Adipocyte differentiation induces dynamic changes in NF-κB expression and activity

Anders H. Berg, Ying Lin, Michael P. Lisanti, Philipp E. Scherer

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Abstract

The adipocyte exerts an important role in energy homeostasis, both as depot for energy-rich triglycerides and as a source for metabolic hormones. Adipocytes also contribute to inflammation and the innate immune response. Although it can be physiologically beneficial to combine these two functions in a single cell type under some circumstances, the proinflammatory signals emanating from adipocytes in the obese state can have local and systemic effects that promote atherosclerosis and insulin resistance. The transcriptional machinery in the adipocyte that mediates these pro-inflammatory responses has remained poorly characterized to date. In particular, no information is currently available on the NF-κB family of transcription factors. Here, we show that adipogenesis is associated with changes in amount and subunit composition of the NF-κB complexes. NF-κB subunits p65 (RelA), p68 (RelB), and IκB are upregulated during fat cell differentiation. Correspondingly, basal NF-κB nuclear gel shift and luciferase reporter assays are induced in parallel during differentiation. Surprisingly, endotoxin sensitivity of the classical NF-κB pathway is substantially delayed and attenuated despite increased overall inflammatory response in the mature adipocyte, as judged by induction of IL-6 and TNF-α. As a reflection of the constitutively elevated NF-κB activity in the mature adipocyte, adipocytes (but not preadipocytes) exert a strong inflammatory stimulus on macrophages in vitro, suggesting a cross talk between adipocytes and interstitial macrophages in adipose tissue in vivo. These effects are mediated by a secretory product of adipocytes that is unlikely to be IL-6 or TNF-α.

Original languageEnglish (US)
Pages (from-to)E1178-E1188
JournalAmerican Journal of Physiology - Endocrinology and Metabolism
Volume287
Issue number6 50-6
DOIs
StatePublished - Dec 1 2004

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Keywords

  • Inflammation
  • Nuclear factor-κB

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Physiology
  • Physiology (medical)

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