Essential role of Card11 in airway hyperresponsiveness in high-fat diet-induced obese mice

Abstract

A high-fat diet (HFD) can induce airway hyperresponsiveness (AHR) in obese mice, independent of allergic sensitization. This study aimed to identify the key molecules related to AHR in HFD-induced obese mice. In a cluster analysis of time series gene expression in the adipose and lung tissues of HFD-induced obese mice, we identified the Caspase Recruitment Domain Family Member 11 (Card11) gene as an essential molecule. We measured CARD11 expression in peripheral blood mononuclear cells (PBMCs) from obese individuals with asthma and performed Card11 signal inhibition in HFD-induced obese mice via Card11 siRNA. Card11 expression was significantly increased in M1 macrophages (IL-1β+CD11c+CD206- in CD11b+) in adipose tissue and in ILC3s (RORγt+ in IL7R+ of Lin-) in lung tissue from HFD-induced obese mice. In addition, CARD11+ populations among ILC3s and LPS-stimulated IL-1β+CD16+ monocytes from the PBMCs of obese individuals with asthma were significantly greater than those from obese controls or nonobese individuals with asthma. AHR in HFD-induced obese mice disappeared when we inhibited the Card11 signaling pathway by administering Card11 siRNA during the first or last seven weeks of the 13-week HFD feeding. Finally, we confirmed that Card11 siRNA decreased the number of M1 macrophages in adipose tissue and the number of ILC3s in lung tissue in vitro. Card11 significantly contributes to the development of AHR in HFD-induced obese mice by affecting immune cells in both adipose and lung tissues. The middle stage of HFD feeding seemed to be critical for these processes. Obesity is a metabolic disease and a major risk factor for several non-communicable diseases. The link between obesity and asthma is not fully understood. The study used a murine model to investigate how obesity affects asthma. Researchers fed mice a high-fat diet and analyzed gene expression in their adipose and lung tissues. They identified the Card11 gene as a key player in airway hyperresponsiveness in obese mice. This was an experimental study involving mice. Results showed that Card11 expression increased in immune cells from both adipose and lung tissues of obese mice. Inhibiting Card11 reduced AHR and inflammation. Researchers concluded that Card11 is crucial in obesity-related asthma. Future studies could explore Card11 as a therapeutic target for asthma in obese individuals. This summary was initially drafted using artificial intelligence, then revised and fact-checked by the author.