Depot and sex-specific implications for adipose tissue expandability and functional traits in adulthood of late prenatal and early postnatal malnutrition in a precocial sheep model.

The aim was to investigate long-term, tissue and sex-specific impacts of pre and postnatal malnutrition on expandability and functional traits of different adipose tissues. Twin-pregnant ewes were fed NORM (~requirements), LOW (50% of NORM) or HIGH (150%/110% of energy/protein) diets the last 6 weeks prepartum (term ~147-days). Lambs received moderate, low-fat (CONV) or high-carbohydrate-high-fat (HCHF) diets from 3 days until 6 months of age, and thereafter CONV diet. At 2½ years of age (adulthood), histomorphometric and gene expression patterns were characterized in subcutaneous (SUB), perirenal (PER), mesenteric (MES), and epicardial (EPI) adipose tissues. SUB had sex-specific (♂<♀) upper-limits for adipocyte size and cell-number indices, irrespective of early life nutrition. PER mass and contents of adipocytes were highest in females and HIGH♂, whereas adipocyte cross-sectional area was lowest in LOW♂. Pre/postnatal nutrition affected gene expression sex-specifically in SUB + PER, but unrelated to morphological changes. In PER, LOW/LOW♂ were specific targets of gene expression changes. EPI was affected by postnatal nutrition, and HCHF sheep had enlarged adipocytes and upregulated expressions for adipogenic and lipogenic genes. Conclusion: upper-limits for SUB expandability were markedly lower in males. Major targets for prenatal malnutrition were PER and males. LOW♂ had the lowest PER expandability, whereas HIGH♂ had an adaptive advantage due to increased hypertrophic ability equivalent to females. Fixed expandability in SUB meant PER became a determining factor for MES and ectopic fat deposition, rendering LOW♂ particularly predisposed for obesity-associated metabolic risks. EPI, in contrast to other tissues, was targeted particularly by early postnatal obesity, resulting in adipocyte hypertrophy in adulthood.