Trans-10, cis-12 conjugated linoleic acid modulates offspring hepatic lipid metabolism by activating AMPK pathway associated with altered gut microbiota.

OBJECTIVE: Trans-10, cis-12 conjugated linoleic acid (t10c12-CLA) can affect lipid metabolism, leading to weight loss and attracting widespread attention. However, its suitability for use in lactating mothers remains unclear. A transgenic mouse, named Pai (homozygous) and Pai/wt (heterozygous), capable of producing endogenous t10c12-CLA was successfully established.

METHODS: In this study, embryo transfer technology was utilized to transplant embryos of wild-type (wt) mice into the transgenic mice, in order to investigate the effects of t10c12-CLA on biometric and reproductive parameters.

RESULTS: Embryo transfer efficiency remained unchanged following the procedure. The male-to-female ratio of offspring in Pai/wt group was significantly higher than that in wt and Pai groups. Additionally, the birth weight, 21-day body weight, serum glucose level and triglyceride level of pups in Pai group were significantly lower than those in wt group. Simultaneously, the Pai pups exhibited modulated gut microbiota composition and regulated metabolic profiles in white adipose tissue and liver. Further investigations in liver tissue and HepG2 cells revealed that these effects featured suppressed lipogenesis (FASN, ChREBP), enhanced fatty acid oxidation (CPT1A) through activation of AMPK pathway in liver.

CONCLUSIONS: Maternal t10c12-CLA could suppress lipogenesis and lower lipid levels by activating the AMPK pathway, and alter the composition of gut microbiota, thereby impacting offspring lipid metabolism.