Obesity accelerates thymic aging
Open Access
- 29 October 2009
- journal article
- Published by American Society of Hematology in Blood
- Vol. 114 (18), 3803-3812
- https://doi.org/10.1182/blood-2009-03-213595
Abstract
As the expanding obese population grows older, their successful immunologic aging will be critical to enhancing the health span. Obesity increases risk of infections and cancer, suggesting adverse effects on immune surveillance. Here, we report that obesity compromises the mechanisms regulating T-cell generation by inducing premature thymic involution. Diet-induced obesity reduced thymocyte counts and significantly increased apoptosis of developing T-cell populations. Obesity accelerated the age-related reduction of T-cell receptor (TCR) excision circle bearing peripheral lymphocytes, an index of recently generated T cells from thymus. Consistent with reduced thymopoiesis, dietary obesity led to reduction in peripheral naive T cells with increased frequency of effector-memory cells. Defects in thymopoiesis in obese mice were related with decrease in the lymphoid-primed multipotent progenitor (Lin−Sca1+Kit+ Flt3+) as well as common lymphoid progenitor (Lin−Sca1+CD117loCD127+) pools. The TCR spectratyping analysis showed that obesity compromised V-β TCR repertoire diversity. Furthermore, the obesity induced by melanocortin 4 receptor deficiency also constricted the T-cell repertoire diversity, recapitulating the thymic defects observed with diet-induced obesity. In middle-aged humans, progressive adiposity with or without type 2 diabetes also compromised thymic output. Collectively, these findings establish that obesity constricts T-cell diversity by accelerating age-related thymic involution.Keywords
This publication has 57 references indexed in Scilit:
- Reduction of T cell–derived ghrelin enhances proinflammatory cytokine expression: implications for age-associated increases in inflammationBlood, 2009
- Deficient Ghrelin Receptor-mediated Signaling Compromises Thymic Stromal Cell Microenvironment by Accelerating Thymic AdiposityPublished by Elsevier BV ,2009
- Selective impairment in dendritic cell function and altered antigen‐specific CD8+ T‐cell responses in diet‐induced obese mice infected with influenza virusImmunology, 2009
- Diet-induced obesity in mice causes changes in immune responses and bone loss manifested by bacterial challengeProceedings of the National Academy of Sciences of the United States of America, 2007
- Cause-Specific Excess Deaths Associated With Underweight, Overweight, and ObesityJAMA, 2007
- The central melanocortin system directly controls peripheral lipid metabolismJCI Insight, 2007
- Ghrelin promotes thymopoiesis during agingJCI Insight, 2007
- Multiple prethymic defects underlie age-related loss of T progenitor competenceBlood, 2007
- Inflammation and metabolic disordersNature, 2006
- Beneficial effects of leptin on obesity, T cell hyporesponsiveness, and neuroendocrine/metabolic dysfunction of human congenital leptin deficiencyJCI Insight, 2002