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Cardiac N⁶-methyladenosine and Secreted TGF-β1 Mediate Myocardial Control of Systemic Metabolic Homeostasis

Longenecker, Jacob Z
http://orcid.org/0000-0003-4701-0890
http://rave.ohiolink.edu/etdc/view?acc_num=osu1637588928950409

Abstract Details

2021, Doctor of Philosophy, Ohio State University, Molecular, Cellular and Developmental Biology.
Proper maintenance of cardiac function in the response to stress is necessary to ensure survival of the organism and is predicated upon the complex regulation of diverse pathways. How the heart contributes to the systemic response to nutrient overload is not well understood. Here, we show the importance of this regulation in the heart to the maintenance of whole-body metabolism by identifying novel roles for cardiac RNA modifications and the secretion of cardiac-derived factors in the response to diet-induced stress. Mice with either reduced cardiac m⁶A abundance or expressing a constitutively active form of TGF-β1 that is readily secreted into circulation display a remarkable protection against western diet feeding, gaining less weight and experiencing decreased glucose dysregulation. Conversely, mice with increased cardiac m⁶A abundance developed a more severe phenotype in response to diet stress. The mechanisms underlying these findings are likely mediated by mitochondria, as seahorse assays preformed on mitochondria isolated from these mice displayed changes to overall flux through the electron transport chain. Indeed, the role of mitochondrial function in the maintenance of metabolism is well described in the literature. The simultaneous perturbation of gene expression seen locally in the heart and in the peripheral tissues in response are evidence supporting a critical for the endocrine function of the heart in the maintenance of systemic homeostasis. These novel insights represent exciting new avenues for the treatment of obesity.
Federica Accornero (Advisor)
Douglas Lewandowski (Committee Member)
Christoph Lepper (Committee Member)
Wayne Miles (Committee Member)
Noah Weisleder (Committee Member)
179 p.
Cellular Biology; Molecular Biology; Physiology
TGF-B1; m6A; heart; adipose; obesity; mitochondria; cardiokine

Recommended Citations

Citations

  • Longenecker, J. Z. (2021). Cardiac N⁶-methyladenosine and Secreted TGF-β1 Mediate Myocardial Control of Systemic Metabolic Homeostasis [Doctoral dissertation, Ohio State University]. OhioLINK Electronic Theses and Dissertations Center. http://rave.ohiolink.edu/etdc/view?acc_num=osu1637588928950409

    APA Style (7th edition)

  • Longenecker, Jacob. Cardiac N⁶-methyladenosine and Secreted TGF-β1 Mediate Myocardial Control of Systemic Metabolic Homeostasis. 2021. Ohio State University, Doctoral dissertation. OhioLINK Electronic Theses and Dissertations Center, http://rave.ohiolink.edu/etdc/view?acc_num=osu1637588928950409.

    MLA Style (8th edition)

  • Longenecker, Jacob. "Cardiac N⁶-methyladenosine and Secreted TGF-β1 Mediate Myocardial Control of Systemic Metabolic Homeostasis." Doctoral dissertation, Ohio State University, 2021. http://rave.ohiolink.edu/etdc/view?acc_num=osu1637588928950409

    Chicago Manual of Style (17th edition)

osu1637588928950409
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This open access ETD is published by The Ohio State University and OhioLINK.