Gut microbiota directs PPAR γ‐driven reprogramming of the liver circadian clock by nutritional challenge

M Murakami, P Tognini, Y Liu, KL Eckel‐Mahan… - EMBO …, 2016 - embopress.org
EMBO reports, 2016embopress.org
The liver circadian clock is reprogrammed by nutritional challenge through the rewiring of
specific transcriptional pathways. As the gut microbiota is tightly connected to host
metabolism, whose coordination is governed by the circadian clock, we explored whether
gut microbes influence circadian homeostasis and how they distally control the peripheral
clock in the liver. Using fecal transplant procedures we reveal that, in response to high‐fat
diet, the gut microbiota drives PPAR γ‐mediated activation of newly oscillatory …
Abstract
The liver circadian clock is reprogrammed by nutritional challenge through the rewiring of specific transcriptional pathways. As the gut microbiota is tightly connected to host metabolism, whose coordination is governed by the circadian clock, we explored whether gut microbes influence circadian homeostasis and how they distally control the peripheral clock in the liver. Using fecal transplant procedures we reveal that, in response to high‐fat diet, the gut microbiota drives PPARγ‐mediated activation of newly oscillatory transcriptional programs in the liver. Moreover, antibiotics treatment prevents PPARγ‐driven transcription in the liver, underscoring the essential role of gut microbes in clock reprogramming and hepatic circadian homeostasis. Thus, a specific molecular signature characterizes the influence of the gut microbiome in the liver, leading to the transcriptional rewiring of hepatic metabolism.
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