Toll-like receptor signaling links dietary fatty acids to the metabolic syndrome

Curr Opin Lipidol. 2009 Oct;20(5):379-85. doi: 10.1097/MOL.0b013e32832fa5c4.


Purpose of review: Dietary saturated fatty acids (SFAs) have been implicated in promoting the metabolic syndrome and atherosclerotic cardiovascular disease. Recent evidence suggests that SFAs promote the metabolic syndrome by activating Toll-like receptor 4 (TLR4). Here we examine emerging molecular evidence that SFAs directly engage pathways of innate immunity, thereby promoting inflammatory aspects of the metabolic syndrome.

Recent findings: Accumulation of SFA in the body is tightly regulated by stearoyl-CoA desaturase 1, an enzyme that converts endogenous SFA to monounsaturated fatty acids. Recent studies have demonstrated that the accumulation of SFA seen with genetic deletion or inhibition of stearoyl-CoA desaturase 1 promotes inflammation, TLR4 hypersensitivity, and accelerated atherosclerosis. Therefore, stearoyl-CoA desaturase 1 may play an unexpected role in suppressing inflammation by preventing excessive accumulation of endogenous SFA-derived TLR4 agonists. In parallel, several independent laboratories have demonstrated that TLR4 is necessary for dietary SFAs to induce obesity, insulin resistance, and vascular inflammation in rodent models.

Summary: The metabolic syndrome and atherosclerotic cardiovascular disease have long been linked to dietary SFA intake and inflammation. Recent mechanistic insights into how SFAs and downstream metabolites can potentiate inflammation-driven metabolic disease are discussed here.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, N.I.H., Intramural
  • Review

MeSH terms

  • Animals
  • Dietary Fats / adverse effects*
  • Humans
  • Immunity, Innate / drug effects
  • Inflammation / chemically induced
  • Inflammation / complications
  • Inflammation / metabolism
  • Metabolic Syndrome / chemically induced*
  • Metabolic Syndrome / complications
  • Metabolic Syndrome / immunology
  • Metabolic Syndrome / metabolism*
  • Signal Transduction* / drug effects
  • Toll-Like Receptors / metabolism*


  • Dietary Fats
  • Toll-Like Receptors