2018 Fiscal Year Final Research Report

Challenge to clarify the physiological basis of obesity paradox using intravital microscopy

Research Project

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Project/Area Number	16K15680
Research Category	Grant-in-Aid for Challenging Exploratory Research
Allocation Type	Multi-year Fund
Research Field	Anesthesiology
Research Institution	Kyorin University
Principal Investigator	Mitsuda Shingo 杏林大学, 医学部, 助教 (80636431)
Co-Investigator(Kenkyū-buntansha)	鵜澤康二杏林大学, 医学部, 助教 (30530703) 牛山明国立保健医療科学院, その他部局等, 上席主任研究官 (60291118)
Project Period (FY)	2016-04-01 – 2019-03-31
Keywords	肥満パラドックス / 敗血症 / グリコカリックス / 微小循環 / 重症病態
Outline of Final Research Achievements	The “obesity paradox” is a medical hypothesis which holds that obese people may be protective and associated with higher survival than lean people. However, little is known about physiological basis that support the mechanism of obesity paradox. Therefore, we aim to elucidate the differences in vascular endothelial glycocalyx (GCX) with intravital microscopy among three groups of mice, that fed different fat content diet. The GCXIs of the high fat(H) group and medium fat (M)group were significantly higher than that of the L group (p <0.05). There was a positive correlation between vessel diameter and GCXI in the H and M group, but not in the L group.In the H and M group, the GCX layer thickened with an increase in the diameter of the vessels. However, the thickness of GCX remained unchanged in the L groups under similar conditions. Thus, GCX thickness may play a key role in beneficial impact on pathological changes in obesity paradox.
Free Research Field	麻酔科学
Academic Significance and Societal Importance of the Research Achievements	実験ではグリコカリックスの厚みに着目し、高脂肪食群、中脂肪食群、低脂肪食群の３群を作成し、脳軟膜上の微小血管のグリコカリックスの観察を行い、中脂肪食群及び高脂肪群は低脂肪食群と比較しグリコカリックスが有意に厚い結果が得られた。このようなグリコカリックスの厚みの差異が重症病態において有利に働くことは容易に想像ができ、さらなる今後の研究が期待される。これまで肥満パラドックスに関する報告は疫学的なものがほとんどであり、本研究のようにその病態生理を解明しようとし、基礎実験、特に血管内皮細胞上のグリコカリックスに着目したものは世界初の報告であると考えられ、学術的、社会的意義は大きかったと考えられる。