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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 #321824

Research Project: Biology of Obesity Prevention

Location: Healthy Body Weight Research

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

Author
item Larson, Kate
item Dekrey, Emilie
item Garcia Garcia, Rolando
item Johnson, William - Former ARS Employee
item Uthus, Eric - Former ARS Employee
item Roemmich, James

Submitted to: Journal of Nutritional Biochemistry
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 1/18/2016
Publication Date: 5/1/2016
Publication URL: http://handle.nal.usda.gov/10113/62896
Citation: Claycombe, K.J., Dekrey, E.E., Garcia Garcia, R.A., Johnson, W.T., Uthus, E., Roemmich, J.N. 2016. 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. Journal of Nutritional Biochemistry. 31:133-121.

Interpretive Summary: A maternal low protein diet can reduce offspring birth weight which can lead to rapid weight gain of fat tissue during adolescence and into adulthood and increase the risk for insulin resistance. An important regulator of body and white adipose tissue weight is beige color adipocytes that are found in the subcutaneous, or under the skin, adipose tissue. Compared to white color fat cells in fat tissue that are associated with internal organs (called visceral adipose tissue), the beige color fat cells have higher numbers of mitochondria that are well known for their fat metabolizing ability. Using a rat model, we found that a maternal low protein followed by postnatal high fat diet results in increased offspring obesity and subcutaneous fat tissue weight possibly due to decreased beige color adipocyte numbers and beige color adipocyte’s fat metabolizing capacity caused by reduced numbers of mitochondria. These results indicate that a maternal low protein and postnatal high fat diets increase the risk for offspring obesity and risk for type 2 diabetes by reduced fat metabolism in the subcutaneous fat tissue by decreased beige color fat cells.

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 finding 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 may cause offspring obesity and metabolic alterations.