β-hydroxybutyrate suppresses pathological changes of blood-induced arthropathy in rats

Abstract Arthropathy is a common complication in haemophilia and decreases quality of life. It has been known that concentrations of β-hydroxybutyrate (BHB) in blood are increased by a ketogenic diet, and elevated levels of circulating BHB restricts the progression of inflammation-mediated joint pat...

Full description

Saved in:
Bibliographic Details
Main Authors: Ryohei Kawasaki, Asuka Sakata, Kohei Tatsumi, Seiji Mitani, Maiko Takeda, Shogo Kasuda, Naoki Matsumoto, Suguru Harada, Tetsuhiro Soeda, Yukiko Nishida, Yasushi Yoshimura, Midori Shima
Format: Article
Language:English
Published: Nature Portfolio 2024-11-01
Series:Scientific Reports
Online Access:https://doi.org/10.1038/s41598-024-77074-6
Tags: Add Tag
No Tags, Be the first to tag this record!
_version_ 1846147923799179264
author Ryohei Kawasaki
Asuka Sakata
Kohei Tatsumi
Seiji Mitani
Maiko Takeda
Shogo Kasuda
Naoki Matsumoto
Suguru Harada
Tetsuhiro Soeda
Yukiko Nishida
Yasushi Yoshimura
Midori Shima
author_facet Ryohei Kawasaki
Asuka Sakata
Kohei Tatsumi
Seiji Mitani
Maiko Takeda
Shogo Kasuda
Naoki Matsumoto
Suguru Harada
Tetsuhiro Soeda
Yukiko Nishida
Yasushi Yoshimura
Midori Shima
author_sort Ryohei Kawasaki
collection DOAJ
description Abstract Arthropathy is a common complication in haemophilia and decreases quality of life. It has been known that concentrations of β-hydroxybutyrate (BHB) in blood are increased by a ketogenic diet, and elevated levels of circulating BHB restricts the progression of inflammation-mediated joint pathological changes. We hypothesized that elevation of blood BHB concentrations could be effective for reducing the progression of bleeding-induced arthropathy by moderating the inflammatory responses of macrophages. In this study, we investigated whether BHB alleviates the arthropathy caused by repeated intra-articular blood injection in rats. To increase blood BHB levels, rats were fed with ketogenic diet. Repeated intra-articular blood injection induced significant joint swelling, whereas ketogenic diet intake significantly increased blood BHB concentrations and ameliorated the joint swelling. The periarticular tissue-fibrosis observed in the control diet intake group appeared to be significantly alleviated in the ketogenic diet intake group. In addition, the IL-1β, which is involved in the progression of arthropathy, levels in the supernatants of blood-exposed macrophages derived from THP-1 cell line were significantly suppressed by BHB supplementation. In summary, BHB moderated the pathological joint changes caused by intra-articular blood exposure.
format Article
id doaj-art-e4317ddda0cd4c68b9459e14c15cdd6d
institution Kabale University
issn 2045-2322
language English
publishDate 2024-11-01
publisher Nature Portfolio
record_format Article
series Scientific Reports
spelling doaj-art-e4317ddda0cd4c68b9459e14c15cdd6d2024-12-01T12:20:50ZengNature PortfolioScientific Reports2045-23222024-11-0114111210.1038/s41598-024-77074-6β-hydroxybutyrate suppresses pathological changes of blood-induced arthropathy in ratsRyohei Kawasaki0Asuka Sakata1Kohei Tatsumi2Seiji Mitani3Maiko Takeda4Shogo Kasuda5Naoki Matsumoto6Suguru Harada7Tetsuhiro Soeda8Yukiko Nishida9Yasushi Yoshimura10Midori Shima11Medicinal Biology of Thrombosis and Hemostasis, Nara Medical UniversityMedicinal Biology of Thrombosis and Hemostasis, Nara Medical UniversityMedicinal Biology of Thrombosis and Hemostasis, Nara Medical UniversityAdvanced Medical Science of Thrombosis and Hemostasis, Nara Medical UniversityDepartment of Diagnostic Pathology, Nara Medical UniversityDepartment of Legal Medicine, Nara Medical UniversityMedicinal Biology of Thrombosis and Hemostasis, Nara Medical UniversityMedicinal Biology of Thrombosis and Hemostasis, Nara Medical UniversityMedicinal Biology of Thrombosis and Hemostasis, Nara Medical UniversityMedicinal Biology of Thrombosis and Hemostasis, Nara Medical UniversityProduct Research Department, Medical Affairs Division, Chugai Pharmaceutical Co., LtdMedicinal Biology of Thrombosis and Hemostasis, Nara Medical UniversityAbstract Arthropathy is a common complication in haemophilia and decreases quality of life. It has been known that concentrations of β-hydroxybutyrate (BHB) in blood are increased by a ketogenic diet, and elevated levels of circulating BHB restricts the progression of inflammation-mediated joint pathological changes. We hypothesized that elevation of blood BHB concentrations could be effective for reducing the progression of bleeding-induced arthropathy by moderating the inflammatory responses of macrophages. In this study, we investigated whether BHB alleviates the arthropathy caused by repeated intra-articular blood injection in rats. To increase blood BHB levels, rats were fed with ketogenic diet. Repeated intra-articular blood injection induced significant joint swelling, whereas ketogenic diet intake significantly increased blood BHB concentrations and ameliorated the joint swelling. The periarticular tissue-fibrosis observed in the control diet intake group appeared to be significantly alleviated in the ketogenic diet intake group. In addition, the IL-1β, which is involved in the progression of arthropathy, levels in the supernatants of blood-exposed macrophages derived from THP-1 cell line were significantly suppressed by BHB supplementation. In summary, BHB moderated the pathological joint changes caused by intra-articular blood exposure.https://doi.org/10.1038/s41598-024-77074-6
spellingShingle Ryohei Kawasaki
Asuka Sakata
Kohei Tatsumi
Seiji Mitani
Maiko Takeda
Shogo Kasuda
Naoki Matsumoto
Suguru Harada
Tetsuhiro Soeda
Yukiko Nishida
Yasushi Yoshimura
Midori Shima
β-hydroxybutyrate suppresses pathological changes of blood-induced arthropathy in rats
Scientific Reports
title β-hydroxybutyrate suppresses pathological changes of blood-induced arthropathy in rats
title_full β-hydroxybutyrate suppresses pathological changes of blood-induced arthropathy in rats
title_fullStr β-hydroxybutyrate suppresses pathological changes of blood-induced arthropathy in rats
title_full_unstemmed β-hydroxybutyrate suppresses pathological changes of blood-induced arthropathy in rats
title_short β-hydroxybutyrate suppresses pathological changes of blood-induced arthropathy in rats
title_sort β hydroxybutyrate suppresses pathological changes of blood induced arthropathy in rats
url https://doi.org/10.1038/s41598-024-77074-6
work_keys_str_mv AT ryoheikawasaki bhydroxybutyratesuppressespathologicalchangesofbloodinducedarthropathyinrats
AT asukasakata bhydroxybutyratesuppressespathologicalchangesofbloodinducedarthropathyinrats
AT koheitatsumi bhydroxybutyratesuppressespathologicalchangesofbloodinducedarthropathyinrats
AT seijimitani bhydroxybutyratesuppressespathologicalchangesofbloodinducedarthropathyinrats
AT maikotakeda bhydroxybutyratesuppressespathologicalchangesofbloodinducedarthropathyinrats
AT shogokasuda bhydroxybutyratesuppressespathologicalchangesofbloodinducedarthropathyinrats
AT naokimatsumoto bhydroxybutyratesuppressespathologicalchangesofbloodinducedarthropathyinrats
AT suguruharada bhydroxybutyratesuppressespathologicalchangesofbloodinducedarthropathyinrats
AT tetsuhirosoeda bhydroxybutyratesuppressespathologicalchangesofbloodinducedarthropathyinrats
AT yukikonishida bhydroxybutyratesuppressespathologicalchangesofbloodinducedarthropathyinrats
AT yasushiyoshimura bhydroxybutyratesuppressespathologicalchangesofbloodinducedarthropathyinrats
AT midorishima bhydroxybutyratesuppressespathologicalchangesofbloodinducedarthropathyinrats