Susceptibility of Nrf2-null mice to steatohepatitis and cirrhosis upon consumption of a high-fat diet is associated with oxidative stress, perturbation of the unfolded protein response, and disturbance in the expression of metabolic enzymes but not with insulin resistance.

Plasma leptin and insulin levels were similar in RC-fed Nrf2 −/− and Nrf2 +/+ mice, but consistent with their increased body fat content, HF-fed Nrf2 −/− and Nrf2 +/+ mice displayed increased plasma leptin and insulin levels, with a nonsignificant trend for reduced leptin levels in Nrf2 −/− mice ( Fig. 1G and H ).

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