Evidence map›Paper›PMID 27100622›Full record

ArticleEndocrinology2016

Retinol-Binding Protein 4 Induces Cardiomyocyte Hypertrophy by Activating TLR4/MyD88 Pathway.

Wei Gao, Hao Wang, Lin Zhang, Yang Cao, Ji-Zhang Bao, Zheng-Xia Liu, Lian-Sheng Wang, Qin Yang, Xiang Lu

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

Article in Endocrinology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 47 papers.

0numbers the graph read from it
0cells of the map it votes in
47citing papers in PubMed
1.9field-weighted citation impact, top 14% 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

47 citing papers in PubMed, 60 citations in OpenAlex.

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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

9 authors at 4 institutions in 2 countries.

Wei GaoDepartment of Geriatrics (W.G., Z.-X.L., X.L.), the Second Affiliated Hospital of Nanjing Medical University, Nanjing 210011, China; Department of Medicine, Physiology, and Biophysics (W.G., L.Z., Y.C., J.-Z.B., Q.Y.), Center for Diabetes Research and Treatment, Center for Epigenetics and Metabolism, University of California, Irvine, Irvine, California 92697; and Department of Cardiology (H.W., L.-S.W.), the First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, China.
Hao WangDepartment of Geriatrics (W.G., Z.-X.L., X.L.), the Second Affiliated Hospital of Nanjing Medical University, Nanjing 210011, China; Department of Medicine, Physiology, and Biophysics (W.G., L.Z., Y.C., J.-Z.B., Q.Y.), Center for Diabetes Research and Treatment, Center for Epigenetics and Metabolism, University of California, Irvine, Irvine, California 92697; and Department of Cardiology (H.W., L.-S.W.), the First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, China.
Lin ZhangDepartment of Geriatrics (W.G., Z.-X.L., X.L.), the Second Affiliated Hospital of Nanjing Medical University, Nanjing 210011, China; Department of Medicine, Physiology, and Biophysics (W.G., L.Z., Y.C., J.-Z.B., Q.Y.), Center for Diabetes Research and Treatment, Center for Epigenetics and Metabolism, University of California, Irvine, Irvine, California 92697; and Department of Cardiology (H.W., L.-S.W.), the First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, China.
Yang CaoDepartment of Geriatrics (W.G., Z.-X.L., X.L.), the Second Affiliated Hospital of Nanjing Medical University, Nanjing 210011, China; Department of Medicine, Physiology, and Biophysics (W.G., L.Z., Y.C., J.-Z.B., Q.Y.), Center for Diabetes Research and Treatment, Center for Epigenetics and Metabolism, University of California, Irvine, Irvine, California 92697; and Department of Cardiology (H.W., L.-S.W.), the First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, China.
Ji-Zhang BaoDepartment of Geriatrics (W.G., Z.-X.L., X.L.), the Second Affiliated Hospital of Nanjing Medical University, Nanjing 210011, China; Department of Medicine, Physiology, and Biophysics (W.G., L.Z., Y.C., J.-Z.B., Q.Y.), Center for Diabetes Research and Treatment, Center for Epigenetics and Metabolism, University of California, Irvine, Irvine, California 92697; and Department of Cardiology (H.W., L.-S.W.), the First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, China.
Zheng-Xia LiuDepartment of Geriatrics (W.G., Z.-X.L., X.L.), the Second Affiliated Hospital of Nanjing Medical University, Nanjing 210011, China; Department of Medicine, Physiology, and Biophysics (W.G., L.Z., Y.C., J.-Z.B., Q.Y.), Center for Diabetes Research and Treatment, Center for Epigenetics and Metabolism, University of California, Irvine, Irvine, California 92697; and Department of Cardiology (H.W., L.-S.W.), the First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, China.
Lian-Sheng WangDepartment of Geriatrics (W.G., Z.-X.L., X.L.), the Second Affiliated Hospital of Nanjing Medical University, Nanjing 210011, China; Department of Medicine, Physiology, and Biophysics (W.G., L.Z., Y.C., J.-Z.B., Q.Y.), Center for Diabetes Research and Treatment, Center for Epigenetics and Metabolism, University of California, Irvine, Irvine, California 92697; and Department of Cardiology (H.W., L.-S.W.), the First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, China.
Qin YangDepartment of Geriatrics (W.G., Z.-X.L., X.L.), the Second Affiliated Hospital of Nanjing Medical University, Nanjing 210011, China; Department of Medicine, Physiology, and Biophysics (W.G., L.Z., Y.C., J.-Z.B., Q.Y.), Center for Diabetes Research and Treatment, Center for Epigenetics and Metabolism, University of California, Irvine, Irvine, California 92697; and Department of Cardiology (H.W., L.-S.W.), the First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, China.
Xiang LuDepartment of Geriatrics (W.G., Z.-X.L., X.L.), the Second Affiliated Hospital of Nanjing Medical University, Nanjing 210011, China; Department of Medicine, Physiology, and Biophysics (W.G., L.Z., Y.C., J.-Z.B., Q.Y.), Center for Diabetes Research and Treatment, Center for Epigenetics and Metabolism, University of California, Irvine, Irvine, California 92697; and Department of Cardiology (H.W., L.-S.W.), the First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, China.
Second Affiliated Hospital of Nanjing Medical University · CNUniversity of California, Irvine · USJiangsu Province Hospital · CNNanjing Medical University · CN

Funding

Nicotinamide N-methyltransferase is a novel regulator of energy expenditureR01DK100385 · NIDDK · UNIVERSITY OF CALIFORNIA-IRVINE · PI YANG, QIN · 2014 to 2018
$1.7M
NIDDK NIH HHS R01 DK100385
6 · The paper itself

Abstract

Insulin resistance plays a major role in the development and progression of cardiac hypertrophy and heart failure. Heart failure in turn promotes insulin resistance and increases the risk for diabetes. The vicious cycle determines significant mortality in patients with heart failure and diabetes. However, the underlying mechanisms for the vicious cycle are not fully elucidated. Here we show that circulating levels and adipose expression of retinol-binding protein 4 (RBP4), an adipokine that contributes to systemic insulin resistance, were elevated in cardiac hypertrophy induced by transverse aortic constriction and angiotensin-II (Ang-II) infusion. Ang-II increased RBP4 expression in adipocytes, which was abolished by losartan, an Ang-II receptor blocker. The elevated RBP4 in cardiac hypertrophy may have pathophysiological consequences because RBP4 increased cell size, enhanced protein synthesis, and elevated the expression of hypertrophic markers including Anp, Bnp, and Myh7 in primary cardiomyocytes. Mechanistically, RBP4 induced the expression and activity of toll-like receptor 4 (TLR4) and myeloid differentiation primary response gene 88 (MyD88) in cardiomyocytes, resulting in enhanced inflammation and reactive oxygen species production. Inhibition or knockdown of the TLR4/MyD88 pathway attenuated inflammatory and hypertrophic responses to RBP4 stimulation. Importantly, RBP4 also reduced the expression of glucose transporter-4 and impaired insulin-stimulated glucose uptake in cardiomyocytes. This impairment was ameliorated in cardiomyocytes from TLR4 knockout mice. Therefore, RBP4 may be a critical modulator promoting the vicious cycle of insulin resistance and heart failure by activating TLR4/MyD88-mediated inflammatory pathways. Potentially, lowering RBP4 might break the vicious cycle and improve both insulin resistance and cardiac hypertrophy.

Indexed as

AdipocytesAngiotensin IIAnimalsBlotting, WesternCardiomegalyCells, CulturedInflammationLosartanMaleMiceMice, Inbred C57BLMyeloid Differentiation Factor 88Myocytes, CardiacOxidative StressPolymerase Chain ReactionReactive Oxygen SpeciesAngiotensin IILosartanMyd88 protein, mouseMyeloid Differentiation Factor 88Rbp4 protein, mouseReactive Oxygen SpeciesRetinol-Binding Proteins, PlasmaToll-Like Receptor 4

Identifiers

PMID27100622
PMCPMC4891784
OpenAlexW2339983898

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.