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B expression and activity
1 Division of Endocrinology, Department of Cell Biology, Albert Einstein College of Medicine, Bronx, NY, USA
2 Division of Endocrinology, Department of Molecular Pharmacology, Albert Einstein College of Medicine, Bronx, NY, USA
3 Division of Endocrinology, Department of Cell Biology, Albert Einstein College of Medicine, Bronx, NY, USA; Division of Endocrinology, Department of Molecular Pharmacology, Albert Einstein College of Medicine, Bronx, NY, USA; Division of Endocrinology, Department of Medicine and the Diabetes Research and Training Center, Albert Einstein College of Medicine, Bronx, NY, USA
* To whom correspondence should be addressed. E-mail: scherer{at}aecom.yu.edu.
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. While it can be
physiologically beneficial to combine these two functions in a single cell type under
some circumstances, the pro-inflammatory signals emanating from adipocytes in the
obese state can have local and systemic effects that promote atherosclerosis and insulin
resistance. The transcriptional machinery in place 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
B family of transcription factors. Here, we
show that adipogenesis is associated with changes in amount and subunit composition of
the NFB complexes. NFB subunits p65 (RelA), p68 (RelB), and IB are upregulated
during fat cell differentiation. Correspondingly, basal NFB nuclear gel shift and
luciferase reporter assays are induced in parallel during differentiation. Surprisingly,
endotoxin sensitivity of the classical NFB pathway is substantially delayed and
attenuated despite increased overall inflammatory response in the mature adipocyte as
judged by induction of IL-6 and TNF
. As a reflection of the constitutively elevated
NFB activity in the mature adipocyte, adipocytes (but not pre-adipocytes) 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, which is unlikely to be IL-6 or TNF.
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