Evidence map›Paper›PMID 34876290›Full record

ArticleSurgery2022

Itaconate and leptin affecting PPARγ in M2 macrophages: A potential link to early-onset colorectal cancer.

Katharina M Scheurlen, Dylan L Snook, Mary N Walter, Cheyenne N Cook, Casey R Fiechter, Jianmin Pan, Robert J Beal, Susan Galandiuk

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

Article in Surgery, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
15citing papers in PubMed, 1 pooled it
1.0field-weighted citation impact, top 25% 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

15 citing papers in PubMed, 1 synthesis or guideline pooled it, 16 citations in OpenAlex.

  1. Pooled it
  2. Review
  3. Gut microbes · 2025
    Article
  4. Article
  5. Review
  6. Review
  7. The role and therapeutic potential of itaconate in lung disease.Cellular & molecular biology letters · 2024
    Review
  8. Review
  9. Article
  10. Review
  11. Metabolism, metabolites, and macrophages in cancer.Journal of hematology & oncology · 2023
    Review
  12. Article
  13. Review
  14. Review
  15. Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

8 authors at 1 institution in 1 country.

Katharina M ScheurlenDepartment of Surgery, Price Institute of Surgical Research, University of Louisville, Louisville, KY.
Dylan L SnookDepartment of Surgery, Price Institute of Surgical Research, University of Louisville, Louisville, KY.
Mary N WalterDepartment of Surgery, Price Institute of Surgical Research, University of Louisville, Louisville, KY.
Cheyenne N CookDepartment of Surgery, Price Institute of Surgical Research, University of Louisville, Louisville, KY.
Casey R FiechterDepartment of Surgery, Price Institute of Surgical Research, University of Louisville, Louisville, KY.
Jianmin PanBiostatistics Shared Facility, James Graham Brown Cancer Center, University of Louisville, Louisville, KY.
Robert J BealDepartment of Surgery, Price Institute of Surgical Research, University of Louisville, Louisville, KY.
Susan GalandiukDepartment of Surgery, Price Institute of Surgical Research, University of Louisville, Louisville, KY. Electronic address: susan.galandiuk@louisville.edu.
University of Louisville · US

Funding

University of Louisville Cancer Education ProgramR25CA134283 · NCI · UNIVERSITY OF LOUISVILLE · PI HEIN, DAVID W, KIDD, LA CREIS RENEE · 2011 to 2022
$3.1M
NCI NIH HHS R25 CA134283
6 · The paper itself

Abstract

backgroundAlong with the rising incidence of obesity, there has been an increase in patients diagnosed with early-onset colorectal cancer (<50 years old). In colorectal cancer, worse patient survival is associated with certain cytokine expression and downregulation of peroxisome proliferator activated receptor gamma expression. The effects of the obesity hormone leptin and macrophage-specific metabolite itaconate on these mechanisms are poorly understood. We investigated their impact on peroxisome proliferator activated receptor gamma and macrophage cytokine expression in vitro.

methodsM2-like macrophages were treated with either leptin, 4-octyl itaconate, or dimethyl itaconate in a dose- and time-dependent manner. Gene expression after treatment with 4 doses (D1-4) of each compound was analyzed at 4 time points (3, 6, 18, and 24 hours).

resultsPeroxisome proliferator activated receptor gamma was downregulated after 4-octyl itaconate treatment at 18 hours (FC -32.67, P ≤ .001). Interleukin-8 was upregulated after leptin and dimethyl itaconate treatment at 6 hours (FC 26.35 at D4, P ≤ .001, and FC 23.26 at D3, P = .006). Dimethyl itaconate upregulated IL-1β at 24 hours (FC 18.00 at D4, P ≤ .001). Tumor necrosis factor-α showed maximum downregulation after 4-octyl itaconate at 18 hours (FC -103.25 at D4, P ≤ .001).

conclusionsItaconate downregulates peroxisome proliferator activated receptor gamma as a tumor-suppressing factor and upregulates anti-inflammatory cytokines in M2-like macrophages. Itaconate provides a link between obesity and colorectal cancer and may be a key regulator in early-onset colorectal cancer.

Indexed as

Cell Culture TechniquesColorectal NeoplasmsHumansInterleukin-1betaInterleukin-8LeptinPPAR gammaSuccinatesTime FactorsTumor-Associated MacrophagesTumor Necrosis Factor-alpha4-octyl itaconatedimethyl itaconateIL1B protein, humanInterleukin-1betaInterleukin-8LeptinPPAR gammaSuccinatesTumor Necrosis Factor-alpha

Identifiers

PMID34876290
PMCPMC8885843
OpenAlexW4200580047

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.