4.7 Article

Low Neonatal Plasma n-6/n-3 PUFA Ratios Regulate Offspring Adipogenic Potential and Condition Adult Obesity Resistance

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DIABETES
卷 67, 期 4, 页码 651-661

出版社

AMER DIABETES ASSOC
DOI: 10.2337/db17-0890

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资金

  1. National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) [K01-DK-109079]
  2. Office of Research on Women's Health Building Interdisciplinary Research Careers in Women's Health Scholar Award [K12-HD-057022]
  3. Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) [T32-HD-007186]
  4. Colorado NIDDK-Nutrition and Obesity Research Center [P30-DK-048520]
  5. NIDDK [R24-DK-090964]
  6. NICHD [P01-HD-038129, R01-HD-075285]
  7. EUNICE KENNEDY SHRIVER NATIONAL INSTITUTE OF CHILD HEALTH & HUMAN DEVELOPMENT [K12HD057022, P50HD073063, T32HD007186, P01HD038129, R01HD075285] Funding Source: NIH RePORTER
  8. NATIONAL CANCER INSTITUTE [R01CA164166] Funding Source: NIH RePORTER
  9. NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASES [P30DK048520, K01DK109079, R24DK090964] Funding Source: NIH RePORTER

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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 wildtype pups receiving low n-6/n-3 ratios had more adipocytes that were smaller in size; decreased Ppar gamma 2, Fabp4, and Plin1; several lipid metabolism mRNAs; coincident hyper-methylation of the PPAR gamma 2 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.

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