High‐Fat Diet from Weaning until Early Adulthood Impairs T Cell Development in the Thymus

Abstract The growing prevalence of childhood obesity has become a serious health problem over the past few decades. Although the immune system is greatly affected by childhood obesity, whether obesity influences the T cell development in the thymus is poorly understood. In this study, we used a high‐fat diet (HFD)‐induced obesity mice model to study the influence of HFD from weaning on the thymus. C57BL/6 mice (male, 3 weeks old) were fed a HFD or standard diet (lean controls) for 6 weeks. The bodyweight of mice fed with an HFD was 28% higher than that in the control group, while the thymus weight of HFD mice decreased by 15% compared with controls. As expected, thymic triacylglycerol content of the HFD mice increased by 37% compared to the control mice. Importantly, the frequencies of CD4 + and CD8 + single‐positive (SP) thymocytes decreased by 38% and 44%, respectively. The apoptotic analysis revealed that thymic tissue of HFD mice had a higher level of Annexin‐V positive thymocytes than control animals. Furthermore, the immunoblotting analysis showed that survival signal pathways in the thymus were impaired in the HFD mice, including the AKT/mTOR and ERK pathways. With the analysis of T‐cell receptor excision circles (TREC), we found that HFD‐induced obesity decreased recent thymic emigrants in spleen tissue. Our findings indicate that HFD from the weaning period impairs T cell development in the thymus, possibly by induction of apoptosis of thymocytes, involving disruption of survival signal pathways.