Metabolic syndrome as a risk factor for neurological disorders - PubMed (original) (raw)

Review

Metabolic syndrome as a risk factor for neurological disorders

Akhlaq A Farooqui et al. Cell Mol Life Sci. 2012 Mar.

Abstract

The metabolic syndrome is a cluster of common pathologies: abdominal obesity linked to an excess of visceral fat, insulin resistance, dyslipidemia and hypertension. At the molecular level, metabolic syndrome is accompanied not only by dysregulation in the expression of adipokines (cytokines and chemokines), but also by alterations in levels of leptin, a peptide hormone released by white adipose tissue. These changes modulate immune response and inflammation that lead to alterations in the hypothalamic 'bodyweight/appetite/satiety set point,' resulting in the initiation and development of metabolic syndrome. Metabolic syndrome is a risk factor for neurological disorders such as stroke, depression and Alzheimer's disease. The molecular mechanism underlying the mirror relationship between metabolic syndrome and neurological disorders is not fully understood. However, it is becoming increasingly evident that all cellular and biochemical alterations observed in metabolic syndrome like impairment of endothelial cell function, abnormality in essential fatty acid metabolism and alterations in lipid mediators along with abnormal insulin/leptin signaling may represent a pathological bridge between metabolic syndrome and neurological disorders such as stroke, Alzheimer's disease and depression. The purpose of this review is not only to describe the involvement of brain in the pathogenesis of metabolic syndrome, but also to link the pathogenesis of metabolic syndrome with neurochemical changes in stroke, Alzheimer's disease and depression to a wider audience of neuroscientists with the hope that this discussion will initiate more studies on the relationship between metabolic syndrome and neurological disorders.

© Springer Basel AG 2011

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Figures

Fig. 1

Fig. 1

Leptin and insulin signaling in the brain. IRS-2 Insulin receptor substrate-2, Atk/PKB serine/threonine protein kinase, JAK-2 Janus kinase 2, STAT3 Signal transducer and activator of transcription 3, Grb2 growth factor receptor binding-2, PY phosphotyrosine, PIP phosphatidylinositol 4,5-bisphosphate, PDK phosphoinositide-dependent kinase, PP2A protein phosphatase type 2A, PKCζ protein kinase Cζ, DAG diacylglycerol

Fig. 2

Fig. 2

Metabolic syndrome and increased risk of heart disease and stroke. FFA Free fatty acids, SNS activity sympathetic nervous system activity, ROS reactive oxygen species, AGES advanced glycated end products

Fig. 3

Fig. 3

Abnormal insulin receptor signaling and increased risk of Alzheimer’s disease. IRS Insulin receptor substrate, PtdIns 3K phosphatidylinositol 3 kinase, GSK-3 glycogen synthase kinase 3, APP amyloid precursor protein, Aβ beta amyloid, Akt serine/threonine protein kinase, upward arrow indicates increase and downward arrow indicates decrease

Fig. 4

Fig. 4

Stress results in the development of metabolic syndrome and depression. FFA Free fatty acids, IRS insulin receptor substrate, upward arrow indicates increase

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References

    1. Flegal KM, Carroll MD, Ogden CL, Curtin R. Prevalence and trends in obesity among US adults, 1999–2008. JAMA. 2010;303:235–241. doi: 10.1001/jama.2009.2014. - DOI - PubMed
    1. Reaven GM, Laws A. Insulin resistance: the metabolic syndrome X. NJ: Humana Press Totowa; 1999.
    1. Grundy SM, Hansen B, Smith SC, Jr, Cleeman JI, Kahn RA, American Heart Association Clinical management of metabolic syndrome report of the American Heart Association/National Heart, Lung, and Blood Institute/American Diabetes Association conference on scientific issues related to management. Circulation. 2004;109:551–556. doi: 10.1161/01.CIR.0000112379.88385.67. - DOI - PubMed
    1. Groenendijk M, Cantor RM, Blom NH, Rotter JI, de Bruin TW, Dallinga-Thie GM. Association of plasma lipids and apolipoproteins with the insulin response element in the apoC-III promoter region in familial combined hyperlipidemia. J Lipid Res. 1999;40:1036–1044. - PubMed
    1. Mooradian AD, Haas MJ, Wong NC. Transcriptional control of apolipoprotein A-I gene expression in diabetes. Diabetes. 2004;53:513–520. doi: 10.2337/diabetes.53.3.513. - DOI - PubMed

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