| First Author | Korach-André M | Year | 2011 |
| Journal | Proc Natl Acad Sci U S A | Volume | 108 |
| Issue | 1 | Pages | 403-8 |
| PubMed ID | 21173252 | Mgi Jnum | J:262347 |
| Mgi Id | MGI:6162335 | Doi | 10.1073/pnas.1017884108 |
| Citation | Korach-Andre M, et al. (2011) Both liver-X receptor (LXR) isoforms control energy expenditure by regulating brown adipose tissue activity. Proc Natl Acad Sci U S A 108(1):403-8 |
| abstractText | Brown adipocytes are multilocular lipid storage cells that play a crucial role in nonshivering thermogenesis. Uncoupling protein 1 (UCP1) is a unique feature of brown fat cells that allows heat generation on sympathetic nervous system stimulation. As conventional transcriptional factors that are activated in various signaling pathways, liver-X receptors (LXRs) play important roles in many physiological processes. The role of LXRs in the regulation of energy homeostasis remains unclear, however. Female WT, LXRalphabeta(-/-), LXRalpha(-/-), and LXRbeta(-/-) mice were fed with either a normal diet (ND) or a high-carbohydrate diet (HCD) supplemented with or without GW3965-LXR agonist. LXRalphabeta(-/-) mice exhibited higher energy expenditure (EE) as well as higher UCP1 expression in brown adipose tissue (BAT) compared with WT mice on the HCD. In addition, long-term treatment of WT mice with GW3965 showed lower EE at thermoneutrality (30 degrees C) and lower Ucp1 expression level in BAT. Furthermore, H&E staining of the BAT of LXRalphabeta(-/-) mice exhibited decreased lipid droplet size compared with WT mice on the HCD associated with a more intense UCP1-positive reaction. Quantification of triglyceride (TG) content in BAT showed lower TG accumulation in LXRbeta(-/-) mice compared with WT mice. Surprisingly, GW3965 treatment increased TG content (twofold) in the BAT of WT and LXRalpha(-/-) mice but not in LXRbeta(-/-) mice. Furthermore, glucose transporter (GLUT4) in the BAT of LXRalpha(-/-) and LXRbeta(-/-) mice was sixfold and fourfold increased, respectively, compared with WT mice on the ND. These findings suggest that LXRalpha as well as LXRbeta could play a crucial role in the regulation of energy homeostasis in female mice and may be a potential target for the treatment of obesity and energy regulation. |
