Obesity is also characterized by increased levels of intracellular stress pathway activation including the IKK-NF-κB and the JNK pathways. NF-κB is a transcription factor and a primary regulator of inflammatory responses in many cells. Pro-inflammatory cytokines and molecules, including TNF-α, activate NF-κB by releasing it from its inhibitor, IκB. The release of NF-κB occurs via a kinase complex, IKK. Reduced signaling through the IKK-NF-κB pathway, either by salicylate (the active compound in aspirin) induced inhibition or decreased IKK-β expression, is accompanied by improved insulin sensitivity in vivo (59).

The three members of the JNK group of serine/threonine kinases, JNK-1, JNK-2, and JNK-3, belong to the mitogen-activated protein kinase (MAPK) family and affect development and cell function, mainly through phosphorylation and transcriptional regulation of proteins like c-Jun and JunB (60). An absence of JNK-1 expression results in decreased adiposity, significantly improved insulin sensitivity, and enhanced insulin receptor signaling capacity in two different models of mouse obesity (61). These findings are consistent with inflammation playing a role in the development of obesity-induced complications.

Summary

In summary, the adipocyte and adipose tissue are more than mere storage sites for excess calories. Adipose tissue is a metabolically complex tissue, producing important regulatory compounds, and changing its output of them as tissue mass changes. Both adipose cells and tissues are affected by numerous hormones and compounds produced by other cells and body tissues, which can affect health status. Increasing our knowledge of the mechanisms relating excess adiposity to disease, and enhancement of our ability to mitigate these effects, depend on the continued development of our understanding of the functions of this tissue.

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