Evidence map›Paper›PMID 22896587›Full record

ArticleCirculation research2012

Overexpression of endothelial nitric oxide synthase prevents diet-induced obesity and regulates adipocyte phenotype.

Brian E Sansbury, Timothy D Cummins, Yunan Tang, Jason Hellmann, Candice R Holden, Matthew A Harbeson, Yang Chen, Rakesh P Patel, Matthew Spite, Aruni Bhatnagar and 1 more

Open access · bronzeAbstract read
In one paragraph

Article in Circulation research, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 82 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
82citing papers in PubMed, 1 pooled it
8.4field-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

82 citing papers in PubMed, 1 synthesis or guideline pooled it, 153 citations in OpenAlex.

  1. Pooled it
  2. Trial
  3. Review
  4. Review
  5. Increased cGMP improves microvascular exercise training adaptations in diet-induced obesity.American journal of physiology. Endocrinology and metabolism · 2025
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  10. Endothelial Dysfunction in Obesity and Therapeutic Targets.Advances in experimental medicine and biology · 2024
    Review
  11. Anti-Inflammatory Activity ofPharmaceuticals (Basel, Switzerland) · 2023
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  12. The damaging duo: Obesity and excess dietary salt contribute to hypertension and cardiovascular disease.Obesity reviews : an official journal of the International Association for the Study of Obesity · 2023
    Review
  13. Fine particulate matter (PMThe Science of the total environment · 2023
    Article
  14. Zinc homeostasis and redox alterations in obesity.Frontiers in endocrinology · 2023
    Review
  15. Article
  16. Article
  17. Nitric Oxide Mobilizes Intracellular ZnInternational journal of molecular sciences · 2022
    Article
  18. Article
  19. Article
  20. Targeting the vasculature in cardiometabolic disease.The Journal of clinical investigation · 2022
    Review

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

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

11 authors at 1 institution in 1 country.

Brian E SansburyInstitute of Molecular Cardiology, Department of Medicine, University of Louisville, Louisville, KY 40202, USA.
Timothy D Cummins
Yunan Tang
Jason Hellmann
Candice R Holden
Matthew A Harbeson
Yang Chen
Rakesh P Patel
Matthew Spite
Aruni Bhatnagar
Bradford G Hill
Metabolon (United States) · US

Funding

Project 5 - Metabolomic Analysis of AtherothrombosisP20GM103492 · NIGMS · UNIVERSITY OF LOUISVILLE · PI DEFILIPPIS, ANDREW · 2012 to 2017
$13.8M
STEM CELLS AND DIABETIC CARDIOMYOPATHY PROJ 2 2009P20RR024489 · NCRR · UNIVERSITY OF LOUISVILLE · PI BHATNAGAR, ARUNI · 2008 to 2011
$10.0M
Role of Inflammation-Resolving Lipid Mediators In Ischemic RevascularizationR01HL106173 · NHLBI · UNIVERSITY OF LOUISVILLE · PI SPITE, MATTHEW R · 2011 to 2023
$5.7M
TOXICITY OF 4-HYDROXYALKENALS IN HEARTR01HL055477 · NHLBI · UNIVERSITY OF TEXAS MEDICAL BR GALVESTON · PI BHATNAGAR, ARUNI · 1997 to 2015
$4.4M
CARDIAC METABOLISM OF ENALSR01HL059378 · NHLBI · UNIVERSITY OF TEXAS MEDICAL BR GALVESTON · PI BHATNAGAR, ARUNI · 1998 to 2011
$3.3M
NCRR NIH HHS P20 RR024489NCRR NIH HHS RR024489NHLBI NIH HHS HL106173NHLBI NIH HHS HL55477NHLBI NIH HHS HL59378NHLBI NIH HHS R01 HL055477NHLBI NIH HHS R01 HL059378NHLBI NIH HHS R01 HL106173NIGMS NIH HHS P20 GM103492
6 · The paper itself

Abstract

rationaleEndothelial dysfunction is a characteristic feature of diabetes and obesity in animal models and humans. Deficits in nitric oxide production by endothelial nitric oxide synthase (eNOS) are associated with insulin resistance, which is exacerbated by high-fat diet. Nevertheless, the metabolic effects of increasing eNOS levels have not been studied.

objectiveThe current study was designed to test whether overexpression of eNOS would prevent diet-induced obesity and insulin resistance. METHODS AND

resultsIn db/db mice and in high-fat diet-fed wild-type C57BL/6J mice, the abundance of eNOS protein in adipose tissue was decreased without significant changes in eNOS levels in skeletal muscle or aorta. Mice overexpressing eNOS (eNOS transgenic mice) were resistant to diet-induced obesity and hyperinsulinemia, although systemic glucose intolerance remained largely unaffected. In comparison with wild-type mice, high-fat diet-fed eNOS transgenic mice displayed a higher metabolic rate and attenuated hypertrophy of white adipocytes. Overexpression of eNOS did not affect food consumption or diet-induced changes in plasma cholesterol or leptin levels, yet plasma triglycerides and fatty acids were decreased. Metabolomic analysis of adipose tissue indicated that eNOS overexpression primarily affected amino acid and lipid metabolism; subpathway analysis suggested changes in fatty acid oxidation. In agreement with these findings, adipose tissue from eNOS transgenic mice showed higher levels of PPAR-α and PPAR-γ gene expression, elevated abundance of mitochondrial proteins, and a higher rate of oxygen consumption.

conclusionsThese findings demonstrate that increased eNOS activity prevents the obesogenic effects of high-fat diet without affecting systemic insulin resistance, in part, by stimulating metabolic activity in adipose tissue.

Indexed as

PhenotypeAdipocytesAmino AcidsAnimalsDiet, High-FatDisease Models, AnimalHypertrophyInsulin ResistanceLipid MetabolismMiceMice, Inbred C57BLMice, TransgenicNitric Oxide Synthase Type IIIObesityPPAR alphaPPAR gammaAmino AcidsNitric Oxide Synthase Type IIIPPAR alphaPPAR gamma

Identifiers

PMID22896587
PMCPMC3707504
OpenAlexW2078821762

What OpenQuestion holds

Textmetadata
LicenceTDM
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.