leptin and Virus-Diseases

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.

Topics: Animals; Antiviral Agents; COVID-19; COVID-19 Drug Treatment; Energy Metabolism; Humans; Immune System; Leptin; Obesity; Viral Vaccines; Virus Diseases

Obesity is a globally increasing health problem, entailing diverse comorbidities such as infectious diseases. An obese weight status has marked effects on lung function that can be attributed to mechanical dysfunctions. Moreover, the alterations of adipocyte-derived signal mediators strongly influence the regulation of inflammation, resulting in chronic low-grade inflammation. Our review summarizes the known effects regarding pulmonary bacterial and viral infections. For this, we discuss model systems that allow mechanistic investigation of the interplay between obesity and lung infections. Overall, obesity gives rise to a higher susceptibility to infectious pathogens, but the pathogenetic process is not clearly defined. Whereas, viral infections often show a more severe course in obese patients, the same patients seem to have a survival benefit during bacterial infections. In particular, we summarize the main mechanical impairments in the pulmonary tract caused by obesity. Moreover, we outline the main secretory changes within the expanded adipose tissue mass, resulting in chronic low-grade inflammation. Finally, we connect these altered host factors to the influence of obesity on the development of lung infection by summarizing observations from clinical and experimental data.

Topics: Adipocytes; Adipokines; Adiponectin; Adipose Tissue; Animals; Anti-Inflammatory Agents; Bacterial Infections; Cells, Cultured; Comorbidity; Female; Humans; Inflammation; Leptin; Lung; Macrophages; Male; Mice; Obesity; Risk Factors; Virus Diseases

Being overweight and obese has become an increasingly serious clinical and socioeconomic problem worldwide. The rapidly rising prevalence of obesity has prompted studies on modifiable, causative factors and novel treatment options for this disorder. Recent evidence indicates that excessive weight gain that leads to being overweight and obese may result from alterations in gut microflora. Studies in humans and animals demonstrated that the composition of gut microbiota may differ in lean and obese subjects, suggesting that these differences result in the increased efficiency of caloric extraction from food, enhanced lipogenesis, and impaired central and peripheral regulation of energy balance. Other studies revealed an excessive increase in body weight in a significant percentage of people infected with human adenoviruses SMAM-1 and Ad-36. Dysregulation of adipocyte function by viruses appears to be the most likely cause of excessive fat accumulation in these individuals. Studies on the pathomechanisms related to the pathogenesis of obesity indicated that a high-fat diet triggers the inflammatory response in the hypothalamus, an event that promotes weight gain and further defends elevated body weight through the initiation of central leptin and insulin resistance and impairment of regenerative capacity of hypothalamic neurons. Exposure to a high-calorie diet appears to predispose individuals to obesity not only because of excessive caloric intake but also because of the induction of microbiota- and central inflammatory response-dependent changes that lead to a dysregulation of energy balance.

Topics: Animals; Bacterial Infections; Body Weight; Energy Intake; Energy Metabolism; Gastrointestinal Tract; Humans; Hypothalamus; Inflammation; Insulin Resistance; Leptin; Obesity; Virus Diseases

Topics: Humans; Lactoferrin; Lectins; Leptin; Milk, Human; Neuropeptides; Nutritional Physiological Phenomena; Virus Diseases; Viruses; Vitamin A

The immune system is closely integrated with the neuroendocrine system, and infection-induced increases in cytokines such as IL-1, IL-6 and TNF have numerous effects on the central nervous system. These include stimulation of the hypothalamus-pituitary-adrenal (HPA) axis, as well as of leptin production. The increase in leptin causes loss of appetite, which may be deleterious for children who are living under conditions of poverty, have frequent infections and are often already undernourished. These cytokines may also be involved in problems of obesity, since they activate the HPA-axis and since TNF is produced by fat cells and can cause insulin resistance. The immune system originally developed for hunter-gatherers may not be well adapted to the pathology of poverty or that of excess.

Topics: Adaptation, Physiological; Adult; Bacterial Infections; Child; Cytokines; Humans; Hypothalamo-Hypophyseal System; Immune System; Immune Tolerance; Infant, Newborn; Insulin; Insulin Resistance; Leptin; Neurotransmitter Agents; Nutrition Disorders; Nutritional Physiological Phenomena; Obesity; Pituitary-Adrenal System; Poverty; Risk Factors; Virus Diseases