Obesity and Leptin Resistance in the Regulation of the Type I Interferon Early Response and the Increased Risk for Severe COVID-19.

Department of Laboratory Medicine, University Medical Center Groningen, University of Groningen, 9713 GZ Groningen, The Netherlands. Center for Primary Health Care Research, Lund University, 205 02 Malmö, Sweden. Faculty of Biomedical and Health Sciences, Universidad Europea de Madrid, 28670 Madrid, Spain. Centro de Estudios Avanzados en Nutrición (CEAN), 11007 Cádiz, Spain. Natura Foundation, 3281 NC Numansdorp, The Netherlands. Faculty of Sport Sciences, Universidad Europea de Madrid, 28670 Madrid, Spain. Physical Activity and Health Research Group ('PaHerg'), Research Institute of the Hospital 12 de Octubre ('imas12'), 28041 Madrid, Spain. Biomedical Research Networking Center on Frailty and Healthy Aging (CIBERFES), 28029 Madrid, Spain. Stanford 1000 Immunomes Project, Stanford University School of Medicine, Stanford, CA 94305, USA. Buck Artificial Intelligence Platform, The Buck Institute for Research on Aging, Novato, CA 94945, USA. Edifice Health Inc., San Mateo, CA 94401, USA. Austral Institute for Applied Artificial Intelligence, Institute for Research in Translational Medicine (IIMT), Universidad Austral, National Scientific and Technical Research Council (CONICET), Buenos Aires 2290, Argentina.

Nutrients. 2022;(7)
Full text from:

Abstract

Obesity, and obesity-associated conditions such as hypertension, chronic kidney disease, type 2 diabetes, and cardiovascular disease, are important risk factors for severe Coronavirus disease-2019 (COVID-19). The common denominator is metaflammation, a portmanteau of metabolism and inflammation, which is characterized by chronically elevated levels of leptin and pro-inflammatory cytokines. These induce the "Suppressor Of Cytokine Signaling 1 and 3" (SOCS1/3), which deactivates the leptin receptor and also other SOCS1/3 sensitive cytokine receptors in immune cells, impairing the type I and III interferon early responses. By also upregulating SOCS1/3, Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV)-2 adds a significant boost to this. The ensuing consequence is a delayed but over-reactive immune response, characterized by high-grade inflammation (e.g., cytokine storm), endothelial damage, and hypercoagulation, thus leading to severe COVID-19. Superimposing an acute disturbance, such as a SARS-CoV-2 infection, on metaflammation severely tests resilience. In the long run, metaflammation causes the "typical western" conditions associated with metabolic syndrome. Severe COVID-19 and other serious infectious diseases can be added to the list of its short-term consequences. Therefore, preventive measures should include not only vaccination and the well-established actions intended to avoid infection, but also dietary and lifestyle interventions aimed at improving body composition and preventing or reversing metaflammation.

Methodological quality

Publication Type : Review

Metadata