Evidence mapPaperPMID 35237909Full record

ArticleEndocrine2022

Metformin enhances LDL-cholesterol uptake by suppressing the expression of the pro-protein convertase subtilisin/kexin type 9 (PCSK9) in liver cells.

Amjad Ali, Hema Unnikannan, Jasmin Shafarin, Khuloud Bajbouj, Jalal Taneera, Jibran Sualeh Muhammad, Haydar Hasan, Albert Salehi, Samir Awadallah, Mawieh Hamad

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Article in Endocrine, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.

0numbers the graph read from it
0cells of the map it votes in
3citing papers in PubMed
1.0field-weighted citation impact, top 28% 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

3 citing papers in PubMed, 11 citations in OpenAlex.

  1. Review
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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 2 countries.

Amjad AliSharjah Institute for Medical Research, University of Sharjah, Sharjah, United Arab Emirates.
Hema UnnikannanSharjah Institute for Medical Research, University of Sharjah, Sharjah, United Arab Emirates.
Jasmin ShafarinSharjah Institute for Medical Research, University of Sharjah, Sharjah, United Arab Emirates.
Khuloud BajboujSharjah Institute for Medical Research, University of Sharjah, Sharjah, United Arab Emirates.
Jalal TaneeraSharjah Institute for Medical Research, University of Sharjah, Sharjah, United Arab Emirates.
Jibran Sualeh MuhammadSharjah Institute for Medical Research, University of Sharjah, Sharjah, United Arab Emirates.
Haydar HasanDepartment of Clinical Nutrition and Dietetics, College of Health Sciences, University of Sharjah, Sharjah, United Arab Emirates.
Albert SalehiDepartment of Clinical science, UMAS, Clinical Research Center, Lund University, Malmö, Sweden.
Samir AwadallahSharjah Institute for Medical Research, University of Sharjah, Sharjah, United Arab Emirates. sawadallah@sharjah.ac.ae.
Mawieh HamadSharjah Institute for Medical Research, University of Sharjah, Sharjah, United Arab Emirates. mabdelhaq@sharjah.ac.ae.ORCID 0000-0002-6769-1091
University of Sharjah · AELund University · SE

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

purposeMetformin (MF) intake associates with reduced levels of circulating low-density lipoprotein-cholesterol (LDL-C). This has been attributed to the activation of AMPK, which differentially regulates the expression of multiple genes involved in cholesterol synthesis and trafficking. However, the exact mechanism underlying the LDL-C lowering effect of MF remains ambiguous.

methodsMF-treated Hep-G2 and HuH7 cells were evaluated for cell viability and the expression status of key lipid metabolism-related genes along with LDL-C uptake efficiency.

resultsMF treatment resulted in decreased expression and secretion of PCSK9, increased expression of LDLR and enhanced LDL-C uptake in hepatocytes. It also resulted in increased expression of activated AMPK (p-AMPK) and decreased expression of SREBP2 and HNF-1α proteins. Transcriptomic analysis of MF-treated Hep-G2 cells confirmed these findings and showed that other key lipid metabolism-related genes including those that encode apolipoproteins (APOB, APOC2, APOC3 and APOE), MTTP and LIPC are downregulated. Lastly, MF treatment associated with reduced HMG-CoA reductase expression and activity.

conclusionsThese findings suggest that MF treatment reduces circulating LDL-C levels by suppressing PCSK9 expression and enhancing LDLR expression; hence the potential therapeutic utility of MF in hypercholesterolemia.

Indexed as

MetforminProprotein Convertase 9AMP-Activated Protein KinasesCholesterol, LDLHepatocytesHep G2 CellsHumansLiverReceptors, LDLSubtilisinAMP-Activated Protein KinasesCholesterol, LDLMetforminPCSK9 protein, humanProprotein Convertase 9Receptors, LDLSubtilisinHNF-1αLDL-cholesterolLDLRMetforminPCSK9SREBP2

Identifiers

PMID35237909
OpenAlexW4214908606

What Socratic holds

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Registered trials

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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.