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

Erin Stephenson, Sridhar Jaligama, Alyse Ragauskas, , Jyothi Parvathareddy, Matthew Peloquin, Jordy Saravia, Joan Han, Stephania Cormier and

American Journal of Physiology - Endocrinology And Metabolism 2016. 310: E1003-E1015.

Abstract

We have investigated the effects of in utero exposure to Environmentally Persistent Free Radicals (EPFR's) 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 weeks, 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. Up-regulation 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.

Author Contributions

Erin Stephenson

Data Curation Formal Analysis Funding Acquisition Investigation Methodology Resources Visualization Writing - Original Draft Writing - Review and Editing

Sridhar Jaligama

Investigation Methodology Writing - Review and Editing

Alyse Ragauskas

Formal Analysis Investigation Methodology Writing - Review and Editing

JeAnna Redd

Data Curation Investigation Writing - Review and Editing

Jyothi Parvathareddy

Investigation Writing - Review and Editing

Matthew Peloquin

Investigation Methodology Writing - Review and Editing

Jordy Saravia

Formal Analysis Investigation Methodology Writing - Review and Editing

Joan Han

Formal Analysis Funding Acquisition Investigation Methodology Validation Writing - Review and Editing

Stephania Cormier

Conceptualization Formal Analysis Funding Acquisition Methodology Resources Writing - Original Draft Writing - Review and Editing

Dave Bridges

Conceptualization Data Curation Formal Analysis Funding Acquisition Investigation Methodology Project Administration Resources Visualization Writing - Original Draft Writing - Review and Editing

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