Evidence map›Paper›PMID 40858101›Full record

ArticleCell metabolism2025

Genetics-nutrition interactions control diurnal enhancer-promoter dynamics and liver lipid metabolism.

Dishu Zhou, Ying Chen, Panpan Liu, Kun Zhu, Juliet Holder-Haynes, S Julie-Ann Lloyd, Cam Mong La, Inna I Astapova, Seunghee Choa, Ying Xiong and 13 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Cell metabolism, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing papers in PubMed
–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

1 citing paper in PubMed.

  1. Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

23 authors.

Dishu ZhouState Key Laboratory of Cellular Stress Biology, Engineering Research Centre of Molecular Diagnostics of the Ministry of Education, National Institute for Data Science in Health and Medicine Engineering, Faculty of Medicine and Life Sciences, School of Life Sciences, Xiamen University, Xiamen 361102, Fujian, China; Division of Diabetes, Endocrinology, and Metabolism, Department of Medicine, Baylor College of Medicine, Houston, TX 77030, USA.
Ying ChenDivision of Diabetes, Endocrinology, and Metabolism, Department of Medicine, Baylor College of Medicine, Houston, TX 77030, USA.
Panpan LiuDivision of Diabetes, Endocrinology, and Metabolism, Department of Medicine, Baylor College of Medicine, Houston, TX 77030, USA.
Kun ZhuInstitute for Diabetes, Obesity, and Metabolism, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA 19104, USA.
Juliet Holder-HaynesWeight Loss and Metabolic Center, Department of Surgery, Baylor College of Medicine, Houston, TX 77030, USA.
S Julie-Ann LloydWeight Loss and Metabolic Center, Department of Surgery, Baylor College of Medicine, Houston, TX 77030, USA.
Cam Mong LaDivision of Diabetes, Endocrinology, and Metabolism, Department of Medicine, Baylor College of Medicine, Houston, TX 77030, USA.
Inna I AstapovaDivision of Diabetes, Endocrinology, and Metabolism, Department of Medicine, Baylor College of Medicine, Houston, TX 77030, USA.
Seunghee ChoaDivision of Diabetes, Endocrinology, and Metabolism, Department of Medicine, Baylor College of Medicine, Houston, TX 77030, USA.
Ying XiongDepartment of Genetics and Genome Sciences, Case Western Reserve University School of Medicine, Cleveland, OH 44106, USA.
Hosung BaeDepartment of Biological Chemistry, Chao Family Comprehensive Cancer Center, University of California Irvine School of Medicine, Irvine, CA 92697, USA.
Marlene AguilarChildren's Nutrition Research Center, Department of Pediatrics, Baylor College of Medicine, Houston, TX 77030, USA.
Hongyuan YangDepartment of Integrative Biology and Pharmacology, University of Texas Health Science Center at Houston, Houston, TX 77030, USA.
Yu A AnDepartment of Anesthesiology, Critical Care and Pain Medicine, Center for Perioperative Medicine, McGovern Medical School, University of Texas Health Science Center at Houston, Houston, TX 77030, USA.
Zheng SunDivision of Diabetes, Endocrinology, and Metabolism, Department of Medicine, Baylor College of Medicine, Houston, TX 77030, USA.
Mark A HermanDivision of Diabetes, Endocrinology, and Metabolism, Department of Medicine, Baylor College of Medicine, Houston, TX 77030, USA.
Xia GaoChildren's Nutrition Research Center, Department of Pediatrics, Baylor College of Medicine, Houston, TX 77030, USA.
Liming PeiCenter for Mitochondrial and Epigenomic Medicine, Cardiovascular Institute, Department of Pathology and Laboratory Medicine, Children's Hospital of Philadelphia and Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
Cholsoon JangDepartment of Biological Chemistry, Chao Family Comprehensive Cancer Center, University of California Irvine School of Medicine, Irvine, CA 92697, USA.
Joshua D RabinowitzDepartment of Chemistry, Lewis Institute for Cancer Research, Princeton University, Princeton, NJ 08544, USA.
Samer G MattarWeight Loss and Metabolic Center, Department of Surgery, Baylor College of Medicine, Houston, TX 77030, USA.
Yongyou ZhangState Key Laboratory of Cellular Stress Biology, Engineering Research Centre of Molecular Diagnostics of the Ministry of Education, National Institute for Data Science in Health and Medicine Engineering, Faculty of Medicine and Life Sciences, School of Life Sciences, Xiamen University, Xiamen 361102, Fujian, China. Electronic address: yongyouzhang@xmu.edu.cn.
Dongyin GuanDivision of Diabetes, Endocrinology, and Metabolism, Department of Medicine, Baylor College of Medicine, Houston, TX 77030, USA. Electronic address: dongyin.guan@bcm.edu.

Funding

Tumor BiologyP30CA125123 · NCI · BAYLOR COLLEGE OF MEDICINE · PI Martha P Mims · 2007 to 2026
$73.9M
Tissue Analysis & Molecular Imaging CoreP30DK056338 · NIDDK · BAYLOR COLLEGE OF MEDICINE · PI James Versalovic · 2001 to 2026
$28.3M
Organ Specific Project - HeartU54HL165442 · NHLBI · CHILDREN'S HOSP OF PHILADELPHIA · PI PEI, LIMING · 2022 to 2025
$7.6M
Novel biological insights by utilizing mitochondrial genome information from HuBMAP resourcesU01HL166058 · NHLBI · CHILDREN'S HOSP OF PHILADELPHIA · PI PEI, LIMING, WALLACE, DOUGLAS C · 2022 to 2025
$2.1M
Coordinated regulation of mitochondrial and cellular functions by nuclear receptorsR01DK111495 · NIDDK · CHILDREN'S HOSP OF PHILADELPHIA · PI PEI, LIMING · 2017 to 2021
$2.0M
Elucidating dietary fructose and alcohol interactions during liver cancer developmentR01AA029124 · NIAAA · UNIVERSITY OF CALIFORNIA-IRVINE · PI JANG, CHOLSOON · 2021 to 2025
$2.0M
Inter- and transgenerational effects of paternal arsenic exposureR01ES034768 · NIEHS · BAYLOR COLLEGE OF MEDICINE · PI Zheng Sun · 2023 to 2026
$1.9M
3D Circadian Enhancer-Promoter Interactions Mediated by ESRRG in NAFLD-to-HCC ProgressionR37CA296577 · NCI · BAYLOR COLLEGE OF MEDICINE · PI Dongyin Guan · 2025 to 2026
$1.1M
Circadian clock gene Rev-erb in memory dysfunction in Alzheimer's diseaseR01AG069966 · NIA · BAYLOR COLLEGE OF MEDICINE · PI SUN, ZHENG · 2024 to 2025
$1.1M
Understanding methionine metabolism and its therapeutic potential in cancerR00CA237618 · NCI · BAYLOR COLLEGE OF MEDICINE · PI GAO, XIA · 2022 to 2024
$747k
Defining the role of non-clock genes in circadian physiology and pathophysiologyK01DK125602 · NIDDK · UNIVERSITY OF PENNSYLVANIA · PI GUAN, DONGYIN · 2020 to 2023
$562k
NCI NIH HHS P30 CA125123NCI NIH HHS R00 CA237618NCI NIH HHS R37 CA296577NHLBI NIH HHS U01 HL166058NHLBI NIH HHS U54 HL165442NIAAA NIH HHS R01 AA029124NIA NIH HHS R01 AG069966NIDDK NIH HHS K01 DK125602NIDDK NIH HHS P30 DK056338NIDDK NIH HHS R01 DK111495NIEHS NIH HHS R01 ES034768
6 · The paper itself

Abstract

The circadian clock controls 24-h rhythmic processes. However, how genetic variations outside clock genes impact peripheral diurnal rhythms remains largely unknown. Here, we find that genetic variation contributes to different diurnal patterns of hepatic gene expression in both humans and mice. Nutritional challenges alter the rhythmicity of gene expression in mouse liver in a strain-specific manner. Remarkably, genetics and nutrition interdependently control more than 80% of rhythmic gene and enhancer-promoter interactions (E-PIs), with a noncanonical clock regulator, estrogen-related receptor gamma (ESRRγ), emerging as a top transcription factor during motif mining. Knockout of Esrrγ abolishes strain-specific metabolic processes in response to diet in mice, while single-nucleotide polymorphisms (SNPs) associated with rhythmic gene expression are enriched in E-PIs in steatotic human livers and correlate with lipid metabolism traits. These findings reveal a previously underappreciated temporal aspect of genetics-environment interaction in regulating lipid metabolic traits, with implications for individual variations in obesity-associated disease susceptibility and personalized chronotherapy.

Indexed as

Circadian RhythmEnhancer Elements, GeneticLipid MetabolismLiverPromoter Regions, GeneticAnimalsCircadian ClocksFemaleHumansMaleMiceMice, Inbred C57BLMice, KnockoutPolymorphism, Single NucleotideReceptors, EstrogenReceptors, Estrogen3D enhancer-promoter interactiondiurnal rhythmgenetic variationhuman metabolic traitsmetabolic disorders

Identifiers

PMID40858101
PMCPMC12923262

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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.