title: Maternal high-fat diet consumption modulates hepatic lipid metabolism and microRNA-122 (miR-122) and microRNA-370 (miR-370) expression in offspring.
abstract: 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), β-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 IκB 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 β-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 β-oxidation-related genes and miRNA that can contribute to metabolic disturbances in adult life.
authors.affiliation: Faculdade de Ciências Aplicadas, Universidade Estadual de Campinas-UNICAMP, Rua Pedro Zaccaria, 1300 Jardim Santa Luiza, Limeira, São Paulo, CEP 13484350, Brazil.
authors.forename: R O
authors.initials: RO
authors.lastname: Benatti
authors.affiliation: Faculdade de Ciências Aplicadas, Universidade Estadual de Campinas-UNICAMP, Rua Pedro Zaccaria, 1300 Jardim Santa Luiza,Limeira, São Paulo, CEP 13484350, Brazil.
authors.forename: A M
authors.initials: AM
authors.lastname: Melo
authors.affiliation: Faculdade de Ciências Aplicadas, Universidade Estadual de Campinas-UNICAMP, Rua Pedro Zaccaria, 1300 Jardim Santa Luiza,Limeira, São Paulo, CEP 13484350, Brazil.
authors.forename: F O
authors.initials: FO
authors.lastname: Borges
authors.affiliation: Faculdade de Nutrição, Universidade Federal do Mato Grosso-UFMT, Cuiabá, Mato Grosso, Brazil.
authors.forename: L M
authors.initials: LM
authors.lastname: Ignacio-Souza
authors.affiliation: Faculdade de Ciências Aplicadas, Universidade Estadual de Campinas-UNICAMP, Rua Pedro Zaccaria, 1300 Jardim Santa Luiza,Limeira, São Paulo, CEP 13484350, Brazil.
authors.forename: L A P
authors.initials: LA
authors.lastname: Simino
authors.affiliation: Faculdade de Ciências Aplicadas, Universidade Estadual de Campinas-UNICAMP, Rua Pedro Zaccaria, 1300 Jardim Santa Luiza,Limeira, São Paulo, CEP 13484350, Brazil.
authors.forename: M
authors.initials: M
authors.lastname: Milanski
authors.affiliation: Departamento de Medicina Interna,Faculdade de Ciências Médicas, Universidade Estadual de Campinas-UNICAMP,Campinas, São Paulo,Brazil.
authors.forename: L A
authors.initials: LA
authors.lastname: Velloso
authors.affiliation: Faculdade de Ciências Aplicadas, Universidade Estadual de Campinas-UNICAMP, Rua Pedro Zaccaria, 1300 Jardim Santa Luiza,Limeira, São Paulo, CEP 13484350, Brazil.
authors.forename: M A
authors.initials: MA
authors.lastname: Torsoni
authors.affiliation: Faculdade de Ciências Aplicadas, Universidade Estadual de Campinas-UNICAMP, Rua Pedro Zaccaria, 1300 Jardim Santa Luiza,Limeira, São Paulo, CEP 13484350, Brazil.
authors.forename: A S
authors.initials: AS
authors.lastname: Torsoni
mesh_terms: D050154:Adiposity; D000818:Animals; D059305:Diet, High-Fat / Q000009:adverse effects*; D005260:Female; D047109:Fetal Development; D018507:Gene Expression Regulation, Developmental; D018149:Glucose Intolerance / Q000209:etiology / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D007774:Lactation; D050356:Lipid Metabolism; D008099:Liver / Q000201:enzymology / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D008297:Male; D039382:Maternal Nutritional Physiological Phenomena; D051379:Mice; D035683:MicroRNAs / Q000096:biosynthesis*; D009765:Obesity / Q000503:physiopathology; D011247:Pregnancy; D011248:Pregnancy Complications / Q000503:physiopathology; D011897:Random Allocation; D013047:Specific Pathogen-Free Organisms; D014886:Weaning; D015430:Weight Gain
chemical_list: C551449:MIRN370 microRNA, mouse; D035683:MicroRNAs; C544354:Mirn122 microRNA, mouse