TLR4 and insulin resistance

Dorothy D. Sears, Jane J. Kim

Research output: Contribution to journalReview article

105 Citations (Scopus)

Abstract

Chronic inflammation is a key feature of insulin resistance and obesity. Toll-Like Receptor 4 (TLR4), involved in modulating innate immunity, is an important mediator of insulin resistance and its comorbidities. TLR4 contributes to the development of insulin resistance and inflammation through its activation by elevated exogenous ligands (e.g., dietary fatty acids and enteric lipopolysaccharide) and endogenous ligands (e.g., free fatty acids) which are elevated in obese states. TLR4, expressed in insulin target tissues, activates proinflammatory kinases JNK, IKK, and p38 that impair insulin signal transduction directly through inhibitory phosphorylation of insulin receptor substrate (IRS) on serine residues. TLR4 activation also leads to increased transcription of pro-inflammatory genes, resulting in elevation of cytokine, chemokine, reactive oxygen species, and eicosanoid levels that promote further insulin-desensitization within the target cell itself and in other cells via paracrine and systemic effects. Increased understanding of cell type-specific TLR4-mediated effects on insulin action present the opportunity and challenge of developing related therapeutic approaches for improving insulin sensitivity while preserving innate immunity.

Original languageEnglish (US)
Article number212563
JournalGastroenterology Research and Practice
DOIs
StatePublished - Sep 24 2010
Externally publishedYes

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Toll-Like Receptor 4
Insulin Resistance
Insulin
Innate Immunity
MAP Kinase Kinase 4
Ligands
Inflammation
Eicosanoids
Insulin Receptor
Chemokines
Nonesterified Fatty Acids
Serine
Lipopolysaccharides
Comorbidity
Reactive Oxygen Species
Signal Transduction
Fatty Acids
Obesity
Phosphorylation
Cytokines

ASJC Scopus subject areas

  • Hepatology
  • Gastroenterology

Cite this

TLR4 and insulin resistance. / Sears, Dorothy D.; Kim, Jane J.

In: Gastroenterology Research and Practice, 24.09.2010.

Research output: Contribution to journalReview article

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