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      Up to date on cholesterol 7 alpha-hydroxylase (CYP7A1) in bile acid synthesis

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          Abstract

          Cholesterol 7 alpha-hydroxylase (CYP7A1, EC1.14) is the first and rate-limiting enzyme in the classic bile acid synthesis pathway. Much progress has been made in understanding the transcriptional regulation of CYP7A1 gene expression and the underlying molecular mechanisms of bile acid feedback regulation of CYP7A1 and bile acid synthesis in the last three decades. Discovery of bile acid-activated receptors and their roles in the regulation of lipid, glucose and energy metabolism have been translated to the development of bile acid-based drug therapies for the treatment of liver-related metabolic diseases such as alcoholic and non-alcoholic fatty liver diseases, liver cirrhosis, diabetes, obesity and hepatocellular carcinoma. This review will provide an update on the advances in our understanding of the molecular biology and mechanistic insights of the regulation of CYP7A1 in bile acid synthesis in the last 40 years.

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          Global burden of NAFLD and NASH: trends, predictions, risk factors and prevention

          Zobair Younossi, Quentin M Anstee, Milena Marietti … (2018)
          NAFLD is one of the most important causes of liver disease worldwide and will probably emerge as the leading cause of end-stage liver disease in the coming decades, with the disease affecting both adults and children. The epidemiology and demographic characteristics of NAFLD vary worldwide, usually parallel to the prevalence of obesity, but a substantial proportion of patients are lean. The large number of patients with NAFLD with potential for progressive liver disease creates challenges for screening, as the diagnosis of NASH necessitates invasive liver biopsy. Furthermore, individuals with NAFLD have a high frequency of metabolic comorbidities and could place a growing strain on health-care systems from their need for management. While awaiting the development effective therapies, this disease warrants the attention of primary care physicians, specialists and health policy makers.
          Article 0 comments Cited 1618 times – based on 0 reviews     Review now
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            The orphan nuclear receptor REV-ERBalpha controls circadian transcription within the positive limb of the mammalian circadian oscillator.

            Nicolas Preitner, Francesca Damiola, Luis-Lopez-Molina … (2002)
            Mammalian circadian rhythms are generated by a feedback loop in which BMAL1 and CLOCK, players of the positive limb, activate transcription of the cryptochrome and period genes, components of the negative limb. Bmal1 and Per transcription cycles display nearly opposite phases and are thus governed by different mechanisms. Here, we identify the orphan nuclear receptor REV-ERBalpha as the major regulator of cyclic Bmal1 transcription. Circadian Rev-erbalpha expression is controlled by components of the general feedback loop. Thus, REV-ERBalpha constitutes a molecular link through which components of the negative limb drive antiphasic expression of components of the positive limb. While REV-ERBalpha influences the period length and affects the phase-shifting properties of the clock, it is not required for circadian rhythm generation.
            Article 0 comments Cited 615 times – based on 0 reviews     Review now
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              Identification of a nuclear receptor for bile acids.

              M. Makishima, A. Okamoto, J Repa … (1999)
              Bile acids are essential for the solubilization and transport of dietary lipids and are the major products of cholesterol catabolism. Results presented here show that bile acids are physiological ligands for the farnesoid X receptor (FXR), an orphan nuclear receptor. When bound to bile acids, FXR repressed transcription of the gene encoding cholesterol 7alpha-hydroxylase, which is the rate-limiting enzyme in bile acid synthesis, and activated the gene encoding intestinal bile acid-binding protein, which is a candidate bile acid transporter. These results demonstrate a mechanism by which bile acids transcriptionally regulate their biosynthesis and enterohepatic transport.
              Article 0 comments Cited 577 times – based on 0 reviews     Review now
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                Author and article information

                Journal
                Journal ID (nlm-journal-id): 101705555
                Journal ID (pubmed-jr-id): 46534
                Journal ID (nlm-ta): Liver Res
                Journal ID (iso-abbrev): Liver Res
                Title: Liver research
                ISSN (Print): 2096-2878
                ISSN (Electronic): 2542-5684
                Publication date Nihms-submitted: 2 September 2020
                Publication date (Electronic): 3 June 2020
                Publication date (Print): June 2020
                Publication date PMC-release: 20 July 2021
                Volume: 4
                Issue: 2
                Pages: 47-63
                Affiliations
                Department of Integrative Medical Sciences, Northeast Ohio Medical University, Rootstown, OH, USA
                Author notes

                Authors’ contributions

                J. Y. L. Chiang conceived, wrote, and edited the manuscript and figures. J. M. Ferrell wrote and edited the manuscript and figures.

                [* ]Corresponding author. jchiang@ 123456neomed.edu (J.Y.L. Chiang).
                Article
                Manuscript ID: NIHMS1625271
                DOI: 10.1016/j.livres.2020.05.001
                PMC ID: 8291349
                PubMed ID: 34290896
                SO-VID: 2e934174-0247-400e-916b-ef311ccbaa15
                License:

                This is an open access article under the CC BY-NC-ND license ( http://creativecommons.org/licenses/by-nc-nd/4.0/).

                History
                Categories
                Subject: Article

                Keywords: cholesterol 7 alpha-hydroxylase (cyp7a1),bile acid metabolism,farnesoid x receptor (fxr),takeda g protein-coupled receptor 5 (tgr5),bile acid receptors,liver metabolism
                Data availability:
                Keywords: cholesterol 7 alpha-hydroxylase (cyp7a1), bile acid metabolism, farnesoid x receptor (fxr), takeda g protein-coupled receptor 5 (tgr5), bile acid receptors, liver metabolism

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