Evidence map›Paper›PMID 30343673›Full record

ArticleBiology of sex differences2018

Tissue-specific pathways and networks underlying sexual dimorphism in non-alcoholic fatty liver disease.

Zeyneb Kurt, Rio Barrere-Cain, Jonnby LaGuardia, Margarete Mehrabian, Calvin Pan, Simon T Hui, Frode Norheim, Zhiqiang Zhou, Yehudit Hasin, Aldons J Lusis and 1 more

Open access · goldAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Biology of sex differences, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 46 papers.

0numbers the graph read from it
0cells of the map it votes in
46citing papers in PubMed
6.8field-weighted citation impact, top 2% of its field
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

46 citing papers in PubMed, 84 citations in OpenAlex.

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  17. Maternal obesity alters offspring liver and skeletal muscle metabolism in early post-puberty despite maintaining a normal post-weaning dietary lifestyle.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2022
    Article
  18. Article
  19. Article
  20. Gender Differences in Nonalcoholic Fatty Liver Disease.Euroasian journal of hepato-gastroenterology · 2022
    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

11 authors at 1 institution in 1 country.

Zeyneb KurtDepartment of Integrative Biology and Physiology, University of California, Los Angeles, Los Angeles, CA, USA.
Rio Barrere-CainDepartment of Integrative Biology and Physiology, University of California, Los Angeles, Los Angeles, CA, USA.
Jonnby LaGuardiaDepartment of Integrative Biology and Physiology, University of California, Los Angeles, Los Angeles, CA, USA.
Margarete MehrabianDepartment of Medicine/Division of Cardiology, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA, USA.
Calvin PanDepartment of Medicine/Division of Cardiology, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA, USA.
Simon T HuiDepartment of Medicine/Division of Cardiology, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA, USA.
Frode NorheimDepartment of Medicine/Division of Cardiology, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA, USA.
Zhiqiang ZhouDepartment of Medicine/Division of Cardiology, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA, USA.
Yehudit HasinDepartment of Medicine/Division of Cardiology, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA, USA.
Aldons J LusisDepartment of Medicine/Division of Cardiology, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA, USA. jlusis@mednet.ucla.edu.
Xia YangDepartment of Integrative Biology and Physiology, University of California, Los Angeles, Los Angeles, CA, USA. xyang123@ucla.edu.
University of California, Los Angeles · US

Funding

UCLA Clinical Translational Science InstituteUL1TR001881 · NCATS · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI ARLEEN F. BROWN, ARASH NAEIM · 2016 to 2026
$118.1M
ULTRASTRUCTURE OF THE INTIMA IN EARLY LESION FORMATIONP01HL030568 · NHLBI · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI FOGELMAN, ALAN M · 1985 to 2019
$55.2M
Systems genomics of metabolic syndrome traitsP01HL028481 · NHLBI · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI LUSIS, ALDONS JAKE · 1985 to 2019
$50.2M
DHA Reverses Gene Network Signatures of Fructose-induced Metabolic SyndromeR01DK104363 · NIDDK · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI YANG, XIA · 2015 to 2019
$2.4M
NCATS NIH HHS UL1 TR001881NHLBI NIH HHS P01 HL028481NHLBI NIH HHS P01 HL030568NIDDK NIH HHS R01 DK104363NIH HHS 30568NIH HHS DK104363NIH HHS HL28481
6 · The paper itself

Abstract

backgroundNon-alcoholic fatty liver disease (NAFLD) encompasses benign steatosis and more severe conditions such as non-alcoholic steatohepatitis (NASH), cirrhosis, and liver cancer. This chronic liver disease has a poorly understood etiology and demonstrates sexual dimorphisms. We aim to examine the molecular mechanisms underlying sexual dimorphisms in NAFLD pathogenesis through a comprehensive multi-omics study. We integrated genomics (DNA variations), transcriptomics of liver and adipose tissue, and phenotypic data of NAFLD derived from female mice of ~ 100 strains included in the hybrid mouse diversity panel (HMDP) and compared the NAFLD molecular pathways and gene networks between sexes.

resultsWe identified both shared and sex-specific biological processes for NAFLD. Adaptive immunity, branched chain amino acid metabolism, oxidative phosphorylation, and cell cycle/apoptosis were shared between sexes. Among the sex-specific pathways were vitamins and cofactors metabolism and ion channel transport for females, and phospholipid, lysophospholipid, and phosphatidylinositol metabolism and insulin signaling for males. Additionally, numerous lipid and insulin-related pathways and inflammatory processes in the adipose and liver tissue appeared to show more prominent association with NAFLD in male HMDP. Using data-driven network modeling, we identified plausible sex-specific and tissue-specific regulatory genes as well as those that are shared between sexes. These key regulators orchestrate the NAFLD pathways in a sex- and tissue-specific manner. Gonadectomy experiments support that sex hormones may partially underlie the sexually dimorphic genes and pathways involved in NAFLD.

conclusionsOur multi-omics integrative study reveals sex- and tissue-specific genes, processes, and networks underlying sexual dimorphism in NAFLD and may facilitate sex-specific precision medicine.

Indexed as

Sex CharacteristicsAdipose TissueAnimalsCastrationFemaleGenomicsLipid MetabolismLiverMaleMice, Inbred C57BLNon-alcoholic Fatty Liver DiseaseSignal TransductionTranscriptomeBayesian networksCoexpression networksHybrid mouse diversity panelKey regulator genesMulti-omics integrationNon-alcoholic fatty liver disease (NAFLD)Sexual dimorphism

Identifiers

PMID30343673
PMCPMC6196429
OpenAlexW2897917666

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Registered trials

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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.