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PMID: 21531334 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

The microbiome and butyrate regulate energy metabolism and autophagy in the mammalian colon.

Cell metabolism ·Vol. 13 ·No. 5 ·2011-05-04 ·Pages 517-26

Donohoe DR, Garge N, Zhang X, Sun W, O'Connell TM, Bunger MK, Bultman SJ

Abstract

The microbiome is being characterized by large-scale sequencing efforts, yet it is not known whether it regulates host metabolism in a general versus tissue-specific manner or which bacterial metabolites are important. Here, we demonstrate that microbiota have a strong effect on energy homeostasis in the colon compared to other tissues. This tissue specificity is due to colonocytes utilizing bacterially produced butyrate as their primary energy source. Colonocytes from germfree mice are in an energy-deprived state and exhibit decreased expression of enzymes that catalyze key steps in intermediary metabolism including the TCA cycle. Consequently, there is a marked decrease in NADH/NAD(+), oxidative phosphorylation, and ATP levels, which results in AMPK activation, p27(kip1) phosphorylation, and autophagy. When butyrate is added to germfree colonocytes, it rescues their deficit in mitochondrial respiration and prevents them from undergoing autophagy. The mechanism is due to butyrate acting as an energy source rather than as an HDAC inhibitor.

MeSH Terms
AMP-Activated Protein Kinases/metabolism Animals Autophagy Biomarkers/metabolism Blotting, Western Butyrates/pharmacology Cells, Cultured Colon/cytology,metabolism Cyclin-Dependent Kinase Inhibitor p27/metabolism Energy Metabolism Gene Expression Profiling Germ-Free Life Glucose/metabolism Magnetic Resonance Spectroscopy Male Metabolomics Metagenome Mice Mice, Inbred C57BL Mitochondria/metabolism NAD/metabolism Oligonucleotide Array Sequence Analysis Oxidative Phosphorylation Phosphorylation Signal Transduction
Chemicals
Biomarkers Butyrates NAD Cyclin-Dependent Kinase Inhibitor p27 AMP-Activated Protein Kinases Glucose
Authors & Affiliations
7 authors, click to expand affiliations / ORCID
Donohoe Dallas R
Department of Genetics, University of North Carolina at Chapel Hill, 27599-7264, USA.
Garge Nikhil
Zhang Xinxin
Sun Wei
O'Connell Thomas M
Bunger Maureen K
Bultman Scott J
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Article Info
Journal
Cell metabolism
Abbr.
Cell Metab
ISSN
1932-7420
DOI
10.1016/j.cmet.2011.02.018
Published
2011-05-04
Pages
517-26
Language
English
Region
United States
NLM ID
101233170
PMCID
PMC3099420
Subset
IM
Grants
NCI NIH HHS · CA125237 · United States
NIEHS NIH HHS · P30 ES010126 · United States
NCI NIH HHS · R01 CA125237 · United States
NIDDK NIH HHS · P30 DK034987 · United States
NIDDK NIH HHS · P30 DK 34987 · United States
PHS HHS · P40RRO118603 · United States
NCI NIH HHS · R01 CA125237-04 · United States
NIEHS NIH HHS · P30-ES10126 · United States
Databases
GEO
GSE27590
Corrections
CommentIn
PMID: 21531329
External Links
PubMed source DOI: 10.1016/j.cmet.2011.02.018 PMC Full Text View journal details
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