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Investigating the role of FoxN3 in cardiac energy substrate selection.

Semester: Summer 2023

Presentation description

Cardiovascular disease is a chronic and complex condition with high mortality rates, especially in individuals with co-morbidities such as diabetes mellitus (DM). DM and heart failure are interlinked, as alterations in glucose and hormone levels affect myocardial substrate selection and energy production, leading to glucotoxicity and dysfunction. Glucagon, a hormone that stimulates glucose release, can be beneficial in acute cardiac situations, but chronic activation of its receptor can exacerbate cardiac impairment. The Summers-Holland lab has recently shown that blocking the glucagon receptor with the antibody REMD 2.59 lowers blood glucose, reduces lipid accumulation and toxic metabolites, and improves cardiac function in diabetic mice. However, the molecular mechanisms and cell-specific effects of REMD 2.59 in the heart are unknown. We hypothesize that Forkhead Box Family N, Member 3 (FOXN3) mediates the cardioprotective effects of REMD 2.59. FOXN3 is a transcriptional repressor that inhibits MYC, a key regulator of glucose metabolism. FOXN3 has been implicated in genetic cardiac hypertrophy and glucose metabolism, and our preliminary data suggest that FOXN3 responds to glucagon, is stabilized by REMD 2.59, and its global deletion causes cardiac dysfunction and increased mortality. A failing heart will attempt to compensate by increasing glucose oxidation from fatty acid, but this is less efficient and does not produce as much ATP. FOXN3 was previously investigated in the liver, but its role in the heart is novel and has not been studied before. Using cell culture and transgenic mouse models, antagonist challenges, and cardiac echography, we will elucidate how FOXN3 expression modulates cardiac outcomes in REMD 2.59 treated mice and cells.

Presenter Name: Dylan Skrzynski

Presentation Type: Poster
Presentation Format: In Person
Presentation #111
College: Health
School / Department: Nutrition and Integrative Physiology
Research Mentor: Scott Summers
Date | Time: Thursday, Aug 3rd | 10:30 AM