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Am J Physiol Endocrinol Metab. 2016 Jun 1;310(11):E1003-15. doi: 10.1152/ajpendo.00521.2015. Epub 2016 Apr 26.

Exposure to environmentally persistent free radicals during gestation lowers energy expenditure and impairs skeletal muscle mitochondrial function in adult mice.

Author information

1
Department of Physiology, University of Tennessee Health Science Center, Memphis, Tennessee; Department of Pediatrics, University of Tennessee Health Science Center, Memphis, Tennessee; and Children's Foundation Research Institute, Le Bonheur Children's Hospital, Memphis, Tennessee.
2
Department of Pediatrics, University of Tennessee Health Science Center, Memphis, Tennessee; and Children's Foundation Research Institute, Le Bonheur Children's Hospital, Memphis, Tennessee.
3
Department of Physiology, University of Tennessee Health Science Center, Memphis, Tennessee; Department of Pediatrics, University of Tennessee Health Science Center, Memphis, Tennessee; and Children's Foundation Research Institute, Le Bonheur Children's Hospital, Memphis, Tennessee davebrid@umich.edu.

Abstract

We have investigated the effects of in utero exposure to environmentally persistent free radicals (EPFRs) on growth, metabolism, energy utilization, and skeletal muscle mitochondria in a mouse model of diet-induced obesity. Pregnant mice were treated with laboratory-generated, combustion-derived particular matter (MCP230). The adult offspring were placed on a high-fat diet for 12 wk, after which we observed a 9.8% increase in their body weight. The increase in body size observed in the MCP230-exposed mice was not associated with increases in food intake but was associated with a reduction in physical activity and lower energy expenditure. The reduced energy expenditure in mice indirectly exposed to MCP230 was associated with reductions in skeletal muscle mitochondrial DNA copy number, lower mRNA levels of electron transport genes, and reduced citrate synthase activity. Upregulation of key genes involved in ameliorating oxidative stress was also observed in the muscle of MCP230-exposed mice. These findings suggest that gestational exposure to MCP230 leads to a reduction in energy expenditure at least in part through alterations to mitochondrial metabolism in the skeletal muscle.

KEYWORDS:

environmentally persistent free radicals; in utero exposure; mitochondria; oxidative stress; skeletal muscle

PMID:
27117006
PMCID:
PMC4935140
DOI:
10.1152/ajpendo.00521.2015
[Indexed for MEDLINE]
Free PMC Article

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