Baat Gene Knockout Alters Post-Natal Development, the Gut Microbiome, and Reveals Unusual Bile Acids in Mice
Bile acids (BAs) are steroid detergents in bile that contribute to fat absorption, cell signaling, and microbiome interactions. The final step in their synthesis is amino acid conjugation with either glycine or taurine in the liver by the enzyme bile acid-CoA:amino acid N-acyltransferase (BAAT). Her...
| Main Authors: | , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2022-12-01
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| Series: | Journal of Lipid Research |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S0022227522001304 |
| _version_ | 1798004637263986688 |
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| author | Kerri A. Neugebauer Maxwell Okros Douglas V. Guzior Jeremiah Feiner Nicholas J. Chargo Madison Rzepka Anthony L. Schilmiller Sandra O’Reilly A. Daniel Jones Victoria E. Watson James P. Luyendyk Laura R. McCabe Robert A. Quinn |
| author_facet | Kerri A. Neugebauer Maxwell Okros Douglas V. Guzior Jeremiah Feiner Nicholas J. Chargo Madison Rzepka Anthony L. Schilmiller Sandra O’Reilly A. Daniel Jones Victoria E. Watson James P. Luyendyk Laura R. McCabe Robert A. Quinn |
| author_sort | Kerri A. Neugebauer |
| collection | DOAJ |
| description | Bile acids (BAs) are steroid detergents in bile that contribute to fat absorption, cell signaling, and microbiome interactions. The final step in their synthesis is amino acid conjugation with either glycine or taurine in the liver by the enzyme bile acid-CoA:amino acid N-acyltransferase (BAAT). Here, we describe the microbial, chemical, and physiological consequences of Baat gene knockout. Baat-/- mice were underweight after weaning but quickly exhibited catch-up growth. At three weeks of age, KO animals had increased phospholipid excretion and decreased subcutaneous fat pad mass, liver mass, glycogen staining in hepatocytes, and hepatic vitamin A stores, but these were less marked in adulthood. Additionally, KO mice had an altered microbiome in early life. Their BA pool was highly enriched in cholic acid but not completely devoid of conjugated BAs. KO animals had 27-fold lower taurine-conjugated BAs than wild type in their liver but similar concentrations of glycine-conjugated BAs and higher microbially conjugated BAs. Furthermore, the BA pool in Baat-/- was enriched in a variety of unusual BAs that were putatively sourced from cysteamine conjugation with subsequent oxidation and methylation of the sulfur group mimicking taurine. Antibiotic treatment of KO mice indicated the microbiome was not the likely source of the unusual conjugations, instead, the unique BAs in KO animals were likely derived from the peroxisomal acyltransferases Acnat1 and Acnat2, which are duplications of Baat in the mouse genome that are inactivated in humans. This study demonstrates that BA conjugation is important for early life development of mice. |
| first_indexed | 2024-04-11T12:26:49Z |
| format | Article |
| id | doaj.art-4d5c996a9607462c81dbbb41bd122fda |
| institution | Directory Open Access Journal |
| issn | 0022-2275 |
| language | English |
| last_indexed | 2024-04-11T12:26:49Z |
| publishDate | 2022-12-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Journal of Lipid Research |
| spelling | doaj.art-4d5c996a9607462c81dbbb41bd122fda2022-12-22T04:23:54ZengElsevierJournal of Lipid Research0022-22752022-12-016312100297Baat Gene Knockout Alters Post-Natal Development, the Gut Microbiome, and Reveals Unusual Bile Acids in MiceKerri A. Neugebauer0Maxwell Okros1Douglas V. Guzior2Jeremiah Feiner3Nicholas J. Chargo4Madison Rzepka5Anthony L. Schilmiller6Sandra O’Reilly7A. Daniel Jones8Victoria E. Watson9James P. Luyendyk10Laura R. McCabe11Robert A. Quinn12Department of Biochemistry and Molecular Biology, Michigan State University, East Lansing, MI, USADepartment of Biochemistry and Molecular Biology, Michigan State University, East Lansing, MI, USADepartment of Biochemistry and Molecular Biology, Michigan State University, East Lansing, MI, USA; Department of Microbiology and Molecular Genetics, Michigan State University, East Lansing, MI, USADepartment of Biochemistry and Molecular Biology, Michigan State University, East Lansing, MI, USADepartment of Physiology, Michigan State University, East Lansing, MI, USADepartment of Biochemistry and Molecular Biology, Michigan State University, East Lansing, MI, USAMass Spectrometry and Metabolomics Core, Michigan State University, East Lansing, MI, USADepartment of Physiology, Michigan State University, East Lansing, MI, USADepartment of Biochemistry and Molecular Biology, Michigan State University, East Lansing, MI, USADepartment of Pathobiology and Diagnostic Investigation, College of Veterinary Medicine, Michigan State University, East Lansing, MI, USADepartment of Pathobiology and Diagnostic Investigation, College of Veterinary Medicine, Michigan State University, East Lansing, MI, USA; Department of Pharmacology and Toxicology, Michigan State University, East Lansing, MI, USADepartment of Physiology, Michigan State University, East Lansing, MI, USADepartment of Biochemistry and Molecular Biology, Michigan State University, East Lansing, MI, USA; For correspondence: Robert A. QuinnBile acids (BAs) are steroid detergents in bile that contribute to fat absorption, cell signaling, and microbiome interactions. The final step in their synthesis is amino acid conjugation with either glycine or taurine in the liver by the enzyme bile acid-CoA:amino acid N-acyltransferase (BAAT). Here, we describe the microbial, chemical, and physiological consequences of Baat gene knockout. Baat-/- mice were underweight after weaning but quickly exhibited catch-up growth. At three weeks of age, KO animals had increased phospholipid excretion and decreased subcutaneous fat pad mass, liver mass, glycogen staining in hepatocytes, and hepatic vitamin A stores, but these were less marked in adulthood. Additionally, KO mice had an altered microbiome in early life. Their BA pool was highly enriched in cholic acid but not completely devoid of conjugated BAs. KO animals had 27-fold lower taurine-conjugated BAs than wild type in their liver but similar concentrations of glycine-conjugated BAs and higher microbially conjugated BAs. Furthermore, the BA pool in Baat-/- was enriched in a variety of unusual BAs that were putatively sourced from cysteamine conjugation with subsequent oxidation and methylation of the sulfur group mimicking taurine. Antibiotic treatment of KO mice indicated the microbiome was not the likely source of the unusual conjugations, instead, the unique BAs in KO animals were likely derived from the peroxisomal acyltransferases Acnat1 and Acnat2, which are duplications of Baat in the mouse genome that are inactivated in humans. This study demonstrates that BA conjugation is important for early life development of mice.http://www.sciencedirect.com/science/article/pii/S0022227522001304steroid detergentsmicrobiome interactionstaurocholic acidconjugationbile acid-CoA:amino acid N-acyltransferaseperoxisomal acyltransferases |
| spellingShingle | Kerri A. Neugebauer Maxwell Okros Douglas V. Guzior Jeremiah Feiner Nicholas J. Chargo Madison Rzepka Anthony L. Schilmiller Sandra O’Reilly A. Daniel Jones Victoria E. Watson James P. Luyendyk Laura R. McCabe Robert A. Quinn Baat Gene Knockout Alters Post-Natal Development, the Gut Microbiome, and Reveals Unusual Bile Acids in Mice Journal of Lipid Research steroid detergents microbiome interactions taurocholic acid conjugation bile acid-CoA:amino acid N-acyltransferase peroxisomal acyltransferases |
| title | Baat Gene Knockout Alters Post-Natal Development, the Gut Microbiome, and Reveals Unusual Bile Acids in Mice |
| title_full | Baat Gene Knockout Alters Post-Natal Development, the Gut Microbiome, and Reveals Unusual Bile Acids in Mice |
| title_fullStr | Baat Gene Knockout Alters Post-Natal Development, the Gut Microbiome, and Reveals Unusual Bile Acids in Mice |
| title_full_unstemmed | Baat Gene Knockout Alters Post-Natal Development, the Gut Microbiome, and Reveals Unusual Bile Acids in Mice |
| title_short | Baat Gene Knockout Alters Post-Natal Development, the Gut Microbiome, and Reveals Unusual Bile Acids in Mice |
| title_sort | baat gene knockout alters post natal development the gut microbiome and reveals unusual bile acids in mice |
| topic | steroid detergents microbiome interactions taurocholic acid conjugation bile acid-CoA:amino acid N-acyltransferase peroxisomal acyltransferases |
| url | http://www.sciencedirect.com/science/article/pii/S0022227522001304 |
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