Department of Biochemistry and Molecular & Cellular Biology, Georgetown University Medical Center, 3970 Reservoir Road, NW, New Research Building, Room E504, Washington, DC, 20057, USA.
Center for Metabolomic Studies, Georgetown University, Washington, DC, USA.
Metabolomics. 2024 Aug 27;20(5):100. doi: 10.1007/s11306-024-02165-4.
White-nose syndrome (WNS) is a fungal wildlife disease of bats that has caused precipitous declines in certain Nearctic bat species. A key driver of mortality is premature exhaustion of fat reserves, primarily white adipose tissue (WAT), that bats rely on to meet their metabolic needs during winter. However, the pathophysiological and metabolic effects of WNS have remained ill-defined. To elucidate metabolic mechanisms associated with WNS mortality, we infected a WNS susceptible species, the Little Brown Myotis (Myotis lucifugus), with Pseudogymnoascus destructans (Pd) and collected WAT biopsies for histology and targeted lipidomics. These results were compared to the WNS-resistant Big Brown Bat (Eptesicus fuscus). A similar distribution in broad lipid class was observed in both species, with total WAT primarily consisting of triacylglycerides. Baseline differences in WAT chemical composition between species showed that higher glycerophospholipids (GPs) levels in E. fuscus were dominated by unsaturated or monounsaturated moieties and n-6 (18:2, 20:2, 20:3, 20:4) fatty acids. Conversely, higher GP levels in M. lucifugus WAT were primarily compounds containing n-3 (20:5 and 22:5) fatty acids. Following Pd-infection, we found that perturbation to WAT reserves occurs in M. lucifugus, but not in the resistant E. fuscus. A total of 66 GPs (primarily glycerophosphocholines and glycerophosphoethanolamines) were higher in Pd-infected M. lucifugus, indicating perturbation to the WAT structural component. In addition to changes in lipid chemistry, smaller adipocyte sizes and increased extracellular matrix deposition was observed in Pd-infected M. lucifugus. This is the first study to describe WAT GP composition of bats with different susceptibilities to WNS and highlights that recovery from WNS may require repair from adipose remodeling in addition to replenishing depot fat during spring emergence.
白鼻综合征(WNS)是一种影响蝙蝠的真菌性野生动物疾病,已导致某些近北极蝙蝠物种数量急剧下降。导致蝙蝠死亡的一个关键因素是脂肪储备过早耗尽,主要是白色脂肪组织(WAT),蝙蝠在冬季依靠这些脂肪储备来满足其代谢需求。然而,WNS 的病理生理学和代谢影响仍不清楚。为了阐明与 WNS 死亡率相关的代谢机制,我们用假丝酵母菌(Pd)感染了一种易感染 WNS 的物种——小褐蝙蝠(Myotis lucifugus),并采集了 WAT 活检进行组织学和靶向脂质组学分析。将这些结果与对 WNS 具有抗性的大褐蝙蝠(Eptesicus fuscus)进行了比较。在这两个物种中观察到广泛脂质类别的相似分布,WAT 主要由三酰基甘油组成。物种之间 WAT 化学成分的基线差异表明,E. fuscus 中较高的甘油磷脂(GP)水平主要由不饱和或单不饱和部分和 n-6(18:2、20:2、20:3、20:4)脂肪酸组成。相反,M. lucifugus WAT 中较高的 GP 水平主要是含有 n-3(20:5 和 22:5)脂肪酸的化合物。在 Pd 感染后,我们发现 M. lucifugus 的 WAT 储备受到了干扰,但在抗性 E. fuscus 中没有。在 Pd 感染的 M. lucifugus 中,共有 66 种甘油磷脂(主要是甘油磷酸胆碱和甘油磷酸乙醇胺)含量升高,表明 WAT 结构成分受到干扰。除了脂质化学的变化外,在 Pd 感染的 M. lucifugus 中还观察到较小的脂肪细胞大小和细胞外基质沉积增加。这是首次描述对白鼻综合征易感性不同的蝙蝠的 WAT GP 组成的研究,并强调了从 WNS 中恢复可能需要除了在春季出现时补充脂肪储备外,还需要从脂肪重塑中恢复。