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ARS Home » Plains Area » Grand Forks, North Dakota » Grand Forks Human Nutrition Research Center » Healthy Body Weight Research » Research » Publications at this Location » Publication #323348
Title: 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

Author
item Larson, Kate
item Dekrey, Emilie
item Garcia Garcia, Rolando
item JOHNSON, WILLIAM THOMAS - Former ARS Employee
item UTHUS, ERIC - Former ARS Employee
item Roemmich, James

Submitted to: Federation of American Societies for Experimental Biology Conference
Publication Type: Abstract Only
Publication Acceptance Date: 2/1/2016
Publication Date: 4/1/2016
Citation: Claycombe, K.J., Dekrey, E.E., Garcia Garcia, R.A., Johnson, W., Uthus, E., Roemmich, J.N. 2016. 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]. Federation of American Societies for Experimental Biology Conference, April 1-6, 2016, San Diego, California. 30:912.11.

Interpretive Summary: We have shown that protein malnutrition during fetal growth followed by postnatal high-fat diets results in a rapid increase in subcutaneous adipose tissue 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 a maternal 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 adipose tissue 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 beige adipocyte 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.

Technical Abstract: We have shown that protein malnutrition during fetal growth followed by postnatal high-fat diets results in a rapid increase in subcutaneous adipose tissue 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 a maternal 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 adipose tissue 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 beige adipocyte 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.