Modulation of sphingolipid metabolism with calorie restriction enhances insulin action in skeletal muscle

J Nutr Biochem. 2015 Jul;26(7):687-95. doi: 10.1016/j.jnutbio.2015.01.007. Epub 2015 Mar 5.


This study sought to investigate the effect of calorie restriction (CR) on skeletal muscle sphingolipid metabolism and its contribution to improved insulin action in rats after a 6-month feeding study. Twenty nine (29) male Fischer 344 rats were randomized to an ad libitum (AL) diet or 30% CR. Dietary intake, body weight and insulin sensitivity were monitored. After 6 months, skeletal muscle (vastus lateralis) was obtained for insulin signaling and lipid profiling. CR significantly decreased insulin and glucose levels and also altered the expression and activity of proteins involved in sphingolipid formation and metabolism. The quantities of ceramides significantly increased in CR animals (P<.05; n=14-15), while ceramide metabolism products (i.e., glycosphingolipids: hexosylceramides and lactosylceramides) significantly decreased (P<.05; n=14-15). Ceramide phosphates, sphingomyelins, sphingosine and sphingosine phosphate were not significantly different between AL and CR groups (P=ns; n=14-15). Lactosylceramide quantities correlated significantly with surrogate markers of insulin resistance (homeostasis model of assessment on insulin resistance) (r=0.7; P<.005). Products of ceramide metabolism (glycosphingolipids), known to interfere with insulin signaling at elevated levels, were significantly reduced in the skeletal muscle of CR animals. The increase in insulin sensitivity is associated with glycosphingolipid levels.

Keywords: Calorie restriction; Glycosphingolipids; Insulin sensitivity; Lipids; Sphingolipids.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Caloric Restriction*
  • Ceramides / metabolism
  • Crosses, Genetic
  • Down-Regulation
  • Gene Expression Regulation, Enzymologic*
  • Glycosphingolipids / metabolism
  • Insulin Resistance*
  • Isoenzymes / metabolism
  • Male
  • Membrane Proteins / metabolism*
  • Muscle, Skeletal / enzymology
  • Muscle, Skeletal / metabolism*
  • Oxidoreductases Acting on CH-CH Group Donors / metabolism*
  • Protein Subunits / metabolism
  • Quadriceps Muscle
  • Random Allocation
  • Rats, Inbred BN
  • Rats, Inbred F344
  • Serine C-Palmitoyltransferase / metabolism*
  • Sphingolipids / metabolism*
  • Sphingosine N-Acyltransferase / metabolism*
  • Up-Regulation


  • Ceramides
  • Glycosphingolipids
  • Isoenzymes
  • Membrane Proteins
  • Protein Subunits
  • Sphingolipids
  • Cers2 protein, rat
  • Oxidoreductases Acting on CH-CH Group Donors
  • Cers1 protein, rat
  • Sphingosine N-Acyltransferase
  • Serine C-Palmitoyltransferase