Abstract

Ceramide and diacylglycerol are linked to insulin resistance in rodents, but in humans the data are inconsistent. Insulin resistance is frequently observed with aging, but the role of ceramide and diacylglycerol is not clarified. Training improves metabolic health and, therefore, we aimed to elucidate the influence of age and high-intensity interval training (HIIT) on ceramide and diacylglycerol content in muscle. Fourteen young (33 ± 1) and 22 older (63 ± 1) overweight to obese subjects performed 6 weeks HIIT three times a week. Maximal oxygen uptake and body composition were measured and muscle biopsies and fasting blood samples were obtained. Muscle ceramide and diacylglycerol were measured by gas-liquid chromatography and proteins in insulin signaling, lipid and glucose metabolism were measured by Western blotting. Content of ceramide and diacylglycerol total, saturated, C16:0 and C18:0 fatty acids and C18:1 ceramide were higher in older compared to young. HIIT reduced saturated and C18:0 ceramides, while the content of the proteins involved in glucose (GLUT4, glycogen synthase, hexokinase II, AKT) and lipid metabolism (adipose triglyceride lipase, fatty acid binding protein) were increased after HIIT. We demonstrate a higher content of saturated ceramide and diacylglycerol fatty acids in the muscle of older subjects compared to young. Moreover, the content of saturated ceramides was reduced and muscle glucose metabolism improved at protein level after HIIT. This study highlights an increased content of saturated ceramides in aging which could be speculated to influence insulin sensitivity.

Highlights

  • Physical function and metabolic health deteriorates with aging which increase the risk of disease [1,2,3]

  • Glycated haemoglobin (HbA1c) and fasting glucose concentration were lower in the young group and fasting insulin concentration was higher whereas no difference was found in a Homeostatic Model Assessment of Insulin Resistance (HOMA-IR) when compared to the older group

  • This study demonstrates a higher content of ceramide and DAG, saturated fatty acids (FA) and C16:0 and C18:0 ceramide and DAG FA in muscle in older overweight to obese compared to young subjects

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Summary

Introduction

Physical function and metabolic health deteriorates with aging which increase the risk of disease [1,2,3]. Insulin sensitivity is frequently reduced with aging which is linked to reduced muscle mass and increased abdominal fat mass [4,5,6,7]. Ceramide and DAG subspecies containing long chain saturated fatty acids (FA) including C16:0 and C18:0 are indicated to be involved in insulin resistance [13,14]. It remains unclear whether age influence muscle bioactive lipid content and species composition independently [15,16,17,18,19]. In a cross-sectional study we observed a lower content of muscle C16:0, C18:0, total saturated ceramide FA and total ceramide with aging in man [20], while other studies have reported a higher content of specific saturated ceramide subspecies and total ceramide [16,21] or no difference [15] in old compared to young

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