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Microbial metabolites regulate host lipid metabolism through NR5A–Hedgehog signalling
- Source :
- Nature Cell Biology. 19:550-557
- Publication Year :
- 2017
- Publisher :
- Springer Science and Business Media LLC, 2017.
-
Abstract
- Microorganisms and their hosts share the same environment, and microbial metabolic molecules (metabolites) exert crucial effects on host physiology. Environmental factors not only shape the composition of the host's resident microorganisms, but also modulate their metabolism. However, the exact molecular relationship among the environment, microbial metabolites and host metabolism remains largely unknown. Here, we discovered that environmental methionine tunes bacterial methyl metabolism to regulate host mitochondrial dynamics and lipid metabolism in Caenorhabditis elegans through an endocrine crosstalk involving NR5A nuclear receptor and Hedgehog signalling. We discovered that methionine deficiency in bacterial medium decreases the production of bacterial metabolites that are essential for phosphatidylcholine synthesis in C. elegans. Reductions of diundecanoyl and dilauroyl phosphatidylcholines attenuate NHR-25, a NR5A nuclear receptor, and release its transcriptional suppression of GRL-21, a Hedgehog-like protein. The induction of GRL-21 consequently inhibits the PTR-24 Patched receptor cell non-autonomously, resulting in mitochondrial fragmentation and lipid accumulation. Together, our work reveals an environment-microorganism-host metabolic axis regulating host mitochondrial dynamics and lipid metabolism, and discovers NR5A-Hedgehog intercellular signalling that controls these metabolic responses with critical consequences for host health and survival.
- Subjects :
- Patched Receptors
0301 basic medicine
Time Factors
animal structures
Genotype
Microbial metabolism
Biology
Mitochondrial Dynamics
Animals, Genetically Modified
03 medical and health sciences
chemistry.chemical_compound
Methionine
Escherichia coli
Animals
Hedgehog Proteins
Caenorhabditis elegans
Caenorhabditis elegans Proteins
Host (biology)
Lipogenesis
Lipid metabolism
Cell Biology
biology.organism_classification
Mitochondria
Cell biology
DNA-Binding Proteins
Hedgehog signalling
Phenotype
030104 developmental biology
chemistry
Nuclear receptor
Biochemistry
Host-Pathogen Interactions
embryonic structures
Phosphatidylcholines
Signal Transduction
Transcription Factors
Subjects
Details
- ISSN :
- 14764679 and 14657392
- Volume :
- 19
- Database :
- OpenAIRE
- Journal :
- Nature Cell Biology
- Accession number :
- edsair.doi.dedup.....d1fc66356da6e27136fe748aa52b60c8