Endocrine Abstracts

Disturbance in insulin signaling under effect of sphingolipids is thought to be the mechanism underlying the obesity-mediated insulin resistance. The work was initiated to study sphingolipid metabolism in tissues of rats with obesity induced by a prolonged high-calorie diet. The lipid extraction and purification was performed by Folch’s method; concentrations of sphingosine and ceramide were measured by Lauter et al. method. In obesity, the levels of total gangliosides in tissues of experimental animals were found to reduce by 16.5% and 35% in the liver and in the skeletal muscles, respectively. This was found to cause changes in cell surface properties and a decline in the glucose transport. In obesity, ratios of some ganglioside fractions were established to be abnormal, as well; thus, in particular, concentrations of GM₃ ganglioside were found to increase by 1.5 and 1.8 times in the liver and skeletal muscles of animals with diet-induced obesity, respectively. A significant increase in GM₃ in obesity could facilitate the insulin resistance onset by blocking insulin signaling on the initial stages of the hormone signal pathway. An imbalance between metabolites of sphingomyelin cycle, a decline in sphingomyelin and accumulation of sphingomyelin metabolites, such as ceramide and sphingosine, were established to take place in the liver and skeletal muscles of obese experimental animals. Ceramide/sphingosine ratios in the liver and skeletal muscles were found to be 1.17 and 1.5, respectively. This is consistent with the findings from studies on stimulation of activity of neutral sphingomyelinase, a key enzyme of sphingomyelin cycle, by 1.25 and 1.45 times in the liver and skeletal muscles, respectively. The activation of sphingomyelin cycle is thought to be an element of metabolic rearrangements in obesity. The increase in ceramide concentrations in tissues of animals with diet-induced obesity appeared to provoke the insulin resistance and type 2 diabetes mellitus onset.