Table 1.
Representative HIF direct or indirect target genes that mediate reprogramming of lipid metabolism under hypoxia.
| Functional Category /Protein Name |
HIF Isoform & Effect | Outcome & Experimental Evidence | Ref. |
|---|---|---|---|
| FA & Lipoprotein Uptake | |||
| PPARγ | HIF-1 Positive | Increased expression HIF-1 binds to the promoter of PPARγ and activates its transcription |
[48] |
| FABP3 | HIF-1 Positive | Increased expression HIF-1α depletion inhibits the induction of FABP3 under hypoxia |
[49] |
| FABP4 | HIF-1 Positive | Increased expression HIF-1 binds to the promoter of FABP4 and activates its transcription |
[50] |
| FABP7 | HIF-1 Positive | Increased expression HIF-1α depletion inhibits the induction of FABP7 under hypoxia |
[49] |
| LRP1 | HIF-1 Positive | Increased expression HIF-1α binds to the LRP1 promoter and activates its transcription |
[51] |
| VDLR | HIF-1 Positive | Increased expression HIF-1α depletion inhibits activation of VDLR promoter under hypoxia |
[52] |
| Reductive Carboxylation of Glutamine | |||
| GLS1 | HIF-1 Positive | Increased expression HIF-1α depletion inhibits the induction of GLS1 under hypoxia |
[58] |
| OGDH2 | HIF-1 Negative | Increased proteolysis SIAH2 (a HIF-1 target) mediates proteolysis of OGDH2 |
[57] |
| Ceramide Salvage | |||
| NEU3 | HIF-2 Positive | Increased expression HIF-2α binds to the NEU3 promoter and activates its transcription |
[101] |
| FA Synthesis | |||
| SREBP-1 | HIF-1 Positive | Up-regulation Inhibition of HIF-1 impairs phospho-SREBP-1 increase under hypoxia |
[59,69] |
| FASN | HIF-1 Positive | Increased expression Inhibition of HIF-1 impairs the induction of FASN under hypoxia Increased binding of SREBP-1 to the FASN promoter under hypoxia |
[59] |
| TG Synthesis | |||
| AGPAT2 | HIF-1 Positive | Increased expression HIF-1 binds to the promoter of AGPAT2 and activates its transcription |
[62] |
| Lipin-1 | HIF-1 Positive | Increased expression HIF-1 binds to the promoter of LPIN1 and activates its transcription |
[63] |
| LD Accumulation | |||
| PLIN2 | HIF-2 Positive | Increased expression HIF-2α depletion inhibits the induction of PLIN2 under hypoxia |
[65] |
| HIG2 | HIF-1 Positive | Increased expression HIF-1 binds to the promoter of HIG2 and activates its transcription |
[66] |
| β-Oxidation | |||
| PGC-1α | HIF-1 & HIF-2 Negative | Reduced expression HIF-1α or HIF-2α depletion inhibits reduction of PGC-1α expression under hypoxia |
[69] |
| CPT1A | HIF-1 & HIF-2 Negative | Reduced expression HIF-1α or HIF-2α depletion inhibit reduction of CPT1A expression under hypoxia |
[69,70] |
| MCAD | HIF-1 Negative | Reduced expression HIF-1α depletion inhibits reduction of MCAD expression under hypoxia |
[71] |
| LCAD | HIF-1 Negative | Reduced expression HIF-1α depletion inhibits reduction of LCAD expression under hypoxia |
[71] |
| PGC-1β | HIF-1 Negative | Reduced expression HIF-1α depletion inhibits reduction of PGC-1β expression under hypoxia |
[71] |