Abstract
The recent pandemic Sars-CoV2 infection and studies on previous influenza epidemic have drawn attention to the association between the obesity and infectious diseases susceptibility and worse outcome. Metabolic complications, nutritional aspects, physical inactivity, and a chronic unbalance in the hormonal and adipocytokine microenvironment are major determinants in the severity of viral infections in obesity. By these pleiotropic mechanisms obesity impairs immune surveillance and the higher leptin concentrations produced by adipose tissue and that characterize obesity substantially contribute to such immune response dysregulation. Indeed, leptin not only controls energy balance and body weight, but also plays a regulatory role in the interplay between energy metabolism and immune system. Since leptin receptor is expressed throughout the immune system, leptin may exert effects on cells of both innate and adaptive immune system. Chronic inflammatory states due to metabolic (i.e., obesity) as well as infectious diseases increase leptin concentrations and consequently lead to leptin resistance further fueling inflammation. Multiple factors, including inflammation and ER stress, contribute to leptin resistance. Thus, if leptin is recognized as one of the adipokines responsible for the low grade inflammation found in obesity, on the other hand, impairments of leptin signaling due to leptin resistance appear to blunt the immunologic effects of leptin and possibly contribute to impaired vaccine-induced immune responses. However, many aspects concerning leptin interactions with inflammation and immune system as well as the therapeutical approaches to overcome leptin resistance and reduced vaccine effectiveness in obesity remain a challenge for future research.
Highlights
Obesity is a worldwide pandemic resulting from a combination of genetic, behavioral, and environmental variables and that dramatically increases morbidity and mortality
Reports on neuraminidase inhibitor oseltamivir, an antiviral used to treat influenza virus infection, suggest that dose adjustment for obese patients is not necessary from a pharmacokinetic perspective, whether the dosage is appropriate to control viral replication is so far unknown [32]. Both obese and lean mice treated with weight-adjusted dosages of oseltamivir before and during pH1N1 infection showed similar rates lung epithelial cell regeneration and were both completely protected from influenza-related mortality [67]
The obesity-related chronic low-grade inflammation, characterized by raised levels of pro-inflammatory molecules (such as leptin, resistin, chemokine (C-C motif) ligand 2 (CCL2), interleukin (IL)-6, IL-1β, IL-8, tumor necrosis factor (TNF)-α) and decreased levels of adiponectin, may have negative effects on the lung parenchyma and bronchi [72]. This chronic inflammatory milieu, together with T-helper (Th)1 to Th2 immune response shift induced by viruses to evade host immunity, can be detrimental to the endothelium leading to vascular complications [73]
Summary
Obesity is a worldwide pandemic resulting from a combination of genetic, behavioral, and environmental variables and that dramatically increases morbidity and mortality. It has been recognized as a leading cause of major health issues, metabolic, cardiovascular, and oncologic diseases [1,2,3]. We review the available evidence on the various aspects of the association between obesity and viral infections and the current understanding of the possible mechanisms underlying this susceptibility to worse outcomes, with particular focus on the role of leptin
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