Evidence map›Paper›PMID 25506548›Full record

ArticleMolecular metabolism2014

GLP-1 receptor agonism ameliorates hepatic VLDL overproduction and de novo lipogenesis in insulin resistance.

Jennifer Taher, Christopher L Baker, Carmelle Cuizon, Hassan Masoudpour, Rianna Zhang, Sarah Farr, Mark Naples, Celine Bourdon, Zdenka Pausova, Khosrow Adeli

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

Article in Molecular metabolism, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
32citing papers in PubMed, 1 pooled it
7.3field-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

32 citing papers in PubMed, 1 synthesis or guideline pooled it, 85 citations in OpenAlex.

  1. Pooled it
  2. Article
  3. Review
  4. Review
  5. Article
  6. Article
  7. Review
  8. Review
  9. Review
  10. Oligonucleotide therapies for nonalcoholic steatohepatitis.Molecular therapy. Nucleic acids · 2024
    Review
  11. Review
  12. Review
  13. Carbohydrate-insulin model: does the conventional view of obesity reverse cause and effect?Philosophical transactions of the Royal Society of London. Series B, Biological sciences · 2023
    Review
  14. Article
  15. Article
  16. Article
  17. Acute Cholesterol-Lowering Effect of Exendin-4 in LdlrJournal of atherosclerosis and thrombosis · 2023
    Article
  18. Article
  19. Review
  20. 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

10 authors at 2 institutions in 1 country.

Jennifer TaherMolecular Structure and Function, Research Institute, The Hospital for Sick Children, Toronto, ON, Canada ; Department of Laboratory Medicine and Pathobiology, University of Toronto, ON, Canada.
Christopher L BakerMolecular Structure and Function, Research Institute, The Hospital for Sick Children, Toronto, ON, Canada.
Carmelle CuizonMolecular Structure and Function, Research Institute, The Hospital for Sick Children, Toronto, ON, Canada.
Hassan MasoudpourMolecular Structure and Function, Research Institute, The Hospital for Sick Children, Toronto, ON, Canada.
Rianna ZhangMolecular Structure and Function, Research Institute, The Hospital for Sick Children, Toronto, ON, Canada.
Sarah FarrMolecular Structure and Function, Research Institute, The Hospital for Sick Children, Toronto, ON, Canada ; Department of Laboratory Medicine and Pathobiology, University of Toronto, ON, Canada.
Mark NaplesMolecular Structure and Function, Research Institute, The Hospital for Sick Children, Toronto, ON, Canada.
Celine BourdonPhysiology and Experimental Medicine, Research Institute, The Hospital for Sick Children, Toronto, ON, Canada.
Zdenka PausovaPhysiology and Experimental Medicine, Research Institute, The Hospital for Sick Children, Toronto, ON, Canada.
Khosrow AdeliMolecular Structure and Function, Research Institute, The Hospital for Sick Children, Toronto, ON, Canada ; Department of Laboratory Medicine and Pathobiology, University of Toronto, ON, Canada.
Hospital for Sick Children · CAUniversity of Toronto · CA

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

BACKGROUND/

objectivesFasting dyslipidemia is commonly observed in insulin resistant states and mechanistically linked to hepatic overproduction of very low density lipoprotein (VLDL). Recently, the incretin hormone glucagon-like peptide-1 (GLP-1) has been implicated in ameliorating dyslipidemia associated with insulin resistance and reducing hepatic lipid stores. Given that hepatic VLDL production is a key determinant of circulating lipid levels, we investigated the role of both peripheral and central GLP-1 receptor (GLP-1R) agonism in regulation of VLDL production.

methodsThe fructose-fed Syrian golden hamster was employed as a model of diet-induced insulin resistance and VLDL overproduction. Hamsters were treated with the GLP-1R agonist exendin-4 by intraperitoneal (ip) injection for peripheral studies or by intracerebroventricular (ICV) administration into the 3rd ventricle for central studies. Peripheral studies were repeated in vagotomised hamsters.

resultsShort term (7-10 day) peripheral exendin-4 enhanced satiety and also prevented fructose-induced fasting dyslipidemia and hyperinsulinemia. These changes were accompanied by decreased fasting plasma glucose levels, reduced hepatic lipid content and decreased levels of VLDL-TG and -apoB100 in plasma. The observed changes in fasting dyslipidemia could be partially explained by reduced respiratory exchange ratio (RER) thereby indicating a switch in energy utilization from carbohydrate to lipid. Additionally, exendin-4 reduced mRNA markers associated with hepatic de novo lipogenesis and inflammation. Despite these observations, GLP-1R activity could not be detected in primary hamster hepatocytes, thus leading to the investigation of a potential brain-liver axis functioning to regulate lipid metabolism. Short term (4 day) central administration of exendin-4 decreased body weight and food consumption and further prevented fructose-induced hypertriglyceridemia. Additionally, the peripheral lipid-lowering effects of exendin-4 were negated in vagotomised hamsters implicating the involvement of parasympathetic signaling.

conclusionExendin-4 prevents fructose-induced dyslipidemia and hepatic VLDL overproduction in insulin resistance through an indirect mechanism involving altered energy utilization, decreased hepatic lipid synthesis and also requires an intact parasympathetic signaling pathway.

Indexed as

apoB100, apolipoproteinB100Fasting dyslipidemiaFFA, free fatty acidGLP-1, glucagon-like peptide-1GLP-1R, GLP-1 receptorGlucagon-like peptide-1 (GLP-1)Hepatic steatosisICV, intracerebroventricularIncretinInsulin resistanceip, intraperitonealRER, respiratory exchange ratioT2D, type 2 diabetesVery low density lipoprotein (VLDL)VLDL, very low density lipoprotein

Identifiers

PMID25506548
PMCPMC4264039
OpenAlexW2036419300

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-ND
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.