Cited by 779Cholesterol and Lipid MetabolismDrug Transport and Resistance MechanismsPeroxisome Proliferator-Activated Receptors

Transcriptional integration of metabolism by the nuclear sterol-activated receptors LXR and FXR

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Calkin, Anna C., Tontonoz, Peter·2012·Nature Reviews Molecular Cell Biology

Abstract

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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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
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
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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