title: Chitinase 3-like-1 regulates both visceral fat accumulation and asthma-like Th2 inflammation.
abstract: BACKGROUND
  Obesity, especially truncal obesity, is a risk factor for asthma incidence, prevalence, and severity. Chitinase 3-like-1 (Chi3l1) is an evolutionarily conserved moiety that plays a critical role in antipathogen and Th2 responses. However, the mechanisms that underlie the association between asthma and obesity and the role(s) of Chi3l1 in fat accumulation have not been defined.
  
  
  OBJECTIVE
  To determine whether Chi3l1 is regulated by a high-fat diet (HFD) and simultaneously plays an important role(s) in the pathogenesis of asthma and obesity.
  
  
  METHODS
  We evaluated the regulation of Chi3l1 by an HFD and Th2 inflammation. We also used genetically modified mice to define the roles of Chi3l1 in white adipose tissue (WAT) accumulation and Th2 inflammation and blockers of sirtuin 1 (Sirt1) to define its roles in these responses. Finally, the human relevance of these findings was assessed with a case-control study involving obese and lean control subjects and those with asthma.
  
  
  RESULTS
  These studies demonstrate that an HFD and aeroallergen challenge augment the expression of WAT and pulmonary Chi3l1. Chi3l1 also played a critical role in WAT accumulation and lung Th2 inflammation. In addition, Chi3l1 inhibited Sirt1 expression, and the deficient visceral fat and Th2 responses in Chi3l1 null mice were reversed by Sirt1 inhibition. Finally, serum and sputum Chi3l1 were positively associated with truncal adiposity, and serum Chi3l1 was associated with persistent asthma and low lung function in obese subjects with asthma.
  
  
  CONCLUSIONS
  Chi3l1 is induced by an HFD and Th2 inflammation, and simultaneously contributes to the genesis of obesity and asthma.
authors: 1 Section of Pulmonary and Critical Care Medicine, Yale University School of Medicine, New Haven, Connecticut.
authors: Farida
authors: F
authors: Ahangari
authors: Akshay
authors: A
authors: Sood
authors: Bing
authors: B
authors: Ma
authors: Seyedtaghi
authors: S
authors: Takyar
authors: Mark
authors: M
authors: Schuyler
authors: Clifford
authors: C
authors: Qualls
authors: Charles S
authors: CS
authors: Dela Cruz
authors: Geoffrey L
authors: GL
authors: Chupp
authors: Chun G
authors: CG
authors: Lee
authors: Jack A
authors: JA
authors: Elias
mesh_terms: D054392:Adipokines / Q000378:metabolism*; D000818:Animals; D001249:Asthma / Q000201:enzymology*; D016022:Case-Control Studies; D000071451:Chitinase-3-Like Protein 1; D005260:Female; D006133:Growth Substances / Q000378:metabolism*; D006801:Humans; D007249:Inflammation / Q000201:enzymology*; D050152:Intra-Abdominal Fat / Q000378:metabolism*; D037102:Lectins / Q000378:metabolism*; D051379:Mice; D009765:Obesity / Q000201:enzymology*; D018418:Th2 Cells / Q000201:enzymology*
chemical_list: D054392:Adipokines; C084533:CHI3L1 protein, human; D000071451:Chitinase-3-Like Protein 1; D006133:Growth Substances; D037102:Lectins
keywords: adipose tissue; allergic Th2 inflammation; asthma; chitinase 3–like-1; sirtuin 1
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