Nrf2 Overexpression in Spontaneously Hypertensive Rats Enhances Adipose Tissue Metabolism through Redox-Mediated Suppression of Mitochondrial Oxidative Phosphorylation.

The spontaneously hypertensive rat (SHR) is a widely used model of essential hypertension that also exhibits metabolic disturbances under specific conditions. Oxidative stress plays a central role in the pathogenesis of both hypertension and metabolic dysfunction, with the transcription factor Nrf2 regulating key antioxidant defenses. Here, we examined whether Nrf2 overexpression in the SHR improves adipose tissue metabolism. A mouse Nrf2 transgene under a universal promoter was markedly overexpressed in white adipose tissue, leading to increased insulin sensitivity, reduced saturated fatty acids, and higher n-3 polyunsaturated fatty acids in adipose membrane phospholipids. Transgenic rats also displayed reduced mitochondrial complex I levels, enhanced antioxidant enzyme activities, and decreased lipoperoxidation. Transcriptomic analysis revealed downregulation of oxidative phosphorylation genes. These findings suggest that Nrf2 overexpression confers antidiabetic and hypolipidemic effects in the SHR, potentially via redox-sensitive remodeling of adipose tissue metabolism. Key words: Nrf2 o Spontaneously hypertensive rat (SHR) o Oxidative stress o Adipose tissue o Metabolism o Mitochondrial function o Oxidative phosphorylation o Antioxidant defense o Insulin sensitivity o Fatty acids o transcriptomics o Transgenic rats o Gene expression.