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

被引:6
|
作者
Li, Hao [1 ]
Wetchapinant, Chattiya [2 ]
Zhang, Liya [3 ]
Wu, Kunpeng [2 ,4 ]
机构
[1] Navy Med Univ, Dept Pathophysiol, 800 Xiangyin Rd, Shanghai 200433, Peoples R China
[2] Fudan Univ, 220 Handan Rd, Shanghai 200433, Peoples R China
[3] Tianjin Med Univ, Baodi Clin Coll, 8 Guangchuan Rd, Tianjin 301800, Peoples R China
[4] Fudan Univ, Huashan Hosp, Dept Hematol, 12 Middle Urumqi Rd, Shanghai 200040, Peoples R China
关键词
Growing period; High-fat diet; T cell development; Thymus; CHILDHOOD OBESITY; LIPOTOXICITY; RISK; MICE;
D O I
10.1002/lipd.12193
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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.
引用
收藏
页码:35 / 44
页数:10
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