title: Expression of NALPs in adipose and the fibrotic progression of non-alcoholic fatty liver disease in obese subjects.
abstract: BACKGROUND
  Visceral obesity is often accompanied by non-alcoholic fatty liver disease (NAFLD). Activation of NACHT, LRR and PYD domains-containing proteins (NALPs) may contribute to the release of pro-inflammatory cytokines by adipose and the obesity-associated progression of NAFLD to non-alcoholic steatohepatitis (NASH).
  
  
  METHODS
  We analyzed visceral adipose expression of various NALPs and its downstream effectors caspase-1, ASC (Apoptosis-associated speck-like protein containing a CARD), IL-18 (Interleukin-18) and IL-1β (Interleukin- 1Beta) in obese subjects (BMI ≥ 35) with biopsy proven NAFLD.
  
  
  RESULTS
  In adipose samples collected from NASH and pericellular fibrosis patients cohorts, expression levels of NALPs and IL-1β were lower than that in non-NASH patients. In portal fibrosis, the levels of mRNA encoding anti-inflammatory NALP6 were upregulated. The expression levels of all NALPs were significantly co-correlated. Circulating IL-18 levels were associated with increased liver injury markers AST and ALT and portal fibrosis.
  
  
  CONCLUSIONS
  Our observations point at a possible shift in inflammation and fibrotic response from adipose tissue to liver and a possible negative feedback regulation of tissue inflammation that may instigate NAFLD severity.
authors.affiliation: Betty and Guy Beatty Obesity and Liver Program, Inova Health System, Falls Church, VA, USA. mehta.rohini@gmail.com.|Center for the Study of Chronic Metabolic Diseases, School of Systems Biology, College of Science, George Mason University, Fairfax, VA, USA. mehta.rohini@gmail.com.
authors.forename: Rohini
authors.initials: R
authors.lastname: Mehta
authors.affiliation: Betty and Guy Beatty Obesity and Liver Program, Inova Health System, Falls Church, VA, USA. aneupane14@gmail.com.|Center for the Study of Chronic Metabolic Diseases, School of Systems Biology, College of Science, George Mason University, Fairfax, VA, USA. aneupane14@gmail.com.
authors.forename: Arpan
authors.initials: A
authors.lastname: Neupane
authors.affiliation: Betty and Guy Beatty Obesity and Liver Program, Inova Health System, Falls Church, VA, USA. wanglei131@gmail.com.|Center for the Study of Chronic Metabolic Diseases, School of Systems Biology, College of Science, George Mason University, Fairfax, VA, USA. wanglei131@gmail.com.
authors.forename: Lei
authors.initials: L
authors.lastname: Wang
authors.affiliation: Betty and Guy Beatty Obesity and Liver Program, Inova Health System, Falls Church, VA, USA. zachary.goodman@inova.org.|Center for Liver Diseases and Department of Medicine, Inova Fairfax Hospital, Falls Church, VA, USA. zachary.goodman@inova.org.
authors.forename: Zachary
authors.initials: Z
authors.lastname: Goodman
authors.affiliation: Betty and Guy Beatty Obesity and Liver Program, Inova Health System, Falls Church, VA, USA. aancha@gmail.com.|Center for the Study of Chronic Metabolic Diseases, School of Systems Biology, College of Science, George Mason University, Fairfax, VA, USA. aancha@gmail.com.
authors.forename: Ancha
authors.initials: A
authors.lastname: Baranova
authors.affiliation: Betty and Guy Beatty Obesity and Liver Program, Inova Health System, Falls Church, VA, USA. zobair.younossi@inova.org.|Center for Liver Diseases and Department of Medicine, Inova Fairfax Hospital, Falls Church, VA, USA. zobair.younossi@inova.org.
authors.forename: Zobair M
authors.initials: ZM
authors.lastname: Younossi
mesh_terms: D048868:Adaptor Proteins, Signal Transducing; D000273:Adipose Tissue / Q000378:metabolism*; D000328:Adult; D020170:Caspase 1 / Q000378:metabolism; D018450:Disease Progression; D015536:Down-Regulation; D005260:Female; D005355:Fibrosis; D006801:Humans; D058847:Inflammasomes / Q000378:metabolism; D020382:Interleukin-18 / Q000378:metabolism; D053583:Interleukin-1beta / Q000378:metabolism; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D065626:Non-alcoholic Fatty Liver Disease / Q000150:complications* / Q000378:metabolism* / Q000473:pathology; D009765:Obesity / Q000150:complications* / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D012097:Repressor Proteins / Q000378:metabolism; D015854:Up-Regulation
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D058847:Inflammasomes; D020382:Interleukin-18; D053583:Interleukin-1beta; D047908:Intracellular Signaling Peptides and Proteins; C466775:NLRP4 protein, human; C468563:NLRP6 protein, human; D012333:RNA, Messenger; D012097:Repressor Proteins; D020170:Caspase 1