SAT072 Choline Deprivation Aggravates Hyperglycemia And Fatty Liver In Non-obese Streptozocin-induced Diabetic Rats

Abstract

Abstract Disclosure: C. Liapi: None. A. Kyriakaki: None. H. Al Humadi: None. R. Al-Saigh1: None. A. Al Humadi: None. A. Lazaris: None. Background: Choline deprivation (CD) is an established model of steatohepatitis. There is a strong association between non-alcoholic fatty liver disease and diabetes mellitus that has a significant impact on the global health system. The combined state of CD and diabetes can resemble common cases in clinical practice including parenteral nutrition, pregnancy, chronic liver disease malnutrition and/ or alcoholism in diabetic individuals. The aim of this study was to investigate the effects of choline deprivation on glycemic control, insulin signaling pathway and lipid metabolism in non-obese streptozocin-induced diabetic rats. Methods: Thirty-two male adult Wistar rats were divided into four groups; control, diabetes (DM), choline-deprived diet (CDD), and combined group (DM+CDD); DM was induced by intraperitoneal streptozotocin administration. Body weight, fasting blood glucose and plasma insulin levels, lipid profile, liver biochemistry, liver histopathology and gene expression of insulin receptor (IR), insulin receptor substrate-1 (IRS-1), glucose transporters 2 & 4 (GLUT-2 & -4) in hepatic tissue, were assessed. Results: The combination group (CDD+DM) showed a significant increase in blood glucose associated with a significant decrease in plasma insulin level and evidence of dyslipidemia with a significant increase in liver enzymes, histopathology showed extensive micro- and macrovesicular steatosis and a significant decrease in weight gain versus the control, CDD and DM group. A significant increase was observed in gene expression of IR, IRS-1, GLUT-2, and GLUT-4 in all the experimental groups versus the control. Conclusion: The combination of choline deficiency and diabetes has drawn some new scenarios on insulin and some hepatic metabolic pathways: (i) plasma insulin resistance with progressive hyperglycemia and hyperlipidemia.(ii) attenuation of hepatic insulin resistance or sensitization of insulin signaling pathways in the liver, due to the hepatotoxic effects of choline deficiency that could ultimately simulate features of the metabolic syndrome, and (iii) experimentally simulation of metabolic conditions seem to act synergistically, leading to poor glycemic control along with aggravation of hepatic steatosis. Presentation: Saturday, June 17, 2023