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

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.