MYC is a transcription factor controlling growth and nutrient metabolism. Luo et al. now link intestinal expression of MYC to impairments in glucose, lipid and body-weight homeostasis by uncovering novel roles of MYC in regulating the glucagon-like peptide GLP1 and the ceramide-biosynthesis regulator CERS4. Myc deletion in the intestinal epithelium prevents or reverses diet-induced obesity and hepatic steatosis in mice. Critically, people with obesity display elevated MYC and CERS4 expression in the ileum, thus further supporting the clinical relevance of these findings.