Evidence map›Paper›PMID 26424786›Full record

ArticleJournal of the American Society of Nephrology : JASN2016

G Protein-Coupled Bile Acid Receptor TGR5 Activation Inhibits Kidney Disease in Obesity and Diabetes.

Xiaoxin X Wang, Michal Herman Edelstein, Uzi Gafter, Liru Qiu, Yuhuan Luo, Evgenia Dobrinskikh, Scott Lucia, Luciano Adorini, Vivette D D'Agati, Jonathan Levi and 5 more

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

Article in Journal of the American Society of Nephrology : JASN, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 122 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
122citing papers in PubMed, 1 pooled it
6.3field-weighted citation impact, top 3% 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

122 citing papers in PubMed, 1 synthesis or guideline pooled it, 202 citations in OpenAlex.

  1. Pooled it
  2. Review
  3. Article
  4. Review
  5. ERRγ deletion in podocytes accelerates aging related kidney disease.bioRxiv : the preprint server for biology · 2026
    Article
  6. Article
  7. Review
  8. Review
  9. Review
  10. Review
  11. Review
  12. Review
  13. Review
  14. Article
  15. Review
  16. Review
  17. Review
  18. Article
  19. Article
  20. Article

62 more citing papers are in PubMed but not listed here.

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

15 authors at 8 institutions in 3 countries.

Xiaoxin X WangDepartment of Medicine, Division of Renal Diseases and Hypertension, University of Colorado Anschutz Medical Campus, Aurora, Colorado; Xiaoxin.Wang@ucdenver.edu Moshe.Levi@ucdenver.edu.
Michal Herman EdelsteinRabin Medical Center, Department of Nephrology and Hypertension; Felsenstein Medical Research Center, Sackler School of Medicine, Tel Aviv University, Israel;
Uzi GafterRabin Medical Center, Department of Nephrology and Hypertension; Felsenstein Medical Research Center, Sackler School of Medicine, Tel Aviv University, Israel;
Liru QiuDepartment of Medicine, Division of Renal Diseases and Hypertension, University of Colorado Anschutz Medical Campus, Aurora, Colorado;
Yuhuan LuoDepartment of Medicine, Division of Renal Diseases and Hypertension, University of Colorado Anschutz Medical Campus, Aurora, Colorado;
Evgenia DobrinskikhDepartment of Medicine, Division of Renal Diseases and Hypertension, University of Colorado Anschutz Medical Campus, Aurora, Colorado;
Scott LuciaDepartment of Medicine, Division of Renal Diseases and Hypertension, University of Colorado Anschutz Medical Campus, Aurora, Colorado;
Luciano AdoriniIntercept, New York, New York;
Vivette D D'AgatiDepartment of Pathology, Columbia University, College of Physicians and Surgeons, New York, New York;
Jonathan LeviNational Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland;
Avi RosenbergNational Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland;
Jeffrey B KoppNational Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland;
David R GiusNorthwestern University Feinberg School of Medicine, Chicago, Illinois; and.
Moin A SaleemUniversity of Bristol, Southmead Hospital, Bristol, United Kingdom.
Moshe LeviDepartment of Medicine, Division of Renal Diseases and Hypertension, University of Colorado Anschutz Medical Campus, Aurora, Colorado; Xiaoxin.Wang@ucdenver.edu Moshe.Levi@ucdenver.edu.
University of Colorado Anschutz Medical Campus · USNational Institutes of Health · USColumbia University · USIntercept Pharmaceuticals (United States) · USNorthwestern University · USRabin Medical Center · ILTel Aviv University · ILUniversity of Bristol · GB

Funding

Coordinating and Bioinformatics Unit for the MMPC/DiaCompU24DK076169 · NIDDK · AUGUSTA UNIVERSITY · PI MCINDOE, RICHARD A. · 2006 to 2018
$42.4M
Loss of mtSIRT3, Decreased MnSOD Activity, and IR Induced Genomic InstabilityR01CA152601 · NCI · VANDERBILT UNIVERSITY · PI BONINI, MARCELO G. · 2010 to 2019
$3.5M
Treatment of Kidney Disease in Diabetes and ObesityR01DK098336 · NIDDK · UNIVERSITY OF COLORADO DENVER · PI LEVI, MOSHE · 2013 to 2016
$1.3M
Nephropathy in Obesity and Diabetes: Prevention and TreatmentI01BX001954 · VA · VA EASTERN COLORADO HEALTH CARE SYSTEM · PI LEVI, MOSHE · 2014 to 2017
–
BLRD VA I01 BX001954NCI NIH HHS R01 CA152601NIDDK NIH HHS R01 DK098336NIDDK NIH HHS U24 DK076169
6 · The paper itself

Abstract

Obesity and diabetes mellitus are the leading causes of renal disease. In this study, we determined the regulation and role of the G protein-coupled bile acid receptor TGR5, previously shown to be regulated by high glucose and/or fatty acids, in obesity-related glomerulopathy (ORG) and diabetic nephropathy (DN). Treatment of diabetic db/db mice with the selective TGR5 agonist INT-777 decreased proteinuria, podocyte injury, mesangial expansion, fibrosis, and CD68 macrophage infiltration in the kidney. INT-777 also induced renal expression of master regulators of mitochondrial biogenesis, inhibitors of oxidative stress, and inducers of fatty acid β-oxidation, including sirtuin 1 (SIRT1), sirtuin 3 (SIRT3), and Nrf-1. Increased activity of SIRT3 was evidenced by normalization of the increased acetylation of mitochondrial superoxide dismutase 2 (SOD2) and isocitrate dehydrogenase 2 (IDH2) observed in untreated db/db mice. Accordingly, INT-777 decreased mitochondrial H2O2 generation and increased the activity of SOD2, which associated with decreased urinary levels of H2O2 and thiobarbituric acid reactive substances. Furthermore, INT-777 decreased renal lipid accumulation. INT-777 also prevented kidney disease in mice with diet-induced obesity. In human podocytes cultured with high glucose, INT-777 induced mitochondrial biogenesis, decreased oxidative stress, and increased fatty acid β-oxidation. Compared with normal kidney biopsy specimens, kidney specimens from patients with established ORG or DN expressed significantly less TGR5 mRNA, and levels inversely correlated with disease progression. Our results indicate that TGR5 activation induces mitochondrial biogenesis and prevents renal oxidative stress and lipid accumulation, establishing a role for TGR5 in inhibiting kidney disease in obesity and diabetes.

Indexed as

AnimalsBile Acids and SaltsCholic AcidsDiabetic NephropathiesHumansHydrogen PeroxideKidney DiseasesMaleMiceObesityOxidative StressPodocytesReceptors, G-Protein-CoupledSignal TransductionSuperoxide DismutaseSuperoxide Dismutase 26alpha-ethyl-23(S)-methylcholic acidBile Acids and SaltsCholic AcidsGpbar1 protein, mouseHydrogen PeroxideReceptors, G-Protein-CoupledSuperoxide DismutaseSuperoxide Dismutase 2diabetic nephropathymetabolismmitochondriaobesityoxidative stress

Identifiers

PMID26424786
PMCPMC4849814
OpenAlexW2175806733

What OpenQuestion holds

Textmetadata
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.