Hepatic circadian clock oscillators and nuclear receptors integrate microbiome-derived signals
The liver is a key organ of metabolic homeostasis with functions that oscillate in response to food intake. Although liver and gut microbiome crosstalk has been reported, microbiome-mediated effects on peripheral circadian clocks and their output genes are less well known. Here, we report that germ-...
| Main Authors: | , , , , , , , , , , , , , , , , , |
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| Format: | Journal Article |
| Language: | English |
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2016
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| Online Access: | https://hdl.handle.net/10356/80202 http://hdl.handle.net/10220/40393 |
| _version_ | 1811696971947180032 |
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| author | Montagner, Alexandra Korecka, Agata Polizzi, Arnaud Lippi, Yannick Blum, Yuna Canlet, Cécile Tremblay-Franco, Marie Gautier-Stein, Amandine Burcelin, Rémy Yen, Yi-Chun Je, Hyunsoo Shawn Maha, Al-Asmakh Mithieux, Gilles Arulampalam, Velmurugesan Lagarrigue, Sandrine Guillou, Hervé Pettersson, Sven Wahli, Walter |
| author2 | Lee Kong Chian School of Medicine (LKCMedicine) |
| author_facet | Lee Kong Chian School of Medicine (LKCMedicine) Montagner, Alexandra Korecka, Agata Polizzi, Arnaud Lippi, Yannick Blum, Yuna Canlet, Cécile Tremblay-Franco, Marie Gautier-Stein, Amandine Burcelin, Rémy Yen, Yi-Chun Je, Hyunsoo Shawn Maha, Al-Asmakh Mithieux, Gilles Arulampalam, Velmurugesan Lagarrigue, Sandrine Guillou, Hervé Pettersson, Sven Wahli, Walter |
| author_sort | Montagner, Alexandra |
| collection | NTU |
| description | The liver is a key organ of metabolic homeostasis with functions that oscillate in response to food intake. Although liver and gut microbiome crosstalk has been reported, microbiome-mediated effects on peripheral circadian clocks and their output genes are less well known. Here, we report that germ-free (GF) mice display altered daily oscillation of clock gene expression with a concomitant change in the expression of clock output regulators. Mice exposed to microbes typically exhibit characterized activities of nuclear receptors, some of which (PPARα, LXRβ) regulate specific liver gene expression networks, but these activities are profoundly changed in GF mice. These alterations in microbiome-sensitive gene expression patterns are associated with daily alterations in lipid, glucose, and xenobiotic metabolism, protein turnover, and redox balance, as revealed by hepatic metabolome analyses. Moreover, at the systemic level, daily changes in the abundance of biomarkers such as HDL cholesterol, free fatty acids, FGF21, bilirubin, and lactate depend on the microbiome. Altogether, our results indicate that the microbiome is required for integration of liver clock oscillations that tune output activators and their effectors, thereby regulating metabolic gene expression for optimal liver function. |
| first_indexed | 2024-10-01T07:47:51Z |
| format | Journal Article |
| id | ntu-10356/80202 |
| institution | Nanyang Technological University |
| language | English |
| last_indexed | 2024-10-01T07:47:51Z |
| publishDate | 2016 |
| record_format | dspace |
| spelling | ntu-10356/802022022-02-16T16:30:52Z Hepatic circadian clock oscillators and nuclear receptors integrate microbiome-derived signals Montagner, Alexandra Korecka, Agata Polizzi, Arnaud Lippi, Yannick Blum, Yuna Canlet, Cécile Tremblay-Franco, Marie Gautier-Stein, Amandine Burcelin, Rémy Yen, Yi-Chun Je, Hyunsoo Shawn Maha, Al-Asmakh Mithieux, Gilles Arulampalam, Velmurugesan Lagarrigue, Sandrine Guillou, Hervé Pettersson, Sven Wahli, Walter Lee Kong Chian School of Medicine (LKCMedicine) Singapore Centre for Environmental Life Sciences Engineering Medicine The liver is a key organ of metabolic homeostasis with functions that oscillate in response to food intake. Although liver and gut microbiome crosstalk has been reported, microbiome-mediated effects on peripheral circadian clocks and their output genes are less well known. Here, we report that germ-free (GF) mice display altered daily oscillation of clock gene expression with a concomitant change in the expression of clock output regulators. Mice exposed to microbes typically exhibit characterized activities of nuclear receptors, some of which (PPARα, LXRβ) regulate specific liver gene expression networks, but these activities are profoundly changed in GF mice. These alterations in microbiome-sensitive gene expression patterns are associated with daily alterations in lipid, glucose, and xenobiotic metabolism, protein turnover, and redox balance, as revealed by hepatic metabolome analyses. Moreover, at the systemic level, daily changes in the abundance of biomarkers such as HDL cholesterol, free fatty acids, FGF21, bilirubin, and lactate depend on the microbiome. Altogether, our results indicate that the microbiome is required for integration of liver clock oscillations that tune output activators and their effectors, thereby regulating metabolic gene expression for optimal liver function. Published version 2016-04-12T03:01:28Z 2019-12-06T13:42:49Z 2016-04-12T03:01:28Z 2019-12-06T13:42:49Z 2016 Journal Article Montagner, A., Korecka, A., Polizzi, A., Lippi, Y., Blum, Y., Canlet, C., Tremblay-Franco, M., Gautier-Stein, A., Burcelin, R., Yen, Y. C., Je, H. S., Maha, A. A., Mithieux, G., Arulampalam, V., Lagarrigue, S., Guillou, H., Pettersson, S., & Wahli, W. (2016). Hepatic circadian clock oscillators and nuclear receptors integrate microbiome-derived signals. Scientific Reports, 6, 20127-. 2045-2322 https://hdl.handle.net/10356/80202 http://hdl.handle.net/10220/40393 10.1038/srep20127 26879573 en Scientific Reports This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ 14 p. application/pdf |
| spellingShingle | Medicine Montagner, Alexandra Korecka, Agata Polizzi, Arnaud Lippi, Yannick Blum, Yuna Canlet, Cécile Tremblay-Franco, Marie Gautier-Stein, Amandine Burcelin, Rémy Yen, Yi-Chun Je, Hyunsoo Shawn Maha, Al-Asmakh Mithieux, Gilles Arulampalam, Velmurugesan Lagarrigue, Sandrine Guillou, Hervé Pettersson, Sven Wahli, Walter Hepatic circadian clock oscillators and nuclear receptors integrate microbiome-derived signals |
| title | Hepatic circadian clock oscillators and nuclear receptors integrate microbiome-derived signals |
| title_full | Hepatic circadian clock oscillators and nuclear receptors integrate microbiome-derived signals |
| title_fullStr | Hepatic circadian clock oscillators and nuclear receptors integrate microbiome-derived signals |
| title_full_unstemmed | Hepatic circadian clock oscillators and nuclear receptors integrate microbiome-derived signals |
| title_short | Hepatic circadian clock oscillators and nuclear receptors integrate microbiome-derived signals |
| title_sort | hepatic circadian clock oscillators and nuclear receptors integrate microbiome derived signals |
| topic | Medicine |
| url | https://hdl.handle.net/10356/80202 http://hdl.handle.net/10220/40393 |
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