Table 2.

Summary of key studies on hepatocyte-specific HIF modulation

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