Dataset Information

Circadian transcriptional pathway atlas highlights a proteasome switch in intermittent fasting.

ABSTRACT: While intermittent fasting is a safe strategy to benefit health, it remains unclear whether a "timer" exists in vivo to record fasting duration and trigger a transcriptional switch. Here, we map a circadian transcriptional pathway atlas from 600 samples across four metabolic tissues of mice under five feeding regimens. Results show that 95.6% of detected canonical pathways are rhythmic in a tissue-specific and feeding-regimen-specific manner, while only less than 25% of them induce changes in transcriptional function. Fasting for 16 h initiates a circadian resonance of 43 pathways in the liver, and the resonance punctually switches following refeeding. The hepatic proteasome coordinates the resonance, and most genes encoding proteasome subunits display a 16-h fasting-dependent transcriptional switch. These findings indicate that the hepatic proteasome may serve as a fasting timer and a coordinator of pathway transcriptional resonance, which provide a target for revealing the underlying mechanism of intermittent fasting.

SUBMITTER: Wei F

PROVIDER: S-EPMC9671760 | biostudies-literature | 2022 Oct

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Circadian transcriptional pathway atlas highlights a proteasome switch in intermittent fasting.

Wei Fang F Gong Lijun L Lu Siyu S Zhou Yiming Y Liu Li L Duan Zhigui Z Xiang Rong R Gonzalez Frank J FJ Li Guolin G

Cell reports 20221001 4

While intermittent fasting is a safe strategy to benefit health, it remains unclear whether a "timer" exists in vivo to record fasting duration and trigger a transcriptional switch. Here, we map a circadian transcriptional pathway atlas from 600 samples across four metabolic tissues of mice under five feeding regimens. Results show that 95.6% of detected canonical pathways are rhythmic in a tissue-specific and feeding-regimen-specific manner, while only less than 25% of them induce changes in tr ...[more]

PMID: 36288692

Similar Datasets

Project description:BackgroundInflammation contributes to the poor prognosis of intracerebral hemorrhage (ICH). Intermittent fasting (IF) has been shown to be protective against inflammation in multiple pathogenic processes. In the present study, we aimed to investigated the beneficial effects of IF in attenuating neuroinflammation and neurological deficits in a mouse model of ICH and to investigate the underlying mechanism.MethodsICH was modeled by intrastriatal injection of autologous blood and IF was modeled by every-other-day feeding in male control mice (C57BL/6), mice with and microglia specific knockout Sirt3f/f;Cx3cr1-Cre (Sirt3 cKO), and Sirt3f/f (wild-type) mice. Brain tissues and arterial blood were harvested at 1, 3, 7 and 28 days after ICH for immunohistochemistry analysis of Iba-1, DARPP-32 and HO-1, morphological analysis by HE staining and inflammatory factor release tests by ELISA. Neurological functions were approached by corner test and cylinder test. Fluorescent double-labeled staining of Iba-1 with CD16, Arg1 or Sirt3 was used to provide direct image of co-expression of these molecules in microglia. TUNEL, cleaved caspase-3 and Nissl staining was performed to evaluate cellular injuries.ResultsIF alleviated neurological deficits in both acute and chronic phases after ICH. Morphologically, IF enhanced hematoma clearance, reduced brain edema in acute phase and attenuated striatum atrophy in chronic phase. In addition, IF decreased the numbers of TUNEL+ cells and increased Nissl+ neuron number at day 1, 3 and 7 after ICH. IF suppressed CD16+Iba-1+ microglia activation at day 3 after ICH and reduced inflammatory releases, such as IL-1β and TNF-α. The above effects of IF were attenuated by microglia Sirt3 deletion partly because of an inhibition of Nrf2/HO-1 signaling pathway. Interestingly, IF increased Iba-1+ microglia number at day 7 which mainly expressed Arg1 while decreased the proinflammatory factor levels. In mice with microglia-specific Sirt3 deletion, the effects of IF on Iba-1+ microglia activation and anti-inflammatory factor expressions were attenuated when compared with wild-type Sirt3f/f mice.ConclusionsIF protects against ICH by suppressing the inflammatory responses via the Sirt3/Nrf2/HO-1 pathway.

Dataset Information

Circadian transcriptional pathway atlas highlights a proteasome switch in intermittent fasting.

Publications

Circadian transcriptional pathway atlas highlights a proteasome switch in intermittent fasting.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets