Biology subjects

Ortiz, R. M.

Publications and source records attributed to Ortiz, R. M..

2 recordsLinked to original sources

bioRxiv2025

Exogenous Thyroxine Increases Cardiac Nrf2-TRX in Insulin Resistant 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 (ROS) 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: (1) lean control, Long Evans Tokushima Otsuka (LETO; n=6), (2) LETO + T4 (8 g/100g BM/day for 5 weeks; n=7), (3) untreated OLETF (n=6), and (4) 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. Additionally, T4 normalized lipid peroxidation (4-hydroxynonenal) and tumor necrosis factor- (TNF-) 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 thyroid hormone treatment may have cardioprotective effects mediated by Nrf2 in the heart during metabolic syndrome (MetS).

physiology↗

bioRxiv2021

Mass Recovery following Caloric Restriction Reverses Lipolysis and Proteolysis, but not Gluconeogenesis, in Insulin Resistant OLETF Rats

Caloric restriction (CR) is one of the most important behavioral interventions to reduce excessive abdominal adiposity, which is a risk factor for the development of insulin resistance. Previous metabolomics studies have characterized substrate metabolism during healthy conditions; however, the effects of CR and subsequent mass recovery on shifts in substrate metabolism during insulin resistance (IR) have not been widely investigated. To assess the effects of acute CR and the subsequent mass recovery on shifts in substrate metabolism, a cohort of 15-week old Long Evans Tokushima Otsuka (LETO) and Otsuka Long Evans Tokushima Fatty (OLETF) rats were calorie restricted (CR: 50% x 10 days) with or without partial body mass recovery (PR; 73% x 7 days), along with their respective ad libitum controls. End-of-study plasma samples were analyzed for primary carbon metabolites by gas chromatography (GC) time-of-flight (TOF) mass spectrometry (MS) data acquisition. Data analysis included PCA, Pearson correlation vs previously reported variables (adipose and body masses, and insulin resistance index, IRI), and metabolomics maps (MetaMapp) generated for the most significant group comparisons. All treatments elicited a significant group differentiation in at least one principal component. CR improved TCA cycle in OLETF, and increased lipolysis and proteolysis. These changes were reversed after PR except for gluconeogenesis. Plasma lipid concentrations were inversely correlated to IRI in LETO, but not OLETF. These shifts in substrate metabolism suggest that the CR-induced decreases in adipose may not be sufficient to more permanently alter substrate metabolism to improve IR status during metabolic syndrome.

physiology↗