Overexpression in DMH of lean rats ↑ food intake, body weight and obesity brought on by a high fat diet; knockdown in DMH ↓ NPY innervation of the dorsal vagal complex and affected CCK satiation. Npy knockdown in OLETF rats ↓ basally elevated DMH Npy and ↓ BW, hyperphagia, glucose intolerance, insulin insensitivity, plasma leptin, and triglycerides. This evidence concerns the gene LEP and obesity due to melanocortin 4 receptor deficiency.