| First Author | Sharma M | Year | 2020 |
| Journal | Sci Rep | Volume | 10 |
| Issue | 1 | Pages | 5555 |
| PubMed ID | 32221369 | Mgi Jnum | J:298429 |
| Mgi Id | MGI:6480106 | Doi | 10.1038/s41598-020-62272-9 |
| Citation | Sharma M, et al. (2020) Enhanced glycolysis and HIF-1alpha activation in adipose tissue macrophages sustains local and systemic interleukin-1beta production in obesity. Sci Rep 10(1):5555 |
| abstractText | During obesity, macrophages infiltrate the visceral adipose tissue and promote inflammation that contributes to type II diabetes. Evidence suggests that the rewiring of cellular metabolism can regulate macrophage function. However, the metabolic programs that characterize adipose tissue macrophages (ATM) in obesity are poorly defined. Here, we demonstrate that ATM from obese mice exhibit metabolic profiles characterized by elevated glycolysis and oxidative phosphorylation, distinct from ATM from lean mice. Increased activation of HIF-1alpha in ATM of obese visceral adipose tissue resulted in induction of IL-1beta and genes in the glycolytic pathway. Using a hypoxia-tracer, we show that HIF-1alpha nuclear translocation occurred both in hypoxic and non-hypoxic ATM suggesting that both hypoxic and pseudohypoxic stimuli activate HIF-1alpha and its target genes in ATM during diet-induced obesity. Exposure of macrophages to the saturated fatty acid palmitate increased glycolysis and HIF-1alpha expression, which culminated in IL-1beta induction thereby simulating pseudohypoxia. Using mice with macrophage-specific targeted deletion of HIF-1alpha, we demonstrate the critical role of HIF-1alpha-derived from macrophages in regulating ATM accumulation, and local and systemic IL-1beta production, but not in modulating systemic metabolic responses. Collectively, our data identify enhanced glycolysis and HIF-1alpha activation as drivers of low-grade inflammation in obesity. |
