Nour Jasmine, Moregola Annalisa, Svecla Monika, Da Dalt Lorenzo, Bellini Rossella, Neyrolles Olivier, Fadini Gian Paolo, Rombouts Yoann, Albiero Mattia, Bonacina Fabrizia, Norata Giuseppe Danilo
Department of Excellence of Pharmacological and Biomolecular Sciences, University of Milan, 20133 Milan, Italy.
Institut de Pharmacologie et de Biologie Structurale, IPBS, University of Toulouse, CNRS, UPS, 31400 Toulouse, France.
Metabolites. 2022 Dec 1;12(12):1205. doi: 10.3390/metabo12121205.
The mannose receptor C-type 1 (Mrc1) is a C-type lectin receptor expressed on the immune cells and sinusoidal endothelial cells (ECs) of several tissues, including the bone marrow (BM). Parallel to systemic metabolic alterations and hematopoietic cell proliferation, high-fat diet (HFD) feeding increases the expression of Mrc1 in sinusoidal ECs, thus calling for the investigation of its role in bone marrow cell reprogramming and the metabolic profile during obesity. mice and wild-type (WT) littermates were fed an HFD (45% Kcal/diet) for 20 weeks. Weight gain was monitored during the diet regimen and glucose and insulin tolerance were assessed. Extensive flow cytometry profiling, histological, and proteomic analyses were performed. After HFD feeding, mice presented impaired medullary hematopoiesis with reduced myeloid progenitors and mature cells in parallel with an increase in BM adipocytes compared to controls. Accordingly, circulating levels of neutrophils and pro-inflammatory monocytes decreased in mice together with reduced infiltration of macrophages in the visceral adipose tissue and the liver compared to controls. Liver histological profiling coupled with untargeted proteomic analysis revealed that mice presented decreased liver steatosis and the downregulation of proteins belonging to pathways involved in liver dysfunction. This profile was reflected by improved glucose and insulin response and reduced weight gain during HFD feeding in mice compared to controls. Our data show that during HFD feeding, mannose receptor deficiency impacts BM and circulating immune cell subsets, which is associated with reduced systemic inflammation and resistance to obesity development.
甘露糖受体C型1（Mrc1）是一种C型凝集素受体，在包括骨髓（BM）在内的多种组织的免疫细胞和窦状内皮细胞（ECs）上表达。与全身代谢改变和造血细胞增殖同时发生的是，高脂饮食（HFD）喂养会增加窦状内皮细胞中Mrc1的表达，因此需要研究其在肥胖期间骨髓细胞重编程和代谢谱中的作用。将基因敲除小鼠和野生型（WT）同窝小鼠喂食HFD（45%千卡/饮食）20周。在饮食方案期间监测体重增加情况，并评估葡萄糖和胰岛素耐受性。进行了广泛的流式细胞术分析、组织学分析和蛋白质组学分析。与对照组相比，HFD喂养后，基因敲除小鼠的髓系造血功能受损，髓系祖细胞和成熟细胞减少，同时骨髓脂肪细胞增加。因此，与对照组相比，基因敲除小鼠循环中的中性粒细胞和促炎单核细胞水平降低，内脏脂肪组织和肝脏中的巨噬细胞浸润也减少。肝脏组织学分析与非靶向蛋白质组学分析表明，基因敲除小鼠的肝脏脂肪变性减少，与肝功能障碍相关途径中的蛋白质下调。与对照组相比，基因敲除小鼠在HFD喂养期间的葡萄糖和胰岛素反应改善，体重增加减少，这反映了这种情况。我们的数据表明，在HFD喂养期间，甘露糖受体缺乏会影响骨髓和循环免疫细胞亚群，这与全身炎症减少和对肥胖发展的抵抗力有关。
