title: Decreased beige adipocyte number and mitochondrial respiration coincide with increased histone methyl transferase (G9a) and reduced FGF21 gene expression in Sprague-Dawley rats fed prenatal low protein and postnatal high-fat diets.
abstract: We have shown that prenatal low-protein (LP) followed by postnatal high-fat (HF) diets result in a rapid increase in subcutaneous adipose tissue (subc-AT) mass in the offspring, contributing to development of obesity and insulin resistance. Studies have shown that a key transcription factor, PR domain containing 16 (PRDM16), and fibroblast growth factor 21 (FGF21) are involved in conversion of precursor cells into mitochondria (mt)-enriched beige adipocytes (BA). Our hypothesis is that a maternal LP and postnatal HF diets increase the risk of obesity and insulin resistance in offspring, in part, by reducing the conversion of precursor cell into BA in the subc-AT of offspring. Using obese-prone Sprague-Dawley rats fed 8% LP or 20% normal-protein (NP) diets for 3 weeks prior to conception and throughout pregnancy and lactation followed by 12 weeks of 10% normal-fat (NF) or 45% HF diet feeding, we investigated whether prenatal LP and postnatal HF diets affect BA number and oxidative respiratory function in subc-AT. Results showed that subc-AT and liver FGF21, PRDM16 and BA marker CD137 mRNA increase with postnatal HF diet in maternal NP group rats. In contrast, rats fed maternal LP and postnatal HF diets showed no increase in subc-AT mt copy number, oxygen consumption rate, FGF21, PRDM16 and CD137 mRNA, whereas protein expression of an inhibitor for FGF21 transcription (histone methyltransferase, G9a) increased. These findings suggest that LPHF diets cause offspring metabolic alterations by reduced BA and FGF21 mRNA and increased G9a protein expression in subc-AT.
authors.affiliation: USDA-ARS, Grand Forks Human Nutrition Research Center, Grand Forks, ND, 58203. Electronic address: kate.claycombe@ars.usda.gov.
authors.forename: Kate J
authors.initials: KJ
authors.lastname: Claycombe
authors.affiliation: USDA-ARS, Grand Forks Human Nutrition Research Center, Grand Forks, ND, 58203.
authors.forename: Emilie E
authors.initials: EE
authors.lastname: Vomhof-DeKrey
authors.affiliation: USDA-ARS, Grand Forks Human Nutrition Research Center, Grand Forks, ND, 58203.
authors.forename: Rolando
authors.initials: R
authors.lastname: Garcia
authors.affiliation: USDA-ARS, Grand Forks Human Nutrition Research Center, Grand Forks, ND, 58203.
authors.forename: William Thomas
authors.initials: WT
authors.lastname: Johnson
authors.affiliation: USDA-ARS, Grand Forks Human Nutrition Research Center, Grand Forks, ND, 58203.
authors.forename: Eric
authors.initials: E
authors.lastname: Uthus
authors.affiliation: USDA-ARS, Grand Forks Human Nutrition Research Center, Grand Forks, ND, 58203.
authors.forename: James N
authors.initials: JN
authors.lastname: Roemmich
mesh_terms: D017667:Adipocytes / Q000166:cytology*; D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D059305:Diet, High-Fat; D004044:Dietary Proteins / Q000008:administration & dosage*; D005260:Female; D005346:Fibroblast Growth Factors / Q000378:metabolism*; D000076983:Histone Methyltransferases; D011495:Histone-Lysine N-Methyltransferase / Q000378:metabolism*; D008297:Male; D008928:Mitochondria / Q000378:metabolism*; D011247:Pregnancy; D051381:Rats; D017207:Rats, Sprague-Dawley; D014157:Transcription Factors / Q000378:metabolism
chemical_list: D015415:Biomarkers; D004044:Dietary Proteins; D014157:Transcription Factors; C414620:fibroblast growth factor 21; D005346:Fibroblast Growth Factors; D000076983:Histone Methyltransferases; D011495:Histone-Lysine N-Methyltransferase
keywords: Beige adipocyte; FGF21; G9a; Mitochondrial respiration; Postnatal high-fat diet; Prenatal low-protein diet; Subcutaneous adipose tissue