Adipocyte-Specific IKKβ Signaling Suppresses Adipose Tissue Inflammation through an IL-13-Dependent Paracrine Feedback Pathway

Hyokjoon Kwon, Sarnia Laurent, Yan Tang, Haihong Zong, Pratibha Vemulapalli, Jeffrey E. Pessin

Research output: Contribution to journalArticle

24 Citations (Scopus)

Abstract

Adipose tissue inflammation is one pathway shown to mediate insulin resistance in obese humans and rodents. Obesity induces dynamic cellular changes in adipose tissue to increase proinflammatory cytokines and diminish anti-inflammatory cytokines. However, we have found that anti-inflammatory interleukin-13 (IL-13) is unexpectedly induced in adipose tissue of obese humans and high-fat diet (HFD)-fed mice, and the source of IL-13 is primarily the adipocyte. Moreover, HFD-induced proinflammatory cytokines such as tumor necrosis factor alpha (TNF-α) and IL-1β mediate IL-13 production in adipocytes in an IKKβ-dependent manner. In contrast, adipocyte-specific IKKβ-deficient mice show diminished IL-13 expression and enhanced inflammation after HFD feeding, resulting in a worsening of the insulin-resistant state. Together these data demonstrate that although IKKβ activates the expression of proinflammatory mediators, in adipocytes, IKKβ signaling also induces the expression of the anti-inflammatory cytokine IL-13, which plays a unique protective role by limiting adipose tissue inflammation and insulin resistance. IKKβ is known to be a proinflammatory mediator. However, IKKβ in adipocytes also mediates IL-13 expression to suppress high-fat-diet-induced inflammation in adipose tissue. This feedback mechanism may be the molecular basis of diet-induced chronic low-grade inflammation, resulting in systemic insulin resistance.

Original languageEnglish (US)
Pages (from-to)1574-1584
Number of pages11
JournalCell Reports
Volume9
Issue number5
DOIs
StatePublished - Dec 11 2014

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Interleukin-13
Adipocytes
Adipose Tissue
Nutrition
High Fat Diet
Tissue
Inflammation
Feedback
Fats
Insulin
Cytokines
Insulin Resistance
Anti-Inflammatory Agents
Interleukin-1
Rodentia
Tumor Necrosis Factor-alpha
Obesity
Diet

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

Cite this

Adipocyte-Specific IKKβ Signaling Suppresses Adipose Tissue Inflammation through an IL-13-Dependent Paracrine Feedback Pathway. / Kwon, Hyokjoon; Laurent, Sarnia; Tang, Yan; Zong, Haihong; Vemulapalli, Pratibha; Pessin, Jeffrey E.

In: Cell Reports, Vol. 9, No. 5, 11.12.2014, p. 1574-1584.

Research output: Contribution to journalArticle

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