1. LXRs regulate the balance between fat storage and oxidation
- Author
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Nada Y. Kalaany, Karine Gauthier, David J. Mangelsdorf, Tatsuya Kitazume, Julian A. Peterson, Jay D. Horton, Antonio C. Bianco, Pradeep P.A. Mammen, Daniel J. Garry, and Ann Marie Zavacki
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medicine.medical_specialty ,Physiology ,Receptors, Cytoplasmic and Nuclear ,Adipose tissue ,Hyperlipidemias ,Oxidative phosphorylation ,digestive system ,Mice ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,Internal medicine ,medicine ,polycyclic compounds ,Animals ,Obesity ,Receptor ,Liver X receptor ,Molecular Biology ,Liver X Receptors ,030304 developmental biology ,Mice, Knockout ,0303 health sciences ,Chemistry ,Cholesterol ,Lipid metabolism ,Cell Biology ,Lipid Metabolism ,Orphan Nuclear Receptors ,DNA-Binding Proteins ,Endocrinology ,Adipose Tissue ,Liver ,Lipogenesis ,lipids (amino acids, peptides, and proteins) ,Lipid Peroxidation ,Insulin Resistance ,Oxidation-Reduction ,030217 neurology & neurosurgery ,Transcription Factors ,Hormone - Abstract
SummaryDespite the well-established role of liver X receptors (LXRs) in regulating cholesterol homeostasis, their contribution to lipid homeostasis remains unclear. Here we show that LXR null mice are defective in hepatic lipid metabolism and are resistant to obesity when challenged with a diet containing both high fat and cholesterol. This phenotype is dependent on the presence of dietary cholesterol and is accompanied by the aberrant production of thyroid hormone in liver. Interestingly, the inability of LXR−/− mice to induce SREBP-1c-dependent lipogenesis does not explain the LXR−/− phenotype, since SREBP-1c null mice are not obesity resistant. Instead, the LXR−/− response is due to abnormal energy dissipation resulting from uncoupled oxidative phosphorylation and ectopic expression of uncoupling proteins in muscle and white adipose. These studies suggest that, by selectively sensing the cholesterol component of a lipid-rich diet, LXRs govern the balance between storage and oxidation of dietary fat.
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