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已发表论文
FGF21加重肥胖诱导的气道高反应性和FGFR1依赖性肥大细胞活化
Authors Ren L, Xuan L, Zhang J, Zhang W, An Z
Received 10 October 2025
Accepted for publication 17 January 2026
Published 24 January 2026 Volume 2026:19 570000
DOI https://doi.org/10.2147/JIR.S570000
Checked for plagiarism Yes
Review by Single anonymous peer review
Peer reviewer comments 4
Editor who approved publication: Dr Tara Strutt
Lulu Ren,1 Lingling Xuan,1 Jie Zhang,1 Wen Zhang,2 Zhuoling An2
1Medical Research Center, Beijing Institute of Respiratory Medicine and Beijing Chao-Yang Hospital, Capital Medical University, Beijing, People’s Republic of China; 2Department of Pharmacy, Beijing Chao-Yang Hospital, Capital Medical University, Beijing, 100020, People’s Republic of China
Correspondence: Lulu Ren, Medical Research Center, Beijing Institute of Respiratory Medicine and Beijing Chao-Yang Hospital, Capital Medical University, 8 Gongren Tiyuchang Nanlu, Beijing, 100020, People’s Republic of China, Tel +86-010-85231720, Email lulu1993217@163.com Zhuoling An, Department of Pharmacy, Beijing Chao-Yang Hospital, Capital Medical University, 8 Gongren Tiyuchang Nanlu, Beijing, 100020, People’s Republic of China, Tel +86-010-85231464, Email anzhuoling@163.com
Introduction: Obesity is a well-established risk factor for asthma pathogenesis. However, the underlying mechanisms remain incompletely understood, and effective therapeutic interventions are currently lacking, making asthma management in obese individuals particularly challenging. Asthma is characterized by chronic airway inflammation, eosinophilic infiltration, and airway hyperresponsiveness (AHR). In this study, we investigated the novel role of fibroblast growth factor 21 (FGF21), a stress-inducible hepatokine with pleiotropic metabolic regulatory functions, in obesity-associated AHR using a diet-induced obesity mouse model (n = 10).
Material and Methods: Serum samples were collected from obese and lean asthma patients, along with relevant clinical indicators, including body mass index (BMI), forced expiratory volume in 1 second (FEV1%), and the FEV1/forced vital capacity (FVC) ratio, to facilitate the investigation. Moreover, diet-induced obese mice with innate AHR (male, n = 10) were employed to clarify the effects of FGF21 and FGF21-neutralizing antibody on obesity induced AHR. In vitro, LAD2 human mast cells and P815 murine mast cells activated by compound 48/80 were used to elucidate the underlying mechanisms.
Results: Our findings demonstrate that serum FGF21 levels exhibit reportedly elevated in participants with obesity and are associated with impaired pulmonary function. In diet-induced obese (DIO) mice, FGF21 levels were increased in both serum and bronchoalveolar lavage fluid (BALF). In vivo investigations demonstrate that administration of recombinant FGF21 exacerbated AHR in DIO mice, whereas FGF21-neutralizing antibody treatment ameliorated obesity-induced AHR and suppressed mast cell infiltration. Mechanistically, FGF21 was found to potentiate mast cell activation through cholesterol biosynthesis modulation. Crucially, pharmacological inhibition of FGFR1 abrogated FGF21-induced mast cell hyperactivity and cholesterol synthesis, indicating FGFR1-dependent signaling in this process.
Conclusion: These findings may represent the FGF21/FGFR1 axis as a potential therapeutic target for obesity-related AHR and asthma.
Keywords: obesity, airway hyperresponsiveness, FGF21, mast cell
1Medical Research Center, Beijing Institute of Respiratory Medicine and Beijing Chao-Yang Hospital, Capital Medical University, Beijing, People’s Republic of China; 2Department of Pharmacy, Beijing Chao-Yang Hospital, Capital Medical University, Beijing, 100020, People’s Republic of China
Correspondence: Lulu Ren, Medical Research Center, Beijing Institute of Respiratory Medicine and Beijing Chao-Yang Hospital, Capital Medical University, 8 Gongren Tiyuchang Nanlu, Beijing, 100020, People’s Republic of China, Tel +86-010-85231720, Email lulu1993217@163.com Zhuoling An, Department of Pharmacy, Beijing Chao-Yang Hospital, Capital Medical University, 8 Gongren Tiyuchang Nanlu, Beijing, 100020, People’s Republic of China, Tel +86-010-85231464, Email anzhuoling@163.com
Introduction: Obesity is a well-established risk factor for asthma pathogenesis. However, the underlying mechanisms remain incompletely understood, and effective therapeutic interventions are currently lacking, making asthma management in obese individuals particularly challenging. Asthma is characterized by chronic airway inflammation, eosinophilic infiltration, and airway hyperresponsiveness (AHR). In this study, we investigated the novel role of fibroblast growth factor 21 (FGF21), a stress-inducible hepatokine with pleiotropic metabolic regulatory functions, in obesity-associated AHR using a diet-induced obesity mouse model (n = 10).
Material and Methods: Serum samples were collected from obese and lean asthma patients, along with relevant clinical indicators, including body mass index (BMI), forced expiratory volume in 1 second (FEV1%), and the FEV1/forced vital capacity (FVC) ratio, to facilitate the investigation. Moreover, diet-induced obese mice with innate AHR (male, n = 10) were employed to clarify the effects of FGF21 and FGF21-neutralizing antibody on obesity induced AHR. In vitro, LAD2 human mast cells and P815 murine mast cells activated by compound 48/80 were used to elucidate the underlying mechanisms.
Results: Our findings demonstrate that serum FGF21 levels exhibit reportedly elevated in participants with obesity and are associated with impaired pulmonary function. In diet-induced obese (DIO) mice, FGF21 levels were increased in both serum and bronchoalveolar lavage fluid (BALF). In vivo investigations demonstrate that administration of recombinant FGF21 exacerbated AHR in DIO mice, whereas FGF21-neutralizing antibody treatment ameliorated obesity-induced AHR and suppressed mast cell infiltration. Mechanistically, FGF21 was found to potentiate mast cell activation through cholesterol biosynthesis modulation. Crucially, pharmacological inhibition of FGFR1 abrogated FGF21-induced mast cell hyperactivity and cholesterol synthesis, indicating FGFR1-dependent signaling in this process.
Conclusion: These findings may represent the FGF21/FGFR1 axis as a potential therapeutic target for obesity-related AHR and asthma.
Keywords: obesity, airway hyperresponsiveness, FGF21, mast cell