PMID- 38387134 OWN - NLM STAT- MEDLINE DCOM- 20240304 LR - 20240304 IS - 1950-6007 (Electronic) IS - 0753-3322 (Linking) VI - 172 DP - 2024 Mar TI - Label-free analysis of the beta-hydroxybutyricacid drug on mitochondrial redox states repairment in type 2 diabetic mice by resonance raman scattering. PG - 116320 LID - S0753-3322(24)00201-4 [pii] LID - 10.1016/j.biopha.2024.116320 [doi] AB - BACKGROUND: Mitochondrial redox imbalance underlies the pathophysiology of type2 diabetes mellitus (T2DM), and is closely related to tissue damage and dysfunction. Studies have shown the beneficial effects of dietary strategies that elevate beta-hydroxybutyrate (BHB) levels in alleviating T2DM. Nevertheless, the role of BHB has not been clearly elucidated. METHODS: We performed a spectral study to visualize the preventive effects of BHB on blood and multiorgan mitochondrial redox imbalance in T2DM mice via using label-free resonance Raman spectroscopy (RRS), and further explored the impact of BHB therapy on the pathology of T2DM mice by histological and biochemical analyses. FINDINGS: Our data revealed that RRS-based mitochondrial redox states assay enabled clear and reliable identification of the improvement of mitochondrial redox imbalance by BHB, evidenced by the reduction of Raman peak intensity at 750 cm(-1), 1128 cm(-1) and 1585 cm(-1) in blood, tissue as well as purified mitochondria of db/db mice and the increase of tissue mitochondrial succinic dehydrogenase (SDH) staining after BHB treatment. Exogenous supplementation of BHB was also found to attenuate T2DM pathology related to mitochondrial redox states, involving organ injury, blood glucose control, insulin resistance and systemic inflammation. INTERPRETATION: Our findings provide strong evidence for BHB as a potential therapeutic strategy targeting mitochondria for T2DM. CI - Copyright (c) 2024 The Authors. Published by Elsevier Masson SAS.. All rights reserved. FAU - Wang, Na AU - Wang N AD - Taizhou Hospital, Zhejiang University School of Medicine, Linhai, China; Key Laboratory of Minimally Invasive Techniques & Rapid Rehabilitation of Digestive System Tumor of Zhejiang Province, Taizhou Hospital of Zhejiang Province Affiliated to Wenzhou Medical University, Linhai, China. FAU - Yang, Anqi AU - Yang A AD - Centre for Optical and Electromagnetic Research, National Engineering Research Center for Optical Instruments, Zhejiang Provincial Key Laboratory for Sensing Technologies, Zhejiang University, Hangzhou 310058, China. FAU - Tian, Xiong AU - Tian X AD - Key Laboratory of Minimally Invasive Techniques & Rapid Rehabilitation of Digestive System Tumor of Zhejiang Province, Taizhou Hospital of Zhejiang Province Affiliated to Wenzhou Medical University, Linhai, China. FAU - Liao, Jiaqi AU - Liao J AD - Centre for Optical and Electromagnetic Research, National Engineering Research Center for Optical Instruments, Zhejiang Provincial Key Laboratory for Sensing Technologies, Zhejiang University, Hangzhou 310058, China. FAU - Yang, Zhenyu AU - Yang Z AD - Key Laboratory of Minimally Invasive Techniques & Rapid Rehabilitation of Digestive System Tumor of Zhejiang Province, Taizhou Hospital of Zhejiang Province Affiliated to Wenzhou Medical University, Linhai, China. FAU - Pan, Yixiao AU - Pan Y AD - Key Laboratory of Minimally Invasive Techniques & Rapid Rehabilitation of Digestive System Tumor of Zhejiang Province, Taizhou Hospital of Zhejiang Province Affiliated to Wenzhou Medical University, Linhai, China. FAU - Guo, Yiqing AU - Guo Y AD - Key Laboratory of Minimally Invasive Techniques & Rapid Rehabilitation of Digestive System Tumor of Zhejiang Province, Taizhou Hospital of Zhejiang Province Affiliated to Wenzhou Medical University, Linhai, China. FAU - He, Sailing AU - He S AD - Taizhou Hospital, Zhejiang University School of Medicine, Linhai, China; Centre for Optical and Electromagnetic Research, National Engineering Research Center for Optical Instruments, Zhejiang Provincial Key Laboratory for Sensing Technologies, Zhejiang University, Hangzhou 310058, China; School of Electrical Engineering, Royal Institute of Technology, Stockholm S-100 44, Sweden. Electronic address: sailing@kth.se. LA - eng PT - Journal Article DEP - 20240222 PL - France TA - Biomed Pharmacother JT - Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie JID - 8213295 RN - TZP1275679 (3-Hydroxybutyric Acid) SB - IM MH - Mice MH - Animals MH - *Diabetes Mellitus, Experimental MH - Spectrum Analysis, Raman MH - 3-Hydroxybutyric Acid/pharmacology MH - Mitochondria MH - Oxidation-Reduction MH - *Diabetes Mellitus, Type 2/drug therapy OTO - NOTNLM OT - Label-free OT - Mitochondrial redox state OT - Raman spectroscopy OT - Type 2 diabetes OT - beta-hydroxybutyric acid COIS- Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. EDAT- 2024/02/23 00:42 MHDA- 2024/03/04 06:42 CRDT- 2024/02/22 18:02 PHST- 2023/12/23 00:00 [received] PHST- 2024/02/08 00:00 [revised] PHST- 2024/02/19 00:00 [accepted] PHST- 2024/03/04 06:42 [medline] PHST- 2024/02/23 00:42 [pubmed] PHST- 2024/02/22 18:02 [entrez] AID - S0753-3322(24)00201-4 [pii] AID - 10.1016/j.biopha.2024.116320 [doi] PST - ppublish SO - Biomed Pharmacother. 2024 Mar;172:116320. doi: 10.1016/j.biopha.2024.116320. Epub 2024 Feb 22.