Gut microbes and the liver circadian clock partition glucose and lipid metabolism
Circadian rhythms govern glucose homeostasis, and their dysregulation leads to complex metabolic diseases. Gut microbes exhibit diurnal rhythms that influence host circadian networks and metabolic processes, yet underlying mechanisms remain elusive. Here, we showed hierarchical, bidirectional commun...
| Main Authors: | , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
American Society for Clinical Investigation
2023-09-01
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| Series: | The Journal of Clinical Investigation |
| Subjects: | |
| Online Access: | https://doi.org/10.1172/JCI162515 |
| _version_ | 1827768094647386112 |
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| author | Katya Frazier Sumeed Manzoor Katherine Carroll Orlando DeLeon Sawako Miyoshi Jun Miyoshi Marissa St. George Alan Tan Evan A. Chrisler Mariko Izumo Joseph S. Takahashi Mrinalini C. Rao Vanessa A. Leone Eugene B. Chang |
| author_facet | Katya Frazier Sumeed Manzoor Katherine Carroll Orlando DeLeon Sawako Miyoshi Jun Miyoshi Marissa St. George Alan Tan Evan A. Chrisler Mariko Izumo Joseph S. Takahashi Mrinalini C. Rao Vanessa A. Leone Eugene B. Chang |
| author_sort | Katya Frazier |
| collection | DOAJ |
| description | Circadian rhythms govern glucose homeostasis, and their dysregulation leads to complex metabolic diseases. Gut microbes exhibit diurnal rhythms that influence host circadian networks and metabolic processes, yet underlying mechanisms remain elusive. Here, we showed hierarchical, bidirectional communication among the liver circadian clock, gut microbes, and glucose homeostasis in mice. To assess this relationship, we utilized mice with liver-specific deletion of the core circadian clock gene Bmal1 via Albumin-cre maintained in either conventional or germ-free housing conditions. The liver clock, but not the forebrain clock, required gut microbes to drive glucose clearance and gluconeogenesis. Liver clock dysfunctionality expanded proportions and abundances of oscillating microbial features by 2-fold relative to that in controls. The liver clock was the primary driver of differential and rhythmic hepatic expression of glucose and fatty acid metabolic pathways. Absent the liver clock, gut microbes provided secondary cues that dampened these rhythms, resulting in reduced lipid fuel utilization relative to carbohydrates. All together, the liver clock transduced signals from gut microbes that were necessary for regulating glucose and lipid metabolism and meeting energy demands over 24 hours. |
| first_indexed | 2024-03-11T12:07:22Z |
| format | Article |
| id | doaj.art-2b3926a172264fbfb7638c31f72999c6 |
| institution | Directory Open Access Journal |
| issn | 1558-8238 |
| language | English |
| last_indexed | 2024-03-11T12:07:22Z |
| publishDate | 2023-09-01 |
| publisher | American Society for Clinical Investigation |
| record_format | Article |
| series | The Journal of Clinical Investigation |
| spelling | doaj.art-2b3926a172264fbfb7638c31f72999c62023-11-07T16:20:51ZengAmerican Society for Clinical InvestigationThe Journal of Clinical Investigation1558-82382023-09-0113318Gut microbes and the liver circadian clock partition glucose and lipid metabolismKatya FrazierSumeed ManzoorKatherine CarrollOrlando DeLeonSawako MiyoshiJun MiyoshiMarissa St. GeorgeAlan TanEvan A. ChrislerMariko IzumoJoseph S. TakahashiMrinalini C. RaoVanessa A. LeoneEugene B. ChangCircadian rhythms govern glucose homeostasis, and their dysregulation leads to complex metabolic diseases. Gut microbes exhibit diurnal rhythms that influence host circadian networks and metabolic processes, yet underlying mechanisms remain elusive. Here, we showed hierarchical, bidirectional communication among the liver circadian clock, gut microbes, and glucose homeostasis in mice. To assess this relationship, we utilized mice with liver-specific deletion of the core circadian clock gene Bmal1 via Albumin-cre maintained in either conventional or germ-free housing conditions. The liver clock, but not the forebrain clock, required gut microbes to drive glucose clearance and gluconeogenesis. Liver clock dysfunctionality expanded proportions and abundances of oscillating microbial features by 2-fold relative to that in controls. The liver clock was the primary driver of differential and rhythmic hepatic expression of glucose and fatty acid metabolic pathways. Absent the liver clock, gut microbes provided secondary cues that dampened these rhythms, resulting in reduced lipid fuel utilization relative to carbohydrates. All together, the liver clock transduced signals from gut microbes that were necessary for regulating glucose and lipid metabolism and meeting energy demands over 24 hours.https://doi.org/10.1172/JCI162515Metabolism |
| spellingShingle | Katya Frazier Sumeed Manzoor Katherine Carroll Orlando DeLeon Sawako Miyoshi Jun Miyoshi Marissa St. George Alan Tan Evan A. Chrisler Mariko Izumo Joseph S. Takahashi Mrinalini C. Rao Vanessa A. Leone Eugene B. Chang Gut microbes and the liver circadian clock partition glucose and lipid metabolism The Journal of Clinical Investigation Metabolism |
| title | Gut microbes and the liver circadian clock partition glucose and lipid metabolism |
| title_full | Gut microbes and the liver circadian clock partition glucose and lipid metabolism |
| title_fullStr | Gut microbes and the liver circadian clock partition glucose and lipid metabolism |
| title_full_unstemmed | Gut microbes and the liver circadian clock partition glucose and lipid metabolism |
| title_short | Gut microbes and the liver circadian clock partition glucose and lipid metabolism |
| title_sort | gut microbes and the liver circadian clock partition glucose and lipid metabolism |
| topic | Metabolism |
| url | https://doi.org/10.1172/JCI162515 |
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