How an altered adiponectin level during early diabetic pregnancy influences embryonic lipid metabolism

Aim: An experimentally-induced maternal diabetes mellitus leads to a strongly increased level of intracellular lipid droplets in early embryos, correlating with increased adiponectin levels in the uterine environment (Schindler et al. Endocrinology 2013 and 2014). Adiponectin maintains energy homeostasis and may affect early embryo lipid metabolism. The object of current study was to find a potential link between adiponectin and the disturbed embryonic lipid metabolism in a diabetic pregnancy.

Methods: The effect of adiponectin was investigated in embryos from two experimental models, in i) in vivo blastocysts from rabbits with an experimentally-induced diabetes mellitus and ii) embryos cultured in vitro with adiponectin (1 µg/ml). To prove AMPK-dependency of lipogenic signal pathways, blastocysts were cultured with the specific inhibitor Compound C. All experiments were repeated at least 3 times. Expression of molecules involved in lipid metabolism was analysed by RT-qPCR and Western Blot.

Results: Adiponectin regulated AMPK and ACC phosphorylation in vivo and in vitro. A significant increased expression of PPARa and PPARg was detected in adiponectin-exposed embryos, accompanied by an increased expression of carnitine palmityl transferase 1 (CPT1), which is the key enzyme of b-oxidation. Furthermore, the expression of the fatty acid transporter, CD36, and the hormone-sensitive lipase (HSL) were upregulated by adiponectin.

Conclusion: We show that adiponectin stimulates AMPK signalling in mammalian embryos, which affects embryonic lipid metabolism. Therefore, the observed increased intracellular lipid accumulation in embryos from diabetic mothers could be a consequence of increased uterine adiponectin levels in a diabetic pregnancy.