Our work shows that even heterozygous loss of function of one Cyp51 allele from the cholesterol synthesis leads to significant phenotype differences in male and female mice, where Cyp51+/− males are more affected by harmful cholesterol lipid profile and hepatomegaly, but also Cyp51+/− females reveal risk factors of the fatty liver disease. This evidence concerns the gene CYP51A1 and fatty liver disease.