Department of Pathology, Albert Einstein College of Medicine, Bronx, New York, USA.
J Infect Dis. 2010 Oct 1;202(7):1104-13. doi: 10.1086/656189.
Mice carrying a defective leptin receptor gene (db/db mice) are metabolically challenged and upon infection with Trypanosoma cruzi (Brazil strain) suffer high mortality. In genetically modified db/db mice, (NSE-Rb db/db mice), central leptin signaling is reconstituted only in the brain, which is sufficient to correct the metabolic defects. NSE-Rb db/db mice were infected with T. cruzi to determine the impact of the lack of leptin signaling on infection in the absence of metabolic dysregulation. Parasitemia levels, mortality rates, and tissue parasitism were statistically significantly increased in infected db/db mice compared with those in infected NSE-Rb db/db and FVB wild-type mice. There was a reduction in fat mass and blood glucose level in infected db/db mice. Plasma levels of several cytokines and chemokines were statistically significantly increased in infected db/db mice compared with those in infected FVB and NSE-Rb db/db mice. These findings suggest that leptin resistance in individuals with obesity and diabetes mellitus may have adverse consequences in T. cruzi infection.
携带瘦素受体基因缺陷（db/db 小鼠）的小鼠在代谢方面受到挑战，并且在感染克氏锥虫（巴西株）后死亡率很高。在基因修饰的 db/db 小鼠（NSE-Rb db/db 小鼠）中，仅在大脑中重建了中央瘦素信号，这足以纠正代谢缺陷。NSE-Rb db/db 小鼠被感染克氏锥虫，以确定在没有代谢失调的情况下，缺乏瘦素信号对感染的影响。与感染 NSE-Rb db/db 和 FVB 野生型小鼠的感染小鼠相比，感染 db/db 小鼠的寄生虫血症水平、死亡率和组织寄生虫感染均显著增加。感染 db/db 小鼠的脂肪量和血糖水平降低。与感染 FVB 和 NSE-Rb db/db 小鼠相比，感染 db/db 小鼠的几种细胞因子和趋化因子的血浆水平显著升高。这些发现表明，肥胖和糖尿病患者的瘦素抵抗可能对克氏锥虫感染产生不利影响。
