Preprint Article Version 1 Preserved in Portico This version is not peer-reviewed

BCG Vaccination Suppresses Glucose Intolerance Progression in High-Fat Diet-Fed C57BL/6 Mice

Version 1 : Received: 10 May 2024 / Approved: 11 May 2024 / Online: 13 May 2024 (07:59:41 CEST)

How to cite: Arakawa, H.; Inafuku, M. BCG Vaccination Suppresses Glucose Intolerance Progression in High-Fat Diet-Fed C57BL/6 Mice. Preprints 2024, 2024050750. https://doi.org/10.20944/preprints202405.0750.v1 Arakawa, H.; Inafuku, M. BCG Vaccination Suppresses Glucose Intolerance Progression in High-Fat Diet-Fed C57BL/6 Mice. Preprints 2024, 2024050750. https://doi.org/10.20944/preprints202405.0750.v1

Abstract

Background and Objectives: Mycobacterium bovis Bacillus Calmette–Guérin (BCG) vaccine administration has been suggested to prevent glucose metabolism abnormalities and fatty liver in genetically obese ob/ob mice; however, it is not clear whether the beneficial effects of BCG are also observed in the progression of glucose intolerance induced by a high-fat diet (HFD). Therefore, the effects of BCG vaccination on changes in glucose tolerance and insulin response were investigated in HFD-fed C57BL/6 mice. Materials and Methods: We used the BCG Tokyo 172 strain to determine its effects on abnormalities in glucose metabolism. For vaccination, five-week-old male mice were injected intraperitoneally with BCG and maintained on an HFD three weeks later. The mice were regularly subjected to intraperitoneal glucose tolerance and insulin tolerance tests (IGTT and ITT). These tests were also performed in mice transplanted with bone marrow cells from BCG-vaccinated donor mice. Results: Significant effects of BCG vaccination on blood glucose levels in IGTT and ITT were observed from week 12 of the experiment. BCG vaccination significantly improved changes in fasting glucose and insulin levels, insulin resistance indexes, and glucagon-to-insulin ratios by HFD at the end of the experiment. Significant inhibitory effects in IGTT and ITT on glucose intolerance were also observed by transplantation with bone marrow cells derived from BCG-vaccinated donor mice. Conclusions: BCG vaccination significantly delayed glucose intolerance progression, suggesting a beneficial effect of BCG on the pathogenesis of type 2 diabetes. It has also been demonstrated that the effects of BCG vaccination may be at least partially due to an immune memory (trained immunity) for hematopoietic stem and progenitor cells of the bone marrow.

Keywords

BCG; glucose intolerance; insulin resistance; trained immunity; nonalcoholic fatty liver disease

Subject

Medicine and Pharmacology, Dietetics and Nutrition

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