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Diabetes ; 67(4): 651-661, 2018 04.
Artigo em Inglês | MEDLINE | ID: mdl-29138256

RESUMO

Adipose tissue expansion progresses rapidly during postnatal life, influenced by both prenatal maternal factors and postnatal developmental cues. The ratio of omega-6 (n-6) relative to n-3 polyunsaturated fatty acids (PUFAs) is believed to regulate perinatal adipogenesis, but the cellular mechanisms and long-term effects are not well understood. We lowered the fetal and postnatal n-6/n-3 PUFA ratio exposure in wild-type offspring under standard maternal dietary fat amounts to test the effects of low n-6/n-3 ratios on offspring adipogenesis and adipogenic potential. Relative to wild-type pups receiving high perinatal n-6/n-3 ratios, subcutaneous adipose tissue in 14-day-old wild-type pups receiving low n-6/n-3 ratios had more adipocytes that were smaller in size; decreased Pparγ2, Fabp4, and Plin1; several lipid metabolism mRNAs; coincident hypermethylation of the PPARγ2 proximal promoter; and elevated circulating adiponectin. As adults, offspring that received low perinatal n-6/n-3 ratios were diet-induced obesity (DIO) resistant and had a lower positive energy balance and energy intake, greater lipid fuel preference and non-resting energy expenditure, one-half the body fat, and better glucose clearance. Together, the findings support a model in which low early-life n-6/n-3 ratios remodel adipose morphology to increase circulating adiponectin, resulting in a persistent adult phenotype with improved metabolic flexibility that prevents DIO.


Assuntos
Adipogenia , Glicemia/metabolismo , Ácidos Graxos Ômega-3/sangue , Ácidos Graxos Ômega-6/sangue , Metabolismo dos Lipídeos , Obesidade/epidemiologia , Efeitos Tardios da Exposição Pré-Natal/epidemiologia , Adipócitos/citologia , Adiponectina/metabolismo , Animais , Animais Recém-Nascidos , Proliferação de Células , Tamanho Celular , Metilação de DNA , Dieta Hiperlipídica , Gorduras na Dieta , Ingestão de Energia , Metabolismo Energético , Proteínas de Ligação a Ácido Graxo/metabolismo , Feminino , Camundongos , Obesidade/sangue , PPAR gama/metabolismo , Perilipina-1/metabolismo , Gravidez , Efeitos Tardios da Exposição Pré-Natal/sangue , Regiões Promotoras Genéticas , RNA Mensageiro/metabolismo , Fatores de Risco
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