Table 1.

Summary of key studies on adipocyte-specific HIF modulation

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