Decreased beige adipocyte number and mitochondrial respiration coincide with reduced FGF21 gene expression in Sprague Dawley rats fed prenatal low protein and postnatal high fat diets

Abstract

We have shown that protein malnutrition during fetal growth followed bypostnatal high‐fat diets results in a rapid increase in subcutaneous adiposetissue mass in the offspring contributing to development of obesity and insulin resistance. Recent studies have shown that the absence of a key transcription factor PR domain containing 16 (PRDM16) and fibroblast growth factor 21 (FGF21)are involved in conversion of precursor white adipocytes into more mitochondrial enriched and metabolically active beige adipocytes cause marked enlargement of the subcutaneous adipose tissue. Our hypothesis is that amaternal LP and postnatal HF diets increase the risk of development of obesity and insulin resistance in offspring, in part, by reducing the conversion of precursor white adipocytes into beige adipocytes in the subcutaneous adiposetissue of offspring. Using obese‐prone Sprague‐Dawley rats fed 8% low protein(LP) or 20% normal protein (NP) diets for 3 wk prior to conception and throughout pregnancy and lactation followed by 12 wks of 10% normal fat (NF) or 45% high fat (HF) diet feeding, we investigated whether prenatal LP and postnatal HF diets affect beige adipocyte number and oxidative respiratory function in subcutaneous adipose tissue. Results showed that subcutaneous adipose and liver fibroblast growth factor 21 (FGF21), PRDM16, and beigeadipocyte marker CD137, mRNA increase with postnatal HF diet in maternal NP group mice. In contrast, mice fed maternal LP and postnatal HF diets showed no increase in subcutaneous adipose tissue mitochondrial copy number, oxygen consumption rate, FGF21, PRDM16, and CD137 mRNA. These findings suggest that high‐fat diet fed offspring from mothers that consumed a low‐protein diet have reduced induction of beige adipocytes in subcutaneous adipose tissue and that this may be part of the mechanism by which maternal protein malnutrition causes offspring obesity and metabolic alterations.Support or Funding InformationThis work was supported by USDA Agricultural Research Service Project #3062‐51000‐052‐00D.