The Effects of Exogenous Thyroxine on Cardiac Antioxidant Defense and PTEN-induced putative kinase 1 in Insulin Resistance Rats

Cardiovascular (CVD) is the leading cause of death, afflicting 1 in 5 American adults, CVD a primary outcome of metabolic syndrome (MetS). MetS is defined as a cluster factor of conditions including obesity, hypertension, dyslipidemia, glucose intolerance with or without insulin resistance, and a proinflammatory or prothrombotic state. Thyroid hormone (TH) treatment has shown to mitigate oxidative injury by enhancing antioxidant defense through modulation of substrate utilization. Our previous findings demonstrated that exogenous thyroxine (exoT4) treatment increased the protein expression of cardiac thioredoxin during MetS, indicating an upregulation in antioxidant defense. Additionally, exoT4 induced an upregulation in NADPH oxidase 4 (NOX4) during MetS, similar to lean strain control levels. Impaired redox balance is a key factor of diabetic cardiomyopathy and mitochondrial dysfunction contributing to disease progression Thus, maintaining mitochondrial quality and integrity mitigating oxidative damage, hence we hypothesized that exoT4 treatment increases the expression of (PINK1). Insulin resistant, Otsuka Long Evan Tokushima Fatty (OLETF) rats, a model of MetS, were used to assess the effects of exoT4 on cardiovascular tissue. Rats were assigned four groups: (1) lean, control Long Evans Tokushima Otsuka (LETO; n=6), (2) LETO + T4 (n=7), (8ug/100g BM/d x 5 wks; n=7), (3) untreated OLETF (n=6), and (4) OLETF + T4 (n=7). While we continue to generate the data, we expect to see an increase of PINK1 expression in treated OLETF vs untreated OLETF, and an increase in LETO vs OLETF. This data will provide insights on mitochondrial biogenesis in the heart of Mets. American Heart Association grant #946746 UROC SOAR 2024 UROC Academic Year Research This abstract was presented at the American Physiology Summit 2025 and is only available in HTML format. There is no downloadable file or PDF version. The Physiology editorial board was not involved in the peer review process.