Transcriptional integration of metabolism by the nuclear sterol-activated receptors LXR and FXR
Open accessAbstract
Nuclear receptors are integrators of hormonal and nutritional signals, mediating changes to metabolic pathways within the body. Given that modulation of lipid and glucose metabolism has been linked to diseases including type 2 diabetes, obesity and atherosclerosis, a greater understanding of pathways that regulate metabolism in physiology and disease is crucial. The liver X receptors (LXRs) and the farnesoid X receptors (FXRs) are activated by oxysterols and bile acids, respectively. Mounting evidence indicates that these nuclear receptors have essential roles, not only in the regulation of cholesterol and bile acid metabolism but also in the integration of sterol, fatty acid and glucose metabolism.
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The reductions in beta-adrenoreceptor density and affinity appeared greater for DCA, a secondary bile acid.
“Although it was not specifically compared in this adrenoreceptor study, the reductions in receptor density and affinity appeared greater for DCA, a secondary bile acid.”
From Dietary metabolism, the gut microbiome, and heart failure (2019) · cites this paper as [134]
At increased concentrations of bile acids (10−3M), significant reductions in both receptor density and affinity of beta-adrenoreceptors were observed.
“at increased concentrations of bile acids (10−3M), significant reductions in both receptor density and affinity of beta-adrenoreceptors were observed134.”
From Dietary metabolism, the gut microbiome, and heart failure (2019) · cites this paper as [134]
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The IDOL-UBE2D complex mediates sterol-dependent degradation of the LDL receptor
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Calkin, A. C., Goult, B. T., Zhang, L., Fairall, L., Hong, C., Schwabe, J. W. R., & Tontonoz, P. (2011) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1111589108 · Cited by 62 · see citing works
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“LXRs control the expression of a battery of genes involved in cholesterol, fatty acid and phospholipid metabolism through direct binding to LXR response elements (LXREs) in their target promoters (Calkin and Tontonoz, 2012; Hong and Tontonoz, 2014).”
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Self-citation
- Authors
- Calkin, A. C., & Tontonoz, P.
- Affiliations
- Howard Hughes Medical Institute (US)
- Corresponding author
- Calkin, Anna C.
- Tontonoz, Peter
- Venue
- Nature Reviews Molecular Cell Biology
- Published
- 2012-03-14
- Volume
- 13
- Issue
- 4
- Pages
- 213-224
- ISSN
- 1471-0072 (ISSN-L)
- 1471-0080
- PMC
- PMC3597092
- OpenAlex
- W2005911243
- Cited by
- 779
- References
- 119
- Citations by year
- 2026: 38 · 2025: 34 · 2024: 58 · 2023: 48 · 2022: 53 · 2021: 56 · 2020: 63 · 2019: 47 · 2018: 53 · 2017: 56 · 2016: 66 · 2015: 63 · 2014: 61 · 2013: 62 · 2012: 19
- FWCI
- 12.69
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Nature Reviews Molecular Cell Biology (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- Howard Hughes Medical Institute
- National Heart, Lung, and Blood Institute (HL030568, HL066088, P01HL030568, R01HL066088)
- Topics
- Health Sciences › Medicine › Surgery › Cholesterol and Lipid Metabolism
- Health Sciences › Medicine › Oncology › Drug Transport and Resistance Mechanisms
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Peroxisome Proliferator-Activated Receptors
- Keywords
- liver X receptor, farnesoid X receptor, nuclear receptors, oxysterols, bile acids, cholesterol metabolism, bile acid metabolism, sterol metabolism, fatty acid metabolism, glucose metabolism, type 2 diabetes, obesity, atherosclerosis, transcriptional regulation
- MeSH terms
- Liver X Receptors, Receptor, Farnesoid X-Activated, Animals, Bile Acids and Salts, Cholesterol, Diabetes Mellitus, Type 2, Gene Expression Regulation, Glucose, Humans, Obesity, Sterols, Transcription, Genetic, RNA-Binding Proteins, Receptors, Cytoplasmic and Nuclear, Atherosclerosis, Lipid Metabolism, Orphan Nuclear Receptors
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