title: Toll-like receptor status in obesity and metabolic syndrome: a translational perspective.
abstract: BACKGROUND
  The prevalence of both obesity and metabolic syndrome (MetS) is increasing at alarming rates globally. Both predispose to diabetes, cardiovascular disease, fatty liver disease, obstructive sleep apnea, and certain cancers. Understanding the mechanisms contributing to increased cardiometabolic risk in obesity and MetS is of utmost importance.
  
  
  METHODS
  For this review, we performed a detailed literature search on PubMed of all publications related to Toll-like receptors (TLRs) and obesity and MetS for the last 20 years.
  
  
  RESULTS
  The TLRs are well-characterized immune receptors that enhance inflammation. The recognition of pathogen-associated molecular patterns and endogenous (host-derived) ligands released by various cell types triggers activation and expression of TLRs. TLRs, especially TLR2 and TLR4, induce insulin resistance, which is pivotal in the pathogenesis of obesity and MetS. Both obesity and MetS are characterized by low-grade chronic inflammation, possibly triggered by activation of TLR2 and TLR4. TLRs, especially TLR4, are activated by fatty acids and endotoxinemia (a marker of gut permeability), features of both obesity and MetS, resulting in activation of nuclear factor-κB and increased release of inflammatory biomediators such as IL-6, IL-1β, TNF-α, and monocyte chemotactic protein-1, which play a role in the pathophysiology of obesity and MetS. Reduction of calories, exercise, and nutraceutical and pharmacological agents can modulate TLRs.
  
  
  CONCLUSIONS
  In this review, we present evidence for a pivotal role of TLR-induced inflammation in both obesity and MetS and speculate that targeting these TLRs can forestall their adverse sequelae of diabetes and cardiovascular disease.
authors.affiliation: Laboratory of Atherosclerosis and Metabolic Research, and Division of Endocrinology, Metabolism, and Diabetes (I.J., H.K.), Department of Internal Medicine, University of California at Davis, Sacramento, California 95817; VA Medical Center (I.J.), Mather, California 95655; and Texas Children's Hospital (S.D.), Houston, Texas 77030.
authors.forename: Ishwarlal
authors.initials: I
authors.lastname: Jialal
authors.forename: Harmeet
authors.initials: H
authors.lastname: Kaur
authors.forename: Sridevi
authors.initials: S
authors.lastname: Devaraj
mesh_terms: D000818:Animals; D006801:Humans; D007249:Inflammation / Q000378:metabolism; D024821:Metabolic Syndrome / Q000378:metabolism*; D053594:Myeloid Differentiation Factor 88 / Q000502:physiology; D009765:Obesity / Q000378:metabolism*; D012307:Risk Factors; D015398:Signal Transduction / Q000502:physiology; D051193:Toll-Like Receptors / Q000378:metabolism*
chemical_list: C507779:MYD88 protein, human; D053594:Myeloid Differentiation Factor 88; D051193:Toll-Like Receptors