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The Role of Steroidogenic Factor 1 Cells in Modulating Skeletal Muscle Thermogenesis

Shemery, Ashley M
http://orcid.org/0000-0002-6858-3471
http://rave.ohiolink.edu/etdc/view?acc_num=kent1586019493695577

Abstract Details

2020, PHD, Kent State University, College of Arts and Sciences / School of Biomedical Sciences.
With nearly 70% of Americans overweight or obese, uncovering ways to increase energy expenditure is critical for treating obesity. Skeletal muscle has a substantial capacity for increasing energy expenditure and is clinically relevant as it makes up 40% of total human body mass, accounts for 20-30% of total resting oxygen uptake, and is the primary site for glucose uptake and fatty acid oxidation. Moreover, improved muscle function and metabolism are linked to leanness. Steroidogenic factor-1 (SF-1) cells in the ventromedial hypothalamus (VMH) regulate body weight by modulating peripheral metabolism, including skeletal muscle metabolism. Interestingly, VMH SF-1 cells are also critical mediators of behavioral responses to predator threat. We have previously shown that predator odor exposure to rats causes a rapid and robust increase in skeletal muscle thermogenesis that is associated with increased physical activity, energy expenditure, and weight loss. VMH SF-1 cells are a likely mediator of these predator odor-induced metabolic responses, but the mechanisms of this dual-processing role are unknown. To explore the underlying mechanisms, we altered VMH SF-1 activity using SF-1-specific designer receptors exclusively activated by designer drugs (DREADDs). We also performed RNA-sequencing and qPCR to reveal how predator odor exposure alters the VMH transcriptome. We found that VMH SF-1 activity is necessary for the muscle thermogenic effect of predator odor when controlling for physical activity. We also found that predator odor induced thermogenesis is dampened in a polygenic model of obesity, but amplifying SF-1 activity partially mitigates this deficit. Further, our gene expression assays revealed that predator odor exposure results in rapid changes in inflammation, oxidative stress, and synaptic plasticity within the VMH. Taken together, our findings show that VMH SF-1 cells mediate the skeletal muscle thermogenic response to predator odor and alter the locomotor efficiency of this response. Separating VMH SF-1 control of skeletal muscle thermogenesis from behavioral, endocrine, and emotional responses to predator threat will be critical in uncovering potential therapeutic targets for treating obesity.
Colleen Novak (Advisor)
John Johnson (Committee Member)
Jasnow Aaron (Committee Member)
Barkley Jacob (Committee Member)
Frazier Gail (Committee Member)
234 p.
Biomedical Research; Cellular Biology; Molecular Biology; Neurosciences
ventromedial hypothalamus; skeletal muscle; thermogenesis; obesity; energy expenditure; DREADD; RNA-seq; VMH; SF-1; high capacity runners; low capacity runners; HCR; LCR; predator threat; stress; physical activity; synaptic plasticity

Recommended Citations

Citations

  • Shemery, A. M. (2020). The Role of Steroidogenic Factor 1 Cells in Modulating Skeletal Muscle Thermogenesis [Doctoral dissertation, Kent State University]. OhioLINK Electronic Theses and Dissertations Center. http://rave.ohiolink.edu/etdc/view?acc_num=kent1586019493695577

    APA Style (7th edition)

  • Shemery, Ashley. The Role of Steroidogenic Factor 1 Cells in Modulating Skeletal Muscle Thermogenesis. 2020. Kent State University, Doctoral dissertation. OhioLINK Electronic Theses and Dissertations Center, http://rave.ohiolink.edu/etdc/view?acc_num=kent1586019493695577.

    MLA Style (8th edition)

  • Shemery, Ashley. "The Role of Steroidogenic Factor 1 Cells in Modulating Skeletal Muscle Thermogenesis." Doctoral dissertation, Kent State University, 2020. http://rave.ohiolink.edu/etdc/view?acc_num=kent1586019493695577

    Chicago Manual of Style (17th edition)

kent1586019493695577
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This open access ETD is published by Kent State University and OhioLINK.