Contrary to what is seen in ob/ob mice, db/db, mice have a natural mutation in the leptin receptor (ob-Rb) gene; however, in line with what is found in ob/ob mice, db/db animals also only develop obesity, insulin resistance, and macrovesicular steatosis and require a “second hit” to progress from steatosis to steatohepatitis [19]. This evidence concerns the gene RB1 and steatosis.