title: 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.
authors.affiliation: Houston Methodist Research Institute, Center for Diabetes Research, Weill Cornell Medical College, Houston, TX 77030, USA; Houston Methodist Research Institute, Department of Systems Medicine and Bioengineering, Data Science Laboratory, Weill Cornell Medical College, Houston, TX 77030, USA.
authors.forename: Zheng
authors.initials: Z
authors.lastname: Yin
authors.affiliation: Houston Methodist Research Institute, Center for Diabetes Research, Weill Cornell Medical College, Houston, TX 77030, USA.
authors.forename: Tuo
authors.initials: T
authors.lastname: Deng
authors.affiliation: Houston Methodist Research Institute, Center for Biostatistics, Houston, TX 77030, USA.
authors.forename: Leif E
authors.initials: LE
authors.lastname: Peterson
authors.affiliation: Houston Methodist Research Institute, Center for Diabetes Research, Weill Cornell Medical College, Houston, TX 77030, USA; Guizhou Provincial People's Hospital, Guiyang 550002, China.
authors.forename: Richeng
authors.initials: R
authors.lastname: Yu
authors.affiliation: Houston Methodist Research Institute, Center for Diabetes Research, Weill Cornell Medical College, Houston, TX 77030, USA.
authors.forename: Jianxin
authors.initials: J
authors.lastname: Lin
authors.affiliation: Houston Methodist Research Institute, Center for Diabetes Research, Weill Cornell Medical College, Houston, TX 77030, USA.
authors.forename: Dale J
authors.initials: DJ
authors.lastname: Hamilton
authors.affiliation: Department of Surgery, Houston Methodist Hospital, Houston, TX 77030, USA.
authors.forename: Patrick R
authors.initials: PR
authors.lastname: Reardon
authors.affiliation: Department of Surgery, Houston Methodist Hospital, Houston, TX 77030, USA.
authors.forename: Vadim
authors.initials: V
authors.lastname: Sherman
authors.affiliation: Houston Methodist Research Institute, Center for Diabetes Research, Weill Cornell Medical College, Houston, TX 77030, USA.
authors.forename: Glenn E
authors.initials: GE
authors.lastname: Winnier
authors.affiliation: Houston Methodist Research Institute, Department of Systems Medicine and Bioengineering, Data Science Laboratory, Weill Cornell Medical College, Houston, TX 77030, USA.
authors.forename: Ming
authors.initials: M
authors.lastname: Zhan
authors.affiliation: Houston Methodist Research Institute, Center for Diabetes Research, Weill Cornell Medical College, Houston, TX 77030, USA.
authors.forename: Christopher J
authors.initials: CJ
authors.lastname: Lyon
authors.affiliation: Houston Methodist Research Institute, Department of Systems Medicine and Bioengineering, Data Science Laboratory, Weill Cornell Medical College, Houston, TX 77030, USA. Electronic address: stwong@tmhs.org.
authors.forename: Stephen T C
authors.initials: ST
authors.lastname: Wong
authors.affiliation: Houston Methodist Research Institute, Center for Diabetes Research, Weill Cornell Medical College, Houston, TX 77030, USA. Electronic address: WAHsuehMD@gmail.com.
authors.forename: Willa A
authors.initials: WA
authors.lastname: Hsueh
mesh_terms: D017667:Adipocytes / Q000378:metabolism* / Q000473:pathology; D000273:Adipose Tissue / Q000378:metabolism* / Q000473:pathology; D000818:Animals; D053468:CARD Signaling Adaptor Proteins; D002352:Carrier Proteins / Q000235:genetics* / Q000378:metabolism; D020170:Caspase 1 / Q000235:genetics / Q000378:metabolism; D003598:Cytoskeletal Proteins / Q000235:genetics* / Q000378:metabolism; D005260:Female; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D000949:Histocompatibility Antigens Class II / Q000235:genetics / Q000378:metabolism; D006801:Humans; D007249:Inflammation / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D007371:Interferon-gamma / Q000235:genetics / Q000378:metabolism; D053583:Interleukin-1beta / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D008875:Middle Aged; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein; D009765:Obesity / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D015398:Signal Transduction; D017154:Stromal Cells / Q000378:metabolism / Q000473:pathology; D059467:Transcriptome
chemical_list: D053468:CARD Signaling Adaptor Proteins; D002352:Carrier Proteins; D003598:Cytoskeletal Proteins; D000949:Histocompatibility Antigens Class II; D053583:Interleukin-1beta; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein; C453881:NLRP3 protein, human; C402202:PYCARD protein, human; D007371:Interferon-gamma; D020170:Caspase 1
keywords: Adipocyte; Inflammasome; NOD-like receptor pathway; Network modeling; Obesity; Transcriptome analysis