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Vishwa Deep Dixit, DVM, PhD

Waldemar Von Zedtwitz Professor of Pathology and Professor of Immunobiology; Director, Yale Center for Research on Aging (Y-Age), Pathology

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Vishwa Deep Dixit, DVM, PhD
Dixit Lab

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Research Summary

A major goal of Dixit lab is to obtain creative insights that advance knowledge in the field of Immune-Metabolic interactions that drive adiposity and age-related chronic diseases. Studies focus on understanding the mechanisms and consequences of aberrant immune-cell activation in adipose tissue microenvironment and age-related ectopic adipocyte development in lymphoid microenvironment like thymus and bone marrow. The long-term goal of Dixit lab is to understand the mechanisms of immune-metabolic crosstalk and to help develop novel approaches to regulate the aberrant immune cell activation and inflammation as means to enhance healthspan and lifespan.

Extensive Research Description

Dixit’s research is focused on Immunometabolism with the goal to reveal molecular targets that can be harnessed to enhance healthspan with longevity. His laboratory found that pro-longevity hormone FGF21 protects against thymic degeneration and T cell senescence during aging. The ongoing work on this project utilizes various genetic and pharmacological approaches to regulate FGF21 signaling and determine its mechanism of action in control of age-related inflammation and immune-senescence.

Dixit lab has identified a specialized macrophage subset called the Nerve-associated macrophages (NAMs) that resides on sympathetic nerves and controls the bioavailability of catecholamines in tissue microenvironments. The identity of NAMs their function and role in health and disease are unclear and are a major focus of his lab.

Dixit and collaborators help define the role of innate immune sensor NLRP3 inflammasome in age-related chronic diseases, insulin-resistance, type 2 diabetes and immune-senescence and development of inflammation. His lab has also identified that ketone metabolite β-hydroxybutyrate (BHB) is a therapeutic target to lower the NLRP3 inflammasome -dependent chronic inflammatory diseases. The ongoing work in Dixitlab is investigating metabolic regulators of inflammasome deactivation and mechanism of age-related inflammation as a trigger for chronic disease. The Dixit lab uses reverse translation approach, where his group has established the impact of caloric restriction (CR) on human physiology and immunometabolism and are using animal models to test causality to develop CR-mimetic targets that could potentially confer pro-longevity benefits of CR.

The research in Dixit Lab is funded by the National Institutes of Health and Cure Alzheimer Fund.

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Public Health Interests

Aging; Immunology; Obesity

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Selected Publications

  • Caloric restriction in humans reveals immunometabolic regulators of health span.Spadaro O, Youm Y, Shchukina I, Ryu S, Sidorov S, Ravussin A, Nguyen K, Aladyeva E, Predeus AN, Smith SR, Ravussin E, Galban C, Artyomov MN, Dixit VD. Caloric restriction in humans reveals immunometabolic regulators of health span. Science (New York, N.Y.) 2022, 375: 671-677. PMID: 35143297, DOI: 10.1126/science.abg7292.
  • Ketogenic diet restrains aging-induced exacerbation of coronavirus infection in mice.Ryu S, Shchukina I, Youm YH, Qing H, Hilliard B, Dlugos T, Zhang X, Yasumoto Y, Booth CJ, Fernández-Hernando C, Suárez Y, Khanna K, Horvath TL, Dietrich MO, Artyomov M, Wang A, Dixit VD. Ketogenic diet restrains aging-induced exacerbation of coronavirus infection in mice. ELife 2021, 10 PMID: 34151773, PMCID: PMC8245129, DOI: 10.7554/eLife.66522.
  • IL-33 causes thermogenic failure in aging by expanding dysfunctional adipose ILC2.Goldberg EL, Shchukina I, Youm YH, Ryu S, Tsusaka T, Young KC, Camell CD, Dlugos T, Artyomov MN, Dixit VD. IL-33 causes thermogenic failure in aging by expanding dysfunctional adipose ILC2. Cell Metabolism 2021, 33: 2277-2287.e5. PMID: 34473956, PMCID: PMC9067336, DOI: 10.1016/j.cmet.2021.08.004.
  • IL-27 signalling promotes adipocyte thermogenesis and energy expenditure.Wang Q, Li D, Cao G, Shi Q, Zhu J, Zhang M, Cheng H, Wen Q, Xu H, Zhu L, Zhang H, Perry RJ, Spadaro O, Yang Y, He S, Chen Y, Wang B, Li G, Liu Z, Yang C, Wu X, Zhou L, Zhou Q, Ju Z, Lu H, Xin Y, Yang X, Wang C, Liu Y, Shulman GI, Dixit VD, Lu L, Yang H, Flavell RA, Yin Z. IL-27 signalling promotes adipocyte thermogenesis and energy expenditure. Nature 2021, 600: 314-318. PMID: 34819664, DOI: 10.1038/s41586-021-04127-5.
  • Ketogenesis activates metabolically protective γδ T cells in visceral adipose tissue.Goldberg EL, Shchukina I, Asher JL, Sidorov S, Artyomov MN, Dixit VD. Ketogenesis activates metabolically protective γδ T cells in visceral adipose tissue. Nature Metabolism 2020, 2: 50-61. PMID: 32694683, DOI: 10.1038/s42255-019-0160-6.
  • Dietary Regulation of Immunity.Lee AH, Dixit VD. Dietary Regulation of Immunity. Immunity 2020, 53: 510-523. PMID: 32937152, PMCID: PMC7491384, DOI: 10.1016/j.immuni.2020.08.013.
  • Ketogenic diet activates protective γδ T cell responses against influenza virus infection.Goldberg EL, Molony RD, Kudo E, Sidorov S, Kong Y, Dixit VD, Iwasaki A. Ketogenic diet activates protective γδ T cell responses against influenza virus infection. Science Immunology 2019, 4 PMID: 31732517, PMCID: PMC7189564, DOI: 10.1126/sciimmunol.aav2026.
  • Aging Induces an Nlrp3 Inflammasome-Dependent Expansion of Adipose B Cells That Impairs Metabolic Homeostasis.Camell CD, Günther P, Lee A, Goldberg EL, Spadaro O, Youm YH, Bartke A, Hubbard GB, Ikeno Y, Ruddle NH, Schultze J, Dixit VD. Aging Induces an Nlrp3 Inflammasome-Dependent Expansion of Adipose B Cells That Impairs Metabolic Homeostasis. Cell Metabolism 2019, 30: 1024-1039.e6. PMID: 31735593, PMCID: PMC6944439, DOI: 10.1016/j.cmet.2019.10.006.
  • Loss of Nucleobindin-2 Causes Insulin Resistance in Obesity without Impacting Satiety or Adiposity.Ravussin A, Youm YH, Sander J, Ryu S, Nguyen K, Varela L, Shulman GI, Sidorov S, Horvath TL, Schultze JL, Dixit VD. Loss of Nucleobindin-2 Causes Insulin Resistance in Obesity without Impacting Satiety or Adiposity. Cell Reports 2018, 24: 1085-1092.e6. PMID: 30067966, PMCID: PMC6223120, DOI: 10.1016/j.celrep.2018.06.112.
  • IGF1 Shapes Macrophage Activation in Response to Immunometabolic Challenge.Spadaro O, Camell CD, Bosurgi L, Nguyen KY, Youm YH, Rothlin CV, Dixit VD. IGF1 Shapes Macrophage Activation in Response to Immunometabolic Challenge. Cell Reports 2017, 19: 225-234. PMID: 28402847, PMCID: PMC5513500, DOI: 10.1016/j.celrep.2017.03.046.
  • β-Hydroxybutyrate Deactivates Neutrophil NLRP3 Inflammasome to Relieve Gout Flares.Goldberg EL, Asher JL, Molony RD, Shaw AC, Zeiss CJ, Wang C, Morozova-Roche LA, Herzog RI, Iwasaki A, Dixit VD. β-Hydroxybutyrate Deactivates Neutrophil NLRP3 Inflammasome to Relieve Gout Flares. Cell Reports 2017, 18: 2077-2087. PMID: 28249154, PMCID: PMC5527297, DOI: 10.1016/j.celrep.2017.02.004.
  • Inflammasome-driven catecholamine catabolism in macrophages blunts lipolysis during ageing.Camell CD, Sander J, Spadaro O, Lee A, Nguyen KY, Wing A, Goldberg EL, Youm YH, Brown CW, Elsworth J, Rodeheffer MS, Schultze JL, Dixit VD. Inflammasome-driven catecholamine catabolism in macrophages blunts lipolysis during ageing. Nature 2017, 550: 119-123. PMID: 28953873, PMCID: PMC5718149, DOI: 10.1038/nature24022.
  • Carnitine acetyltransferase (CRAT) expression in macrophages is dispensable for nutrient stress sensing and inflammation.Goldberg EL, Dixit VD. Carnitine acetyltransferase (CRAT) expression in macrophages is dispensable for nutrient stress sensing and inflammation. Molecular Metabolism 2017, 6: 219-225. PMID: 28180063, PMCID: PMC5279934, DOI: 10.1016/j.molmet.2016.12.008.
  • Growth Hormone Receptor Deficiency Protects against Age-Related NLRP3 Inflammasome Activation and Immune Senescence.Spadaro O, Goldberg EL, Camell CD, Youm YH, Kopchick JJ, Nguyen KY, Bartke A, Sun LY, Dixit VD. Growth Hormone Receptor Deficiency Protects against Age-Related NLRP3 Inflammasome Activation and Immune Senescence. Cell Reports 2016, 14: 1571-1580. PMID: 26876170, PMCID: PMC5992590, DOI: 10.1016/j.celrep.2016.01.044.
  • Prolongevity hormone FGF21 protects against immune senescence by delaying age-related thymic involution.Youm YH, Horvath TL, Mangelsdorf DJ, Kliewer SA, Dixit VD. Prolongevity hormone FGF21 protects against immune senescence by delaying age-related thymic involution. Proceedings Of The National Academy Of Sciences Of The United States Of America 2016, 113: 1026-31. PMID: 26755598, PMCID: PMC4743827, DOI: 10.1073/pnas.1514511113.
  • Regulation of Nlrp3 inflammasome by dietary metabolites.Camell C, Goldberg E, Dixit VD. Regulation of Nlrp3 inflammasome by dietary metabolites. Seminars In Immunology 2015, 27: 334-42. PMID: 26776831, PMCID: PMC4821737, DOI: 10.1016/j.smim.2015.10.004.
  • Drivers of age-related inflammation and strategies for healthspan extension.Goldberg EL, Dixit VD. Drivers of age-related inflammation and strategies for healthspan extension. Immunological Reviews 2015, 265: 63-74. PMID: 25879284, PMCID: PMC4400872, DOI: 10.1111/imr.12295.
  • The ketone metabolite β-hydroxybutyrate blocks NLRP3 inflammasome-mediated inflammatory disease.Youm YH, Nguyen KY, Grant RW, Goldberg EL, Bodogai M, Kim D, D'Agostino D, Planavsky N, Lupfer C, Kanneganti TD, Kang S, Horvath TL, Fahmy TM, Crawford PA, Biragyn A, Alnemri E, Dixit VD. The ketone metabolite β-hydroxybutyrate blocks NLRP3 inflammasome-mediated inflammatory disease. Nature Medicine 2015, 21: 263-9. PMID: 25686106, PMCID: PMC4352123, DOI: 10.1038/nm.3804.
  • Inactivation of C/ebp homologous protein-driven immune-metabolic interactions exacerbate obesity and adipose tissue leukocytosis.Grant R, Nguyen KY, Ravussin A, Albarado D, Youm YH, Dixit VD. Inactivation of C/ebp homologous protein-driven immune-metabolic interactions exacerbate obesity and adipose tissue leukocytosis. The Journal Of Biological Chemistry 2014, 289: 14045-55. PMID: 24662293, PMCID: PMC4022874, DOI: 10.1074/jbc.M113.545921.
  • Canonical Nlrp3 inflammasome links systemic low-grade inflammation to functional decline in aging.Youm YH, Grant RW, McCabe LR, Albarado DC, Nguyen KY, Ravussin A, Pistell P, Newman S, Carter R, Laque A, Münzberg H, Rosen CJ, Ingram DK, Salbaum JM, Dixit VD. Canonical Nlrp3 inflammasome links systemic low-grade inflammation to functional decline in aging. Cell Metabolism 2013, 18: 519-32. PMID: 24093676, PMCID: PMC4017327, DOI: 10.1016/j.cmet.2013.09.010.
  • The Nlrp3 inflammasome promotes age-related thymic demise and immunosenescence.Youm YH, Kanneganti TD, Vandanmagsar B, Zhu X, Ravussin A, Adijiang A, Owen JS, Thomas MJ, Francis J, Parks JS, Dixit VD. The Nlrp3 inflammasome promotes age-related thymic demise and immunosenescence. Cell Reports 2012, 1: 56-68. PMID: 22832107, PMCID: PMC3883512, DOI: 10.1016/j.celrep.2011.11.005.
  • Impact of immune-metabolic interactions on age-related thymic demise and T cell senescence.Dixit VD. Impact of immune-metabolic interactions on age-related thymic demise and T cell senescence. Seminars In Immunology 2012, 24: 321-30. PMID: 22546243, DOI: 10.1016/j.smim.2012.04.002.
  • Immunological complications of obesity.Kanneganti TD, Dixit VD. Immunological complications of obesity. Nature Immunology 2012, 13: 707-12. PMID: 22814340, DOI: 10.1038/ni.2343.
  • The NLRP3 inflammasome instigates obesity-induced inflammation and insulin resistance.Vandanmagsar B, Youm YH, Ravussin A, Galgani JE, Stadler K, Mynatt RL, Ravussin E, Stephens JM, Dixit VD. The NLRP3 inflammasome instigates obesity-induced inflammation and insulin resistance. Nature Medicine 2011, 17: 179-88. PMID: 21217695, PMCID: PMC3076025, DOI: 10.1038/nm.2279.
  • Elimination of the NLRP3-ASC inflammasome protects against chronic obesity-induced pancreatic damage.Youm YH, Adijiang A, Vandanmagsar B, Burk D, Ravussin A, Dixit VD. Elimination of the NLRP3-ASC inflammasome protects against chronic obesity-induced pancreatic damage. Endocrinology 2011, 152: 4039-45. PMID: 21862613, PMCID: PMC3199005, DOI: 10.1210/en.2011-1326.
  • Thiazolidinedione treatment and constitutive-PPARgamma activation induces ectopic adipogenesis and promotes age-related thymic involution.Youm YH, Yang H, Amin R, Smith SR, Leff T, Dixit VD. Thiazolidinedione treatment and constitutive-PPARgamma activation induces ectopic adipogenesis and promotes age-related thymic involution. Aging Cell 2010, 9: 478-89. PMID: 20374200, PMCID: PMC2910128, DOI: 10.1111/j.1474-9726.2010.00574.x.
  • Thymic fatness and approaches to enhance thymopoietic fitness in aging.Dixit VD. Thymic fatness and approaches to enhance thymopoietic fitness in aging. Current Opinion In Immunology 2010, 22: 521-8. PMID: 20650623, PMCID: PMC2993497, DOI: 10.1016/j.coi.2010.06.010.
  • Obesity increases the production of proinflammatory mediators from adipose tissue T cells and compromises TCR repertoire diversity: implications for systemic inflammation and insulin resistance.Yang H, Youm YH, Vandanmagsar B, Ravussin A, Gimble JM, Greenway F, Stephens JM, Mynatt RL, Dixit VD. Obesity increases the production of proinflammatory mediators from adipose tissue T cells and compromises TCR repertoire diversity: implications for systemic inflammation and insulin resistance. Journal Of Immunology (Baltimore, Md. : 1950) 2010, 185: 1836-45. PMID: 20581149, PMCID: PMC4829921, DOI: 10.4049/jimmunol.1000021.
  • Inhibition of thymic adipogenesis by caloric restriction is coupled with reduction in age-related thymic involution.Yang H, Youm YH, Dixit VD. Inhibition of thymic adipogenesis by caloric restriction is coupled with reduction in age-related thymic involution. Journal Of Immunology (Baltimore, Md. : 1950) 2009, 183: 3040-52. PMID: 19648267, PMCID: PMC2731487, DOI: 10.4049/jimmunol.0900562.
  • Obesity accelerates thymic aging.Yang H, Youm YH, Vandanmagsar B, Rood J, Kumar KG, Butler AA, Dixit VD. Obesity accelerates thymic aging. Blood 2009, 114: 3803-12. PMID: 19721009, PMCID: PMC2773495, DOI: 10.1182/blood-2009-03-213595.
  • Adipose-immune interactions during obesity and caloric restriction: reciprocal mechanisms regulating immunity and health span.Dixit VD. Adipose-immune interactions during obesity and caloric restriction: reciprocal mechanisms regulating immunity and health span. Journal Of Leukocyte Biology 2008, 84: 882-92. PMID: 18579754, PMCID: PMC2638733, DOI: 10.1189/jlb.0108028.
  • Ghrelin promotes thymopoiesis during aging.Dixit VD, Yang H, Sun Y, Weeraratna AT, Youm YH, Smith RG, Taub DD. Ghrelin promotes thymopoiesis during aging. The Journal Of Clinical Investigation 2007, 117: 2778-90. PMID: 17823656, PMCID: PMC1964507, DOI: 10.1172/JCI30248.
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