In line with these observations, CRISPR-mediated TET3 knockdown in AGRP neurons induced hyperphagia, obesity, and diabetes, as determined by increased food intake (Figure 6A), increased body weight and fat mass (Figure 6, B–D), decreased energy expenditure (Figure 6E), elevated blood insulin, glucose, and leptin levels (Figure 6, F–H), and decreased glucose tolerance and insulin sensitivity (Figure 6, I and J), in both female (Figure 6, A–J) and male (Supplemental Figure 4) mice. Here, INS is linked to obesity due to melanocortin 4 receptor deficiency.