Evidence map›Paper›PMID 30057115›Full record

ArticleCell2018

Diet-Induced Circadian Enhancer Remodeling Synchronizes Opposing Hepatic Lipid Metabolic Processes.

Dongyin Guan, Ying Xiong, Patricia C Borck, Cholsoon Jang, Paschalis-Thomas Doulias, Romeo Papazyan, Bin Fang, Chunjie Jiang, Yuxiang Zhang, Erika R Briggs and 5 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Cell, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 125 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
125citing papers in PubMed, 1 pooled it
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

125 citing papers in PubMed, 1 synthesis or guideline pooled it.

  1. Pooled it
  2. Review
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  8. Mutually exclusive alternative pre-mRNA splicing promotes adaptive metabolic stress signaling by JNK.Proceedings of the National Academy of Sciences of the United States of America · 2026
    Article
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  17. Molecular targets of bempedoic acid and related decoy fatty acids.Trends in endocrinology and metabolism: TEM · 2025
    Review
  18. Review
  19. Chrononutrition: Potential, Challenges, and Application in Managing Obesity.International journal of molecular sciences · 2025
    Review
  20. Single-Cell Multiomic Analysis of Circadian Rhythmicity in Mouse Liver.bioRxiv : the preprint server for biology · 2025
    Article

65 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

15 authors.

Dongyin GuanInstitute for Diabetes, Obesity, and Metabolism, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA 19104, USA; Division of Endocrinology, Diabetes, and Metabolism, Department of Medicine, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA 19104, USA.
Ying XiongInstitute for Diabetes, Obesity, and Metabolism, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA 19104, USA; Division of Endocrinology, Diabetes, and Metabolism, Department of Medicine, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA 19104, USA.
Patricia C BorckInstitute for Diabetes, Obesity, and Metabolism, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA 19104, USA; Division of Endocrinology, Diabetes, and Metabolism, Department of Medicine, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA 19104, USA.
Cholsoon JangLewis-Sigler Institute for Integrative Genomics and Department of Chemistry, Princeton University, Princeton, NJ 08544, USA.
Paschalis-Thomas DouliasChildren's Hospital of Philadelphia Research Institute and Departments of Pediatrics and Systems Pharmacology & Translational Therapeutics, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA 19104, USA.
Romeo PapazyanInstitute for Diabetes, Obesity, and Metabolism, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA 19104, USA; Division of Endocrinology, Diabetes, and Metabolism, Department of Medicine, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA 19104, USA.
Bin FangInstitute for Diabetes, Obesity, and Metabolism, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA 19104, USA; Division of Endocrinology, Diabetes, and Metabolism, Department of Medicine, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA 19104, USA.
Chunjie JiangInstitute for Diabetes, Obesity, and Metabolism, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA 19104, USA; Division of Endocrinology, Diabetes, and Metabolism, Department of Medicine, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA 19104, USA.
Yuxiang ZhangInstitute for Diabetes, Obesity, and Metabolism, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA 19104, USA; Division of Endocrinology, Diabetes, and Metabolism, Department of Medicine, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA 19104, USA.
Erika R BriggsInstitute for Diabetes, Obesity, and Metabolism, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA 19104, USA; Division of Endocrinology, Diabetes, and Metabolism, Department of Medicine, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA 19104, USA.
Wenxiang HuInstitute for Diabetes, Obesity, and Metabolism, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA 19104, USA; Division of Endocrinology, Diabetes, and Metabolism, Department of Medicine, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA 19104, USA.
David StegerInstitute for Diabetes, Obesity, and Metabolism, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA 19104, USA; Division of Endocrinology, Diabetes, and Metabolism, Department of Medicine, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA 19104, USA.
Harry IschiropoulosChildren's Hospital of Philadelphia Research Institute and Departments of Pediatrics and Systems Pharmacology & Translational Therapeutics, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA 19104, USA.
Joshua D RabinowitzLewis-Sigler Institute for Integrative Genomics and Department of Chemistry, Princeton University, Princeton, NJ 08544, USA.
Mitchell A LazarInstitute for Diabetes, Obesity, and Metabolism, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA 19104, USA; Division of Endocrinology, Diabetes, and Metabolism, Department of Medicine, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA 19104, USA; Department of Genetics, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA 19104, USA. Electronic address: lazar@pennmedicine.upenn.edu.

Funding

VIRAL VECTOR COREP30DK019525 · NIDDK · UNIVERSITY OF PENNSYLVANIA · PI Patrick Seale · 1986 to 2026
$48.3M
Translational Research Support CoreP30ES013508 · NIEHS · UNIVERSITY OF PENNSYLVANIA · PI Rebecca A Simmons · 2006 to 2026
$35.3M
REV-ERB Nuclear Receptors in Circadian Rhythm and MetabolismR01DK045586 · NIDDK · UNIVERSITY OF PENNSYLVANIA · PI MITCHELL A. LAZAR · 1992 to 2026
$12.0M
Reactive Species in Vascular Disease: Mechanisms of InjuryR01HL054926 · NHLBI · UNIVERSITY OF PENNSYLVANIA · PI ISCHIROPOULOS, HARRY · 1997 to 2023
$7.7M
Transcriptional and epigenomic control of adipose tissue development and functionR01DK098542 · NIDDK · UNIVERSITY OF PENNSYLVANIA · PI STEGER, DAVID J. · 2013 to 2017
$1.7M
Mechanisms of high fat diet-induced circadian hepatic transcription and lipid metabolism reprogrammingF32DK116519 · NIDDK · UNIVERSITY OF PENNSYLVANIA · PI GUAN, DONGYIN · 2018 to 2020
$148k
NHLBI NIH HHS R01 HL054926NIDDK NIH HHS F32 DK116519NIDDK NIH HHS P30 DK019525NIDDK NIH HHS R01 DK045586NIDDK NIH HHS R01 DK098542NIEHS NIH HHS P30 ES013508
6 · The paper itself

Abstract

Overnutrition disrupts circadian metabolic rhythms by mechanisms that are not well understood. Here, we show that diet-induced obesity (DIO) causes massive remodeling of circadian enhancer activity in mouse liver, triggering synchronous high-amplitude circadian rhythms of both fatty acid (FA) synthesis and oxidation. SREBP expression was rhythmically induced by DIO, leading to circadian FA synthesis and, surprisingly, FA oxidation (FAO). DIO similarly caused a high-amplitude circadian rhythm of PPARα, which was also required for FAO. Provision of a pharmacological activator of PPARα abrogated the requirement of SREBP for FAO (but not FA synthesis), suggesting that SREBP indirectly controls FAO via production of endogenous PPARα ligands. The high-amplitude rhythm of PPARα imparted time-of-day-dependent responsiveness to lipid-lowering drugs. Thus, acquisition of rhythmicity for non-core clock components PPARα and SREBP1 remodels metabolic gene transcription in response to overnutrition and enables a chronopharmacological approach to metabolic disorders.

Indexed as

Circadian RhythmAnimalsDietGene Expression RegulationLipid MetabolismLipogenesisLiverMaleMiceMice, Inbred C57BLObesityPPAR alphaSterol Regulatory Element Binding Protein 1PPAR alphaSrebf1 protein, mouseSterol Regulatory Element Binding Protein 1chronotherapycircadian rhythmsdiet-induced obesityenhancersfatty acid oxidationfatty liverlipogenesisPPARSREBP

Identifiers

PMID30057115
PMCPMC6086765

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.