Evidence map›Paper›PMID 35222262›Full record

ArticleFrontiers in endocrinology2021

Medications Activating Tubular Fatty Acid Oxidation Enhance the Protective Effects of Roux-en-Y Gastric Bypass Surgery in a Rat Model of Early Diabetic Kidney Disease.

William P Martin, Yeong H D Chuah, Mahmoud Abdelaal, Anders Pedersen, Daniel Malmodin, Sanna Abrahamsson, Michaela Hutter, Catherine Godson, Eoin P Brennan, Lars Fändriks and 2 more

Open access · goldAbstract read
In one paragraph

Article in Frontiers in endocrinology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
7citing papers in PubMed, 1 pooled it
0.9field-weighted citation impact, top 27% 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

7 citing papers in PubMed, 1 synthesis or guideline pooled it, 8 citations in OpenAlex.

  1. Pooled it
  2. How to individualize renoprotective therapy in obese patients with chronic kidney disease: a commentary by the Diabesity Working Group of the ERA.Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association · 2025
    Review
  3. Review
  4. Review
  5. Article
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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

12 authors at 2 institutions in 3 countries.

William P MartinDiabetes Complications Research Centre, School of Medicine, Conway Institute, University College Dublin, Dublin, Ireland.
Yeong H D ChuahDiabetes Complications Research Centre, School of Medicine, Conway Institute, University College Dublin, Dublin, Ireland.
Mahmoud AbdelaalDiabetes Complications Research Centre, School of Medicine, Conway Institute, University College Dublin, Dublin, Ireland.
Anders PedersenSwedish NMR Centre, University of Gothenburg, Gothenburg, Sweden.
Daniel MalmodinSwedish NMR Centre, University of Gothenburg, Gothenburg, Sweden.
Sanna AbrahamssonBioinformatics Core Facility, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
Michaela HutterDiabetes Complications Research Centre, School of Medicine, Conway Institute, University College Dublin, Dublin, Ireland.
Catherine GodsonDiabetes Complications Research Centre, School of Medicine, Conway Institute, University College Dublin, Dublin, Ireland.
Eoin P BrennanDiabetes Complications Research Centre, School of Medicine, Conway Institute, University College Dublin, Dublin, Ireland.
Lars FändriksInstitute of Clinical Sciences, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
Carel W le RouxDiabetes Complications Research Centre, School of Medicine, Conway Institute, University College Dublin, Dublin, Ireland.
Neil G DochertyDiabetes Complications Research Centre, School of Medicine, Conway Institute, University College Dublin, Dublin, Ireland.
University College Dublin · IEUniversity of Gothenburg · SE

Funding

Wellcome TrustWellcome Trust 203930/B/16/Z
6 · The paper itself

Abstract

Background: Roux-en-Y gastric bypass surgery (RYGB) improves biochemical and histological parameters of diabetic kidney disease (DKD). Targeted adjunct medical therapy may enhance renoprotection following RYGB. Methods: The effects of RYGB and RYGB plus fenofibrate, metformin, ramipril, and rosuvastatin (RYGB-FMRR) on metabolic control and histological and ultrastructural indices of glomerular and proximal tubular injury were compared in the Zucker Diabetic Sprague Dawley (ZDSD) rat model of DKD. Renal cortical transcriptomic (RNA-sequencing) and urinary metabolomic ( Results: RYGB-FMRR was superior to RYGB alone with respect to metabolic control, albuminuria, and histological and ultrastructural indices of glomerular injury. RYGB-FMRR reversed DKD-associated changes in mitochondrial morphology in the proximal tubule to a greater extent than RYGB. Attenuation of transcriptomic pathway level activation of pro-fibrotic responses was greater after RYGB-FMRR than RYGB. Fenofibrate was found to be the principal medication effector of gene expression changes following RYGB-FMRR, which led to the transcriptional induction of PPARα-regulated genes that are predominantly expressed in the proximal tubule and which regulate peroxisomal and mitochondrial fatty acid oxidation (FAO). After omics integration, expression of these FAO transcripts positively correlated with urinary levels of PPARα-regulated nicotinamide metabolites and negatively correlated with urinary tricarboxylic acid (TCA) cycle intermediates. Changes in FAO transcripts and nicotinamide and TCA cycle metabolites following RYGB-FMRR correlated strongly with improvements in glomerular and proximal tubular injury. Conclusions: Integrative multi-omic analyses point to PPARα-stimulated FAO in the proximal tubule as a dominant effector of treatment response to combined surgical and medical therapy in experimental DKD. Synergism between RYGB and pharmacological stimulation of FAO represents a promising combinatorial approach to the treatment of DKD in the setting of obesity.

Indexed as

Diabetes MellitusDiabetic NephropathiesGastric BypassAnimalsFatty AcidsRatsRats, Sprague-DawleyRats, ZuckerFatty Acidsbariatric surgerydiabetic kidney diseasefatty acid oxidationmetabolomemitochondriaperoxisomePPAR-alphatranscriptome

Identifiers

PMID35222262
PMCPMC8867227
OpenAlexW4210673653

What OpenQuestion holds

Textmetadata
LicenceCC BY
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.