Evidence map›Paper›PMID 30226473›Full record

ArticleThe Journal of clinical investigation2018

A carnosine analog mitigates metabolic disorders of obesity by reducing carbonyl stress.

Ethan J Anderson, Giulio Vistoli, Lalage A Katunga, Katsuhiko Funai, Luca Regazzoni, T Blake Monroe, Ettore Gilardoni, Luca Cannizzaro, Mara Colzani, Danilo De Maddis and 5 more

Open access · bronzeAbstract read
In one paragraph

Article in The Journal of clinical investigation, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 63 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
63citing papers in PubMed, 2 pooled it
7.2field-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

63 citing papers in PubMed, 2 syntheses or guidelines pooled it, 110 citations in OpenAlex.

  1. Pooled it
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  7. Histidine-Containing Dipeptides in Obesity and Cardiometabolic Health: A Systematic Scoping Review.Obesity reviews : an official journal of the International Association for the Study of Obesity · 2025
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3 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

15 authors at 5 institutions in 2 countries.

Ethan J AndersonDepartment of Pharmaceutical Sciences and Experimental Therapeutics, College of Pharmacy, Fraternal Order of Eagles Diabetes Research Center, University of Iowa, Iowa City, Iowa, USA.
Giulio VistoliDepartment of Pharmaceutical Sciences, University of Milan, Milan, Italy.
Lalage A KatungaDepartment of Pharmacology and Toxicology, East Carolina University, Greenville, North Carolina, USA.
Katsuhiko FunaiDiabetes and Metabolism Research Center, University of Utah, Salt Lake City, Utah, USA.
Luca RegazzoniDepartment of Pharmaceutical Sciences, University of Milan, Milan, Italy.
T Blake MonroeDepartment of Pharmaceutical Sciences and Experimental Therapeutics, College of Pharmacy, Fraternal Order of Eagles Diabetes Research Center, University of Iowa, Iowa City, Iowa, USA.
Ettore GilardoniDepartment of Pharmaceutical Sciences, University of Milan, Milan, Italy.
Luca CannizzaroDepartment of Pharmaceutical Sciences, University of Milan, Milan, Italy.
Mara ColzaniDepartment of Pharmaceutical Sciences, University of Milan, Milan, Italy.
Danilo De MaddisDepartment of Pharmaceutical Sciences, University of Milan, Milan, Italy.
Giuseppe RossoniDepartment of Medical Biotechnology and Translational Medicine, University of Milan, Milan, Italy.
Renato CanevottiFlamma S.p.A., Chignolo d'Isola, Bergamo, Italy.
Stefania GagliardiFlamma S.p.A., Chignolo d'Isola, Bergamo, Italy.
Marina CariniDepartment of Pharmaceutical Sciences, University of Milan, Milan, Italy.
Giancarlo AldiniDepartment of Pharmaceutical Sciences, University of Milan, Milan, Italy.
University of Milan · ITUniversity of Bergamo · ITUniversity of Iowa · USEast Carolina University · USUniversity of Utah · US

Funding

PE methylation in skeletal muscle energy efficiencyR01DK107397 · NIDDK · UTAH STATE HIGHER EDUCATION SYSTEM--UNIVERSITY OF UTAH · PI FUNAI, KATSUHIKO · 2017 to 2025
$3.8M
Predoctoral Training in the Pharmacological SciencesT32GM067795 · NIGMS · UNIVERSITY OF IOWA · PI STRACK, STEFAN · 2004 to 2021
$3.4M
Myocardial redox status, catecholamine metabolism and post-operative arrhythmiaR01HL122863 · NHLBI · UNIVERSITY OF IOWA · PI ANDERSON, ETHAN JOHN · 2014 to 2018
$2.1M
SKELETAL MUSCLE DE NOVO LIPOGENESIS AND THE GLUCOSE-FATTY ACID CYCLEK01DK095774 · NIDDK · WASHINGTON UNIVERSITY · PI FUNAI, KATSUHIKO · 2013 to 2016
$512k
Toxic neurotransmitter metabolites in aged and diabetic human myocardiumR21AG057006 · NIA · UNIVERSITY OF IOWA · PI ANDERSON, ETHAN JOHN, DOORN, JONATHAN A · 2017 to 2018
$419k
Supplement to DK109888R03DK109888 · NIDDK · UNIVERSITY OF UTAH · PI FUNAI, KATSUHIKO · 2016 to 2017
$208k
NHLBI NIH HHS R01 HL122863NIA NIH HHS R21 AG057006NIDDK NIH HHS K01 DK095774NIDDK NIH HHS R01 DK107397NIDDK NIH HHS R03 DK109888NIGMS NIH HHS T32 GM067795
6 · The paper itself

Abstract

Sugar- and lipid-derived aldehydes are reactive carbonyl species (RCS) frequently used as surrogate markers of oxidative stress in obesity. A pathogenic role for RCS in metabolic diseases of obesity remains controversial, however, partly because of their highly diffuse and broad reactivity and the lack of specific RCS-scavenging therapies. Naturally occurring histidine dipeptides (e.g., anserine and carnosine) show RCS reactivity, but their therapeutic potential in humans is limited by serum carnosinases. Here, we present the rational design, characterization, and pharmacological evaluation of carnosinol, i.e., (2S)-2-(3-amino propanoylamino)-3-(1H-imidazol-5-yl)propanol, a derivative of carnosine with high oral bioavailability that is resistant to carnosinases. Carnosinol displayed a suitable ADMET (absorption, distribution, metabolism, excretion, and toxicity) profile and was determined to have the greatest potency and selectivity toward α,β-unsaturated aldehydes (e.g., 4-hydroxynonenal, HNE, ACR) among all others reported thus far. In rodent models of diet-induced obesity and metabolic syndrome, carnosinol dose-dependently attenuated HNE adduct formation in liver and skeletal muscle, while simultaneously mitigating inflammation, dyslipidemia, insulin resistance, and steatohepatitis. These improvements in metabolic parameters with carnosinol were not due to changes in energy expenditure, physical activity, adiposity, or body weight. Collectively, our findings illustrate a pathogenic role for RCS in obesity-related metabolic disorders and provide validation for a promising new class of carbonyl-scavenging therapeutic compounds rationally derived from carnosine.

Indexed as

CarnosineDiabetes Mellitus, ExperimentalObesityAnimalsDipeptidasesHumansMaleMiceMice, Mutant StrainsMuscle, SkeletalOxidative StressRatsRats, Sprague-Dawleyaminoacyl-histidine dipeptidaseCarnosineDipeptidasesDiabetesDrug therapyEndocrinologyMetabolismObesity

Identifiers

PMID30226473
PMCPMC6264636
OpenAlexW2890125882

What OpenQuestion holds

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Read underepoch 390

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 OpenQuestion graph.