Transcriptome analysis of human adipocytes implicates the NOD-like receptor pathway in obesity-induced adipose inflammation

Abstract

Adipose tissue inflammation increases with obesity, but adipocyte vs. immune cell contributions are unclear. In the present study, transcriptome analyses were performed on highly-purified subcutaneous adipocytes from lean and obese women, and differentially expressed genes/pathways were determined in both adipocyte and stromal vascular fraction (SVF) samples. Adipocyte but not SVF expression of NOD-like receptor pathway genes, including NLRP3 and PYCARD, which regulate caspase-1-mediated IL-1β secretion, correlated with adiposity phenotypes and adipocyte class II major histocompatibility complex (MHCII) gene expression, but only MHCII remained after adjusting for age and body mass index. IFNγ stimulated adipocyte MHCII, NLRP3 and caspase-1 expression, while adipocyte MHCII-mediated CD4+ T cell activation, an important factor in adipose inflammation, induced IFNγ-dependent adipocyte IL-1β secretion. These results uncover a dialogue regulated by interactions among T cell IFNγ and adipocyte MHCII and NLRP3 inflammasome activity that appears to initiate and escalate adipose tissue inflammation during obesity.

The Roles of the NLRP3 Inflammasome in Neurodegenerative and Metabolic Diseases and in Relevant Advanced Therapeutic Interventions

“…Furthermore, a reduction in the secretion of insulin-sensitive adipokines accompanied by oversecretion of proinflammatory cytokines (TNF-α, IL-1β, and IL-6) is closely related to the etiology of various metabolic conditions. Other studies also point to the participation of NLRP3 in obesity because of its overexpression in AT [11,[69][70][71][72][73]. Moreover, the results of studies on mouse models of obesity are consistent with this observation [74,75].…”

Mitophagy: a balance regulator of NLRP3 inflammasome activation

“…Other groups showed that saturated fatty acid-induced inflammation causes mitochondrial impairment in adipocytes, while saturated fatty acids can upregulate NLRP3 inflammasome activation (38, 39). Also, a higher level of NLRP3 inflammasome components were detected in obese patients, and active caspase-1 were increased with obesity development in adipose tissues (40). Interestingly, caspase-1 deficient mice gained less weight and they had less adipose tissue formation in the HFD-induced obesity mouse model (41).…”

Inflammasomes: mechanism of action, role in disease, and therapeutics

“…The expression of human NLRP3 and ASC/PYCARD is upregulated in adipocytes from obese patients 119 . Caspase-1 expression was found in both human and mouse adipose tissues and increases with adipocyte differentiation and obesity development 120 .…”