Abstract | RATIONALE:
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. OBJECTIVES: 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. MEASUREMENTS AND MAIN 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:
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Authors | Farida Ahangari, Akshay Sood, Bing Ma, Seyedtaghi Takyar, Mark Schuyler, Clifford Qualls, Charles S Dela Cruz, Geoffrey L Chupp, Chun G Lee, Jack A Elias |
Journal | American journal of respiratory and critical care medicine
(Am J Respir Crit Care Med)
Vol. 191
Issue 7
Pg. 746-57
(Apr 01 2015)
ISSN: 1535-4970 [Electronic] United States |
PMID | 25629580
(Publication Type: Journal Article, Research Support, N.I.H., Extramural)
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Chemical References |
- Adipokines
- CHI3L1 protein, human
- Chitinase-3-Like Protein 1
- Growth Substances
- Lectins
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Topics |
- Adipokines
(metabolism)
- Animals
- Asthma
(enzymology)
- Case-Control Studies
- Chitinase-3-Like Protein 1
- Female
- Growth Substances
(metabolism)
- Humans
- Inflammation
(enzymology)
- Intra-Abdominal Fat
(metabolism)
- Lectins
(metabolism)
- Mice
- Obesity
(enzymology)
- Th2 Cells
(enzymology)
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