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Reduced DMPC and PMPC in lung surfactant promote SARS-CoV-2 infection in obesity.
Du, Kang; Sun, Ling; Luo, Zichen; Cao, Yang; Sun, Qiushi; Zhang, Kangzhen; Faizy, Ahmed; Piomelli, Daniele; Lu, Xiang; Shan, Jinjun; Yang, Qin.
Afiliación
  • Du K; Department of Medicine, Physiology and Biophysics, UCI Diabetes Center, University of California Irvine, Irvine, CA 92697, USA.
  • Sun L; Institute of Pediatrics, Jiangsu Key Laboratory of Pediatric Respiratory Disease, Medical Metabolomics Center, Nanjing University of Chinese Medicine, Nanjing 210023, China.
  • Luo Z; Institute of Pediatrics, Jiangsu Key Laboratory of Pediatric Respiratory Disease, Medical Metabolomics Center, Nanjing University of Chinese Medicine, Nanjing 210023, China.
  • Cao Y; Department of Medicine, Physiology and Biophysics, UCI Diabetes Center, University of California Irvine, Irvine, CA 92697, USA.
  • Sun Q; Department of Medicine, Physiology and Biophysics, UCI Diabetes Center, University of California Irvine, Irvine, CA 92697, USA.
  • Zhang K; Department of Medicine, Physiology and Biophysics, UCI Diabetes Center, University of California Irvine, Irvine, CA 92697, USA.
  • Faizy A; Department of Anatomy and Neurobiology, University of California, Irvine, CA 92697-4625, USA; Department of Biological Chemistry, University of California, Irvine, CA 92697-4625, USA.
  • Piomelli D; Department of Anatomy and Neurobiology, University of California, Irvine, CA 92697-4625, USA; Department of Biological Chemistry, University of California, Irvine, CA 92697-4625, USA.
  • Lu X; Department of Geriatrics, Sir Run Run Shaw Hospital, Nanjing Medical University, Nanjing 211166, China.
  • Shan J; Institute of Pediatrics, Jiangsu Key Laboratory of Pediatric Respiratory Disease, Medical Metabolomics Center, Nanjing University of Chinese Medicine, Nanjing 210023, China. Electronic address: jshan@njucm.edu.cn.
  • Yang Q; Department of Medicine, Physiology and Biophysics, UCI Diabetes Center, University of California Irvine, Irvine, CA 92697, USA. Electronic address: qin.yang@uci.edu.
Metabolism ; 131: 155181, 2022 06.
Article en En | MEDLINE | ID: mdl-35311662
ABSTRACT

OBJECTIVE:

Obesity is an established risk factor for higher SARS-CoV-2 viral loads, severe COVID-19 pneumonia requiring hospitalization, and worse outcomes. However, the underlying mechanisms for the increased risk are not well understood. SARS-CoV-2 is a respiratory virus with the primary route of entry through the lungs, where the Spike protein of SARS-CoV-2 binds to the ACE2 receptor on pneumocytes. Lung surfactant produced by type II pneumocytes plays a major role in respiratory defense against infections. Surfactant predominantly contains lipids, especially phosphatidylcholines (PC), and obesity is characterized by aberrant lipid metabolism. We hypothesized that altered lipid composition in lung surfactant in obesity may promote SARS-CoV-2 infection, leading to severe COVID-19 disease.

METHODS:

Lipidomic analysis of lung tissue and bronchoalveolar lavage fluid (BALF) was performed using LC-MS/MS. The effects of PCs on SARS-CoV-2 pseudovirus infection were studied in HEK293T cells with ACE2 overexpression and in Vero-E6 cells with endogenous ACE2 expression. For the cell-cell fusion assay, HEK293T-ACE2 and HEK293T expressing SARS-CoV-2 Spike/eGFP were used as the target and effector cells, respectively.

RESULTS:

Lipidomic analysis revealed that myristic acid-containing dimyristoyl-PC (DMPC) and palmitoylmyristoyl-PC (PMPC) were reduced in lung tissue and BALF from high fat diet-induced obese mice. DMPC and PMPC markedly inhibited wild type and D614G mutant SARS-CoV-2 infection in HEK293T-ACE2 and Vero-E6 cells. Feeding obese mice with trimyristin, the triglycerides of myristic acid, increased DMPC and PMPC levels in lung surfactant. Lipid extract from BALF of trimyristin-treated obese mice mitigated the elevated wild type and D614G mutant SARS-CoV-2 infection. The inhibitory effects of DMPC and PMPC on SARS-CoV-2 infection were reversed by cholesterol.

CONCLUSIONS:

The reduced DMPC and PMPC in lung surfactant may promote SARS-CoV-2 infection. Increasing DMPC and PMPC in lung surfactant could be an innovative strategy for preventing and treating severe COVID-19 disease in obesity.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Contexto en salud: 4_TD Problema de salud: 4_pneumonia Asunto principal: COVID-19 Tipo de estudio: Risk_factors_studies Límite: Animals / Humans Idioma: En Revista: Metabolism Año: 2022 Tipo del documento: Article País de afiliación: Estados Unidos

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Contexto en salud: 4_TD Problema de salud: 4_pneumonia Asunto principal: COVID-19 Tipo de estudio: Risk_factors_studies Límite: Animals / Humans Idioma: En Revista: Metabolism Año: 2022 Tipo del documento: Article País de afiliación: Estados Unidos
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