hepatic steatosis resulted from attenuated lipid metabolism via down-regulating pAMPK and fatty acid synthase. These results suggest that the systemic impact of chronic t10c12-CLA is dose-dependent in lean female mammals, low doses of t10c12-CLA may play an active role via the FGF21 and/or adrenaline pathways while its high-dose exposure may cause hormones overproduction and pose a safety risk.