| First Author | Voisin M | Year | 2021 |
| Journal | Commun Biol | Volume | 4 |
| Issue | 1 | Pages | 420 |
| PubMed ID | 33772096 | Mgi Jnum | J:306519 |
| Mgi Id | MGI:6714994 | Doi | 10.1038/s42003-021-01925-5 |
| Citation | Voisin M, et al. (2021) Inhibiting LXRalpha phosphorylation in hematopoietic cells reduces inflammation and attenuates atherosclerosis and obesity in mice. Commun Biol 4(1):420 |
| abstractText | Atherosclerosis and obesity share pathological features including inflammation mediated by innate and adaptive immune cells. LXRalpha plays a central role in the transcription of inflammatory and metabolic genes. LXRalpha is modulated by phosphorylation at serine 196 (LXRalpha pS196), however, the consequences of LXRalpha pS196 in hematopoietic cell precursors in atherosclerosis and obesity have not been investigated. To assess the importance of LXRalpha phosphorylation, bone marrow from LXRalpha WT and S196A mice was transplanted into Ldlr(-/-) mice, which were fed a western diet prior to evaluation of atherosclerosis and obesity. Plaques from S196A mice showed reduced inflammatory monocyte recruitment, lipid accumulation, and macrophage proliferation. Expression profiling of CD68(+) and T cells from S196A mouse plaques revealed downregulation of pro-inflammatory genes and in the case of CD68(+) upregulation of mitochondrial genes characteristic of anti-inflammatory macrophages. Furthermore, S196A mice had lower body weight and less visceral adipose tissue; this was associated with transcriptional reprograming of the adipose tissue macrophages and T cells, and resolution of inflammation resulting in less fat accumulation within adipocytes. Thus, reducing LXRalpha pS196 in hematopoietic cells attenuates atherosclerosis and obesity by reprogramming the transcriptional activity of LXRalpha in macrophages and T cells to promote an anti-inflammatory phenotype. |
