Adipose Tissue Caveolin-1 Upregulation in Obesity Involves TNF-α/NF-κB Mediated Signaling

Abstract

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-α), and the nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB). 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-α exhibited reduced levels of CAV1 mRNA/proteins, which were elevated by administering exogenous TNF-α. Mechanistically, TNF-α induces CAV1 gene transcription by mediating NF-κB binding to its two regulatory elements located in the CAV1 proximal regulatory region. The interplay between CAV1 and the TNF-α signaling pathway is intriguing and has potential as a target for therapeutic interventions in obesity and metabolic syndromes.

Study on Potential Differentially Expressed Genes in Idiopathic Pulmonary Fibrosis by Bioinformatics and Next-Generation Sequencing Data Analysis

“…It should be noted that there were some DEGs that were not shared among IPF networks, but have been proven to play indispensable roles in IPF in recent years. Involvement of highly significant DEGs [131], SLC7A11 [132], CLIC5 [133], VIP (vasoactive intestinal peptide) [134], SMAD6 [135], BMPR2 [136], APOA1 [137], IN-SIG1 [138], TLR3 [139], NLRP12 [140], ADRB1 [141], TLR8 [142], GATA3 [143], CCR2 [144], TLR7 [145], CCRL2 [146], BMPER (BMP binding endothelial regulator) [147], CAV1 [148], TFPI (tissue factor pathway inhibitor) [149], FADS1 [150], SUCNR1 [151], CADM2 [152], SLC19A3 [153], SGCG (sarcoglycan gamma) [154] [177], WNT3A [178], APOH (apolipoprotein H) [179], CHRM3 [180], CD36 [181], TRIB3 [182], PCSK9 [183], ACVR1C [184], GPD1 [123], FFAR4 [185], GPX3 [186], FGF2 [187], FASN (fatty acid synthase) [188], DGAT2 [189], DACH1 [190], PNPLA3 [191], FGF9 [192], SLC7A11 [193], VIP (vasoactive intestinal peptide) [194], KL (klotho)…”

“…Biomarkers includingNEK7 [718], CAV1 [720], TRIB3 [707], has-mir-8057 [828], hsa-mir-1537-5p [829], STAT1 [830], and TP53 [831] are highly associated with viral respiratory diseases.Biomarkers including NEK7 [449], TRIB3 [452], CAV1 [463],NFYA (nuclear transcription factor Y subunit alpha) [817], STAT1 [832], and TP53 [833] played an important role in the pulmonary hypertension. Biomarkers including CAV1 [148], TRIB3 [120], STAT1 [834], TP53 [835], and NFKB1 [836] have been reported in obesity. Biomarkers including CAV1 [258], hsa-mir-19b-3p [837], SRF (serum response factor) [838], and TP53 [839] play an important role in the regulation of chronic obstructive pulmonary disease.…”

Study on potential differentially expressed genes in idiopathic pulmonary fibrosis by bioinformatics and next generation sequencing data analysis

“…Signaling pathways include GPCR ligand binding [89], neutrophil degranulation [90], immune system [91], metabolism of lipids [92] and signal transduction [93] made great contribution to the development of IPF. MAP3K15 [94], PRTN3 [95], CX3CR1 [96], AGRP (agouti related neuropeptide) [97], MPO (myeloperoxidase) [98], CD5L [99], S100A8 [100], NPR3 [101], VEGFD (vascular endothelial growth factor D) [102], CXCL11 [103], IL1A [104], CBS (cystathionine beta-synthase) [105], WNT7A [106], SCD (stearoyl-CoA desaturase) [107], LRP2 [108], SLC6A4 [109], BDNF (brain derived neurotrophic factor) [110], CXCL10 [111], ANGPTL7 [112], S100A9 [113], NPY1R [114], IL1B [115], GPIHBP1 [116], CYP1B1 [117], CD36 [118], MACROD2 [119], TRIB3 [120], SPX (spexin hormone) [121], PCSK9 [122], GPD1 [123], CDH13 [124], FFAR4 [125], FGF2 [126], FASN (fatty acid synthase) [127], DGAT2 [128], DACH1 [129], PNPLA3 [130], FGF9 [131], SLC7A11 [132], CLIC5 [133], VIP (vasoactive intestinal peptide) [134], SMAD6 [135], BMPR2 [136], APOA1 [137], INSIG1 [138], TLR3 [139], NLRP12 [140], ADRB1 [141], TLR8 [142], GATA3 [143], CCR2 [144], TLR7 [145], CCRL2 [146], BMPER (BMP binding endothelial regulator) [147], CAV1 [148], TFPI (tissue factor pathway inhibitor) [149], FADS1 [150], SUCNR1 [151], CADM2 [152], SLC19A3 [153], SGCG (sarcoglycan gamma) [154], ADH1B [155], NEGR1 [156], HSD17B12 [157], OXTR (oxytocin receptor) [158] and ANKK1 […”

“…NEK7 [449], TRIB3 [452], CAV1 [463], NFYA (nuclear transcription factor Y subunit alpha) [817], STAT1 [832] and TP53 [833] were significantly altered expression in pulmonary hypertension. CAV1 [148], TRIB3 [120], STAT1 [834], TP53 [835] and NFKB1 [836] are crucial for obesity pathogenesis. CAV1 [258], hsa-mir-19b-3p [837], SRF (serum response factor) [838] and TP53 [839] might play a central role in the development of chronic obstructive pulmonary disease.…”