Table 1 Some of the key studies published previously that investigated the adipocyte-specific disruption of HIF signaling in mice fed a high-fat diet.
From: Sensing the oxygen and temperature in the adipose tissues – who’s sensing what?
Gene | Promoter | Methods | Effects | Phenotype | References |
|---|---|---|---|---|---|
Hif-1α | aP2 | Cre-ERT2/loxP | ↓ HIF-1α in adipocytes upon tamoxifen treatment | ↓ body weight gain ↑ PGC-1α protein expression and mitochondrial functions | |
Cre/loxP | ↓ HIF-1α in adipocytes | ↑ insulin sensitivity ↓ adipose tissue inflammation | |||
knock-in of human HIF1A lacking the DNA binding domain | ↓ HIF-1α in adipocytes | ↑ body weight gain ↓ insulin sensitivity ↓ core body temperature ↓ Pgc-1α and UCP1 gene and protein expression ↑ adipose tissue fibrosis | |||
Hif-1β | aP2 | Cre/loxP | ↓ HIF-1α in adipocytes (theoretically ↓HIF-1α, HIF-2α, and HIF-3α in adipocytes) | ↓ body weight gain ↑ insulin sensitivity | |
Hif-2α | Fabp4 | Cre/loxP | ↓ HIF-2α in adipocytes | ↑ body weight gain ↓ insulin sensitivity ↑ adipose tissue inflammation and hypoxia ↓ adipose tissue vascularization | |
N/A | knock-in amino acid substituted (S304M) human HIF-2α | ↓ HIF-2 activity in all tissues | ↑ body weight gain ↑ adipogenesis | ||
Phd2 | aP2 | Cre/loxP | ↑ HIF-1α and HIF-2α in adipocytes | ↓ body weight gain ↑ insulin sensitivity ↑ vascularity in adipose tissues ↑ glycolytic gene expression ↑ oxygen consumption | |
Vhl | aP2/Fabp4 | Cre/loxP | ↑ HIF-1α, HIF-2α, and HIF-3α in adipocytes | No difference in the body weight gain compared to WT mice ↓ visceral fat mass (but not brown adipose tissues) Cardiomegaly (HIF-2α dependent) ↓ blood glucose levels (more pronounced in female mice) ↓ serum glycerol levels ↑ circulating lymphocytes (more pronounced in female mice)↑ inflammatory gene expression in adipose tissues |
