Dora A Mendez, Jenifer Hernández García, José G Soñanez-Organis, Marisol Hernández Garcia, Guillermo Vazquez-Anaya, Akira Nishiyama, José Pablo Vázquez-Medina, Rudy M Ortiz
{"title":"外源性甲状腺素增加胰岛素抵抗雄性OLETF大鼠心脏Nrf2-TRX并减少氧化损伤","authors":"Dora A Mendez, Jenifer Hernández García, José G Soñanez-Organis, Marisol Hernández Garcia, Guillermo Vazquez-Anaya, Akira Nishiyama, José Pablo Vázquez-Medina, Rudy M Ortiz","doi":"10.1530/JOE-25-0164","DOIUrl":null,"url":null,"abstract":"<p><p>Cardiovascular disease (CVD) is the leading cause of death among individuals with type II diabetes (T2D), affecting approximately 30 million people in the United States. During insulin resistance, the heart undergoes a metabolic shift, leading to increased reactive oxygen species generation, lipotoxicity, and mitochondrial dysfunction, ultimately contributing to cardiovascular dysfunction. The effects of thyroid hormones (THs) on redox biology and oxidative stress remain inconclusive, necessitating further investigation. In this study, insulin-resistant Otsuka Long Evans Tokushima Fatty (OLETF) rats were used to assess the impact of exogenous thyroxine (exoT4) on NADPH oxidases (NOX) and antioxidant defenses in the heart. Rats were assigned to four groups: i) lean control, Long Evans Tokushima Otsuka (LETO; n = 6), ii) LETO + T4 (8 μg/100 g BM/day for 5 weeks; n = 7), iii) untreated OLETF (n = 6), and iv) OLETF + T4 (n = 7). NOX4 mRNA expression was two-fold greater in OLETF rats compared to LETO. T4 treatment increased NOX4 protein abundance by 56% in OLETF. In addition, T4 normalized lipid peroxidation (4-hydroxynonenal) and tumor necrosis factor-α (TNF-α) levels while increasing nuclear factor erythroid 2-related factor 2 (Nrf2) mRNA expression by 158% compared to LETO and enhancing nuclear Nrf2 protein expression by 45% compared to untreated OLETF. Thioredoxin (TRX) expression, suppressed in OLETF, was increased by 88% following T4 treatment. ExoT4 increased mitofusin 2 (Mfn2) protein abundance in OLETF by 49% compared to LETO. These findings suggest that TH treatment may have cardioprotective effects mediated by Nrf2 in the heart during metabolic syndrome (MetS).</p>","PeriodicalId":15740,"journal":{"name":"Journal of Endocrinology","volume":" ","pages":""},"PeriodicalIF":3.9000,"publicationDate":"2025-08-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Exogenous thyroxine increases cardiac Nrf2-TRX and reduces oxidative injury in insulin-resistant male OLETF rats.\",\"authors\":\"Dora A Mendez, Jenifer Hernández García, José G Soñanez-Organis, Marisol Hernández Garcia, Guillermo Vazquez-Anaya, Akira Nishiyama, José Pablo Vázquez-Medina, Rudy M Ortiz\",\"doi\":\"10.1530/JOE-25-0164\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><p>Cardiovascular disease (CVD) is the leading cause of death among individuals with type II diabetes (T2D), affecting approximately 30 million people in the United States. During insulin resistance, the heart undergoes a metabolic shift, leading to increased reactive oxygen species generation, lipotoxicity, and mitochondrial dysfunction, ultimately contributing to cardiovascular dysfunction. The effects of thyroid hormones (THs) on redox biology and oxidative stress remain inconclusive, necessitating further investigation. In this study, insulin-resistant Otsuka Long Evans Tokushima Fatty (OLETF) rats were used to assess the impact of exogenous thyroxine (exoT4) on NADPH oxidases (NOX) and antioxidant defenses in the heart. Rats were assigned to four groups: i) lean control, Long Evans Tokushima Otsuka (LETO; n = 6), ii) LETO + T4 (8 μg/100 g BM/day for 5 weeks; n = 7), iii) untreated OLETF (n = 6), and iv) OLETF + T4 (n = 7). NOX4 mRNA expression was two-fold greater in OLETF rats compared to LETO. T4 treatment increased NOX4 protein abundance by 56% in OLETF. In addition, T4 normalized lipid peroxidation (4-hydroxynonenal) and tumor necrosis factor-α (TNF-α) levels while increasing nuclear factor erythroid 2-related factor 2 (Nrf2) mRNA expression by 158% compared to LETO and enhancing nuclear Nrf2 protein expression by 45% compared to untreated OLETF. Thioredoxin (TRX) expression, suppressed in OLETF, was increased by 88% following T4 treatment. ExoT4 increased mitofusin 2 (Mfn2) protein abundance in OLETF by 49% compared to LETO. 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Exogenous thyroxine increases cardiac Nrf2-TRX and reduces oxidative injury in insulin-resistant male OLETF rats.
Cardiovascular disease (CVD) is the leading cause of death among individuals with type II diabetes (T2D), affecting approximately 30 million people in the United States. During insulin resistance, the heart undergoes a metabolic shift, leading to increased reactive oxygen species generation, lipotoxicity, and mitochondrial dysfunction, ultimately contributing to cardiovascular dysfunction. The effects of thyroid hormones (THs) on redox biology and oxidative stress remain inconclusive, necessitating further investigation. In this study, insulin-resistant Otsuka Long Evans Tokushima Fatty (OLETF) rats were used to assess the impact of exogenous thyroxine (exoT4) on NADPH oxidases (NOX) and antioxidant defenses in the heart. Rats were assigned to four groups: i) lean control, Long Evans Tokushima Otsuka (LETO; n = 6), ii) LETO + T4 (8 μg/100 g BM/day for 5 weeks; n = 7), iii) untreated OLETF (n = 6), and iv) OLETF + T4 (n = 7). NOX4 mRNA expression was two-fold greater in OLETF rats compared to LETO. T4 treatment increased NOX4 protein abundance by 56% in OLETF. In addition, T4 normalized lipid peroxidation (4-hydroxynonenal) and tumor necrosis factor-α (TNF-α) levels while increasing nuclear factor erythroid 2-related factor 2 (Nrf2) mRNA expression by 158% compared to LETO and enhancing nuclear Nrf2 protein expression by 45% compared to untreated OLETF. Thioredoxin (TRX) expression, suppressed in OLETF, was increased by 88% following T4 treatment. ExoT4 increased mitofusin 2 (Mfn2) protein abundance in OLETF by 49% compared to LETO. These findings suggest that TH treatment may have cardioprotective effects mediated by Nrf2 in the heart during metabolic syndrome (MetS).
期刊介绍:
Journal of Endocrinology is a leading global journal that publishes original research articles, reviews and science guidelines. Its focus is on endocrine physiology and metabolism, including hormone secretion; hormone action; biological effects. The journal publishes basic and translational studies at the organ, tissue and whole organism level.