Exogenous thyroxine increases cardiac Nrf2-TRX and reduces oxidative injury in insulin-resistant male OLETF rats.

IF 3.9 3区 医学 Q2 ENDOCRINOLOGY & METABOLISM
Journal of Endocrinology Pub Date : 2025-08-25 Print Date: 2025-08-01 DOI:10.1530/JOE-25-0164
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
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引用次数: 0

Abstract

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).

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
心血管疾病(CVD)是导致II型糖尿病(T2D)患者死亡的主要原因,在美国影响了大约3000万人。在胰岛素抵抗期间,心脏发生代谢变化,导致活性氧(ROS)生成增加、脂肪毒性和线粒体功能障碍,最终导致心血管功能障碍。甲状腺激素(THs)对氧化还原生物学和氧化应激的影响尚无定论,需要进一步研究。本研究采用胰岛素抵抗大鼠OLETF (Otsuka Long Evans Tokushima Fatty)来评估外源性甲状腺素(exoT4)对心脏NADPH氧化酶(NOX)和抗氧化防御的影响。将大鼠分为四组:(1)瘦肉对照组,Long Evans Tokushima Otsuka (LETO);n=6), (2) LETO + T4 (8 μg/100g BM/d,连续5周;n=7),(3)未处理OLETF (n=6), (4) OLETF + T4 (n=7)。与LETO相比,OLETF大鼠的NOX4 mRNA表达量增加了两倍。T4处理使OLETF中NOX4蛋白丰度增加56%。此外,与未治疗的OLETF相比,T4使脂质过氧化(4-羟基壬烯醛)和肿瘤坏死因子-α (TNF-α)水平正常化,同时使核因子红细胞2相关因子2 (Nrf2) mRNA表达增加158%,使核Nrf2蛋白表达增加45%。在OLETF中被抑制的硫氧还蛋白(TRX)表达在T4治疗后增加了88%。与LETO相比,ExoT4使OLETF中的mitofusin 2 (Mfn2)蛋白丰度增加了49%。这些发现表明,甲状腺激素治疗可能具有代谢综合征(MetS)期间心脏Nrf2介导的心脏保护作用。
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来源期刊
Journal of Endocrinology
Journal of Endocrinology 医学-内分泌学与代谢
CiteScore
7.90
自引率
2.50%
发文量
113
审稿时长
4-8 weeks
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.
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