Regardless of this distinction, the fact that overweight/obese individuals demonstrate at least normal lipid turnover during exercise contrasts the contention that the pathological accumulation of lipid in muscle and consequent presence of lipotoxic spingolipid metabolites (e.g., ceramide) that adversely affects the insulin signal transduction pathway occurs because of a lipid-oxidizing defect associated with overweight/obesity. This evidence concerns the gene INS and obesity due to melanocortin 4 receptor deficiency.