Lipid overload during gestation and lactation can independently alter lipid homeostasis in offspring and promote metabolic impairment after new challenge to high-fat diet

Autor(es)

de Paula Simino, Lais Angelica ; de Fante, Thais ; Fontana, Marina Figueiredo ; Borges, Fernanda Oliveira ; Torsoni, Marcio Alberto ; Milanski, Marciane ; Velloso, Licio Augusto ; Torsoni, Adriana Souza

• Tipo de documento: Artigo Científico
• Fonte: NUTRITION & METABOLISM; v. 14, FEB 20 2017.
• Citações Web of Science: 9

Resumo

Background: Nutritional 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. Methods: Female 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). Results: In 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. Conclusion: Our 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. (AU)

• Processo FAPESP: 11/22156-7 - O consumo materno de dieta hiperlipídica durante a gestação e lactação e a modulação da expressão de microRNAs relacionados ao metabolismo de lipídeos
• Beneficiário: Adriana Souza Torsoni
• Modalidade de apoio: Auxílio à Pesquisa - Regular
• Processo FAPESP: 13/07607-8 - CMPO - Centro Multidisciplinar de Pesquisa em Obesidade e Doenças Associadas
• Beneficiário: Licio Augusto Velloso
• Modalidade de apoio: Auxílio à Pesquisa - Centros de Pesquisa, Inovação e Difusão - CEPIDs
• Processo FAPESP: 14/18165-9 - Consumo materno de dieta hiperlipídica e a modulação da via anti-inflamatória colinérgica na prole de camundongos
• Beneficiário: Marcio Alberto Torsoni
• Modalidade de apoio: Auxílio à Pesquisa - Regular