Evidence map›Paper›PMID 30312631›Full record

ArticleToxicology and applied pharmacology2019

Polychlorinated biphenyl exposures differentially regulate hepatic metabolism and pancreatic function: Implications for nonalcoholic steatohepatitis and diabetes.

Hongxue Shi, Jian Jan, Josiah E Hardesty, K Cameron Falkner, Russell A Prough, Appakalai N Balamurugan, Sri Prakash Mokshagundam, Suresh T Chari, Matthew C Cave

Erratum issuedOpen access · greenAbstract read
In one paragraph

Article in Toxicology and applied pharmacology, 2019. 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, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
35citing papers in PubMed, 2 pooled it
3.7field-weighted citation impact, top 6% 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, 2 syntheses or guidelines pooled it, 73 citations in OpenAlex.

  1. Pooled it
  2. Pooled it
  3. Article
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  8. Review
  9. Sex-specific effects of acute chlordane exposure in the context of steatotic liver disease, energy metabolism and endocrine disruption.Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association · 2023
    Article
  10. Article
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  12. Article
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  14. Critical Overview on Endocrine Disruptors in Diabetes Mellitus.International journal of molecular sciences · 2023
    Review
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4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

9 authors at 2 institutions in 1 country.

Hongxue ShiDepartment of Pharmacology and Toxicology, School of Medicine, University of Louisville, Louisville, KY, 40202, United States.
Jian JanDepartment of Pharmacology and Toxicology, School of Medicine, University of Louisville, Louisville, KY, 40202, United States.
Josiah E HardestyDepartment of Biochemistry and Molecular Genetics, School of Medicine, University of Louisville, Louisville, KY, 40202, United States.
K Cameron FalknerDepartment of Medicine, Division of Gastroenterology, Hepatology and Nutrition, School of Medicine, University of Louisville, Louisville, KY, 40202, United States.
Russell A ProughDepartment of Biochemistry and Molecular Genetics, School of Medicine, University of Louisville, Louisville, KY, 40202, United States.
Appakalai N BalamuruganDepartment of Surgery, School of Medicine, University of Louisville, Louisville, KY, 40202, United States.
Sri Prakash MokshagundamDepartment of Medicine, Division of Endocrinology, Metabolism & Diabetes, School of Medicine, University of Louisville, Louisville, KY, 40202, United States.
Suresh T ChariDepartment of Internal Medicine, Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN, 55902, United States.
Matthew C CaveDepartment of Pharmacology and Toxicology, School of Medicine, University of Louisville, Louisville, KY, 40202, United States; Department of Biochemistry and Molecular Genetics, School of Medicine, University of Louisville, Louisville, KY, 40202, United States; Department of Medicine, Division of Gastroenterology, Hepatology and Nutrition, School of Medicine, University of Louisville, Louisville, KY, 40202, United States. Electronic address: matt.cave@louisville.edu.
University of Louisville · USMayo Clinic in Arizona · US

Funding

Role of oxidized linoleic acid metabolites in the pathogenesis of alcoholic liver diseaseP20GM113226 · NIGMS · UNIVERSITY OF LOUISVILLE · PI BARVE, SHIRISH S · 2016 to 2025
$24.1M
Superfund Training CoreP42ES023716 · NIEHS · UNIVERSITY OF LOUISVILLE · PI SRIVASTAVA, SANJAY · 2017 to 2025
$18.1M
The Role of Nutrition in the Development/Progression of Alcohol-Induced Organ InjuryP50AA024337 · NIAAA · UNIVERSITY OF LOUISVILLE · PI CRAIG J. MCCLAIN · 2016 to 2026
$17.9M
Environmental Liver DiseaseR35ES028373 · NIEHS · UNIVERSITY OF LOUISVILLE · PI CAVE, MATTHEW C · 2017 to 2024
$4.0M
PCBs worsen obesity/metabolic syndrome through 'toxic metabolic endotoxemia'R01ES021375 · NIEHS · UNIVERSITY OF LOUISVILLE · PI CAVE, MATTHEW C · 2012 to 2016
$1.7M
Polychlorinated biphenyls act through EGFR to worsen NAFLDF31ES028982 · NIEHS · UNIVERSITY OF LOUISVILLE · PI HARDESTY, JOSIAH E · 2017 to 2018
$43k
NIAAA NIH HHS P50 AA024337NIEHS NIH HHS F31 ES028982NIEHS NIH HHS P42 ES023716NIEHS NIH HHS R01 ES021375NIEHS NIH HHS R35 ES028373NIGMS NIH HHS P20 GM113226
6 · The paper itself

Abstract

The endocrine disrupting chemicals, polychlorinated biphenyls (PCBs), have been associated with nonalcoholic steatohepatitis (NASH) and diabetes. However, an integrative analysis of the effects of PCBs on the liver and pancreas has never been performed for the two major PCB subtypes, dioxin-like (DL) and nondioxin-like (NDL), and a mixture of NDL/DL PCBs. Therefore, male C57BL/6 J mice fed a control synthetic diet were treated with either a NDL PCB mixture, Aroclor 1260 (20 mg/kg); a single DL PCB congener, PCB 126 (20 μg/kg); a NDL/DL mixture, Aroclor 1260 plus PCB 126; or vehicle control for 2 weeks. PCB126 had the greatest impact on hepatic lipid metabolism. It caused steatosis due to increased hepatic lipid import with associated hypolipidemia. However, all PCB exposures impacted expression of hepatic lipid metabolism genes in different manners. The 'NASH gene', Pnpla3, was elevated by Aroclor 1260, but decreased by all other exposures. The expression of hepatokines implicated in metabolic syndrome (Fgf21, Igf1, and betatrophin) were differentially regulated. The NDL/DL PCB mixture had the greatest effects on pancreatic histology, including acinar cell atrophy, mild steatosis, and fibrosis without ductal changes or immune cell infiltration. It decreased expression of insulin and altered the expression of genes regulating islet identity. None of these exposures was associated with altered HOMA-IR or HOMA-B. In summary, PCB exposures differentially regulated liver and pancreas structure and function. Novel mechanisms for PCB-induced endocrine/metabolic disruption included altered hepatokines and Pnpla3 as well as 'PCB pancreatopathy' that was associated with altered expression of pancreatic islet identity factors. More research is required to understand fully these findings in the context of human NASH and diabetes.

Indexed as

AcyltransferasesAnimalsAroclorsDiabetes MellitusDisease Models, AnimalEndocrine DisruptorsFibrosisHumansLipid MetabolismLiverMaleMiceMice, Inbred C57BLNon-alcoholic Fatty Liver DiseasePancreasPhospholipases A2, Calcium-Independent3,4,5,3',4'-pentachlorobiphenylAcyltransferasesaroclor 1260AroclorsEndocrine DisruptorsPhospholipases A2, Calcium-IndependentPNPLA3 protein, mousePolychlorinated BiphenylsAhRFGF21Islet IdentityPCBPnpla3

Identifiers

PMID30312631
PMCPMC7059560
OpenAlexW2897158734

What OpenQuestion 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 OpenQuestion graph.