Effect of asprosin on some hormones and metabolic factors in male mice with diabetes

Diabetes Mellitus is one of the biggest public health problems and its, prevalence has been increasing in recent years. Lipid, energy, and glucose metabolisms are affected in Diabetes mellitus due to poor glycemic control, and insulin resistance. In addition, Diabetes mellitus results in an increase in the plasma free fatty acid, triglycerides (TG) and low-density lipoprotein (LDL) levels and decreases in the high-density lipoprotein (HDL) level. Asprosin, which is a hormone released from white adipose tissue, is taken from adipose tissue to the liver, and causes a rapid glucose release from the liver into the circulation. Studies have shown that asprosin level changes in conditions such as diabetes, obesity, polycystic ovary syndrome and metabolic syndrome. It is predicated that asprosin, which increases appetite, can be effective in the regulation of body fat mass and anorexia. It is also known that administration of a single dose of asprosin to healthy mice increases blood glucose levels. Leptin, which is another hormone secreted from a significant amount of adipose tissue, plays a key role in the regulation of energy metabolism. Ghrelin is an orexinergic peptide known to play a role in glucose metabolism secreted from the stomach. the hunger hormone ghrelin has been shown to stimulate appetite by acting similar to asprosin, crossing the blood brain barrier and activating cAMP-dependent-AgRP neurons through the hypothalamic food intake system. Recent studies show that irisin, an adipomyokine, may play a role in the regulation of thermogenesis, total body energy metabolism and glucose homeostasis. The long-term administration of irisin also increases serum asprosin levels in healthy male rats, but not in obese male rats. It is stated that asprosin, which is found to be higher in diabetes, obesity and metabolic syndrome, may be a molecule that should be targeted in the treatment of these diseases. However, it is not known whether repeated asprosin administration changes blood glucose, leptin, ghrelin and irisin levels in healthy and diabetic animals. In addition, the effects of asprosin on TG, cholesterol and LDL accumulation that cause steatohepatitis in the liver of diabetic mice are also unknown. The hypothesis of this study is that the repeated administration of asprosin, which is taken from adipose tissue to the liver and causes glucose release from the liver into the circulation, regulate the blood glucose, leptin, ghrelin and irisin levels that change with diabetes. In addition, it will prevent the increase in TG, cholesterol and LDL in the liver that occurs with steatohepatitis and takes place as a complication of diabetes. This thesis study was carried out using 40 adult male Balb/C mice weighing 25-30 g. The mice were randomly divided into five groups as control, asprosin (1 g/kg), asprosin (10 g/kg), streptozotocin (STZ), STZ +Asprosin (10 g/kg) (n = 8 for each group). Asprosin was injected intraperitoneally (i.p.) four times at 3- day intervals to mice. Serum leptin, ghrelin, irisin levels were measured by enzyme-linked immunosorbent assay (ELISA) method. Liver samples were homogenized. Triglyceride, cholesterol and ldl levels were determined using an autoanalyzer. Shapiro-Wilk test and Levene method were used to determine normality and the homogeneity of variances, respectively. Significant differences between the groups were determined with one-way analysis of variance (ANOVA), followed by post hoc Tukey's test. In this thesis, it was shown for the first time that asprosin, which increases blood glucose in healthy animals, did not change the blood glucose level of diabetic animals. While asprosin decreased irisin level, it increased ghrelin level, but did not change leptin level in diabetic mice. Asprosin reduced the increased levels of hepatic TG, cholesterol, and LDL in diabetic mice. The results of our study show that asprosin may have an important role in the regulation of glucose and energy metabolism. It will also contribute greatly to understanding the relationship of asprosin with diabetes and its complications. Keywords: Asprosin, diabetes mellitus, blood glucose, irisin, ghrelin, leptin