Effects of weight loss and exercise on insulin resistance, and intramyocellular triacylglycerol, diacylglycerol and ceramide

Abstract

Aims/hypothesis: Intramyocellular lipids, including diacylglycerol (DAG) and ceramides, have been linked to insulin resistance. This randomised repeated-measures study examined the effects of diet-induced weight loss (DIWL) and aerobic exercise (EX) on insulin sensitivity and intramyocellular triacylglycerol (IMTG), DAG and ceramide.

Methods: Sixteen overweight to obese adults (BMI 30.6 ± 0.8; 67.2 ± 4.0 years of age) with either impaired fasting glucose, or impaired glucose tolerance completed one of two lifestyle interventions: DIWL (n = 8) or EX (n = 8). Insulin sensitivity was determined using hyperinsulinaemic-euglycaemic clamps. Intramyocellular lipids were measured in muscle biopsies using histochemistry and tandem mass spectrometry.

Results: Insulin sensitivity was improved with DIWL (20.6 ± 4.7%) and EX (19.2 ± 12.9%). Body weight and body fat were decreased by both interventions, with greater decreases in DIWL compared with EX. Muscle glycogen, IMTG content and oxidative capacity were all significantly (p < 0.05) decreased with DIWL and increased with EX. There were decreases in DAG with DIWL (-12.4 ± 14.6%) and EX (-40.9 ± 12.0%). Ceramide decreased with EX (-33.7 ± 11.2%), but not with DIWL. Dihydroceramide was decreased with both interventions. Sphingosine was decreased only with EX. Changes in total DAG, total ceramides and other sphingolipids did not correlate with changes in glucose disposal. Stearoyl-coenzyme A desaturase 1 (SCD1) content was decreased with DIWL (-19.5 ± 8.5%, p < 0.05), but increased with EX (19.6 ± 7.4%, p < 0.05). Diacylglycerol acyltransferase 1 (DGAT1) was unchanged with the interventions.

Conclusions/interpretation: Diet-induced weight loss and exercise training both improved insulin resistance and decreased DAG, while only exercise decreased ceramides, despite the interventions having different effects on IMTG. These alterations may be mediated through differential changes in skeletal muscle capacity for oxidation and triacylglycerol synthesis.

Trial registration: ClinicalTrials.gov NCT00766298.

Conflict of interest statement

Duality of interest The authors report no conflicts of interest.

Figures

Fig. 1

Patient flow diagram

Fig. 2

Insulin sensitivity before (white bars) and after (black bars) a 16 week lifestyle intervention of DIWL (n=8) or EX (n=8). The rate of insulin-stimulated glucose disposal (Rd) was determined using as described in Methods and normalised to FFM. Data are mean ± SEM. Group and intervention effects were explored using a two-way (group×time) repeated-measures ANOVA. *p<0.05 within-group intervention effect

Fig. 3

Skeletal muscle substrate storage and capacity for oxidation before (white bars) and after (black bars) a 16 week lifestyle intervention of DIWL (n=8) or EX (n=8). All measures were performed on biopsy samples of the vastus lateralis. IMCL content, as determined by Oil Red O staining (a); SDH activity staining (b); and glycogen content (c) were determined using histochemical analyses as described in Methods. Data are mean ± SEM. Group and intervention effects were explored using a two-way (group×time) repeated-measures ANOVA. *p<0.05 within-group intervention effect; †p<0.05 between-groups difference

Fig. 4

Skeletal muscle DAG and ceramide before (white bars) and after (black bars) a 16 week lifestyle intervention of DIWL (n=8) or EX (n=8). Data for DAG (a), ceramide (b), dihydroceramide (c), sphingosine (d) and sphingosine 1-phosphate (e) were analysed using tandem mass spectrometry as described in Methods. Data are normalised to the ‘pre’ intervention values of each group. Group and intervention effects were explored using a two-way (group×time) repeated-measures ANOVA. Data were log transformed when ANOVA assumption of normality was not met. *p<0.05 within-group intervention effect; †p<0.05 between-groups difference

Fig. 5

Skeletal muscle SCD1 and DGAT1 before (white bars) and after (black bars) a 16-week lifestyle intervention of DIWL (n=8) or EX (n=8). Skeletal muscle protein production of SCD1 (a) and DGAT1 (b) were determined by western blot analysis as described in Methods. Data were normalised to the ‘pre’ intervention values of each group. Group and intervention effects were explored using a two-way (group×time) repeated-measures analysis of variance. *p<0.05 within-group intervention effect; †p<0.05 between-groups difference