Instituto de Medicina Molecular-João Lobo Antunes, Faculdade de Medicina, Universidade de Lisboa, Lisbon, Portugal.
Institute of Molecular Biosciences, University of Graz, Graz, Austria.
Nat Microbiol. 2023 Nov;8(11):2020-2032. doi: 10.1038/s41564-023-01496-7. Epub 2023 Oct 12.
Trypanosoma brucei causes African trypanosomiasis, colonizing adipose tissue and inducing weight loss. Here we investigated the molecular mechanisms responsible for adipose mass loss and its impact on disease pathology. We found that lipolysis is activated early in infection. Mice lacking B and T lymphocytes fail to upregulate adipocyte lipolysis, resulting in higher fat mass retention. Genetic ablation of the rate-limiting adipose triglyceride lipase specifically from adipocytes (Adipoq-Atgl) prevented the stimulation of adipocyte lipolysis during infection, reducing fat mass loss. Surprisingly, these mice succumbed earlier and presented a higher parasite burden in the gonadal adipose tissue, indicating that host lipolysis limits parasite growth. Consistently, free fatty acids comparable with those of adipose interstitial fluid induced loss of parasite viability. Adipocyte lipolysis emerges as a mechanism controlling local parasite burden and affecting the loss of fat mass in African trypanosomiasis.
布氏锥虫引起非洲锥虫病,定殖于脂肪组织并导致体重减轻。在这里,我们研究了导致脂肪质量损失的分子机制及其对疾病病理的影响。我们发现脂解作用在感染早期被激活。缺乏 B 和 T 淋巴细胞的小鼠不能上调脂肪细胞脂解作用,导致脂肪质量保留更高。从脂肪细胞特异性敲除限速脂肪甘油三酯脂肪酶(Adipoq-Atgl)的基因缺失可防止感染期间脂肪细胞脂解作用的刺激,从而减少脂肪质量损失。令人惊讶的是,这些小鼠更早死亡,并在生殖腺脂肪组织中呈现更高的寄生虫负担,表明宿主脂解作用限制了寄生虫的生长。一致地,与脂肪间质液中的游离脂肪酸相当的物质诱导寄生虫活力丧失。脂肪细胞脂解作用是一种控制局部寄生虫负担并影响非洲锥虫病脂肪质量损失的机制。