Transgenic mice producing the trans 10, cis 12-conjugated linoleic acid present reduced adiposity and increased thermogenesis and fibroblast growth factor 21 (FGF21)

Abstract

Trans 10, cis 12-conjugated linoleic acid (t10c12-CLA) from ruminant-derived foodstuffs can induce body fat loss after oral administration. In the current study, a transgenic mouse that produced t10c12-CLA had been generated by inserting the Propionibacterium acnes isomerase (Pai) expression cassette into the Rosa26 locus, and its male offspring were used to elucidate the enduring influence of t10c12-CLA on overall health. Compared to their wild-type (wt) C57BL/6J littermates, both biallelic Pai/Pai and monoallelic Pai/wt mice exhibited reduced plasma triglycerides levels, and Pai/wt mice exclusively showed increased serum fibroblast growth factor 21. Further analysis of Pai/Pai mice found a decrease in white fat and an increase in brown fat, with more heat release and less physical activity. Analysis of Pai/Pai brown adipose tissues revealed that hyperthermia was associated with the over-expression of carnitine palmitoyltransferase 1B, uncoupling proteins 1 and 2. These findings suggest that the systemic and long-term impact of t10c12-CLA on obesity might be mediated through the pathway of fibroblast growth factor 21 when low doses are administered or through enhanced thermogenesis of brown adipose tissues when high doses are employed.

Keywords: Conjugated linoleic acid; adipose tissue; fibroblast growth factor 21; hypothalamus; obesity; uncoupling protein.