PMID- 32562559 OWN - NLM STAT- MEDLINE DCOM- 20210806 LR - 20210806 IS - 1097-0231 (Electronic) IS - 0951-4198 (Linking) VI - 34 IP - 19 DP - 2020 Oct 15 TI - Pathway attenuation of fatty acid beta-oxidation in the skeletal muscle of a type 2 diabetic mouse model. PG - e8869 LID - 10.1002/rcm.8869 [doi] AB - RATIONALE: Whether catabolic abnormalities of fatty acids exist in the skeletal muscle of type 2 diabetes mellitus (T2DM) has not been determined. In this study, we postulated that a systematic evaluation of the protein abundance and metabolic activity related to fatty acids in the skeletal muscle tissues of a T2DM mouse model was feasible to address this question. METHODS: Mitochondria were extracted from wild-type (WT) and db/db mice followed by quantitative analysis of the proteins involved in mitochondrial fatty acid oxidation (mFAO). The pathway activity of mFAO in skeletal muscle tissues was monitored in vitro using mass spectrometry, and tissue lipidomic analysis was conducted in profiling and target mode to distinguish the levels of long-chain acylcarnitines between WT and db/db mice. RESULTS: Two proteins related to the mFAO pathway were significantly downregulated in the skeletal muscle mitochondria of db/db mice. The measurement of mFAO pathway activity in vitro revealed that the abundance of long-chain acylcarnitines (C14 to C18) in db/db mice was lower than that in WT mice, and the determination of acylcarnitines in skeletal muscle tissues in vivo revealed that most long-chain acylcarnitines were decreased in db/db mice. CONCLUSIONS: The findings of lower abundance of ACAD9 and CPT1B, reduced activity of the mFAO pathway in vitro and decreased acylcarnitines in vivo firmly support that the mFAO pathway in the skeletal muscle of diabetic mice is attenuated, possibly resulting in cell/tissue dysfunction in diabetes. CI - (c) 2020 John Wiley & Sons, Ltd. FAU - Zhou, Yang AU - Zhou Y AD - BGI-Shenzhen, Shenzhen, China. AD - China National GeneBank, BGI-Shenzhen, Shenzhen, China. FAU - Tan, Yifan AU - Tan Y AD - BGI-Shenzhen, Shenzhen, China. AD - China National GeneBank, BGI-Shenzhen, Shenzhen, China. FAU - Hou, Guixue AU - Hou G AD - BGI-Shenzhen, Shenzhen, China. AD - China National GeneBank, BGI-Shenzhen, Shenzhen, China. FAU - Ren, Yan AU - Ren Y AD - BGI-Shenzhen, Shenzhen, China. AD - China National GeneBank, BGI-Shenzhen, Shenzhen, China. FAU - Deng, Yamei AU - Deng Y AD - BGI-Shenzhen, Shenzhen, China. AD - China National GeneBank, BGI-Shenzhen, Shenzhen, China. FAU - Yan, Keqiang AU - Yan K AD - BGI-Shenzhen, Shenzhen, China. AD - China National GeneBank, BGI-Shenzhen, Shenzhen, China. FAU - Zhang, Yue AU - Zhang Y AD - BGI-Shenzhen, Shenzhen, China. AD - China National GeneBank, BGI-Shenzhen, Shenzhen, China. FAU - Lin, Liang AU - Lin L AD - BGI-Shenzhen, Shenzhen, China. AD - China National GeneBank, BGI-Shenzhen, Shenzhen, China. FAU - Lou, Xiaomin AU - Lou X AD - Beijing Institute of Genomics, Chinese Academy of Sciences, Beijing, China. FAU - Liu, Siqi AU - Liu S AUID- ORCID: 0000-0001-9744-3681 AD - BGI-Shenzhen, Shenzhen, China. AD - China National GeneBank, BGI-Shenzhen, Shenzhen, China. LA - eng GR - 31700728/National Natural Science Foundation of China/ GR - DRC-SZ[2016]749/Shenzhen Engineering Laboratory for Proteomics/ PT - Journal Article PL - England TA - Rapid Commun Mass Spectrom JT - Rapid communications in mass spectrometry : RCM JID - 8802365 RN - 0 (Fatty Acids) SB - IM MH - Animals MH - Diabetes Mellitus, Experimental MH - Diabetes Mellitus, Type 2/*metabolism MH - *Fatty Acids/chemistry/metabolism MH - Lipidomics MH - Mice MH - Mice, Inbred C57BL MH - Mitochondria, Muscle/*metabolism MH - Muscle, Skeletal/*cytology MH - Oxidation-Reduction MH - Tandem Mass Spectrometry EDAT- 2020/06/21 06:00 MHDA- 2021/08/07 06:00 CRDT- 2020/06/21 06:00 PHST- 2020/02/17 00:00 [received] PHST- 2020/05/21 00:00 [revised] PHST- 2020/06/09 00:00 [accepted] PHST- 2020/06/21 06:00 [pubmed] PHST- 2021/08/07 06:00 [medline] PHST- 2020/06/21 06:00 [entrez] AID - 10.1002/rcm.8869 [doi] PST - ppublish SO - Rapid Commun Mass Spectrom. 2020 Oct 15;34(19):e8869. doi: 10.1002/rcm.8869.