Date of Graduation
Honors Research Project
Bachelor of Science
Natural Sciences - BS / MD Program
Dr. Huang MD, Ph.D.
Dr. Carlson Ph.D.
Dr. Londraville Ph.D.
Obesity is the most common nutritional disorder in the United States and worldwide. Public health efforts and other anti-obesity measures clearly have not controlled the obesity epidemic. There is a great need to understand the pathogenic mechanisms underlying fat accumulation. Research of the past decade supports a prominent role for diet-induced adipose tissue dysfunction in the development and/or progression of obesity and associated insulin resistance. Potential mechanisms for the development of adipose tissue dysfunction include ectopic (visceral) fat accumulation, genetic factors, and alterations in autophagy and inflammatory processes. However, the molecular mechanisms linking dietary fat intake with alterations in adipose tissue autophagy levels are not well understood. A critical role of protein kinase C beta (PKCβ) in obesity-associated adipose dysfunction is emerging. PKCβ deficiency protects from high fat diet-induced obesity and related complications. High fat diet is also shown to induce adipose PKCβ expression in mice, whereas PKCβ deficiency is reported to stimulate autophagy in a cell culture model. Based on the above results, we hypothesized that high fat diet-induced PKCβ activation in the adipose tissue inhibits autophagy and thereby promotes adipose dysfunction and fat accumulation. We report here that high fat diet-induced adipose PKCβ induction is accompanied by a simultaneous reduction in the ratio of autophagy markers LC3- II/LC3-I protein expression in mice. Importantly, high fat diet was unable to alter this ratio in the adipose tissue of PKCβ deficient mice. These results implicate PKCβ in mediating harmful effects of high fat diet on adipose tissue autophagy levels. It is hoped that understanding the PKCβ based pathogenic mechanisms leading to diet-induced adipose dysfunction will eventually lead to novel therapeutic approaches to combat the obesity epidemic.
Mehta, Neil, "Potential Role of Protein Kinase Cbeta in High Fat Diet-Induced Adipose Dysfunction by Regulating Autophagy Levels" (2015). Honors Research Projects. 198.