Investigation of the effects of betatrophin hormone levels on carbohydrate and lipid metabolism in mice with induced insulin resistance

Betatrophin (ANGPTL8) is a recently identified hormone that is produced in the liver and adipose tissue and its effects and association with carbohydrate and lipid metabolisms are yet undefined. Therefore the aim of this study was to investigate the effects and relationship of this hormone with carbohydrate and lipid metabolisms by using key enzymes in the metabolic pathways for the first time. Forty C57BL6/J type male mice that were 8 and 22 weeks old were used in the study. For each age group, 2 experimental and 2 healthy groups each including 10 test subjects were formed. In the experimental groups, S961 as an insulin antagonist was administrated subcutaneously via osmotic pump while control groups received phosphate buffered saline using the same technique. Insulin tolerance tests were performed subsequently. Although insulin resistance was detected in the 8 week old experimental group, no resistance was observed in the 22 week old group. Following the tests, blood and liver tissue samples were collected in the 8 week old group under general anesthesia. Serum samples that were obtained from collected blood were used for enzyme linked immonusorbent assay (ELISA) and spectrophotometer tests to identify biochemical parameters such as serum betatrophin, fasting blood glucose, postprandial blood glucose, insulin, triglyceride, total cholesterol, HDL and LDL cholesterol. With the real time polimeraze chain reaction (RT-PCR) that was performed using tissue samples, hepatic expression levels of betatrophin, lactate dehydrogenase 5 (LDH5), citrate synthase and acetyl CoA carboxylase 1 (ACC1) were identified. Statistically significant increases were observed in the betatrophin expression, serum betatrophin, fasting and postprandial blood glucose, total cholesterol and triglyceride levels in the 8 week old experimental group. When compared to control group, citrate synthase levels were significantly lower in the experimental group. High correlation was found between betatrophin hormone expression and serum levels and serum triglyceride levels however there was no statistically significant relationship between fasting blood glucose, postprandial blood glucose, insulin, total cholesterol, HDL, LDL cholesterol. No correlations were observed between betatrophin expression levels and LDH5, ACC1 and citrate synthase enzyme expressions. It was concluded that betatrophin hormone levels may have an important role in the regulation of triglyceride metabolism. Also it may be inferred that betatrophin hormone does not regulate carbohydrate and lipid metabolisms via ACC1, LDH5 and citrate synthase. However further studies are needed to support this conclusion. Additionally, a foreknowledge was obtained regarding the relationship between betatrophin hormone levels and aerobic and anaerobic respiration pathways with this study.