Abstract
ABSTRACTDietarytrans10,cis12-conjugated linoleic acid (t10c12-CLA) has been shown to induce white fat reduction. In this study, the transgenic mice that produce endogenous t10c12-CLA were used to determine the long-term impact of this substance on lipid metabolism in lean female mammals. Phenotype profiling showed that the t10c12-CLA did not induce fat loss but resulted in less heat release and oxygen consumption, as well as excessive adrenaline, tumour necrosis factor-alpha, and interleukin-6 in either biallelic Pai/Pai or monoallelic Pai/wt mice compared to their wild-type littermates. Furthermore, the following effects of t10c12-CLA were genotype-specific. Pai/wt mice specifically exhibited increased chronic fibroblast growth factor 21 (FGF21) and reduced physical activities. Contrarily, Pai/Pai mice showed the overproduction of prostaglandin E2 (PGE2), corticosterone, and glucagon, accompanied by hypertriglyceridemia and fatty liver. Further analysis of Pai/Pai livers revealed that the steatosis resulted from attenuated lipid metabolism via down-regulating phosphorylated AMP-activated protein kinase (AMPK) and fatty acid synthase. Analysis of Pai/Pai brown adipose tissue indicated stimulated thermogenesis and lipolysis by up-regulating uncoupling proteins 1 and 2, phosphorylated hormone-sensitive lipase, carnitine palmitoyltransferase 1B, and AMPK, as well as down-regulating phosphorylated AMPK. These results suggest that chronic t10c12-CLA may affect lipid metabolism by stimulating the overproduction of multiple hormones (FGF21, PEG2, adrenaline, etc.) in a dose-dependent manner in lean female mammals. It also suggests that t10c12-CLA-induced fatty liver, inflammation, hypothermia and excess hormones are major health concerns.
Publisher
Cold Spring Harbor Laboratory
Cited by
1 articles.
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