دورية أكاديمية
NUDT7 regulates total hepatic CoA levels and the composition of the intestinal bile acid pool in male mice fed a Western diet.
| العنوان: | NUDT7 regulates total hepatic CoA levels and the composition of the intestinal bile acid pool in male mice fed a Western diet. |
|---|---|
| المؤلفون: | Vickers SD; Department of Biochemistry and Molecular Medicine, West Virginia University, Morgantown, West Virginia, USA., Shumar SA; Department of Biochemistry and Molecular Medicine, West Virginia University, Morgantown, West Virginia, USA., Saporito DC; Department of Biochemistry and Molecular Medicine, West Virginia University, Morgantown, West Virginia, USA., Kunovac A; Division of Exercise Physiology, West Virginia University, Morgantown, West Virginia, USA., Hathaway QA; Division of Exercise Physiology, West Virginia University, Morgantown, West Virginia, USA., Mintmier B; Department of Biochemistry and Molecular Medicine, West Virginia University, Morgantown, West Virginia, USA., King JA; Department of Pathology and Translational Pathobiology, LSU Health Shreveport, Shreveport, Louisiana, USA., King RD; Department of Biochemistry and Molecular Medicine, West Virginia University, Morgantown, West Virginia, USA., Rajendran VM; Department of Biochemistry and Molecular Medicine, West Virginia University, Morgantown, West Virginia, USA., Infante AM; Genomics Core Facility, West Virginia University, Morgantown, West Virginia, USA., Hollander JM; Division of Exercise Physiology, West Virginia University, Morgantown, West Virginia, USA., Leonardi R; Department of Biochemistry and Molecular Medicine, West Virginia University, Morgantown, West Virginia, USA. Electronic address: roleonardi@hsc.wvu.edu. |
| المصدر: | The Journal of biological chemistry [J Biol Chem] 2023 Jan; Vol. 299 (1), pp. 102745. Date of Electronic Publication: 2022 Nov 24. |
| نوع المنشور: | Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't |
| اللغة: | English |
| بيانات الدورية: | Publisher: Elsevier Inc. on behalf of American Society for Biochemistry and Molecular Biology Country of Publication: United States NLM ID: 2985121R Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1083-351X (Electronic) Linking ISSN: 00219258 NLM ISO Abbreviation: J Biol Chem Subsets: MEDLINE |
| أسماء مطبوعة: | Publication: 2021- : [New York, NY] : Elsevier Inc. on behalf of American Society for Biochemistry and Molecular Biology Original Publication: Baltimore, MD : American Society for Biochemistry and Molecular Biology |
| مواضيع طبية MeSH: | Bile Acids and Salts*/metabolism , Diet, Western*, Animals ; Male ; Mice ; Acyl Coenzyme A/metabolism ; Chenodeoxycholic Acid ; Fatty Acids/metabolism ; Liver/metabolism ; Oxidation-Reduction ; Nudix Hydrolases |
| مستخلص: | Nudix hydrolase 7 (NUDT7) is an enzyme that hydrolyzes CoA species, is highly expressed in the liver, and resides in the peroxisomes. Peroxisomes are organelles where the preferential oxidation of dicarboxylic fatty acids occurs and where the hepatic synthesis of the primary bile acids cholic acid and chenodeoxycholic acid is completed. We previously showed that liver-specific overexpression of NUDT7 affects peroxisomal lipid metabolism but does not prevent the increase in total liver CoA levels that occurs during fasting. We generated Nudt7 -/- mice to further characterize the role that peroxisomal (acyl-)CoA degradation plays in the modulation of the size and composition of the acyl-CoA pool and in the regulation of hepatic lipid metabolism. Here, we show that deletion of Nudt7 alters the composition of the hepatic acyl-CoA pool in mice fed a low-fat diet, but only in males fed a Western diet does the lack of NUDT7 activity increase total liver CoA levels. This effect is driven by the male-specific accumulation of medium-chain dicarboxylic acyl-CoAs, which are produced from the β-oxidation of dicarboxylic fatty acids. We also show that, under conditions of elevated synthesis of chenodeoxycholic acid derivatives, Nudt7 deletion promotes the production of tauromuricholic acid, decreasing the hydrophobicity index of the intestinal bile acid pool and increasing fecal cholesterol excretion in male mice. These findings reveal that NUDT7-mediated hydrolysis of acyl-CoA pathway intermediates in liver peroxisomes contributes to the regulation of dicarboxylic fatty acid metabolism and the composition of the bile acid pool. Competing Interests: Conflict of interest The authors declare that they have no conflicts of interest with the contents of this article. (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.) |
| معلومات مُعتمدة: | R01 DK104791 United States DK NIDDK NIH HHS; R21 DK112085 United States DK NIDDK NIH HHS; R35 GM119528 United States GM NIGMS NIH HHS; F31 GM126838 United States GM NIGMS NIH HHS; T32 GM133369 United States GM NIGMS NIH HHS; P20 GM103434 United States GM NIGMS NIH HHS |
| فهرسة مساهمة: | Keywords: Nudix hydrolases; bile acids; cholesterol; dicarboxylic fatty acids; peroxisomes |
| المشرفين على المادة: | 0 (Acyl Coenzyme A) 0 (Bile Acids and Salts) 0GEI24LG0J (Chenodeoxycholic Acid) 0 (Fatty Acids) |
| تواريخ الأحداث: | Date Created: 20221127 Date Completed: 20230201 Latest Revision: 20231213 |
| رمز التحديث: | 20231215 |
| مُعرف محوري في PubMed: | PMC9792899 |
| DOI: | 10.1016/j.jbc.2022.102745 |
| PMID: | 36436558 |
| قاعدة البيانات: | MEDLINE |
Full Text Finder | تدمد: | 1083-351X |
|---|---|
| DOI: | 10.1016/j.jbc.2022.102745 |