PMID- 29307520 OWN - NLM STAT- MEDLINE DCOM- 20181231 LR - 20190501 IS - 1532-8600 (Electronic) IS - 0026-0495 (Print) IS - 0026-0495 (Linking) VI - 82 DP - 2018 May TI - Skeletal muscle ceramides and daily fat oxidation in obesity and diabetes. PG - 118-123 LID - S0026-0495(17)30359-1 [pii] LID - 10.1016/j.metabol.2017.12.012 [doi] AB - BACKGROUND/OBJECTIVES: Ectopic accumulation of lipids in skeletal muscle and the formation of deleterious lipid intermediates is thought to contribute to the development of insulin resistance and type 2 diabetes mellitus (T2DM). Similarly, impaired fat oxidation (metabolic inflexibility) are predictors of weight gain and the development of T2DM; however, no study has investigated the relation between muscle ceramide accumulation and 24-hour macronutrient oxidation. The purpose of this study was to retrospectively explore the relationships between whole body fat oxidation and skeletal muscle ceramide accumulation in obese non-diabetic individuals (ND) and in people with obesity and T2DM. METHODS: Daily substrate oxidation was measured in a respiratory chamber and skeletal muscle ceramides were measured using liquid chromatographyelectrospray ionization tandem-mass spectrometry. RESULTS: After adjusting for sex, age, and BMI, no differences existed between the groups for fat oxidation or 24-h RQ. However, ceramides C18:1, C:20, C22, C24 and C24:1 were significantly higher in people with T2DM compared to ND whereas no differences existed for C16 and C18. Despite low amounts of muscle ceramides, fat oxidation rates were positively associated with ceramide species concentration in ND only. Our data suggests that ceramides do not interfere with whole-body fat oxidation in ND individuals whereas a persistent lipid oversupply results in excessive ceramide muscle accumulation in people with T2DM. CI - Copyright (c) 2018. Published by Elsevier Inc. FAU - Broskey, Nicholas T AU - Broskey NT AD - Pennington Biomedical Research Center, Baton Rouge, LA 70808, United States. FAU - Obanda, Diana N AU - Obanda DN AD - Pennington Biomedical Research Center, Baton Rouge, LA 70808, United States. FAU - Burton, Jeffrey H AU - Burton JH AD - Pennington Biomedical Research Center, Baton Rouge, LA 70808, United States. FAU - Cefalu, William T AU - Cefalu WT AD - Pennington Biomedical Research Center, Baton Rouge, LA 70808, United States. FAU - Ravussin, Eric AU - Ravussin E AD - Pennington Biomedical Research Center, Baton Rouge, LA 70808, United States. Electronic address: eric.ravussin@pbrc.edu. LA - eng SI - ClinicalTrials.gov/NCT00398853 SI - ClinicalTrials.gov/NCT01672632 SI - ClinicalTrials.gov/NCT00936130 GR - R55 DK060126/DK/NIDDK NIH HHS/United States GR - P30 DK072476/DK/NIDDK NIH HHS/United States GR - U54 GM104940/GM/NIGMS NIH HHS/United States GR - R01 DK060412/DK/NIDDK NIH HHS/United States GR - R01 DK060126/DK/NIDDK NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural PT - Research Support, Non-U.S. Gov't DEP - 20180104 PL - United States TA - Metabolism JT - Metabolism: clinical and experimental JID - 0375267 RN - 0 (Ceramides) SB - IM MH - Adult MH - Aged MH - Body Mass Index MH - Ceramides/*metabolism MH - Diabetes Mellitus, Type 2/*metabolism MH - Energy Metabolism/*physiology MH - Female MH - Humans MH - Insulin Resistance/physiology MH - Lipid Metabolism/physiology MH - Male MH - Middle Aged MH - Muscle, Skeletal/*metabolism MH - Obesity/*metabolism MH - Oxidation-Reduction MH - Young Adult PMC - PMC5930033 MID - NIHMS940025 OTO - NOTNLM OT - Energy expenditure OT - Lipotoxicity OT - Type 2 diabetes COIS- Conflicts of Interest The authors have no conflicts of interest to declare. EDAT- 2018/01/09 06:00 MHDA- 2019/01/01 06:00 PMCR- 2019/05/01 CRDT- 2018/01/09 06:00 PHST- 2017/09/21 00:00 [received] PHST- 2017/11/15 00:00 [revised] PHST- 2017/12/27 00:00 [accepted] PHST- 2018/01/09 06:00 [pubmed] PHST- 2019/01/01 06:00 [medline] PHST- 2018/01/09 06:00 [entrez] PHST- 2019/05/01 00:00 [pmc-release] AID - S0026-0495(17)30359-1 [pii] AID - 10.1016/j.metabol.2017.12.012 [doi] PST - ppublish SO - Metabolism. 2018 May;82:118-123. doi: 10.1016/j.metabol.2017.12.012. Epub 2018 Jan 4.