Changes in food intake, metabolic parameters and insulin resistance are induced by an isoenergetic, medium-chain fatty acid diet and are associated with modifications in insulin signalling in isolated rat pancreatic islets

• Published in: British journal of nutrition Vol. 109; no. 12; pp. 2154 - 2165
• Main Authors: Marçal, A. C., Camporez, J. P. G., Lima-Salgado, T. M., Cintra, D. E., Akamine, E. H., Ribeiro, L. M., Almeida, F. N., Zanuto, R. P., Curi, R., Boldrini, S. C., Liberti, E. A., Fiamoncini, J., Hirabara, S. M., Deschamps, F. C., Carpinelli, A. R., Carvalho, C. R. O.
• Format: Journal Article
• Language: English
• Published: Cambridge, UK Cambridge University Press 28-06-2013
• Subjects: Animal models; Animals; Biological and medical sciences; Diet; Dietary Fats - metabolism; Disease Models, Animal; Fatty acids; Fatty Acids - chemistry; Fatty Acids - metabolism; Feeding. Feeding behavior; Fundamental and applied biological sciences. Psychology; Homeostasis; Insulin resistance; Insulin Resistance - physiology; Insulin-Like Growth Factor I - metabolism; Islets of Langerhans - metabolism; Male; Metabolism and Metabolic Studies; Muscle, Skeletal - metabolism; Nutrition; Phosphorylation - physiology; Protein Kinase C - metabolism; Proto-Oncogene Proteins c-akt - metabolism; Rats; Rats, Wistar; Receptor, Insulin - metabolism; Signal transduction; Triglycerides - blood; Triglycerides - chemistry; Vertebrates: anatomy and physiology, studies on body, several organs or systems; Insulin resistance; Pancreatic islets; Insulin signalling; Medium-chain fatty acids; Endocrinopathy; Modification; Pancreatic hormone; Rat; Lipids; Endocrine pancreas; Nutrition; Rodentia; Langerhans islet; Metabolic diseases; Medium chain; Metabolism; Fatty acids; Insulin; Feeding; Target tissue resistance; Vertebrata; Mammalia; Diet; Food intake; Animal
• ISSN: 0007-1145; 1475-2662
• DOI: 10.1017/S0007114512004576

Long-chain fatty acids are capable of inducing alterations in the homoeostasis of glucose-stimulated insulin secretion (GSIS), but the effect of medium-chain fatty acids (MCFA) is poorly elucidated. In the present study, we fed a normoenergetic MCFA diet to male rats from the age of 1 month to the age of 4 months in order to analyse the effect of MCFA on body growth, insulin sensitivity and GSIS. The 45 % MCFA substitution of whole fatty acids in the normoenergetic diet impaired whole body growth and resulted in increased body adiposity and hyperinsulinaemia, and reduced insulin-mediated glucose uptake in skeletal muscle. In addition, the isolated pancreatic islets from the MCFA-fed rats showed impaired GSIS and reduced protein kinase Bα (AKT1) protein expression and extracellular signal-related kinase isoforms 1 and 2 (ERK1/2) phosphorylation, which were accompanied by increased cellular death. Furthermore, there was a mildly increased cholinergic sensitivity to GSIS. We discuss these findings in further detail, and advocate that they might have a role in the mechanistic pathway leading to the compensatory hyperinsulinaemic status found in this animal model.