Evidence map›Paper›PMID 40446956›Full record

ArticleMetabolism: clinical and experimental2025

Hepatic CB1 receptor signaling triggers G

Jie Liu, Anna Oliverio, Grzegorz Godlewski, Radka Kočvarová, Muhammad Arif, Abhishek Basu, Yukun Guan, Dechun Feng, Henry L Puhl, Malliga R Iyer and 4 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Metabolism: clinical and experimental, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
6citing 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

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

  1. Pooled it
  2. Article
  3. Article
  4. Review
  5. CD36 and Its Role in Obesity.Obesity reviews : an official journal of the International Association for the Study of Obesity · 2026
    Review
  6. Cannabis produces acute hyperphagia in humans and rodents via increased reward valuation for, and motivation to, acquire food.Proceedings of the National Academy of Sciences of the United States of America · 2025
    Article
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

14 authors.

Jie LiuLaboratory of Physiologic Studies, National Institute on Alcohol Abuse and Alcoholism (NIAAA), National Institutes of Health (NIH), Bethesda, MD, USA.
Anna OliverioLaboratory of Physiologic Studies, National Institute on Alcohol Abuse and Alcoholism (NIAAA), National Institutes of Health (NIH), Bethesda, MD, USA.
Grzegorz GodlewskiLaboratory of Physiologic Studies, National Institute on Alcohol Abuse and Alcoholism (NIAAA), National Institutes of Health (NIH), Bethesda, MD, USA.
Radka KočvarováInstitute for Drug Research, School of Pharmacy, Faculty of Medicine, The Hebrew University, Jerusalem, Israel.
Muhammad ArifSection on Fibrotic Disorders, NIAAA, NIH, Bethesda, MD, USA.
Abhishek BasuSection on Fibrotic Disorders, NIAAA, NIH, Bethesda, MD, USA.
Yukun GuanLaboratory of Liver Diseases, NIAAA, NIH, Bethesda, MD, USA.
Dechun FengLaboratory of Liver Diseases, NIAAA, NIH, Bethesda, MD, USA.
Henry L PuhlLaboratory of Biophotonic and Quantum Biology, NIAAA, NIH, Bethesda, MD, USA.
Malliga R IyerSection on Medicinal Chemistry, NIAAA, NIH, Bethesda, MD, USA.
Resat CinarSection on Fibrotic Disorders, NIAAA, NIH, Bethesda, MD, USA.
Bin GaoLaboratory of Liver Diseases, NIAAA, NIH, Bethesda, MD, USA.
Joseph TamInstitute for Drug Research, School of Pharmacy, Faculty of Medicine, The Hebrew University, Jerusalem, Israel.
George KunosLaboratory of Physiologic Studies, National Institute on Alcohol Abuse and Alcoholism (NIAAA), National Institutes of Health (NIH), Bethesda, MD, USA. Electronic address: George.Kunos@nih.gov.

Funding

Endocannabinoids And Appetitive FunctionsZ01AA000350 · NIAAA · NATIONAL INSTITUTE ON ALCOHOL ABUSE AND ALCOHOLISM · PI KUNOS, GEORGE · 2001 to 2008
$2.1M
Intramural NIH HHS Z01 AA000350
6 · The paper itself

Abstract

objectivesObesity-induced steatotic liver disease (SLD) is driven by the uptake of adipocyte-derived fatty acids (FAs) into hepatocytes via the FA translocase CD36, which also prevents their consumption by inhibiting AMP kinase (AMPK)-mediated FA oxidation (FAO). We explored the role of hepatocyte CB1 receptors (hCB1R) in controlling hepatic triglyceride (TG) content by regulating CD36 and its downstream targets.

methodshCB1R knockout (hCB1Rko) mice and their control littermates kept on standard or high-fat diet were used to analyze hCB1R-mediated hepatic gene expression profile and lipid metabolism in intact mice and in cultured hepatocytes.

resultsMulti-omics data indicate that hCB1R target a distinct set of genes associated with SLD, including Cd36. In mice with diet-induced obesity, hCB1R signaling via CD36-AMPK-FAO pathway contributes to both the development of SLD and its reversal by CB1R blockade. But, in lean mice hCB1R signaling inhibits CD36 expression and activates AMPK-mediated FAO. These opposite effects were replicated in AML12 mouse hepatocytes incubated with or without oleic acid (OA). OA, an endogenous ligand of GPR3, induced a switch in hCB1R signaling from a G

conclusionsIn the lean state, endocannabinoid activation of hCB1R increases FAO, which mitigates SLD, as reported for chronic marihuana smokers, whereas in obese mice hCB1R tonically inhibit FAO, which promotes SLD and underlies the anti-steatotic effect of peripheral CB1R blockade.

Indexed as

GTP-Binding Protein alpha Subunits, GsLipogenesisLipolysisLiverObesityReceptor, Cannabinoid, CB1AnimalsCD36 AntigensDiet, High-FatHepatocytesMaleMiceMice, Inbred C57BLMice, KnockoutMice, ObeseSignal TransductionCD36 AntigensGTP-Binding Protein alpha Subunits, GsReceptor, Cannabinoid, CB1CD36EndocannabinoidsGPR3Metabolic switchOleic acidSteatotic liver disease

Identifiers

PMID40446956
PMCPMC12369901

What Socratic holds

Textmetadata
LicenceTDM
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 Socratic graph.