Avaliação da expressão hepática de microRNAs relacionados ao metabolismo lipídico na prole de camundongos com obesidade induzida por dieta

Abstract

Maternal consumption of high-fat diet (HFD) during pregnancy and lactation is closely related to liver lipid accumulation, insulin resistance development, and increased serum cytokines in offspring and into adulthood. MicroRNAs (miRNAs) have been implicated in cholesterol biosynthesis and fatty acid metabolism. In the present study we evaluated the modulation of hepatic fatty acid synthesis (de novo), as well as modulation of fatty acid oxidation and miR-122 and miR-370 expression in recently weaned offspring (d28) of mice dams fed high fat diet (group HFD-O) or standard chow (group SC-O) during pregnancy and lactation. Compared with SC-O mice, HFD-O mice weighed more, had a larger adipose tissue mass and were more intolerant to glucose and insulin. HFD-O mice also presented more serum cholesterol, triglycerides, non-esterified fatty acids and hepatic IKK and JNK phosphorylation compared with SC-O mice. Protein levels of FAS, ACC and HMGCR were similar in HFD-O and SC-O mice, whereas SCD1 mRNA and protein were more abundant in HFD-O mice compared with SC-O mice. Interestingly, mRNA expression of βoxidation-related genes ACADVL and CPT1 was decreased in HFD-O mice. Although we did not observe a difference in hepatic HNF4α levels, the expression of miR-122 was reduced but that of miR-370 was increased in HFD-O mice compared with that in SC-O mice. Changes in hepatic lipid metabolism were accompanied by increased triglyceride deposition in HFD-O mice. Taken together, our results strongly suggest that maternal consumption of HFD affects the early lipid metabolism of offspring by modulating the expression of hepatic β-oxidation-related genes and miRNAs that can contribute to metabolic disturbances in adult life.