Gender differences in skeletal muscle sphingolipid and diacylglycerol content of insulin-sensitive and insulin-resistant humans — ASN Events
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Gender differences in skeletal muscle sphingolipid and diacylglycerol content of insulin-sensitive and insulin-resistant humans (#133)

Dorit Samocha-Bonet 1 2 , Katherine Tonks 1 2 3 , Adelle CF Coster 4 , Michael J Christopher 5 , Yvonne Ng 1 , Steven Miller 1 , Carsten Schmitz-Peiffer 1 2 , Georgia Frangioudakis 1 2 , Don J Chisholm 1 2 , Peter J Meikle 5 , David E James 1 2 , Jerry R Greenfield 1 2 3
  1. Garvan Institute of Medical Research, Sydney, NSW, Australia
  2. Faculty of Medicine, University of New South Wales, Sydney, Australia
  3. Department of Endocrinology, St. Vincent’s Hospital, Sydney, Australia
  4. School of Mathematics & Statistics, University of New South Wales, Sydney, NSW, Australia
  5. Baker IDI Heart & Diabetes Institute, Melbourne, NSW, Australia

Background: Ceramide and diacylglycerol (DAG) accumulation in muscle has been implicated in the aetiology of insulin-resistance in rodents and humans. However, the effect of gender on sphingolipid and DAG species and their relationship with insulin sensitivity remain unclear.

Aim: To examine the expression of skeletal muscle lipid species in lean insulin-sensitive, overweight-obese insulin-sensitive, overweight-obese insulin-resistant and type 2 diabetic males and females.

Methods: Lean (BMI<25 kg/m2; 9 males, 13 females), overweight-obese (BMI>25 kg/m2; 18 males, 16 females) and type 2 diabetes subjects (BMI>25 kg/m2; 9 males, 12 females) were studied using hyperinsulinaemic-euglycaemic clamps (80 mU/m2/min). Overweight-obese individuals were classified as insulin-sensitive and insulin-resistant based on being above or below median clamp M-value, respectively with separate cut-offs for males and females (9 and 8 respectively in each group). Vastus lateralis muscle biopsy samples were collected. Lipid species were analysed by electron-spray ionization tandem mass spectrometry.

Results: Average (SD) age was 58±8 years. Females were more insulin-sensitive than males (M-value 79±28 vs. 58±25 µmol/min/kg FFM, P=0.001). However, females had a significantly greater concentration of 3 out of 6 ceramide species (all P≤0.02), 7 out of 17 sphingomyelin species (all P≤0.04) and 1 out of 17 DAG species (P=0.01) than males. M-value correlated inversely with Cer 18:0 and sphingomyelin 18:0 in both genders and with Cer 24:0 in males, but not females. Significant inverse correlations of M-value with DAG and TAG species were only apparent in males. Cer 18:0 was the only lipid that was significantly lower in both insulin-sensitive groups (lean and overweight-obese) compared with both insulin-resistant groups (overweight-obese and type 2 diabetes patients; P<0.05).

Conclusions: Females were more insulin-sensitive than males, but had higher concentrations of specific sphingolipid and DAG species in skeletal muscle. Cer 18:0 associated with insulin resistance in humans, independent of obesity, and may play a role in its development.    

DS-B and KT contributed equally to this work