Maternal consumption of a high-fat diet (HFD) during pregnancy and lactation is closely related to hepatic lipid accumulation, insulin resistance and increased serum cytokine levels in offspring and into their adulthood. MicroRNA (miRNA) have been implicated in cholesterol biosynthesis and fatty acid metabolism. We evaluated the modulation of hepatic fatty acid synthesis (de novo), b-oxidation pathways, and miRNA-122 (miR-122) and miRNA-370 (miR-370) expression in recently weaned offspring (day 28) of mouse dams fed a HFD (HFD-O) or a standard chow (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 (P,0·05). HFD-O mice also presented more levels of serum cholesterol, TAG, NEFA and hepatic IkB kinase and c-Jun N-terminal kinase phosphorylation compared with SC-O mice (P,0·05). Protein levels of fatty acid synthase, acetyl-CoA carboxylase and 3-hydroxy-3-methylglutaryl-CoA reductase were similar in HFD-O and SC-O mice, whereas expression levels of SCD1 mRNA and protein were more abundant in HFD-O mice than in SC-O mice (P,0·05). Interestingly, mRNA expression levels of the b-oxidation-related genes ACADVL and CPT1 were decreased in HFD-O mice (P,0·05). Furthermore, 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 (P,0·05). Changes in hepatic lipid metabolism were accompanied by increased mRNA content of AGPAT1 and TAG deposition in HFD-O mice (P,0·05). Taken together, the present results strongly suggest that maternal consumption of a HFD affects the early lipid metabolism of offspring by modulating the expression of hepatic b-oxidation-related genes and miRNA that can contribute to metabolic disturbances in adult life.
BackgroundNutritional status in early life is critically involved in the metabolic phenotype of offspring. However the changes triggered by maternal consumption of high-fat diet (HFD) in pre- or postnatal period should be better understood. Here we evaluated whether maternal HFD consumption during gestation and lactation could differently affect liver miR-122 and miR-370 expression leading to metabolic damages observed in offspring. Moreover, we investigate whether early overnutrition program offspring to more harmful response to HFD in later life.MethodsFemale mice were fed either a standard chow (SC) diet or a HFD three weeks before and during mating, gestation and/or lactation. Offspring were evaluated on the delivery day (d0), in a cross-fostering model at day 28 (d28) and in adult life, after a re-challenge with a HFD (d82).ResultsIn vitro analysis using liver cell line showed that palmitate could induced decrease in miR-122 and increase in miR-370 expression. Newborn pups (d0) from obese dams showed a decrease in lipid oxidation markers (Cpt1a and Acadvl), an increase in triacylglycerol synthesis markers (Agpat and Gpam), as well as lower miR-122 and higher miR-370 hepatic content that was inversely correlated to maternal serum NEFA and TAG. Pups fostered to SC dams presented an increase in body weight and Agpat/Gpam expression at d28 compared to pups fostered to HFD dams and an inverse correlation was observed between miR-122 hepatic expression and offspring serum TAG. In adult life (d82), the reintroduction of HFD resulted in higher body weight gain and hepatic lipid content. These effects were accompanied by impairment in lipid and glucose metabolism, demonstrated by reduced Cpt1a/Acadvl and increased Agpat/Gpam expression, lower glucose tolerance and insulin sensitivity.ConclusionOur data suggest that both gestational and lactation overnutrition results in metabolic changes that can permanently alter lipid homeostasis in offspring. The presence of fatty acids in maternal blood and milk seem to be responsible for modulating the expression of miR-122 and miR-370, which are involved in liver metabolism. These alterations significantly increase susceptibility to obesity and ectopic lipid accumulation and lead to a more harmful response to HFD in offspring.Electronic supplementary materialThe online version of this article (doi:10.1186/s12986-017-0168-4) contains supplementary material, which is available to authorized users.
Usar a delimitação de bacias hidrográficas como unidade de planejamento ambiental possui uma série de benefícios metodológicos, já que esta delimitação facilita a análise de diversos fatores ambientais que implicam em uma elaboração mais próxima das características reais do ambiente e na melhoria/resolução dos problemas ambientais. Entretanto, o planejamento ambiental não deve focarse somente nos atributos do meio físico, devendo abranger também, com igual importância, os aspectos socioambientais. A ocupação das terras pelo homem se dá a partir de um curso hídrico, em função da disponibilidade de recursos para subsistência, bem como para transporte, assim, vale destacar a importância de um recorte hidrográfico como unidade de análise dos agentes sociais e suas relações com o meio. A partir disso, alcança-se os objetivos deste trabalho ao avaliar os aspectos socioambientais da bacia do córrego Olhos D"Água, entendendo sua importância, uma vez que os agentes sociais usufruem e se interagem com o ambiente.
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