Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2019 Oct;12(5):415-424.
doi: 10.1007/s12265-019-09879-0. Epub 2019 Mar 5.

Adipokine Dysregulation and Insulin Resistance with Atherosclerotic Vascular Disease: Metabolic Syndrome or Independent Sequelae?

Mohan Satish  1 , Shailendra K Saxena  2 , Devendra K Agrawal  3
Affiliations
Review

Adipokine Dysregulation and Insulin Resistance with Atherosclerotic Vascular Disease: Metabolic Syndrome or Independent Sequelae?

Mohan Satish et al. J Cardiovasc Transl Res. 2019 Oct.

Abstract

Adipokine dysregulation and insulin resistance are two hallmark sequelae attributed to the current clinical definition of metabolic syndrome (MetS) that are also linked to atherosclerotic vascular disease. Here, we critically discuss the underlying pathophysiological mechanisms and the interplay between the two sequelae. Adipokine dysregulation is involved with decreased nitric oxide, vascular inflammation, and insulin resistance in itself to promote atherosclerosis. Insulin resistance is involved with endothelial dysfunction by direct and indirect mechanisms that also promote vascular inflammation and atherosclerosis. These mechanisms are discussed in atherosclerosis irrespective of MetS, and to evaluate the possibility of synergism in MetS. High retinol-binding protein-4 (RBP-4) and low cholesterol efflux in MetS may provide evidence of possible synergism and elevated atherosclerotic risk. An adverse adipokine panel that includes fetuin-A and adiponectin can potentially assess atherosclerotic risk in even those without MetS. Genetic possibilities may exist in atherosclerotic vascular diseases secondary to insulin resistance.

Keywords: Adipokines; Atherosclerosis; Endothelial dysfunction; Inflammation; Insulin resistance; Metabolic syndrome.

PubMed Disclaimer

Conflict of interest statement

Conflict of Interest: All authors have read the journal’s policy on disclosure of potential conflicts of interest. Author C has received grants from the National Institutes of Health, State of Nebraska, and Dialysis Clinic Inc. Other authors have no other relevant affiliations or financial or non-financial involvement with any organization or entity with financial or non-financial interest or conflict with the subject matter or materials discussed in the manuscript apart from those disclosed. Author A (MS) declares that he has no conflict of interest. Author B (SKS) declares that he has no conflict of interest. Author C (DKA) declares that he has no conflict of interest.

Figures

Figure 1:
Figure 1:
Schematic diagram showing an association between metabolic syndrome and atherosclerotic vascular disease
Figure 2:
Figure 2:
Mediators involved due to adipokine dysregulation leading to the pathophysiology in the development of atherosclerosis. Adipokines ➔ tumor necrosis factor – alpha (TNF-⍺); extrahepatic angiotensin (AT); retinol-binding protein-4 (RBP-4); fetuin-A, adiponectin, plasminogen activator inhibitor-1 (PAI-1); Mediators Impacted ➔ monocyte chemoattractant protein (MCP-1); C-C chemokine receptor type 2 (CCR2) signaling; endothelial nitric oxide synthase (eNOS); nuclear factor-kappa light-chain-enhancer of activated B cells; *Diagnostic targets ➔ genetic predisposition: adiponectin (AdipoQ gene) polymorphisms and specific microRNAs of adipokine dysregulation promoting atherosclerosis; Therapeutic target ➔ apelin; MetS link ➔ RBP-4; vSMC - vascular smooth muscle cells
Figure 3:
Figure 3:. Insulin Resistance and Development of Atherosclerosis
Signaling pathways ➔ phosphatidylinositol 3-kinase (PI3-K); mitogen-activated protein kinase (MAPK); Mediators ➔ nitric oxide (NO); endothelin-1 (ET-1), vascular cell adhesion molecule-1 (VCAM-1), nuclear factor-kappa light-chain-enhancer of activated B cells, specialized pro-resolving mediators (SPMs); *Diagnostic targets ➔ genetic predisposition to atherosclerosis: genetic variation in haplotype tagging single nucleotide polymorphisms (htSNPs) at the eNOS locus & specific microRNAs of insulin resistance promoting atherosclerosis; Therapeutic targets ➔ upregulation of high-density lipoprotein (HDL) to induce anti-oxidative effect and reduce lipotoxicity and SPM delivery to resolve inflammation associated with insulin resistance.
See this image and copyright information in PMC

References

    1. Kahn R The Metabolic Syndrome: Time for a Critical Appraisal: Joint Statement From the American Diabetes Association and the European Association for the Study of Diabetes: Response to Citrome et al., Giugliano and Esposito, Cheta, and Psaty et al. Diabetes Care 2006;29(1):177–178. doi:10.2337/diacare.29.1.177-a. - DOI - PubMed
    1. Engin A The Definition and Prevalence of Obesity and Metabolic Syndrome. Obesity and Lipotoxicity Advances in Experimental Medicine and Biology 2017:1–17. doi:10.1007/978-3-319-48382-5_1. - DOI - PubMed
    1. Thorn LM, Forsblom C, Waden J, et al. Metabolic Syndrome as a Risk Factor for Cardiovascular Disease, Mortality, and Progression of Diabetic Nephropathy in Type 1 Diabetes. Diabetes Care 2009;32(5):950–952. doi:10.2337/dc08-2022. - DOI - PMC - PubMed
    1. Khan QA, Sola S, Khan BV. The metabolic syndrome: inflammation and endothelial dysfunction. Hospital Physician 2006;42:26–37.
    1. Preventing Chronic Disease Centers for Disease Control and Prevention. https://www.cdc.gov/pcd/issues/2017/16_0287.htm. Published September 20, 2017. Accessed September 2, 2018.

Publication types

MeSH terms