Obesity activates toll-like receptor-mediated proinflammatory signaling cascades in the adipose tissue of mice

Seung Jin Kim, Youngshim Choi, Youn Hee Choi, Taesun Park

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Obesity is characterized by low-grade and chronic inflammation, a phenomenon explained with a new term, metaflammation. Recent studies suggest that adipocytes may play an important role in the physiological regulation of immune responses in fat deposits via toll-like receptor (TLR) signaling cascades. This study investigates the role of the visceral as well as subcutaneous adipose tissues in the development of metaflammation by characterizing the tissue-specific expression profiles of TLRs and downstream signaling molecules and explores the differential responsiveness of TLR-mediated proinflammatory signaling cascades to diet-induced obesity (DIO) and obesity induced by a leptin gene deficiency. The obesity that was induced by a high-fat diet or leptin deficiency up-regulated the expression of TLR1-9 and TLR11-13 in murine adipose tissues, a phenomenon linked with downstream nuclear factor κB, interferon regulatory factors, and STAT-1 activation, and up-regulated the expression of cytokines and chemokines via MyD88-dependent and MyD88-independent cascades. The extent of the obesity-induced up-regulation of most TLR genes and related proinflammatory signaling cascades was much greater in the epididymal adipose tissues than in the subcutaneous fat tissues of the mice with DIO. Furthermore, the magnitudes of the obesity-induced up-regulation of the TLR1, TLR4, TLR5, TLR8, TLR9, and TLR12 genes and most of the downstream signaling molecules and target cytokine genes in the visceral adipose tissue were greater in the DIO mice than in the ob/ob mice. These results suggest that TLRs and related proinflammatory signaling molecules that are overexpressed in enlarged adipose tissues may play an important role in the obesity-associated phenomenon of metaflammation.

Original languageEnglish
Pages (from-to)113-122
Number of pages10
JournalJournal of Nutritional Biochemistry
Issue number2
StatePublished - Feb 2012

Bibliographical note

Funding Information:
This work was supported by a grant of the Korea Health 21 R&D Project, Ministry of Health & Welfare, Republic of Korea (#A080020) and by the SRC program of the Korea Science and Engineering Foundation (KOSEF) grant funded by the Korea government (#2009-0063409).


  • Adipose fat depot
  • High-fat diet
  • Inflammation
  • Ob/ob mice
  • Toll-like receptors


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