Skeletal muscle ceramides and daily fat oxidation in obesity and diabetes

Abstract

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.

Trial registration: ClinicalTrials.gov NCT00398853 NCT01672632 NCT00936130.

Keywords: Energy expenditure; Lipotoxicity; Type 2 diabetes.

Conflict of interest statement

Conflicts of Interest

The authors have no conflicts of interest to declare.

Copyright © 2018. Published by Elsevier Inc.

Figures

Figure 1. Comparison of ceramides between non-diabetic (black) and type 2 diabetic patients (gray) (mean ± SD)

Panel A: Comparison of ceramide species between diabetics and non-diabetics. Panel B: Comparison of total ceramides and total sphingosine between diabetics and non-diabetics. All values were normalized for protein content. Statistical significance (*= p<0.05) was assessed after adjustment for sex, age, and BMI. FFA = free-fatty acid, IMCL = intramyocellular lipids.