Melatonin Rescues Hyperacetylation of Liver and Impaired Enzymatic Activities of Mitochondrial in IVF Offspring.

Abstract

Increased risks of obesity and abnormal glucose metabolism were observed in IVF offspring. However, the underlying molecular mechanism was still unclear. As an important post-translational modification (PTM), lysine acetylation changed with the changes in the metabolic environment and usually occurred on metabolic enzymes to regulate metabolic pathways and enzyme activities and participated in the regulation of downstream metabolites. In our previous study, we proved that supplementation of melatonin in the culture medium improved obesity and metabolic dysfunction in IVF mice. In this study, we further demonstrated that elevated levels of protein acetylation in hepatic cells might be associated with impaired glucose metabolism in IVF offspring, and melatonin could significantly reduce the acetylation level and improve the adverse phenotype of IVF mice. More importantly, we discovered that the supplementation of melatonin in the culture medium during in vitro fertilization significantly enhanced the activity of enzymes, especially citrate synthase (CS) and isocitrate dehydrogenase (IDH) which were involved in tricarboxylic acid recycling and played critical roles in glucose metabolism of liver. Thus, our findings elucidated a new perspective on the mechanisms of metabolic reprogramming of IVF mice.