ArticleNature metabolism2021
Microbial metabolite delta-valerobetaine is a diet-dependent obesogen.
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Article in Nature metabolism, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 49 papers.
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49citing papers in PubMed
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49 citing papers in PubMed, 69 citations in OpenAlex.
- Gut microbiota shaping fatty liver disease progression.Life science alliance · 2027Review
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- Metabolic shifts driven by host-microbial interactions.The FEBS journal · 2026Review
- Microbiome-associated metabolites, valerobetaine and homocarnitine, inhibit carnitine transport via OCTN2.American journal of physiology. Cell physiology · 2026Article
- Enteric populations ofmSphere · 2026Article
- Mass spectrometry-based metabolomics approaches to interrogate host-microbiome interactions in mammalian systems.Natural product reports · 2026Review
- Structural Diversity and Analytical Characterization of Acylhomocarnitines.Journal of proteome research · 2026Article
- Infection with Mycobacterium tuberculosis depletes host fatty acids in humans and non-human primates.EBioMedicine · 2026Article
- Tirzepatide and the gut microbiota-obesity axis: metabolic mechanisms and therapeutic perspectives.Frontiers in microbiology · 2026Review
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- Gut microbiota and metabolites in lipid metabolism and intramuscular fat deposition: mechanisms and implications for meat quality.Journal of animal science and biotechnology · 2025Review
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- Pre-treatment untargeted cerebrospinal fluid metabolomic profiling in tuberculous meningitis uncovers pathways associated with mortality.Med (New York, N.Y.) · 2025Article
- The Microbial Metabolite δ-Valerobetaine Strengthens the Gut Epithelial Barrier.The American journal of pathology · 2025Article
- Serum Metabolite Profile in Progressive Versus Nonprogressive Alcohol-Related Liver Disease: A Cross-Sectional Metabolomics Study.Liver international : official journal of the International Association for the Study of the Liver · 2025Article
- Heme promotes venetoclax resistance in multiple myeloma through MEK-ERK signaling and purine biosynthesis.Blood · 2025Article
- Precision Dietary Intervention: Gut Microbiome and Meta-metabolome as Functional Readouts.Phenomics (Cham, Switzerland) · 2025Review
- Achieving healthy aging through gut microbiota-directed dietary intervention: Focusing on microbial biomarkers and host mechanisms.Journal of advanced research · 2025Review
- Human Milk Archaea Associated with Neonatal Gut Colonization and Its Co-Occurrence with Bacteria.Microorganisms · 2025Article
- Rethinking the rise of early-onset gastrointestinal cancers: a call to action.JNCI cancer spectrum · 2025Article
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Authors and funding
29 authors at 1 institution in 1 country.
Ken H Liu *Division of Pulmonary, Allergy, Critical Care and Sleep Medicine, Department of Medicine, Emory University School of Medicine, Atlanta, GA, USA.ORCID http://orcid.org/0000-0002-9736-5828
Joshua A Owens *Department of Pediatrics, Emory University School of Medicine, Atlanta, GA, USA.ORCID http://orcid.org/0000-0001-7315-2898
Bejan Saeedi *Department of Pathology and Laboratory Medicine, Emory University School of Medicine, Atlanta, GA, USA.
Catherine E CohenDepartment of Pediatrics, Emory University School of Medicine, Atlanta, GA, USA.
Moriah P BellissimoDivision of Endocrinology, Metabolism, and Lipids, Department of Medicine, Emory University School of Medicine, Atlanta, GA, USA.ORCID http://orcid.org/0000-0002-8998-4792
Crystal NaudinDepartment of Pediatrics, Emory University School of Medicine, Atlanta, GA, USA.ORCID http://orcid.org/0000-0001-6171-2640
Trevor DarbyDepartment of Pediatrics, Emory University School of Medicine, Atlanta, GA, USA.ORCID http://orcid.org/0000-0002-7379-3836
Samuel DruzakDepartment of Biochemistry, Emory University School of Medicine, Atlanta, GA, USA.
Kristal Maner-SmithDepartment of Biochemistry, Emory University School of Medicine, Atlanta, GA, USA.
Michael OrrDivision of Pulmonary, Allergy, Critical Care and Sleep Medicine, Department of Medicine, Emory University School of Medicine, Atlanta, GA, USA.
Xin HuDivision of Pulmonary, Allergy, Critical Care and Sleep Medicine, Department of Medicine, Emory University School of Medicine, Atlanta, GA, USA.ORCID http://orcid.org/0000-0003-2747-9085
Jolyn FernandesDivision of Pulmonary, Allergy, Critical Care and Sleep Medicine, Department of Medicine, Emory University School of Medicine, Atlanta, GA, USA.ORCID http://orcid.org/0000-0002-4100-5815
Mary Catherine CamachoDepartment of Pathology and Laboratory Medicine, Emory University School of Medicine, Atlanta, GA, USA.
Sarah Hunter-ChangDepartment of Pathology and Laboratory Medicine, Emory University School of Medicine, Atlanta, GA, USA.
David VanInsbergheDepartment of Pathology and Laboratory Medicine, Emory University School of Medicine, Atlanta, GA, USA.ORCID http://orcid.org/0000-0002-1933-8103
Chunyu MaDivision of Pulmonary, Allergy, Critical Care and Sleep Medicine, Department of Medicine, Emory University School of Medicine, Atlanta, GA, USA.
Thota GaneshDepartment of Pharmacology and Chemical Biology, Emory University School of Medicine, Atlanta, GA, USA.
Samantha M YeligarDivision of Pulmonary, Allergy, Critical Care and Sleep Medicine, Department of Medicine, Emory University School of Medicine, Atlanta, GA, USA.ORCID http://orcid.org/0000-0001-9309-0233
Karan UppalDivision of Pulmonary, Allergy, Critical Care and Sleep Medicine, Department of Medicine, Emory University School of Medicine, Atlanta, GA, USA.
Young-Mi GoDivision of Pulmonary, Allergy, Critical Care and Sleep Medicine, Department of Medicine, Emory University School of Medicine, Atlanta, GA, USA.
Jessica A AlvarezDivision of Endocrinology, Metabolism, and Lipids, Department of Medicine, Emory University School of Medicine, Atlanta, GA, USA.
Miriam B VosDepartment of Pediatrics, Emory University School of Medicine, Atlanta, GA, USA.
Thomas R ZieglerDivision of Endocrinology, Metabolism, and Lipids, Department of Medicine, Emory University School of Medicine, Atlanta, GA, USA.
Michael H WoodworthDivision of Infectious Disease, Department of Medicine, Emory University School of Medicine, Atlanta, GA, USA.ORCID http://orcid.org/0000-0002-6181-4599
Colleen S KraftDepartment of Pathology and Laboratory Medicine, Emory University School of Medicine, Atlanta, GA, USA.
Rheinallt M JonesDepartment of Pediatrics, Emory University School of Medicine, Atlanta, GA, USA.ORCID http://orcid.org/0000-0002-0415-9487
Eric OrtlundDepartment of Biochemistry, Emory University School of Medicine, Atlanta, GA, USA.ORCID http://orcid.org/0000-0001-8855-3029
Andrew S Neish *Department of Pathology and Laboratory Medicine, Emory University School of Medicine, Atlanta, GA, USA. aneish@emory.edu.ORCID http://orcid.org/0000-0002-7090-0237
Dean P Jones *Division of Pulmonary, Allergy, Critical Care and Sleep Medicine, Department of Medicine, Emory University School of Medicine, Atlanta, GA, USA. dpjones@emory.edu.ORCID http://orcid.org/0000-0002-2090-0677
Emory University · US
Funding
Implementing a Maternal health and PRegnancy Outcomes Vision for Everyone (IMPROVE)UL1TR002378 · NCATS · EMORY UNIVERSITY · PI Andres J Garcia, Elizabeth O. Ofili · 2017 to 2026
$92.1MPilot Project ProgramP30ES019776 · NIEHS · EMORY UNIVERSITY · PI Carmen Joseph Marsit · 2013 to 2026
$22.6MDissecting the pathogenesis and outcomes of PSC using multi-omics by studying the exposome and genomeRC2DK118619 · NIDDK · MAYO CLINIC ROCHESTER · PI LAZARIDIS, KONSTANTINOS N · 2018 to 2022
$7.8MMicrobial Influence on Mucosal HomeostasisR01AI064462 · NIAID · EMORY UNIVERSITY · PI NEISH, ANDREW S · 2006 to 2022
$5.5MGraduate Training in the Pharmacological StudiesT32GM008602 · NIGMS · EMORY UNIVERSITY · PI HALL, RANDY A. · 1996 to 2021
$5.1MU2C Experimental CoreU2CES030163 · NIEHS · EMORY UNIVERSITY · PI JONES, DEAN PAUL, LI, SHUZHAO · 2018 to 2021
$3.6MAlcohol-Induced Mitochondrial Derangements Cause Alveolar Macrophage DysfunctionR01AA026086 · NIAAA · EMORY UNIVERSITY · PI YELIGAR, SAMANTHA M. · 2018 to 2022
$1.8MCytoplasmic-nuclear redox signaling: Disruption by dietary cadmium levelsR01ES023485 · NIEHS · EMORY UNIVERSITY · PI GO KANG, YOUNG-MI, JONES, DEAN PAUL · 2014 to 2018
$1.8MControl of Epithelial Proliferation by the MicrobiotaR01CA179424 · NCI · EMORY UNIVERSITY · PI JONES, RHEINALLT MELFYN, NEISH, ANDREW S · 2014 to 2017
$1.3MBiomarker Discovery for Nonalcoholic Fatty Liver Disease in ChildrenR01DK125701 · NIDDK · EMORY UNIVERSITY · PI VOS, MIRIAM B. · 2020 to 2022
$1.0MTemporal dynamics of MDRO eradication after FMTK23AI144036 · NIAID · EMORY UNIVERSITY · PI WOODWORTH, MICHAEL HOLMES · 2019 to 2023
$957kPatient Oriented Research In Clinical NutritionK24DK096574 · NIDDK · EMORY UNIVERSITY · PI ZIEGLER, THOMAS R · 2012 to 2016
$888kNCATS NIH HHS UL1 TR002378NIAAA NIH HHS R00 AA021803NIAAA NIH HHS R01 AA026086NIAID NIH HHS R01 AI064462NIAID NIH HHS UH2 AI132345NIA NIH HHS R03 AG066559NICHD NIH HHS R21 HD089056NIDDK NIH HHS K01 DK102851NIDDK NIH HHS K24 DK096574NIDDK NIH HHS R01 DK125701NIDDK NIH HHS R03 DK117246NIDDK NIH HHS RC2 DK118619NIEHS NIH HHS P30 ES019776NIEHS NIH HHS R01 ES023485NIEHS NIH HHS R21 ES031824NIEHS NIH HHS U2C ES030163NIGMS NIH HHS T32 GM008602NIH HHS S10 OD018006
Abstract
Obesity and obesity-related metabolic disorders are linked to the intestinal microbiome. However, the causality of changes in the microbiome-host interaction affecting energy metabolism remains controversial. Here, we show the microbiome-derived metabolite δ-valerobetaine (VB) is a diet-dependent obesogen that is increased with phenotypic obesity and is correlated with visceral adipose tissue mass in humans. VB is absent in germ-free mice and their mitochondria but present in ex-germ-free conventionalized mice and their mitochondria. Mechanistic studies in vivo and in vitro show VB is produced by diverse bacterial species and inhibits mitochondrial fatty acid oxidation through decreasing cellular carnitine and mitochondrial long-chain acyl-coenzyme As. VB administration to germ-free and conventional mice increases visceral fat mass and exacerbates hepatic steatosis with a western diet but not control diet. Thus, VB provides a molecular target to understand and potentially manage microbiome-host symbiosis or dysbiosis in diet-dependent obesity.
Indexed as
Energy MetabolismHost Microbial InteractionsMicrobiotaAdiposityAnimalsDiet, WesternFatty AcidsGastrointestinal MicrobiomeHumansLipid MetabolismLiverMiceMitochondriaObesityOxidation-ReductionFatty Acids
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