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Controlled Clinical Trial
. 2015 Jul;23(7):1414-21.
doi: 10.1002/oby.21117. Epub 2015 May 12.

Improved Insulin Sensitivity After Exercise Training Is Linked to Reduced Plasma C14:0 Ceramide in Obesity and Type 2 Diabetes

Free PMC article
Controlled Clinical Trial

Improved Insulin Sensitivity After Exercise Training Is Linked to Reduced Plasma C14:0 Ceramide in Obesity and Type 2 Diabetes

Takhar Kasumov et al. Obesity (Silver Spring). .
Free PMC article


Objective: To assess the effect of exercise training on insulin sensitivity and plasma ceramides in obesity and type 2 diabetes (T2D).

Methods: Twenty-four adults with obesity and normal glucose tolerance (NGT, n = 14) or diabetes (n = 10) were studied before and after a 12-week supervised exercise-training program (5 days/week, 1 h/day, 80-85% of maximum heart rate). Changes in body composition were assessed using hydrostatic weighing and computed tomography. Peripheral tissue insulin sensitivity was assessed by a 40 mU/m(2) /min hyperinsulinemic euglycemic clamp. Plasma ceramides (C14:0, C16:0, C18:0, C18:1, C20:0, C24:0, and C24:1) were quantified using electrospray ionization tandem mass spectrometry after separation with HPLC.

Results: Plasma ceramides were similar for the subjects with obesity and NGT and the subjects with diabetes, despite differences in glucose tolerance. Exercise significantly reduced body weight and adiposity and increased peripheral insulin sensitivity in both groups (P < 0.05). In addition, plasma C14:0, C16:0, C18:1, and C24:0 ceramide levels were reduced in all subjects following the intervention (P < 0.05). Decreases in total (r = -0.51, P = 0.02) and C14:0 (r = -0.56, P = 0.009) ceramide were negatively correlated with the increase in insulin sensitivity.

Conclusions: Ceramides are linked to exercise training-induced improvements in insulin sensitivity, and plasma C14:0 ceramide may provide a specific target for investigating lipid-related insulin resistance in obesity and T2D.


Fig. 1
Fig. 1. Exercise training increases insulin-stimulated glucose disposal
Twenty four older obese volunteers underwent twelve weeks of aerobic exercise training 1 h/day, 5 d/wk at 80% HRmax. Individuals were classified as either NGT (n=14) or T2D (n=10) following OGTT screening. White bars indicate pre-study (PRE) data; black bars indicate post-study (POST) data. Insulin-stimulated glucose disposal rates (GDR) during 40 mU/m2/min hyperinsulinemic euglycemic clamps were increased in both groups following exercise (***, P<0.001). Error bars represent mean ± S.E.M.
Fig. 2
Fig. 2. Exercise training lowers fasting plasma ceramide concentrations
Plasma ceramide concentrations were measured before (white bars) and after (black bars) twelve weeks of aerobic exercise training. Panel (A) illustrates subjects with NGT (N=13); Panel (B) illustrates subjects with T2D (N=8 for total ceramide, and N=7 for the C14:0 and C18:1 subspecies). Total plasma ceramide concentrations were significantly attenuated in both groups (inset graphs; ***, P<0.001). In addition, C14:0, C16:0, and C24:0 ceramide sub-species demonstrated significant decreases in both groups following exercise (**, P<0.01; *, P<0.05). C18:1 ceramide was also suppressed, but only in T2D subjects (*, P<0.05; 2way ANOVA timexgroup interaction, P=0.02). Error bars represent mean ± S.E.M.
Fig. 3
Fig. 3. The change in insulin sensitivity is related to the change in fasting plasma ceramides
Simple regression was used to identify the relationship between the exercise-induced changes (Δ) in insulin-stimulated glucose disposal (GDR) and fasting plasma ceramide concentrations. Analysis revealed that increases in GDR were significantly related to decreases in total (Panel A: r = −0.51, P=0.02) and C14:0 (Panel B: r = −0.56, P=0.009) ceramide. NGT (N=13) and T2D (N=8 for total ceramide, and N=7 for the C14:0 subspecies) subjects are presented by open and black squares, respectively.

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