Fructose, derived from sucrose, can affect carbohydrate metabolism by changing intermediate glycolytic metabolites and gene expression patterns of metabolism-related enzymes.24 Moreover, high consumption of fructose causes hepatic steatosis and obesity, while also eliciting metabolic abnormalities such as insulin resistance, leptin resistance and hypertriglyceridemia.24, 25 Thus it is speculated that different phenotype observed in Creb3l4 KO mice, in response to different diets, might be due to the sucrose disaccharide contained in the LFD diet. Here, CREB3L4 is linked to fatty liver disease.