In addition, our goal was to determine a role of G6PD, the key rate-limiting enzyme in the PPP that is induced and activated by hormones (insulin) and diet or oxidative stress (16), in the pathogenesis of HFD-induced obesity, metabolic reprogramming, and multi-organ diseases, using a novel rat model of loss-of-function Mediterranean G6PD variant generated with CRISPR-editing. The gene discussed is G6PD; the disease is obesity due to melanocortin 4 receptor deficiency.