TLR9 regulates adipose tissue inflammation and obesity-related metabolic disorders

Obesity (Silver Spring). 2015 Nov;23(11):2199-206. doi: 10.1002/oby.21215. Epub 2015 Aug 11.


Objective: Recent studies have revealed a link between Toll-like receptor (TLR) signaling and the adipose tissue inflammation associated with obesity. Although TLR9 is known to play an important role in inflammation and innate immunity, its role in mediating adipose tissue inflammation has not yet been investigated. Thus, the objective of this study was to determine the role of TLR9 in regulating immune cells in visceral adipose tissue and maintaining the metabolic homeostasis.

Methods: Wild-type and TLR9-deficient mice were fed with a high-fat diet, and the body weight gain, glucose tolerance, insulin sensitivity, and adipose tissue inflammation were examined.

Results: TLR9-deficient mice gained significantly more weight and body fat under a high-fat diet than wild-type mice and exhibited more severe glucose intolerance and insulin resistance. We also found a dramatic increase of M1 macrophages as well as TH 1 cells in the adipose tissue of TLR9-deficient mice compared to wild-type mice. Furthermore, the levels of various proinflammatory cytokines and chemokines were higher in TLR9-deficient mice.

Conclusions: TLR9 signaling is involved in regulating adipose tissue inflammation and controlling obesity and the metabolic syndrome.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cells, Cultured
  • Cytokines / metabolism
  • Diet, High-Fat
  • Glucose Intolerance / genetics*
  • Glucose Intolerance / immunology
  • Glucose Intolerance / metabolism
  • Inflammation / genetics
  • Inflammation / metabolism
  • Insulin Resistance / genetics*
  • Intra-Abdominal Fat / metabolism
  • Intra-Abdominal Fat / pathology
  • Macrophages / immunology
  • Macrophages / metabolism
  • Male
  • Metabolic Syndrome / genetics*
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Obesity / genetics*
  • Panniculitis / genetics*
  • Panniculitis / pathology
  • Toll-Like Receptor 9 / genetics
  • Toll-Like Receptor 9 / physiology*
  • Weight Gain


  • Cytokines
  • Tlr9 protein, mouse
  • Toll-Like Receptor 9