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Updated: Dec 23, 2025

Differentiated Mouse Adipocytes in Primary Culture: A Model of Insulin Resistance
Published on: February 17, 2023
Interplay between NADH oxidation by complex I, glutathione redox state and sirtuin-3, and its role in the development
Christian Cortés-Rojo1, Manuel Alejandro Vargas-Vargas1, Berenice Eridani Olmos-Orizaba1
1Instituto de Investigaciones Químico-Biológicas, Universidad Michoacana de San Nicolás de Hidalgo, Morelia, Mich 58030, México.
Abstract:
Metabolic diseases are characterized by high NADH/NAD+ ratios due to excessive electron supply, causing defective mitochondrial function and impaired sirtuin-3 (SIRT-3) activity, the latter driving to oxidative stress and altered fatty acid β-oxidation. NADH is oxidized by the complex I in the electron transport chain, thereby factors inhibiting complex I like acetylation, cardiolipin peroxidation, and glutathionylation by low GSH/GSSG ratios affects SIRT3 function by increasing the NADH/NAD+ ratio. In this review, we summarized the evidence supporting a role of the above events in the development of insulin resistance, which is relevant in the pathogenesis of obesity and diabetes. We propose that maintenance of proper NADH/NAD+ and GSH/GSSG ratios are central to ameliorate insulin resistance, as alterations in these redox couples lead to complex I dysfunction, disruption of SIRT-3 activity, ROS production and impaired β-oxidation, the latter two being key effectors of insulin resistance.
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