Evidence map›Paper›PMID 26884397›Full record

ArticleDevelopment (Cambridge, England)2016

Cannabinoid receptor signaling regulates liver development and metabolism.

Leah Y Liu, Kristen Alexa, Mauricio Cortes, Stephanie Schatzman-Bone, Andrew J Kim, Bani Mukhopadhyay, Resat Cinar, George Kunos, Trista E North, Wolfram Goessling

Erratum issuedOpen access · greenAbstract read
In one paragraph

Article in Development (Cambridge, England), 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 35 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
35citing papers in PubMed, 1 pooled it
5.2field-weighted citation impact, top 5% 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

35 citing papers in PubMed, 1 synthesis or guideline pooled it, 55 citations in OpenAlex.

  1. The Role of Cannabidiol in Liver Disease: A Systemic Review.International journal of molecular sciences · 2024
    Pooled it
  2. Review
  3. Article
  4. Article
  5. Article
  6. Article
  7. Review
  8. Article
  9. Article
  10. Review
  11. Zebrafish as an Animal Model in Cannabinoid Research.International journal of molecular sciences · 2023
    Review
  12. Review
  13. Article
  14. Article
  15. Article
  16. Cannabinoids and Chronic Liver Diseases.International journal of molecular sciences · 2022
    Review
  17. Review
  18. Article
  19. Article
  20. Review
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

10 authors at 5 institutions in 1 country.

Leah Y LiuGenetics Division, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA.
Kristen AlexaGenetics Division, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA.
Mauricio CortesDepartment of Pathology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02115, USA.
Stephanie Schatzman-BoneGenetics Division, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA.
Andrew J KimGenetics Division, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA.
Bani MukhopadhyayLaboratory of Physiological Studies, National Institute on Alcohol Abuse and Alcoholism, Bethesda, MD 20982, USA.
Resat CinarLaboratory of Physiological Studies, National Institute on Alcohol Abuse and Alcoholism, Bethesda, MD 20982, USA.
George KunosLaboratory of Physiological Studies, National Institute on Alcohol Abuse and Alcoholism, Bethesda, MD 20982, USA.
Trista E NorthDepartment of Pathology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02115, USA Harvard Stem Cell Institute, Cambridge, MA 02138, USA.
Wolfram GoesslingGenetics Division, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA Harvard Stem Cell Institute, Cambridge, MA 02138, USA Gastroenterology Division, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA Dana-Farber Cancer Institute, Boston, MA 02215, USA Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA wgoessling@partners.org.
Brigham and Women's Hospital · USNational Institute on Alcohol Abuse and Alcoholism · USBeth Israel Deaconess Medical Center · USHarvard Stem Cell Institute · USHarvard University · US

Funding

Endocannabinoids And Energy HomeostasisZIAAA000350 · NIAAA · NATIONAL INSTITUTE ON ALCOHOL ABUSE AND ALCOHOLISM · PI KUNOS, GEORGE · 2009 to 2025
$28.4M
Estrogen Regulation of Hepatic GrowthR01DK090311 · NIDDK · BRIGHAM AND WOMEN'S HOSPITAL · PI GOESSLING, WOLFRAM · 2011 to 2020
$4.9M
Metabolic regulation of hematopoietic stem cell specification and functionR01DK098241 · NIDDK · BOSTON CHILDREN'S HOSPITAL · PI NORTH, TRISTA E. · 2014 to 2018
$2.0M
Integrated signaling of eicosanoids in HSC formation and regenerationR03DK096156 · NIDDK · BETH ISRAEL DEACONESS MEDICAL CENTER · PI NORTH, TRISTA E. · 2012 to 2013
$171k
Endocannabinoid signaling in alcohol induced hepatic steatosisF31AA022548 · NIAAA · HARVARD MEDICAL SCHOOL · PI LIU, LEAH YU · 2013 to 2014
$54k
NIAAA NIH HHS F31 AA022548NIAAA NIH HHS F31AA022548NIDDK NIH HHS R01 DK090311NIDDK NIH HHS R01DK090311PHS HHS R03096156
6 · The paper itself

Abstract

Endocannabinoid (EC) signaling mediates psychotropic effects and regulates appetite. By contrast, potential roles in organ development and embryonic energy consumption remain unknown. Here, we demonstrate that genetic or chemical inhibition of cannabinoid receptor (Cnr) activity disrupts liver development and metabolic function in zebrafish (Danio rerio), impacting hepatic differentiation, but not endodermal specification: loss of cannabinoid receptor 1 (cnr1) and cnr2 activity leads to smaller livers with fewer hepatocytes, reduced liver-specific gene expression and proliferation. Functional assays reveal abnormal biliary anatomy and lipid handling. Adult cnr2 mutants are susceptible to hepatic steatosis. Metabolomic analysis reveals reduced methionine content in Cnr mutants. Methionine supplementation rescues developmental and metabolic defects in Cnr mutant livers, suggesting a causal relationship between EC signaling, methionine deficiency and impaired liver development. The effect of Cnr on methionine metabolism is regulated by sterol regulatory element-binding transcription factors (Srebfs), as their overexpression rescues Cnr mutant liver phenotypes in a methionine-dependent manner. Our work describes a novel developmental role for EC signaling, whereby Cnr-mediated regulation of Srebfs and methionine metabolism impacts liver development and function.

Indexed as

Signal TransductionAnimalsCannabinoidsCell CountCell ProliferationCysteineHepatocytesLiverMetabolomicsMethionineMutationOrgan SizeReceptor, Cannabinoid, CB1Receptor, Cannabinoid, CB2Stem CellsZebrafishCannabinoidsCnr1 protein, zebrafishCnr2 protein, zebrafishCysteineMethionineReceptor, Cannabinoid, CB1Receptor, Cannabinoid, CB2Zebrafish ProteinsCannabinoid receptorLiver developmentMethionineMouseZebrafish

Identifiers

PMID26884397
PMCPMC4760316
OpenAlexW2294282910

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

None linked

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.