Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
6155962 | Translational Research | 2016 | 24 Pages |
Abstract
The metabolic syndrome (MetS) is comprised of a cluster of closely related risk factors, including visceral adiposity, insulin resistance, hypertension, high triglyceride, and low high-density lipoprotein cholesterol; all of which increase the risk for the development of type 2 diabetes and cardiovascular disease. A chronic state of inflammation appears to be a central mechanism underlying the pathophysiology of insulin resistance and MetS. In this review, we summarize recent research which has provided insight into the mechanisms by which inflammation underlies the pathophysiology of the individual components of MetS including visceral adiposity, hyperglycemia and insulin resistance, dyslipidemia, and hypertension. On the basis of these mechanisms, we summarize therapeutic modalities to target inflammation in the MetS and its individual components. Current therapeutic modalities can modulate the individual components of MetS and have a direct anti-inflammatory effect. Lifestyle modifications including exercise, weight loss, and diets high in fruits, vegetables, fiber, whole grains, and low-fat dairy and low in saturated fat and glucose are recommended as a first line therapy. The Mediterranean and dietary approaches to stop hypertension diets are especially beneficial and have been shown to prevent development of MetS. Moreover, the Mediterranean diet has been associated with reductions in total and cardiovascular mortality. Omega-3 fatty acids and peroxisome proliferator-activated receptor α agonists lower high levels of triglyceride; their role in targeting inflammation is reviewed. Angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, and aldosterone blockers comprise pharmacologic therapies for hypertension but also target other aspects of MetS including inflammation. Statin drugs target many of the underlying inflammatory pathways involved in MetS.
Keywords
AMPKEPANF-κBPI3KMMPADMACOXJnkCETPGPRHDLFFACOX-2FOXO1ICAM-1ACE-IiNOSMCP-1SFAABCA1PPAReNOSIRSARBIκBRAASAP-1TLRPKCS1PIKKANGIISOCS-3RVDTregPAI-1SAANLRMTPRCTVCAM-1T-helper cellsLPLVLDLProtectinsoxLDLCoQ10SPMSILRIDLG-protein–coupled receptorGRK2PD1ANGPTLangiopoietin-like proteinc-SrcRVET-regulatory cellACSL1c-Jun N-terminal kinasehigh-density lipoproteinMAPKROSAldoaldosteronecyclooxygenaseMyocardial infarctionangiotensinAngiotensin IIapoapolipoproteinAktSphingosine-1-phosphateArachidonic acidEicosapentaenoic aciddocosahexaenoic acidOmega-3 fatty acidsFree fatty acidssaturated fatty acidsendothelininsulin receptor substrateLOXAnginterleukincoronary artery diseasecardiovascular diseasethromboxaneTriglyceridestumor necrosis factor αToll-like receptorcluster of differentiationDHAdiacylglyceridesasymmetric dimethylarginineCVDDAGSAA, Serum amyloid Asuppressor of cytokine signaling 3inducible nitric oxide synthaseendothelial nitric oxide synthaseMetabolic syndromerenin–angiotensin–aldosterone systemCyclooxygenase-2CADTissue factorTNF-αFetaFetuin APhosphatidylinositol 3-kinaseLeukotrienehepatic lipaseLipoprotein lipaselipoxygenaseOxidized low-density lipoproteinIntermediate-density lipoprotein lipoxinmatrix metalloproteinaseMETSAngiotensin receptor blockerinhibitor of nuclear factor kappa-B kinasePlasminogen activator inhibitor-1angiotensin-converting enzyme inhibitorintercellular adhesion molecule-1vascular cell adhesion molecule-1hazard ratioGlucose transporter type 4Nitric oxidemicrosomal triglyceride transfer proteinForkhead box protein O1monocyte chemoattractant protein-1activator protein 1C-reactive proteinCRPprotein kinase BProtein kinase CProstaglandinsejection fractioncholesterolCholesterol esterreverse cholesterol transportCoenzyme Q10mitogen-activated protein kinasesGluGlut-4GlucoseReactive oxygen speciesNod-like receptorinterleukin receptorPeroxisome proliferator–activated receptor
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Authors
Francine K. Welty, Abdulhamied Alfaddagh, Tarec K. Elajami,