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Differential impacts of late gestational over-and undernutrition on adipose tissue traits and associated visceral obesity risk upon exposure to a postnatal high-fat diet in adolescent sheep

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Abstract

We hypothesized that late gestation malnutrition differentially affects expandability of adipose tissues to predispose for early postnatal visceral adiposity. Twin-lambs born to dams fed HIGH (150%/110% of required energy/protein, respectively), NORM (100% of requirements) or LOW (50% of NORM) diets during the last trimester were used. Postnatally, lambs were raised on moderate (CONV) or high-carbohydrate-high-fat (HCHF) diets. Adipose tissues were sampled at autopsy at 6 months of age (~puberty) to characterize cellularity, adipocyte cross-sectional area and gene expression patterns. HIGH and LOW compared to NORM lambs had reduced intrinsic (under CONV diet) cellularity in subcutaneous and mesenteric (particularly LOW), and reduced obesity-induced (under HCHF diet) hyperplasia in subcutaneous, mesenteric and perirenal (particularly HIGH) adipose tissues. This corresponded with more pronounced HCHF diet-induced hypertrophy in mesenteric (particularly LOW), perirenal (particularly HIGH) and subcutaneous (particularly HIGH) adipose tissues, and tissue-specific reductions in mRNA expressions for lipid metabolism, angiogenesis and adipose development. Gene expression for inflammation and lipid metabolism markers were increased and decreased, respectively, in HCHF lambs (HCHF lambs became obese) in all tissues. Both prenatal over- and undernutrition predisposed for abdominal adiposity and extreme perirenal hypertrophy due to reduced intrinsic (observed under CONV diet) cellularity and impaired ability of subcutaneous, mesenteric and perirenal adipose tissues to expand by hyperplasia rather than hypertrophy on an obesogenic (HCHF) diet.