BACKGROUND: The nature of some of the target genes for liver X receptors (LXRs)-alpha and -beta, such as sterol regulatory element binding protein-1 and ATP-binding cassette transporter proteins, suggests a pivotal role of these nuclear receptors in the regulation of fatty acid and cholesterol homeostasis. The present study aimed to elucidate the physiological relevance of both LXRs with regard to lipid metabolism and macrophage cholesterol efflux. METHODS AND RESULTS: Mice depleted for LXRalpha, LXRbeta, or both were fed low-fat rodent chow for 18 months before investigations. The combined deficiency of LXRalpha and LXRbeta was linked to impaired triglyceride metabolism, increased LDL and reduced HDL cholesterol levels, and cholesterol accumulation in macrophages (foam cells) of the spleen, lung, and arterial wall. CONCLUSIONS: Our data demonstrate the physiological importance of both LXRs in lipid metabolism and strongly indicate that both LXRs have a protective role against the development of atherosclerosis.
BACKGROUND: The nature of some of the target genes for liver X receptors (LXRs)-alpha and -beta, such as sterol regulatory element binding protein-1 and ATP-binding cassette transporter proteins, suggests a pivotal role of these nuclear receptors in the regulation of fatty acid and cholesterol homeostasis. The present study aimed to elucidate the physiological relevance of both LXRs with regard to lipid metabolism and macrophage cholesterol efflux. METHODS AND RESULTS:Mice depleted for LXRalpha, LXRbeta, or both were fed low-fat rodent chow for 18 months before investigations. The combined deficiency of LXRalpha and LXRbeta was linked to impaired triglyceride metabolism, increased LDL and reduced HDL cholesterol levels, and cholesterol accumulation in macrophages (foam cells) of the spleen, lung, and arterial wall. CONCLUSIONS: Our data demonstrate the physiological importance of both LXRs in lipid metabolism and strongly indicate that both LXRs have a protective role against the development of atherosclerosis.
Authors: Christian Bindesbøll; Qiong Fan; Rikke C Nørgaard; Laura MacPherson; Hai-Bin Ruan; Jing Wu; Thomas Å Pedersen; Knut R Steffensen; Xiaoyong Yang; Jason Matthews; Susanne Mandrup; Hilde I Nebb; Line M Grønning-Wang Journal: J Lipid Res Date: 2015-02-27 Impact factor: 5.922
Authors: Ilke Vermeulen; Mark Baird; Juma Al-Dulayymi; Muriel Smet; Jan Verschoor; Johan Grooten Journal: J Lipid Res Date: 2017-02-13 Impact factor: 5.922