摘要：Nutritional status during gestation may lead to a phenomenon known as metabolic programming, which can be triggered by epigenetic mechanisms. The
Let-7 family of microRNAs were one of the first to be discovered, and are closely related to metabolic processes. Bioinformatic analysis revealed that
Prkaa2, the gene that encodes AMPK α2, is a predicted target of
Let-7. Here we aimed to investigate whether
Let-7 has a role in AMPKα2 levels in the NAFLD development in the offspring programmed by maternal obesity.
Let-7 levels were upregulated in the liver of newborn mice from obese dams, while the levels of
Prkaa2 were downregulated.
Let-7 levels strongly correlated with serum glucose, insulin and NEFA, and in vitro treatment of AML12 with glucose and NEFA lead to higher
Let-7 expression. Transfection of
Let-7a mimic lead to downregulation of AMPKα2 levels, while the transfection with
Let-7a inhibitor impaired both NEFA-mediated reduction of
Prkaa2 levels and the fat accumulation driven by NEFA. The transfection of
Let-7a inhibitor in ex-vivo liver slices from the offspring of obese dams restored phospho-AMPKα2 levels. In summary,
Let-7a appears to regulate hepatic AMPKα2 protein levels and lead to the early hepatic metabolic disturbances in the offspring of obese dams.
