Effects of Vagotomy and Fenugreek on Hyperlipidemia and Insulin Resistance

Authors

Rituraj Khound, University of Nebraska-LincolnFollow

First Advisor

Qiaozhu Su

Second Advisor

Dipak Santra

Date of this Version

12-2017

Citation

Khound, R., Santra, D., Su, Q., Effects of Vagotomy and Fenugreek on Hyperlipidemia and Insulin Resistance

Comments

A THESIS Presented to the Faculty of The Graduate College at the University of Nebraska In Fulfillment of the Requirements For the Degree of Master of Science, Major: Nutrition, Under Supervision of Professors Qiaozhu Su and Dipak K. Santra. Lincoln, Nebraska: December 2017

Copyright (c) 2017 Rituraj Khound

Abstract

Hyperlipidemia is the impairment of lipid metabolism marked by abnormally high levels of lipid in circulation. This has been implicated in a number of metabolic diseases including diabetes, cardiovascular diseases, and nonalcoholic fatty liver disease. Insulin resistance is the impairment of insulin action, which leads to several diseases such as obesity and type 2 diabetes. New clinical and therapeutic approaches are warranted for the prevention and treatment of hyperlipidemia and insulin resistance. In our study, we investigated the mechanism underlying the effect of complete disruption of the sub-diaphragmatic vagus nerve (vagotomy) on hyperlipidemia and insulin sensitivity. We observed that vagotomy significantly reduced the fasting and postprandial TG levels and VLDL synthesis. Vagotomy also resulted in elevated circulatory GLP-1 levels which possibly led to reductions in de novo fatty acid synthesis and VLDL production. This surgical procedure also found to ameliorate HFD-induced hyperlipidemia and hepatic steatosis. Significant improvement in insulin sensitivity was also observed in vagotomized mice. We also studied the effect of fenugreek seeds on hyperlipidemia using CREBH-null mouse model. We observed that consumption of fenugreek and treatment with trigonelline, a bioactive compound derived from fenugreek, ameliorated induced hyperlipidemia by upregulating transcription of Insig proteins, preventing VLDL synthesis and enhancing fatty acid oxidation. These findings rationalize the use of vagotomy as an effective clinical procedure to treat obesity and diabetes. The study also substantiates the prospect of using fenugreek as a potent nutraceutical in the treatment of metabolic diseases.

Advisors: Qiaozhu Su and Dipak K. Santra