Susceptibility and Severity of Viral Infections in Obesity: Lessons from Influenza to COVID-19. Does Leptin Play a Role?
Abstract
:1. Introduction
2. Obesity and Risk of Infections
3. Obesity and Viral Infection Outcomes, from Influenza A Virus to SARS-COV-2
4. Obesity and Viral Shedding
5. Obesity and Response to Vaccine and Antivirals
6. Mechanisms That Make Obese Patients Vulnerable to Infections
7. Leptin and Immunometabolism
8. Leptin and Immune System
9. Leptin In Viral Infections
10. Leptin in Obesity: What Role during Viral Infections?
11. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
- Gluvic, Z.; Zaric, B.; Resanovic, I.; Obradovic, M.; Mitrovic, A.; Radak, D.; Isenovic, E.R. Link between Metabolic Syndrome and Insulin Resistance. Curr. Vasc. Pharmacol. 2017, 15, 30–39. [Google Scholar] [CrossRef]
- Tune, J.D.; Goodwill, A.G.; Sassoon, D.J.; Mather, K.J. Cardiovascular consequences of metabolic syndrome. Transl. Res. J. Lab. Clin. Med. 2017, 183, 57–70. [Google Scholar] [CrossRef] [Green Version]
- Vucenik, I.; Stains, J.P. Obesity and cancer risk: Evidence, mechanisms, and recommendations. Ann. N. Y. Acad. Sci. 2012, 1271, 37–43. [Google Scholar] [CrossRef]
- Huttunen, R.; Syrjanen, J. Obesity and the outcome of infection. Lancet Infect. Dis. 2010, 10, 442–443. [Google Scholar] [CrossRef]
- Hussain, A.; Mahawar, K.; Xia, Z.; Yang, W.; El-Hasani, S. Obesity and mortality of COVID-19. Meta-analysis. Obes. Res. Clin. Pract. 2020, 14, 295–300. [Google Scholar] [CrossRef] [PubMed]
- Falagas, M.E.; Kompoti, M. Obesity and infection. Lancet Infect. Dis. 2006, 6, 438–446. [Google Scholar] [CrossRef]
- Falagas, M.E.; Athanasoulia, A.P.; Peppas, G.; Karageorgopoulos, D.E. Effect of body mass index on the outcome of infections: A systematic review. Obes. Rev. Off. J. Int. Assoc. Study Obes. 2009, 10, 280–289. [Google Scholar] [CrossRef]
- Carbone, F.; La Rocca, C.; De Candia, P.; Procaccini, C.; Colamatteo, A.; Micillo, T.; De Rosa, V.; Matarese, G. Metabolic control of immune tolerance in health and autoimmunity. Semin. Immunol. 2016, 28, 491–504. [Google Scholar] [CrossRef] [PubMed]
- Milner, J.J.; Beck, M.A. The impact of obesity on the immune response to infection. Proc. Nutr. Soc. 2012, 71, 298–306. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Zhao, X.; Gang, X.; He, G.; Li, Z.; Lv, Y.; Han, Q.; Wang, G. Obesity Increases the Severity and Mortality of Influenza and COVID-19: A Systematic Review and Meta-Analysis. Front. Endocrinol. 2020, 11, 595109. [Google Scholar] [CrossRef]
- Phung, D.T.; Wang, Z.; Rutherford, S.; Huang, C.; Chu, C. Body mass index and risk of pneumonia: A systematic review and meta-analysis. Obes. Rev. Off. J. Int. Assoc. Study Obes. 2013, 14, 839–857. [Google Scholar] [CrossRef]
- Hall, M.; Pritchard, M.; Dankwa, E.A.; Baillie, J.K.; Carson, G.; Citarella, B.W.; Docherty, A.; Donnelly, C.A.; Dunning, J.; Fraser, C.; et al. ISARIC Clinical Data Report 20 November 2020. medRxiv. 2020. Available online: https://isaric.org/wp-content/uploads/2021/01/ISARIC-Clinical-Data-Report-20.11.202 (accessed on 4 February 2021).
- Popkin, B.M.; Du, S.; Green, W.D.; Beck, M.A.; Algaith, T.; Herbst, C.H.; Alsukait, R.F.; Alluhidan, M.; Alazemi, N.; Shekar, M. Individuals with obesity and COVID-19: A global perspective on the epidemiology and biological relationships. Obes. Rev. Off. J. Int. Assoc. Study Obes. 2020, 21, e13128. [Google Scholar] [CrossRef] [PubMed]
- Simonnet, A.; Chetboun, M.; Poissy, J.; Raverdy, V.; Noulette, J.; Duhamel, A.; Labreuche, J.; Mathieu, D.; Pattou, F.; Jourdain, M.; et al. High Prevalence of Obesity in Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) Requiring Invasive Mechanical Ventilation. Obesity 2020, 28, 1195–1199. [Google Scholar] [CrossRef] [PubMed]
- Winfield, R.D.; Reese, S.; Bochicchio, K.; Mazuski, J.E.; Bochicchio, G.V. Obesity and the Risk for Surgical Site Infection in Abdominal Surgery. Am. Surg. 2016, 82, 331–336. [Google Scholar] [CrossRef]
- Zahr, F.; Genovese, E.; Mathier, M.; Shullo, M.; Lockard, K.; Zomak, R.; McNamara, D.; Toyoda, Y.; Kormos, R.L.; Teuteberg, J.J. Obese patients and mechanical circulatory support: Weight loss, adverse events, and outcomes. Ann. Thorac. Surg. 2011, 92, 1420–1426. [Google Scholar] [CrossRef]
- Crabtree, T.D.; Codd, J.E.; Fraser, V.J.; Bailey, M.S.; Olsen, M.A.; Damiano, R.J., Jr. Multivariate analysis of risk factors for deep and superficial sternal infection after coronary artery bypass grafting at a tertiary care medical center. Semin. Thorac. Cardiovasc. Surg. 2004, 16, 53–61. [Google Scholar] [CrossRef]
- Tjeertes, E.K.; Hoeks, S.E.; Beks, S.B.; Valentijn, T.M.; Hoofwijk, A.G.; Stolker, R.J. Obesity--a risk factor for postoperative complications in general surgery? Bmc Anesthesiol. 2015, 15, 112. [Google Scholar] [CrossRef] [Green Version]
- Vilar-Compte, D.; Mohar, A.; Sandoval, S.; de la Rosa, M.; Gordillo, P.; Volkow, P. Surgical site infections at the National Cancer Institute in Mexico: A case-control study. Am. J. Infect. Control. 2000, 28, 14–20. [Google Scholar] [CrossRef]
- Huttunen, R.; Karppelin, M.; Syrjanen, J. Obesity and nosocomial infections. J. Hosp. Infect. 2013, 85, 8–16. [Google Scholar] [CrossRef] [PubMed]
- Waisbren, E.; Rosen, H.; Bader, A.M.; Lipsitz, S.R.; Rogers, S.O., Jr.; Eriksson, E. Percent body fat and prediction of surgical site infection. J. Am. Coll. Surg. 2010, 210, 381–389. [Google Scholar] [CrossRef]
- Kaspersen, K.A.; Pedersen, O.B.; Petersen, M.S.; Hjalgrim, H.; Rostgaard, K.; Moller, B.K.; Juul-Sorensen, C.; Kotze, S.; Dinh, K.M.; Erikstrup, L.T.; et al. Obesity and risk of infection: Results from the Danish Blood Donor Study. Epidemiology 2015, 26, 580–589. [Google Scholar] [CrossRef] [PubMed]
- Semins, M.J.; Shore, A.D.; Makary, M.A.; Weiner, J.; Matlaga, B.R. The impact of obesity on urinary tract infection risk. Urology 2012, 79, 266–269. [Google Scholar] [CrossRef]
- Thorsteinsdottir, B.; Tleyjeh, I.M.; Baddour, L.M. Abdominal wall cellulitis in the morbidly obese. Scand. J. Infect. Dis. 2005, 37, 605–608. [Google Scholar] [CrossRef] [PubMed]
- Roujeau, J.C.; Sigurgeirsson, B.; Korting, H.C.; Kerl, H.; Paul, C. Chronic dermatomycoses of the foot as risk factors for acute bacterial cellulitis of the leg: A case-control study. Dermatology 2004, 209, 301–307. [Google Scholar] [CrossRef] [Green Version]
- Garcia Hidalgo, L. Dermatological complications of obesity. Am. J. Clin. Dermatol. 2002, 3, 497–506. [Google Scholar] [CrossRef] [PubMed]
- Morens, D.M.; Taubenberger, J.K. Influenza Cataclysm, 1918. N. Engl. J. Med. 2018, 379, 2285–2287. [Google Scholar] [CrossRef]
- Louie, J.K.; Acosta, M.; Samuel, M.C.; Schechter, R.; Vugia, D.J.; Harriman, K.; Matyas, B.T.; California Pandemic Working Group. A novel risk factor for a novel virus: Obesity and 2009 pandemic influenza A (H1N1). Clin. Infect. Dis. Off. Publ. Infect. Dis. Soc. Am. 2011, 52, 301–312. [Google Scholar] [CrossRef] [Green Version]
- Fezeu, L.; Julia, C.; Henegar, A.; Bitu, J.; Hu, F.B.; Grobbee, D.E.; Kengne, A.P.; Hercberg, S.; Czernichow, S. Obesity is associated with higher risk of intensive care unit admission and death in influenza A (H1N1) patients: A systematic review and meta-analysis. Obes. Rev. Off. J. Int. Assoc. Study Obes. 2011, 12, 653–659. [Google Scholar] [CrossRef]
- Kok, J.; Blyth, C.C.; Foo, H.; Bailey, M.J.; Pilcher, D.V.; Webb, S.A.; Seppelt, I.M.; Dwyer, D.E.; Iredell, J.R. Viral pneumonitis is increased in obese patients during the first wave of pandemic A(H1N1) 2009 virus. PLoS ONE 2013, 8, e55631. [Google Scholar] [CrossRef]
- Diaz, E.; Rodriguez, A.; Martin-Loeches, I.; Lorente, L.; Del Mar Martin, M.; Pozo, J.C.; Montejo, J.C.; Estella, A.; Arenzana, A.; Rello, J.; et al. Impact of obesity in patients infected with 2009 influenza A(H1N1). Chest 2011, 139, 382–386. [Google Scholar] [CrossRef]
- Honce, R.; Schultz-Cherry, S. Impact of Obesity on Influenza A Virus Pathogenesis, Immune Response, and Evolution. Front. Immunol. 2019, 10, 1071. [Google Scholar] [CrossRef] [PubMed]
- Segaloff, H.E.; Evans, R.; Arshad, S.; Zervos, M.J.; Archer, C.; Kaye, K.S.; Martin, E.T. The impact of obesity and timely antiviral administration on severe influenza outcomes among hospitalized adults. J. Med. Virol. 2018, 90, 212–218. [Google Scholar] [CrossRef] [PubMed]
- Kwong, J.C.; Campitelli, M.A.; Rosella, L.C. Obesity and respiratory hospitalizations during influenza seasons in Ontario, Canada: A cohort study. Clin. Infect. Dis. Off. Publ. Infect. Dis. Soc. Am. 2011, 53, 413–421. [Google Scholar] [CrossRef] [Green Version]
- Martin, V.; Castilla, J.; Godoy, P.; Delgado-Rodriguez, M.; Soldevila, N.; Fernandez-Villa, T.; Molina, A.J.; Astray, J.; Castro, A.; Gonzalez-Candelas, F.; et al. High Body Mass Index as a Risk Factor for Hospitalization Due to Influenza: A Case-Control Study. Arch. Bronconeumol. 2016, 52, 299–307. [Google Scholar] [CrossRef] [PubMed]
- da Costa, V.G.; Moreli, M.L.; Saivish, M.V. The emergence of SARS, MERS and novel SARS-2 coronaviruses in the 21st century. Arch. Virol. 2020, 165, 1517–1526. [Google Scholar] [CrossRef]
- Drosten, C.; Gunther, S.; Preiser, W.; van der Werf, S.; Brodt, H.R.; Becker, S.; Rabenau, H.; Panning, M.; Kolesnikova, L.; Fouchier, R.A.; et al. Identification of a novel coronavirus in patients with severe acute respiratory syndrome. N. Engl. J. Med. 2003, 348, 1967–1976. [Google Scholar] [CrossRef]
- Zaki, A.M.; van Boheemen, S.; Bestebroer, T.M.; Osterhaus, A.D.; Fouchier, R.A. Isolation of a novel coronavirus from a man with pneumonia in Saudi Arabia. N. Engl. J. Med. 2012, 367, 1814–1820. [Google Scholar] [CrossRef]
- Petrosillo, N.; Viceconte, G.; Ergonul, O.; Ippolito, G.; Petersen, E. COVID-19, SARS and MERS: Are they closely related? Clin. Microbiol. Infect. Off. Publ. Eur. Soc. Clin. Microbiol. Infect. Dis. 2020, 26, 729–734. [Google Scholar] [CrossRef]
- Assiri, A.; McGeer, A.; Perl, T.M.; Price, C.S.; Al Rabeeah, A.A.; Cummings, D.A.; Alabdullatif, Z.N.; Assad, M.; Almulhim, A.; Makhdoom, H.; et al. Hospital outbreak of Middle East respiratory syndrome coronavirus. N. Engl. J. Med. 2013, 369, 407–416. [Google Scholar] [CrossRef]
- Memish, Z.A.; Assiri, A.M.; Al-Tawfiq, J.A. Middle East respiratory syndrome coronavirus (MERS-CoV) viral shedding in the respiratory tract: An observational analysis with infection control implications. Int. J. Infect. Dis. Ijid Off. Publ. Int. Soc. Infect. Dis. 2014, 29, 307–308. [Google Scholar] [CrossRef] [Green Version]
- Arabi, Y.M.; Arifi, A.A.; Balkhy, H.H.; Najm, H.; Aldawood, A.S.; Ghabashi, A.; Hawa, H.; Alothman, A.; Khaldi, A.; Al Raiy, B. Clinical course and outcomes of critically ill patients with Middle East respiratory syndrome coronavirus infection. Ann. Intern. Med. 2014, 160, 389–397. [Google Scholar] [CrossRef] [PubMed]
- Assiri, A.; Al-Tawfiq, J.A.; Al-Rabeeah, A.A.; Al-Rabiah, F.A.; Al-Hajjar, S.; Al-Barrak, A.; Flemban, H.; Al-Nassir, W.N.; Balkhy, H.H.; Al-Hakeem, R.F.; et al. Epidemiological, demographic, and clinical characteristics of 47 cases of Middle East respiratory syndrome coronavirus disease from Saudi Arabia: A descriptive study. Lancet. Infect. Dis. 2013, 13, 752–761. [Google Scholar] [CrossRef] [Green Version]
- Badawi, A.; Ryoo, S.G. Prevalence of comorbidities in the Middle East respiratory syndrome coronavirus (MERS-CoV): A systematic review and meta-analysis. Int. J. Infect. Dis. Ijid Off. Publ. Int. Soc. Infect. Dis. 2016, 49, 129–133. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Centers for Disease Control and Prevention. COVIDView. A Wkly Surveill Summ US COVID-19 Act. Available online: https://www.cdc.gov/coronavirus/2019-ncov/need-extra-precautions/people-with-medical-conditions.html (accessed on 28 January 2021).
- European Centre for Disease Prevention and Control. ECDC’s Weekly COVID-19 Surveillance Report. Available online: https://www.ecdc.europa.eu/en/covid-19/latest-evidence/epidemiology (accessed on 28 January 2021).
- Sattar, N.; McInnes, I.B.; McMurray, J.J.V. Obesity Is a Risk Factor for Severe COVID-19 Infection: Multiple Potential Mechanisms. Circulation 2020, 142, 4–6. [Google Scholar] [CrossRef]
- Richardson, S.; Hirsch, J.S.; Narasimhan, M.; Crawford, J.M.; McGinn, T.; Davidson, K.W.; the Northwell COVID-19 Research Consortium; Barnaby, D.P.; Becker, L.B.; Chelico, J.D.; et al. Presenting Characteristics, Comorbidities, and Outcomes Among 5700 Patients Hospitalized With COVID-19 in the New York City Area. JAMA 2020, 323, 2052–2059. [Google Scholar] [CrossRef] [PubMed]
- Barrasa, H.; Rello, J.; Tejada, S.; Martin, A.; Balziskueta, G.; Vinuesa, C.; Fernandez-Miret, B.; Villagra, A.; Vallejo, A.; San Sebastian, A.; et al. SARS-CoV-2 in Spanish Intensive Care Units: Early experience with 15-day survival in Vitoria. Anaesth. Crit. Care Pain Med. 2020, 39, 553–561. [Google Scholar] [CrossRef] [PubMed]
- Drucker, D.J. Diabetes, obesity, metabolism, and SARS-CoV-2 infection: The end of the beginning. Cell Metab. 2021. [Google Scholar] [CrossRef]
- Kass, D.A.; Duggal, P.; Cingolani, O. Obesity could shift severe COVID-19 disease to younger ages. Lancet 2020, 395, 1544–1545. [Google Scholar] [CrossRef]
- Recalde, M.; Pistillo, A.; Fernandez-Bertolin, S.; Roel, E.; Aragon, M.; Freisling, H.; Prieto-Alhambra, D.; Burn, E.; Duarte-Salles, T. Body mass index and risk of COVID-19 diagnosis, hospitalisation, and death: A population-based multi-state cohort analysis including 2,524,926 people in Catalonia, Spain. medRxiv 2020. [Google Scholar] [CrossRef]
- Maier, H.E.; Lopez, R.; Sanchez, N.; Ng, S.; Gresh, L.; Ojeda, S.; Burger-Calderon, R.; Kuan, G.; Harris, E.; Balmaseda, A.; et al. Obesity Increases the Duration of Influenza A Virus Shedding in Adults. J. Infect. Dis. 2018, 218, 1378–1382. [Google Scholar] [CrossRef] [Green Version]
- Milner, J.J.; Rebeles, J.; Dhungana, S.; Stewart, D.A.; Sumner, S.C.; Meyers, M.H.; Mancuso, P.; Beck, M.A. Obesity Increases Mortality and Modulates the Lung Metabolome during Pandemic H1N1 Influenza Virus Infection in Mice. J. Immunol. 2015, 194, 4846–4859. [Google Scholar] [CrossRef] [Green Version]
- Moriconi, D.; Masi, S.; Rebelos, E.; Virdis, A.; Manca, M.L.; De Marco, S.; Taddei, S.; Nannipieri, M. Obesity prolongs the hospital stay in patients affected by COVID-19, and may impact on SARS-COV-2 shedding. Obes. Res. Clin. Pract. 2020, 14, 205–209. [Google Scholar] [CrossRef] [PubMed]
- Bourgeois, C.; Gorwood, J.; Barrail-Tran, A.; Lagathu, C.; Capeau, J.; Desjardins, D.; Le Grand, R.; Damouche, A.; Bereziat, V.; Lambotte, O. Specific Biological Features of Adipose Tissue, and Their Impact on HIV Persistence. Front. Microbiol. 2019, 10, 2837. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Hoffmann, M.; Kleine-Weber, H.; Schroeder, S.; Kruger, N.; Herrler, T.; Erichsen, S.; Schiergens, T.S.; Herrler, G.; Wu, N.H.; Nitsche, A.; et al. SARS-CoV-2 Cell Entry Depends on ACE2 and TMPRSS2 and Is Blocked by a Clinically Proven Protease Inhibitor. Cell 2020, 181, 271–280 e278. [Google Scholar] [CrossRef]
- Al-Benna, S. Association of high level gene expression of ACE2 in adipose tissue with mortality of COVID-19 infection in obese patients. Obes. Med. 2020, 19, 100283. [Google Scholar] [CrossRef]
- Pinheiro, T.A.; Barcala-Jorge, A.S.; Andrade, J.M.O.; Pinheiro, T.A.; Ferreira, E.C.N.; Crespo, T.S.; Batista-Jorge, G.C.; Vieira, C.A.; Lelis, D.F.; Paraiso, A.F.; et al. Obesity and malnutrition similarly alter the renin-angiotensin system and inflammation in mice and human adipose. J. Nutr. Biochem. 2017, 48, 74–82. [Google Scholar] [CrossRef]
- Yan, J.; Grantham, M.; Pantelic, J.; Bueno de Mesquita, P.J.; Albert, B.; Liu, F.; Ehrman, S.; Milton, D.K.; Consortium, E. Infectious virus in exhaled breath of symptomatic seasonal influenza cases from a college community. Proc. Natl. Acad. Sci. USA 2018, 115, 1081–1086. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Dhurandhar, N.V.; Bailey, D.; Thomas, D. Interaction of obesity and infections. Obes. Rev. Off. J. Int. Assoc. Study Obes. 2015, 16, 1017–1029. [Google Scholar] [CrossRef]
- Sheridan, P.A.; Paich, H.A.; Handy, J.; Karlsson, E.A.; Hudgens, M.G.; Sammon, A.B.; Holland, L.A.; Weir, S.; Noah, T.L.; Beck, M.A. Obesity is associated with impaired immune response to influenza vaccination in humans. Int. J. Obes. 2012, 36, 1072–1077. [Google Scholar] [CrossRef] [Green Version]
- Frasca, D.; Ferracci, F.; Diaz, A.; Romero, M.; Lechner, S.; Blomberg, B.B. Obesity decreases B cell responses in young and elderly individuals. Obesity 2016, 24, 615–625. [Google Scholar] [CrossRef]
- Joshi, S.S.; Davis, R.P.; Ma, M.M.; Tam, E.; Cooper, C.L.; Ramji, A.; Kelly, E.M.; Jayakumar, S.; Swain, M.G.; Jenne, C.N.; et al. Reduced immune responses to hepatitis B primary vaccination in obese individuals with nonalcoholic fatty liver disease (NAFLD). Npj Vaccines 2021, 6, 9. [Google Scholar] [CrossRef]
- Polack, F.P.; Thomas, S.J.; Kitchin, N.; Absalon, J.; Gurtman, A.; Lockhart, S.; Perez, J.L.; Perez Marc, G.; Moreira, E.D.; Zerbini, C.; et al. Safety and Efficacy of the BNT162b2 mRNA Covid-19 Vaccine. N. Engl. J. Med. 2020, 383, 2603–2615. [Google Scholar] [CrossRef] [PubMed]
- Baden, L.R.; El Sahly, H.M.; Essink, B.; Kotloff, K.; Frey, S.; Novak, R.; Diemert, D.; Spector, S.A.; Rouphael, N.; Creech, C.B.; et al. Efficacy and Safety of the mRNA-1273 SARS-CoV-2 Vaccine. N. Engl. J. Med. 2021, 384, 403–416. [Google Scholar] [CrossRef]
- O’Brien, K.B.; Vogel, P.; Duan, S.; Govorkova, E.A.; Webby, R.J.; McCullers, J.A.; Schultz-Cherry, S. Impaired wound healing predisposes obese mice to severe influenza virus infection. J. Infect. Dis. 2012, 205, 252–261. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Hogue, C.W., Jr.; Stearns, J.D.; Colantuoni, E.; Robinson, K.A.; Stierer, T.; Mitter, N.; Pronovost, P.J.; Needham, D.M. The impact of obesity on outcomes after critical illness: A meta-analysis. Intensive Care Med. 2009, 35, 1152–1170. [Google Scholar] [CrossRef]
- Anzueto, A.; Frutos-Vivar, F.; Esteban, A.; Bensalami, N.; Marks, D.; Raymondos, K.; Apezteguia, C.; Arabi, Y.; Hurtado, J.; Gonzalez, M.; et al. Influence of body mass index on outcome of the mechanically ventilated patients. Thorax 2011, 66, 66–73. [Google Scholar] [CrossRef] [Green Version]
- Jones, R.L.; Nzekwu, M.M. The effects of body mass index on lung volumes. Chest 2006, 130, 827–833. [Google Scholar] [CrossRef] [PubMed]
- Kwok, S.; Adam, S.; Ho, J.H.; Iqbal, Z.; Turkington, P.; Razvi, S.; Le Roux, C.W.; Soran, H.; Syed, A.A. Obesity: A critical risk factor in the COVID-19 pandemic. Clin. Obes. 2020, 10, e12403. [Google Scholar] [CrossRef] [PubMed]
- Ryan, D.H.; Ravussin, E.; Heymsfield, S. COVID 19 and the Patient with Obesity—The Editors Speak Out. Obesity 2020, 28, 847. [Google Scholar] [CrossRef] [Green Version]
- Petrovic, V.; Radenkovic, D.; Radenkovic, G.; Djordjevic, V.; Banach, M. Pathophysiology of Cardiovascular Complications in COVID-19. Front. Physiol. 2020, 11, 575600. [Google Scholar] [CrossRef]
- Huttunen, R.; Syrjanen, J. Obesity and the risk and outcome of infection. Int. J. Obes. 2013, 37, 333–340. [Google Scholar] [CrossRef] [Green Version]
- Richard, C.; Wadowski, M.; Goruk, S.; Cameron, L.; Sharma, A.M.; Field, C.J. Individuals with obesity and type 2 diabetes have additional immune dysfunction compared with obese individuals who are metabolically healthy. BMJ Open Diabetes Res. Care 2017, 5, e000379. [Google Scholar] [CrossRef]
- Ahn, S.Y.; Sohn, S.H.; Lee, S.Y.; Park, H.L.; Park, Y.W.; Kim, H.; Nam, J.H. The effect of lipopolysaccharide-induced obesity and its chronic inflammation on influenza virus-related pathology. Environ. Toxicol. Pharmacol. 2015, 40, 924–930. [Google Scholar] [CrossRef]
- Codo, A.C.; Davanzo, G.G.; Monteiro, L.B.; de Souza, G.F.; Muraro, S.P.; Virgilio-da-Silva, J.V.; Prodonoff, J.S.; Carregari, V.C.; de Biagi Junior, C.A.O.; Crunfli, F.; et al. Elevated Glucose Levels Favor SARS-CoV-2 Infection and Monocyte Response through a HIF-1alpha/Glycolysis-Dependent Axis. Cell Metab. 2020, 32, 437–446 e435. [Google Scholar] [CrossRef]
- Teran-Cabanillas, E.; Montalvo-Corral, M.; Caire-Juvera, G.; Moya-Camarena, S.Y.; Hernandez, J. Decreased interferon-alpha and interferon-beta production in obesity and expression of suppressor of cytokine signaling. Nutrition 2013, 29, 207–212. [Google Scholar] [CrossRef]
- Honce, R.; Karlsson, E.A.; Wohlgemuth, N.; Estrada, L.D.; Meliopoulos, V.A.; Yao, J.; Schultz-Cherry, S. Obesity-Related Microenvironment Promotes Emergence of Virulent Influenza Virus Strains. mBio 2020, 11. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Agrawal, M.; Kern, P.A.; Nikolajczyk, B.S. The Immune System in Obesity: Developing Paradigms Amidst Inconvenient Truths. Curr. Diabetes Rep. 2017, 17, 87. [Google Scholar] [CrossRef] [PubMed]
- Green, W.D.; Beck, M.A. Obesity Impairs the Adaptive Immune Response to Influenza Virus. Ann. Am. Thorac. Soc. 2017, 14, S406–S409. [Google Scholar] [CrossRef]
- O’Shea, D.; Corrigan, M.; Dunne, M.R.; Jackson, R.; Woods, C.; Gaoatswe, G.; Moynagh, P.N.; O’Connell, J.; Hogan, A.E. Changes in human dendritic cell number and function in severe obesity may contribute to increased susceptibility to viral infection. Int. J. Obes. 2013, 37, 1510–1513. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Paich, H.A.; Sheridan, P.A.; Handy, J.; Karlsson, E.A.; Schultz-Cherry, S.; Hudgens, M.G.; Noah, T.L.; Weir, S.S.; Beck, M.A. Overweight and obese adult humans have a defective cellular immune response to pandemic H1N1 influenza A virus. Obesity 2013, 21, 2377–2386. [Google Scholar] [CrossRef]
- Nieman, D.C.; Nehlsen-Cannarella, S.I.; Henson, D.A.; Butterworth, D.E.; Fagoaga, O.R.; Warren, B.J.; Rainwater, M.K. Immune response to obesity and moderate weight loss. Int. J. Obes. Relat. Metab. Disord. J. Int. Assoc. Study Obes. 1996, 20, 353–360. [Google Scholar]
- Chan, M.E.; Adler, B.J.; Green, D.E.; Rubin, C.T. Bone structure and B-cell populations, crippled by obesity, are partially rescued by brief daily exposure to low-magnitude mechanical signals. Faseb J. Off. Publ. Fed. Am. Soc. Exp. Biol. 2012, 26, 4855–4863. [Google Scholar] [CrossRef] [Green Version]
- Liu, R.; Nikolajczyk, B.S. Tissue Immune Cells Fuel Obesity-Associated Inflammation in Adipose Tissue and Beyond. Front. Immunol. 2019, 10, 1587. [Google Scholar] [CrossRef] [Green Version]
- Le Bert, N.; Tan, A.T.; Kunasegaran, K.; Tham, C.Y.L.; Hafezi, M.; Chia, A.; Chng, M.H.Y.; Lin, M.; Tan, N.; Linster, M.; et al. SARS-CoV-2-specific T cell immunity in cases of COVID-19 and SARS, and uninfected controls. Nature 2020, 584, 457–462. [Google Scholar] [CrossRef] [PubMed]
- Costanzo, A.E.; Taylor, K.R.; Dutt, S.; Han, P.P.; Fujioka, K.; Jameson, J.M. Obesity impairs gammadelta T cell homeostasis and antiviral function in humans. PLoS ONE 2015, 10, e0120918. [Google Scholar] [CrossRef] [PubMed]
- Perez, L.M.; Pareja-Galeano, H.; Sanchis-Gomar, F.; Emanuele, E.; Lucia, A.; Galvez, B.G. ‘Adipaging’: Ageing and obesity share biological hallmarks related to a dysfunctional adipose tissue. J. Physiol. 2016, 594, 3187–3207. [Google Scholar] [CrossRef] [PubMed]
- Kosaraju, R.; Guesdon, W.; Crouch, M.J.; Teague, H.L.; Sullivan, E.M.; Karlsson, E.A.; Schultz-Cherry, S.; Gowdy, K.; Bridges, L.C.; Reese, L.R.; et al. B Cell Activity Is Impaired in Human and Mouse Obesity and Is Responsive to an Essential Fatty Acid upon Murine Influenza Infection. J. Immunol. 2017, 198, 4738–4752. [Google Scholar] [CrossRef] [Green Version]
- Arai, S.; Maehara, N.; Iwamura, Y.; Honda, S.; Nakashima, K.; Kai, T.; Ogishi, M.; Morita, K.; Kurokawa, J.; Mori, M.; et al. Obesity-associated autoantibody production requires AIM to retain the immunoglobulin M immune complex on follicular dendritic cells. Cell Rep. 2013, 3, 1187–1198. [Google Scholar] [CrossRef] [Green Version]
- Zheng, Q.; Cui, G.; Chen, J.; Gao, H.; Wei, Y.; Uede, T.; Chen, Z.; Diao, H. Regular Exercise Enhances the Immune Response Against Microbial Antigens Through Up-Regulation of Toll-like Receptor Signaling Pathways. Cell. Physiol. Biochem. Int. J. Exp. Cell. Physiol. Biochem. Pharmacol. 2015, 37, 735–746. [Google Scholar] [CrossRef] [PubMed]
- Warren, K.J.; Olson, M.M.; Thompson, N.J.; Cahill, M.L.; Wyatt, T.A.; Yoon, K.J.; Loiacono, C.M.; Kohut, M.L. Exercise Improves Host Response to Influenza Viral Infection in Obese and Non-Obese Mice through Different Mechanisms. PLoS ONE 2015, 10, e0129713. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Micallef, M.; Munro, I.; Phang, M.; Garg, M. Plasma n-3 Polyunsaturated Fatty Acids are negatively associated with obesity. Br. J. Nutr. 2009, 102, 1370–1374. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Calder, P.C. Marine omega-3 fatty acids and inflammatory processes: Effects, mechanisms and clinical relevance. Biochim. Et Biophys. Acta 2015, 1851, 469–484. [Google Scholar] [CrossRef] [PubMed]
- Flier, J.S. The adipocyte: Storage depot or node on the energy information superhighway? Cell 1995, 80, 15–18. [Google Scholar] [CrossRef] [Green Version]
- Klok, M.D.; Jakobsdottir, S.; Drent, M.L. The role of leptin and ghrelin in the regulation of food intake and body weight in humans: A review. Obes. Rev. Off. J. Int. Assoc. Study Obes. 2007, 8, 21–34. [Google Scholar] [CrossRef] [PubMed]
- Ahima, R.S.; Flier, J.S. Leptin. Annu. Rev. Physiol. 2000, 62, 413–437. [Google Scholar] [CrossRef] [Green Version]
- Perez-Perez, A.; Vilarino-Garcia, T.; Fernandez-Riejos, P.; Martin-Gonzalez, J.; Segura-Egea, J.J.; Sanchez-Margalet, V. Role of leptin as a link between metabolism and the immune system. Cytokine Growth Factor Rev. 2017, 35, 71–84. [Google Scholar] [CrossRef]
- Chrousos, G.P. The hypothalamic-pituitary-adrenal axis and immune-mediated inflammation. N. Engl. J. Med. 1995, 332, 1351–1362. [Google Scholar] [CrossRef]
- Satoh, N.; Ogawa, Y.; Katsuura, G.; Numata, Y.; Masuzaki, H.; Yoshimasa, Y.; Nakao, K. Satiety effect and sympathetic activation of leptin are mediated by hypothalamic melanocortin system. Neurosci. Lett. 1998, 249, 107–110. [Google Scholar] [CrossRef]
- Gaillard, R.C.; Spinedi, E.; Chautard, T.; Pralong, F.P. Cytokines, leptin, and the hypothalamo-pituitary-adrenal axis. Ann. N. Y. Acad. Sci. USA 2000, 917, 647–657. [Google Scholar] [CrossRef]
- Zakrzewska, K.E.; Cusin, I.; Sainsbury, A.; Rohner-Jeanrenaud, F.; Jeanrenaud, B. Glucocorticoids as counterregulatory hormones of leptin: Toward an understanding of leptin resistance. Diabetes 1997, 46, 717–719. [Google Scholar] [CrossRef] [Green Version]
- Gualillo, O.; Eiras, S.; Lago, F.; Dieguez, C.; Casanueva, F.F. Elevated serum leptin concentrations induced by experimental acute inflammation. Life Sci. 2000, 67, 2433–2441. [Google Scholar] [CrossRef]
- Tilg, H.; Moschen, A.R. Adipocytokines: Mediators linking adipose tissue, inflammation and immunity. Nat. Reviews. Immunol. 2006, 6, 772–783. [Google Scholar] [CrossRef]
- Iikuni, N.; Lam, Q.L.; Lu, L.; Matarese, G.; La Cava, A. Leptin and Inflammation. Curr. Immunol. Rev. 2008, 4, 70–79. [Google Scholar] [CrossRef] [PubMed]
- Ubags, N.D.; Vernooy, J.H.; Burg, E.; Hayes, C.; Bement, J.; Dilli, E.; Zabeau, L.; Abraham, E.; Poch, K.R.; Nick, J.A.; et al. The role of leptin in the development of pulmonary neutrophilia in infection and acute lung injury. Crit. Care Med. 2014, 42, e143–e151. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Guo, X.; Roberts, M.R.; Becker, S.M.; Podd, B.; Zhang, Y.; Chua, S.C., Jr.; Myers, M.G., Jr.; Duggal, P.; Houpt, E.R.; Petri, W.A., Jr. Leptin signaling in intestinal epithelium mediates resistance to enteric infection by Entamoeba histolytica. Mucosal Immunol. 2011, 4, 294–303. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Shapiro, N.I.; Khankin, E.V.; Van Meurs, M.; Shih, S.C.; Lu, S.; Yano, M.; Castro, P.R.; Maratos-Flier, E.; Parikh, S.M.; Karumanchi, S.A.; et al. Leptin exacerbates sepsis-mediated morbidity and mortality. J. Immunol. 2010, 185, 517–524. [Google Scholar] [CrossRef] [PubMed]
- Fruhbeck, G. Intracellular signalling pathways activated by leptin. Biochem. J. 2006, 393, 7–20. [Google Scholar] [CrossRef] [Green Version]
- Zhou, Y.; Rui, L. Leptin signaling and leptin resistance. Front. Med. 2013, 7, 207–222. [Google Scholar] [CrossRef] [PubMed]
- Fernandez-Riejos, P.; Najib, S.; Santos-Alvarez, J.; Martin-Romero, C.; Perez-Perez, A.; Gonzalez-Yanes, C.; Sanchez-Margalet, V. Role of leptin in the activation of immune cells. Mediat. Inflamm. 2010, 2010, 568343. [Google Scholar] [CrossRef]
- Matarese, G.; Moschos, S.; Mantzoros, C.S. Leptin in immunology. J. Immunol. 2005, 174, 3137–3142. [Google Scholar] [CrossRef] [Green Version]
- Ozata, M.; Ozdemir, I.C.; Licinio, J. Human leptin deficiency caused by a missense mutation: Multiple endocrine defects, decreased sympathetic tone, and immune system dysfunction indicate new targets for leptin action, greater central than peripheral resistance to the effects of leptin, and spontaneous correction of leptin-mediated defects. J. Clin. Endocrinol. Metab. 1999, 84, 3686–3695. [Google Scholar] [CrossRef] [PubMed]
- Zarkesh-Esfahani, H.; Pockley, G.; Metcalfe, R.A.; Bidlingmaier, M.; Wu, Z.; Ajami, A.; Weetman, A.P.; Strasburger, C.J.; Ross, R.J. High-dose leptin activates human leukocytes via receptor expression on monocytes. J. Immunol. 2001, 167, 4593–4599. [Google Scholar] [CrossRef] [Green Version]
- Najib, S.; Sanchez-Margalet, V. Human leptin promotes survival of human circulating blood monocytes prone to apoptosis by activation of p42/44 MAPK pathway. Cell. Immunol. 2002, 220, 143–149. [Google Scholar] [CrossRef]
- Balogh, Z.; Foris, G.; Kosztaczky, B.; Paragh, G., Jr.; Seres, I.; Zsiros, E.; Konya, G.; Paragh, G. The concentration dependent biphasic effect of leptin on endogenous cholesterol synthesis in human monocytes. Peptides 2007, 28, 2081–2083. [Google Scholar] [CrossRef]
- Meier, C.A.; Chicheportiche, R.; Dreyer, M.; Dayer, J.M. IP-10, but not RANTES, is upregulated by leptin in monocytic cells. Cytokine 2003, 21, 43–47. [Google Scholar] [CrossRef]
- Curat, C.A.; Miranville, A.; Sengenes, C.; Diehl, M.; Tonus, C.; Busse, R.; Bouloumie, A. From blood monocytes to adipose tissue-resident macrophages: Induction of diapedesis by human mature adipocytes. Diabetes 2004, 53, 1285–1292. [Google Scholar] [CrossRef] [Green Version]
- Loffreda, S.; Yang, S.Q.; Lin, H.Z.; Karp, C.L.; Brengman, M.L.; Wang, D.J.; Klein, A.S.; Bulkley, G.B.; Bao, C.; Noble, P.W.; et al. Leptin regulates proinflammatory immune responses. Faseb J. Off. Publ. Fed. Am. Soc. Exp. Biol. 1998, 12, 57–65. [Google Scholar]
- Gruen, M.L.; Hao, M.; Piston, D.W.; Hasty, A.H. Leptin requires canonical migratory signaling pathways for induction of monocyte and macrophage chemotaxis. Am. J. Physiol. Cell Physiol. 2007, 293, C1481–C1488. [Google Scholar] [CrossRef] [PubMed]
- Lam, Q.L.; Liu, S.; Cao, X.; Lu, L. Involvement of leptin signaling in the survival and maturation of bone marrow-derived dendritic cells. Eur. J. Immunol. 2006, 36, 3118–3130. [Google Scholar] [CrossRef] [PubMed]
- Caldefie-Chezet, F.; Poulin, A.; Tridon, A.; Sion, B.; Vasson, M.P. Leptin: A potential regulator of polymorphonuclear neutrophil bactericidal action? J. Leukoc. Biol. 2001, 69, 414–418. [Google Scholar]
- Zhou, Y.; Yu, X.; Chen, H.; Sjoberg, S.; Roux, J.; Zhang, L.; Ivoulsou, A.H.; Bensaid, F.; Liu, C.L.; Liu, J.; et al. Leptin Deficiency Shifts Mast Cells toward Anti-Inflammatory Actions and Protects Mice from Obesity and Diabetes by Polarizing M2 Macrophages. Cell Metab. 2015, 22, 1045–1058. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Martin-Romero, C.; Santos-Alvarez, J.; Goberna, R.; Sanchez-Margalet, V. Human leptin enhances activation and proliferation of human circulating T lymphocytes. Cell. Immunol. 2000, 199, 15–24. [Google Scholar] [CrossRef] [PubMed]
- Procaccini, C.; Jirillo, E.; Matarese, G. Leptin as an immunomodulator. Mol. Asp. Med. 2012, 33, 35–45. [Google Scholar] [CrossRef]
- Reis, B.S.; Lee, K.; Fanok, M.H.; Mascaraque, C.; Amoury, M.; Cohn, L.B.; Rogoz, A.; Dallner, O.S.; Moraes-Vieira, P.M.; Domingos, A.I.; et al. Leptin receptor signaling in T cells is required for Th17 differentiation. J. Immunol. 2015, 194, 5253–5260. [Google Scholar] [CrossRef] [Green Version]
- Lord, G.M.; Matarese, G.; Howard, J.K.; Baker, R.J.; Bloom, S.R.; Lechler, R.I. Leptin modulates the T-cell immune response and reverses starvation-induced immunosuppression. Nature 1998, 394, 897–901. [Google Scholar] [CrossRef] [PubMed]
- Procaccini, C.; De Rosa, V.; Galgani, M.; Abanni, L.; Cali, G.; Porcellini, A.; Carbone, F.; Fontana, S.; Horvath, T.L.; La Cava, A.; et al. An oscillatory switch in mTOR kinase activity sets regulatory T cell responsiveness. Immunity 2010, 33, 929–941. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Winer, D.A.; Winer, S.; Shen, L.; Wadia, P.P.; Yantha, J.; Paltser, G.; Tsui, H.; Wu, P.; Davidson, M.G.; Alonso, M.N.; et al. B cells promote insulin resistance through modulation of T cells and production of pathogenic IgG antibodies. Nat. Med. 2011, 17, 610–617. [Google Scholar] [CrossRef] [PubMed]
- Oral, E.A.; Javor, E.D.; Ding, L.; Uzel, G.; Cochran, E.K.; Young, J.R.; DePaoli, A.M.; Holland, S.M.; Gorden, P. Leptin replacement therapy modulates circulating lymphocyte subsets and cytokine responsiveness in severe lipodystrophy. J. Clin. Endocrinol. Metab. 2006, 91, 621–628. [Google Scholar] [CrossRef]
- Farooqi, I.S.; Matarese, G.; Lord, G.M.; Keogh, J.M.; Lawrence, E.; Agwu, C.; Sanna, V.; Jebb, S.A.; Perna, F.; Fontana, S.; et al. Beneficial effects of leptin on obesity, T cell hyporesponsiveness, and neuroendocrine/metabolic dysfunction of human congenital leptin deficiency. J. Clin. Investig. 2002, 110, 1093–1103. [Google Scholar] [CrossRef] [PubMed]
- Paz-Filho, G.; Wong, M.L.; Licinio, J. Ten years of leptin replacement therapy. Obes. Rev. Off. J. Int. Assoc. Study Obes. 2011, 12, e315–e323. [Google Scholar] [CrossRef]
- White, S.J.; Taylor, M.J.; Hurt, R.T.; Jensen, M.D.; Poland, G.A. Leptin-based adjuvants: An innovative approach to improve vaccine response. Vaccine 2013, 31, 1666–1672. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Cauchard, S.; Bermudez-Humaran, L.G.; Blugeon, S.; Laugier, C.; Langella, P.; Cauchard, J. Mucosal co-immunization of mice with recombinant lactococci secreting VapA antigen and leptin elicits a protective immune response against Rhodococcus equi infection. Vaccine 2011, 30, 95–102. [Google Scholar] [CrossRef] [PubMed]
- Wehrens, A.; Aebischer, T.; Meyer, T.F.; Walduck, A.K. Leptin receptor signaling is required for vaccine-induced protection against Helicobacter pylori. Helicobacter 2008, 13, 94–102. [Google Scholar] [CrossRef]
- Maurya, R.; Bhattacharya, P.; Dey, R.; Nakhasi, H.L. Leptin Functions in Infectious Diseases. Front. Immunol. 2018, 9, 2741. [Google Scholar] [CrossRef] [Green Version]
- Radigan, K.A.; Morales-Nebreda, L.; Soberanes, S.; Nicholson, T.; Nigdelioglu, R.; Cho, T.; Chi, M.; Hamanaka, R.B.; Misharin, A.V.; Perlman, H.; et al. Impaired clearance of influenza A virus in obese, leptin receptor deficient mice is independent of leptin signaling in the lung epithelium and macrophages. PLoS ONE 2014, 9, e108138. [Google Scholar] [CrossRef]
- Bedoya, F.; Cheng, G.S.; Leibow, A.; Zakhary, N.; Weissler, K.; Garcia, V.; Aitken, M.; Kropf, E.; Garlick, D.S.; Wherry, E.J.; et al. Viral antigen induces differentiation of Foxp3+ natural regulatory T cells in influenza virus-infected mice. J. Immunol. 2013, 190, 6115–6125. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Fulton, R.B.; Meyerholz, D.K.; Varga, S.M. Foxp3+ CD4 regulatory T cells limit pulmonary immunopathology by modulating the CD8 T cell response during respiratory syncytial virus infection. J. Immunol. 2010, 185, 2382–2392. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Milner, J.J.; Sheridan, P.A.; Karlsson, E.A.; Schultz-Cherry, S.; Shi, Q.; Beck, M.A. Diet-induced obese mice exhibit altered heterologous immunity during a secondary 2009 pandemic H1N1 infection. J. Immunol. 2013, 191, 2474–2485. [Google Scholar] [CrossRef] [Green Version]
- De Rosa, V.; Procaccini, C.; Cali, G.; Pirozzi, G.; Fontana, S.; Zappacosta, S.; La Cava, A.; Matarese, G. A key role of leptin in the control of regulatory T cell proliferation. Immunity 2007, 26, 241–255. [Google Scholar] [CrossRef] [Green Version]
- Qin, L.; Tan, Y.R.; Hu, C.P.; Liu, X.A.; He, R.X. Leptin Is Oversecreted by Respiratory Syncytial Virus-Infected Bronchial Epithelial Cells and Regulates Th2 and Th17 Cell Differentiation. Int. Arch. Allergy Immunol. 2015, 167, 65–71. [Google Scholar] [CrossRef]
- Sinha, U.; Sinharay, K.; Sengupta, N.; Mukhopadhyay, P. Benefits of leptin therapy in HIV patients. Indian J. Endocrinol. Metab. 2012, 16, S637–S643. [Google Scholar] [CrossRef]
- Matarese, G.; Castelli-Gattinara, G.; Cancrini, C.; Bernardi, S.; Romiti, M.L.; Savarese, C.; Di Giacomo, A.; Rossi, P.; Racioppi, L. Serum leptin and CD4+ T lymphocytes in HIV+ children during highly active antiretroviral therapy. Clin. Endocrinol. 2002, 57, 643–646. [Google Scholar] [CrossRef]
- Sanchez-Pozo, C.; Rodriguez-Bano, J.; Dominguez-Castellano, A.; Muniain, M.A.; Goberna, R.; Sanchez-Margalet, V. Leptin stimulates the oxidative burst in control monocytes but attenuates the oxidative burst in monocytes from HIV-infected patients. Clin. Exp. Immunol. 2003, 134, 464–469. [Google Scholar] [CrossRef] [PubMed]
- Takahashi, T.; Yu, F.; Saegusa, S.; Sumino, H.; Nakahashi, T.; Iwai, K.; Morimoto, S.; Kurabayashi, M.; Kanda, T. Impaired expression of cardiac adiponectin in leptin-deficient mice with viral myocarditis. Int. Heart J. 2006, 47, 107–123. [Google Scholar] [CrossRef] [Green Version]
- Webb, S.R.; Loria, R.M.; Madge, G.E.; Kibrick, S. Susceptibility of mice to group B coxsackie virus is influenced by the diabetic gene. J. Exp. Med. 1976, 143, 1239–1248. [Google Scholar] [CrossRef]
- Krebs, D.L.; Hilton, D.J. SOCS proteins: Negative regulators of cytokine signaling. Stem Cells 2001, 19, 378–387. [Google Scholar] [CrossRef]
- Wang, J.; Xu, Y.; Zhang, X.; Wang, S.; Peng, Z.; Guo, J.; Jiang, H.; Liu, J.; Xie, Y.; Wang, J.; et al. Leptin correlates with monocytes activation and severe condition in COVID-19 patients. J. Leukoc. Biol. 2021. [Google Scholar] [CrossRef]
- Hassan, I.H.; Zhang, M.S.; Powers, L.S.; Shao, J.Q.; Baltrusaitis, J.; Rutkowski, D.T.; Legge, K.; Monick, M.M. Influenza A viral replication is blocked by inhibition of the inositol-requiring enzyme 1 (IRE1) stress pathway. J. Biol. Chem. 2012, 287, 4679–4689. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Martin, S.S.; Qasim, A.; Reilly, M.P. Leptin resistance: A possible interface of inflammation and metabolism in obesity-related cardiovascular disease. J. Am. Coll. Cardiol. 2008, 52, 1201–1210. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Ravussin, Y.; LeDuc, C.A.; Watanabe, K.; Mueller, B.R.; Skowronski, A.; Rosenbaum, M.; Leibel, R.L. Effects of chronic leptin infusion on subsequent body weight and composition in mice: Can body weight set point be reset? Mol. Metab. 2014, 3, 432–440. [Google Scholar] [CrossRef] [PubMed]
- Rosenbaum, M.; Murphy, E.M.; Heymsfield, S.B.; Matthews, D.E.; Leibel, R.L. Low dose leptin administration reverses effects of sustained weight-reduction on energy expenditure and circulating concentrations of thyroid hormones. J. Clin. Endocrinol. Metab. 2002, 87, 2391–2394. [Google Scholar] [CrossRef]
- Zhang, A.J.; To, K.K.; Li, C.; Lau, C.C.; Poon, V.K.; Chan, C.C.; Zheng, B.J.; Hung, I.F.; Lam, K.S.; Xu, A.; et al. Leptin mediates the pathogenesis of severe 2009 pandemic influenza A(H1N1) infection associated with cytokine dysregulation in mice with diet-induced obesity. J. Infect. Dis. 2013, 207, 1270–1280. [Google Scholar] [CrossRef]
- St-Pierre, J.; Tremblay, M.L. Modulation of leptin resistance by protein tyrosine phosphatases. Cell Metab. 2012, 15, 292–297. [Google Scholar] [CrossRef] [Green Version]
- Ozcan, L.; Ergin, A.S.; Lu, A.; Chung, J.; Sarkar, S.; Nie, D.; Myers, M.G., Jr.; Ozcan, U. Endoplasmic reticulum stress plays a central role in development of leptin resistance. Cell Metab. 2009, 9, 35–51. [Google Scholar] [CrossRef] [Green Version]
- Martin, S.S.; Sperling, L.S.; Blaha, M.J.; Wilson, P.W.F.; Gluckman, T.J.; Blumenthal, R.S.; Stone, N.J. Clinician-patient risk discussion for atherosclerotic cardiovascular disease prevention: Importance to implementation of the 2013 ACC/AHA Guidelines. J. Am. Coll. Cardiol. 2015, 65, 1361–1368. [Google Scholar] [CrossRef] [Green Version]
- Nave, H.; Mueller, G.; Siegmund, B.; Jacobs, R.; Stroh, T.; Schueler, U.; Hopfe, M.; Behrendt, P.; Buchenauer, T.; Pabst, R.; et al. Resistance of Janus kinase-2 dependent leptin signaling in natural killer (NK) cells: A novel mechanism of NK cell dysfunction in diet-induced obesity. Endocrinology 2008, 149, 3370–3378. [Google Scholar] [CrossRef]
- Papathanassoglou, E.; El-Haschimi, K.; Li, X.C.; Matarese, G.; Strom, T.; Mantzoros, C. Leptin receptor expression and signaling in lymphocytes: Kinetics during lymphocyte activation, role in lymphocyte survival, and response to high fat diet in mice. J. Immunol. 2006, 176, 7745–7752. [Google Scholar] [CrossRef]
- Tsiotra, P.C.; Pappa, V.; Raptis, S.A.; Tsigos, C. Expression of the long and short leptin receptor isoforms in peripheral blood mononuclear cells: Implications for leptin’s actions. Metab. Clin. Exp. 2000, 49, 1537–1541. [Google Scholar] [CrossRef] [PubMed]
- Palmer, G.; Aurrand-Lions, M.; Contassot, E.; Talabot-Ayer, D.; Ducrest-Gay, D.; Vesin, C.; Chobaz-Peclat, V.; Busso, N.; Gabay, C. Indirect effects of leptin receptor deficiency on lymphocyte populations and immune response in db/db mice. J. Immunol. 2006, 177, 2899–2907. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Li, Z.; Oben, J.A.; Yang, S.; Lin, H.; Stafford, E.A.; Soloski, M.J.; Thomas, S.A.; Diehl, A.M. Norepinephrine regulates hepatic innate immune system in leptin-deficient mice with nonalcoholic steatohepatitis. Hepatology 2004, 40, 434–441. [Google Scholar] [CrossRef] [PubMed]
- Odaka, C.; Mizuochi, T. Macrophages are involved in DNA degradation of apoptotic cells in murine thymus after administration of hydrocortisone. Cell Death Differ. 2002, 9, 104–112. [Google Scholar] [CrossRef] [PubMed]
- Guglielmi, V.; Sbraccia, P. Obesity phenotypes: Depot-differences in adipose tissue and their clinical implications. Eat. Weight Disord. Ewd 2018, 23, 3–14. [Google Scholar] [CrossRef]
- de Git, K.C.; Adan, R.A. Leptin resistance in diet-induced obesity: The role of hypothalamic inflammation. Obes. Rev. Off. J. Int. Assoc. Study Obes. 2015, 16, 207–224. [Google Scholar] [CrossRef] [PubMed]
- Uchiyama, T.; Okajima, F.; Mogi, C.; Tobo, A.; Tomono, S.; Sato, K. Alamandine reduces leptin expression through the c-Src/p38 MAP kinase pathway in adipose tissue. PLoS ONE 2017, 12, e0178769. [Google Scholar] [CrossRef]
- van der Voort, P.H.J.; Moser, J.; Zandstra, D.F.; Muller Kobold, A.C.; Knoester, M.; Calkhoven, C.F.; Hamming, I.; van Meurs, M. Leptin levels in SARS-CoV-2 infection related respiratory failure: A cross-sectional study and a pathophysiological framework on the role of fat tissue. Heliyon 2020, 6, e04696. [Google Scholar] [CrossRef]
- Lai, E.; Teodoro, T.; Volchuk, A. Endoplasmic reticulum stress: Signaling the unfolded protein response. Physiology 2007, 22, 193–201. [Google Scholar] [CrossRef]
- Chandra Mouli, K.; Pragathi, D.; Naga Jyothi, U.; Shanmuga Kumar, V.; Himalaya Naik, M.; Balananda, P.; Suman, B.; Seshadri Reddy, V.; Vijaya, T. Leptin inhibitors from fungal endophytes (LIFEs): Will be novel therapeutic drugs for obesity and its associated immune mediated diseases. Med. Hypotheses 2016, 92, 48–53. [Google Scholar] [CrossRef]
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Guglielmi, V.; Colangeli, L.; D’Adamo, M.; Sbraccia, P. Susceptibility and Severity of Viral Infections in Obesity: Lessons from Influenza to COVID-19. Does Leptin Play a Role? Int. J. Mol. Sci. 2021, 22, 3183. https://doi.org/10.3390/ijms22063183
Guglielmi V, Colangeli L, D’Adamo M, Sbraccia P. Susceptibility and Severity of Viral Infections in Obesity: Lessons from Influenza to COVID-19. Does Leptin Play a Role? International Journal of Molecular Sciences. 2021; 22(6):3183. https://doi.org/10.3390/ijms22063183
Chicago/Turabian StyleGuglielmi, Valeria, Luca Colangeli, Monica D’Adamo, and Paolo Sbraccia. 2021. "Susceptibility and Severity of Viral Infections in Obesity: Lessons from Influenza to COVID-19. Does Leptin Play a Role?" International Journal of Molecular Sciences 22, no. 6: 3183. https://doi.org/10.3390/ijms22063183