Table 2.
Gene modulation | Study protocol | Phenotype | Lipogenic genes | β-Oxidation | References |
---|---|---|---|---|---|
HIF-1α and/or HIF-2α overexpression | Alb-Cre × VHLf/f, HIF-1dPA and/or HIF-2dPA |
Severe steatosis in Alb-Cre; VHLf/f and Alb-Cre; HIF1dPA/HIF2dPA mice Moderate steatosis in Alb-Cre; HIF1dPA mice |
ND | ND | Kim et al. [105] |
HIF-1α and/or HIF-2α overexpression | Alb-Cre × VHLf/f ± HIF-1αf/f and/or HIF-2αf/f |
Severe steatosis in mice overexpressing HIF-2α (±HIF-1α) HIF-1α overexpression alone does not cause steatosis |
Downregulation | Suppression | Rankin et al. [89] |
Temporally induced HIF-1α and/or HIF-2α overexpression | SA-Cre-ERT2 × VHLf/f ± HIF-1αf/f and/or HIF-2αf/f |
Severe steatosis in mice overexpressing HIF-2α (±HIF-1α) HIF-1α overexpression does not cause steatosis |
Upregulated after 3 days, downregulated after 14 days | Suppression | Qu et al. [90] |
HIF-1α deletion PHD inhibition |
Alb-Cre × HIF-1αf/f + Lieber-DeCarli diet Dimethyloxalylglycine |
Exacerbated steatosis Increased serum TG Decreased steatosis and liver TG |
Upregulated Downregulated |
Induction ND |
Nishiyama et al. [91] |
HIF-1α overexpression HIF-1α deletion |
Alb-Cre × HIF-1dPA + alcoholic diet Alb-Cre × HIF-1αf/f + alcoholic diet |
Increased steatosis and liver TG, increased serum ALT No increase in ALT, protected against steatosis |
ND ND |
Suppression ND |
Nath et al. [96] |
HIF-1β deletion | Adenoviral Cre injection in HIF-1βf/f mice ± high-fat diet |
Increased gluconeogenesis Mild insulin resistance Decreased liver TG content |
Upregulated | Not affected | Wang et al. [112] |
ND not determined, ALT alanine aminotransferase, TG triglycerides