Background: Obesity, insulin resistance, and type 2 diabetes are related metabolic disorders. Obese adipose tissue can become hypoxic because of the inability of vasculature to keep pace with tissue growth. During the early stages of obesity, relative hypoxia causes an increase in the protein levels of hypoxia-inducible factor 1α (HIF1α). HIF-1 is a transcription factor that mediates adaptive responses to hypoxia and ischaemia. As a transcription factor, HIF-1 regulates the expression of hundreds of genes, including those encoding thermogenic genes in brown / beige fat. Because brown and beige fat consume glucose and lipids to produce heat, we tested whether deletion of HIF1a from brown and beige fat affected glucose tolerance or insulin sensitivity.
Methods:
Transgenic mice with floxed HIF-1a alleles (FC) were crossed with UCP1-Cre mice to generate brown/beige-fat HIF1a-null (bfHIF) mice. To induce obesity mice were fed high fat diet (HFD, 45% energy from fat) for 18 weeks. Glucose (GTT) and insulin (ITT) tolerance tests were performed at 18 weeks.
Results:
On HFD, at 18 weeks, despite similar food intake (4-5g day time, 5-6g night time), bfHIF knockout mice showed a trend to being lighter (mean weight gain= 3.07g KO versus 5.58g WT, p=0.01). However, glucose tolerance and insulin sensitivity demonstrated no significant differences between the groups (p>0.5).
Conclusions:
Deletion of HIF1a from brown/ beige fat had no effect on glucose tolerance or insulin sensitivity on diet-induced obese mice.