Table 1.
Gene modulation | Study protocol | Body weight | Glucose tolerance | Adipocyte phenotype | Adipose tissue inflammation | Vasculature | Hepatic metabolism | References |
---|---|---|---|---|---|---|---|---|
HIF-1α overexpression | aP2-HIF-1α-ODD transgene construct | Increased | Impaired | Increased cell size | Increased | Not affected | Impaired insulin sensitivity, TG increase | Halberg et al. [43] |
HIF-1α or HIF-1β deletion | aP2-Cre × HIF-1αf/f/HIF-1βf/f | Decreased | Improved | Smaller adipocytes | Decreased | ND | Increased insulin sensitivity | Jiang et al. [47] |
HIF-1β deletion | aP2-Cre × HIF-1βf/f | Decreased | Improved | Smaller adipocytes | Unchanged | Reduced permeability | Unchanged lipid accumulation or insulin sensitivity | Lee et al. [53] |
HIF-1α deletion HIF-2α deletion |
aP2-Cre × HIF-1αf/f aP2-Cre × HIF-2αf/f |
Unchanged Increased |
Improved Impaired |
Decreased cell mass and size ND |
Decreased Increased |
Not affected ND |
Decreased steatosis and inflammation ND |
Lee et al. [40] |
HIF-1α deletion | aP2-Dominant-negative (dn)-HIF-1α construct | Increased | Impaired |
‘Whitening’ of BAT Increased WAT mass |
Increased inflammation and fibrosis | Impaired (BAT) | ND | Zhang et al. [69] |
HIF-2α deletion | Fabp4-Cre × HIF-2αf/f | Increased | Impaired |
‘Whitening’ of BAT Increased WAT mass |
Increased inflammation and fibrosis | Impaired |
Increased steatosis and TG accumulation Progression to NASH |
Garcia-Martin et al. [51] |
HIF-1α inhibition |
Compound PX-478 Apn-rtTA × TRE-dn-HIF-1α |
Reduced | Improved | Decreased cell mass and size | Decreased | ND | Decreased steatosis | Sun et al. [48] |
PHD2 inhibition | aP2-Cre × PHD2f/f | Reduced | Improved | Smaller adipocytes | Reduced | Mildly increased | ND | Matsuura et al. [60] |
PHD2 inhibition | aP2-Cre × PHD2f/f | Increased | Unaffected | Larger adipocytes | Unaffected | Increased | Decreased liver TG | Michailidou et al. [62] |
PHD2 inhibition |
PHD2gt/gt mice FG-4497 administration |
Reduced Reduced |
Improved Improved |
Smaller adipocytes Smaller adipocytes |
Decreased Decreased |
Not affected ND |
Decreased steatosis ND |
Rahtu-Korpela et al. [114] |
Outcome values in comparison with WT mice after HFD feeding
ND not determined, TG triglycerides