Adipose Tissue Caveolin-1 Upregulation in Obesity Involves TNF-a/NF-?B Mediated Signaling

Obesity is characterized by chronic low-grade inflammation. Obese people have higher levels of caveolin-1 (CAV1), a structural and functional protein present in adipose tissues (ATs). We aimed to define the inflammatory mediators that influence CAV1 gene regulation and the associated mechanisms in obesity. Using subcutaneous AT from 27 (7 lean and 20 obese) normoglycemic individuals, in vitro human adipocyte models, and in vivo mice models, we found elevated CAV1 expression in obese AT and a positive correlation between the gene expression of CAV1, tumor necrosis factor-alpha (TNF-a.), and the nuclear factor kappa-light-chain-enhancer of activated B cells (NF -KB). CAV1 gene expression was associated with proinflammatory cytokines and chemokines and their cognate receptors (r = 0.447, p = 0.030), but not with anti-inflammatory markers. CAV1 expression was correlated with CD163, indicating a prospective role for CAV1 in the adipose inflammatory microenvironment. Unlike wild-type animals, mice lacking TNF-a. exhibited reduced levels of CAV1 mRNA/proteins, which were elevated by administering exogenous TNF-a.. Mechanistically, TNF-a. induces CAV1 gene transcription by mediating NF -KB binding to its two regulatory elements located in the CAV1 proximal regulatory region. The interplay between CAV1 and the TNF-a. signaling pathway is intriguing and has potential as a target for therapeutic interventions in obesity and metabolic syndromes.