Evidence mapPaperPMID 36259366Full record

ArticleClinical science (London, England : 1979)2022

Dietary restriction and medical therapy drives PPARα-regulated improvements in early diabetic kidney disease in male rats.

William P Martin, Meera Nair, Yeong H D Chuah, Daniel Malmodin, Anders Pedersen, Sanna Abrahamsson, Michaela Hutter, Mahmoud Abdelaal, Jessie A Elliott, Naomi Fearon and 6 more

Open access · hybridAbstract read
In one paragraph

Article in Clinical science (London, England : 1979), 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.

0numbers the graph read from it
0cells of the map it votes in
6citing papers in PubMed
1.7field-weighted citation impact, top 15% 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

6 citing papers in PubMed, 12 citations in OpenAlex.

  1. Article
  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. Article
  4. Review
  5. Article
  6. Article
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

16 authors at 2 institutions in 3 countries.

William P MartinDiabetes Complications Research Centre, School of Medicine, Conway Institute of Biomolecular and Biomedical Research, University College Dublin, Belfield, D04 V1W8 Dublin, Ireland.
Meera NairDiabetes Complications Research Centre, School of Medicine, Conway Institute of Biomolecular and Biomedical Research, University College Dublin, Belfield, D04 V1W8 Dublin, Ireland.
Yeong H D ChuahDiabetes Complications Research Centre, School of Medicine, Conway Institute of Biomolecular and Biomedical Research, University College Dublin, Belfield, D04 V1W8 Dublin, Ireland.
Daniel MalmodinSwedish NMR Centre, University of Gothenburg, 40530 Gothenburg, Sweden.
Anders PedersenSwedish NMR Centre, University of Gothenburg, 40530 Gothenburg, Sweden.
Sanna AbrahamssonBioinformatics Core Facility, Sahlgrenska Academy, University of Gothenburg, 40530 Gothenburg, Sweden.
Michaela HutterDiabetes Complications Research Centre, School of Medicine, Conway Institute of Biomolecular and Biomedical Research, University College Dublin, Belfield, D04 V1W8 Dublin, Ireland.
Mahmoud AbdelaalDiabetes Complications Research Centre, School of Medicine, Conway Institute of Biomolecular and Biomedical Research, University College Dublin, Belfield, D04 V1W8 Dublin, Ireland.
Jessie A ElliottDiabetes Complications Research Centre, School of Medicine, Conway Institute of Biomolecular and Biomedical Research, University College Dublin, Belfield, D04 V1W8 Dublin, Ireland.
Naomi FearonDiabetes Complications Research Centre, School of Medicine, Conway Institute of Biomolecular and Biomedical Research, University College Dublin, Belfield, D04 V1W8 Dublin, Ireland.
Hans EckhardtDiabetes Complications Research Centre, School of Medicine, Conway Institute of Biomolecular and Biomedical Research, University College Dublin, Belfield, D04 V1W8 Dublin, Ireland.
Catherine GodsonDiabetes Complications Research Centre, School of Medicine, Conway Institute of Biomolecular and Biomedical Research, University College Dublin, Belfield, D04 V1W8 Dublin, Ireland.
Eoin P BrennanDiabetes Complications Research Centre, School of Medicine, Conway Institute of Biomolecular and Biomedical Research, University College Dublin, Belfield, D04 V1W8 Dublin, Ireland.ORCID 0000-0003-4908-5474
Lars FändriksInstitute of Clinical Sciences, Sahlgrenska Academy, University of Gothenburg, 40530 Gothenburg, Sweden.ORCID 0000-0003-0736-3034
Carel W le RouxDiabetes Complications Research Centre, School of Medicine, Conway Institute of Biomolecular and Biomedical Research, University College Dublin, Belfield, D04 V1W8 Dublin, Ireland.
Neil G DochertyDiabetes Complications Research Centre, School of Medicine, Conway Institute of Biomolecular and Biomedical Research, University College Dublin, Belfield, D04 V1W8 Dublin, Ireland.
University College Dublin · IEUniversity of Gothenburg · SE

Funding

Wellcome Trust 203930
6 · The paper itself

Abstract

The attenuation of diabetic kidney disease (DKD) by metabolic surgery is enhanced by pharmacotherapy promoting renal fatty acid oxidation (FAO). Using the Zucker Diabetic Fatty and Zucker Diabetic Sprague Dawley rat models of DKD, we conducted studies to determine if these effects could be replicated with a non-invasive bariatric mimetic intervention. Metabolic control and renal injury were compared in rats undergoing a dietary restriction plus medical therapy protocol (DMT; fenofibrate, liraglutide, metformin, ramipril, and rosuvastatin) and ad libitum-fed controls. The global renal cortical transcriptome and urinary 1H-NMR metabolomic profiles were also compared. Kidney cell type-specific and medication-specific transcriptomic responses were explored through in silico deconvolution. Transcriptomic and metabolomic correlates of improvements in kidney structure were defined using a molecular morphometric approach. The DMT protocol led to ∼20% weight loss, normalized metabolic parameters and was associated with reductions in indices of glomerular and proximal tubular injury. The transcriptomic response to DMT was dominated by changes in fenofibrate- and peroxisome proliferator-activated receptor-α (PPARα)-governed peroxisomal and mitochondrial FAO transcripts localizing to the proximal tubule. DMT induced urinary excretion of PPARα-regulated metabolites involved in nicotinamide metabolism and reversed DKD-associated changes in the urinary excretion of tricarboxylic acid (TCA) cycle intermediates. FAO transcripts and urinary nicotinamide and TCA cycle metabolites were moderately to strongly correlated with improvements in glomerular and proximal tubular injury. Weight loss plus pharmacological PPARα agonism is a promising means of attenuating DKD.

Indexed as

Diabetes MellitusDiabetic NephropathiesFenofibrateAnimalsKidneyMaleNiacinamidePPAR alphaRatsRats, Sprague-DawleyRats, ZuckerWeight LossFenofibrateNiacinamidePPAR alphadiabetic nephropathyfatty acid oxidationperoxisome proliferator-activated receptorspreclinicaltranscriptomicsweight loss

Identifiers

PMID36259366
PMCPMC7613831
OpenAlexW4306776547

What Socratic 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 Socratic graph.