Endocannabinoid Regulation of Bone Metabolism in Hibernating Marmots

University Of Massachusetts Amherst, Amherst MA

Investigators

Abstract

One of the goals of comparative physiology is to understand how different physiological systems impact each other. Endocannabinoids are signaling molecules derived from fatty acids that appeared early in evolution and play important roles in regulating numerous physiological processes including those that are altered in hibernation such as bone, fat, and energy metabolism. The research aims to understand how endocannabinoid signaling by fat cells affects bone remodeling in obese, but otherwise healthy hibernating marmots. The planned studies will provide research experiences for undergraduate students to prepare them for advanced education and careers in science. The educational outreach component of this award will help students understand how diet and exercise affect fat accumulation and overall health of organisms. It will also elucidate how some animals have evolved physiological systems that prevent disease during states of obesity and physical inactivity. It will develop an interactive exhibit for K-12 students to explore the differences between the metabolism and physical activity of a hibernating animal and themselves. It will develop research kits for middle school students to measure and understand the calorie content of specific foods. It will also develop a presentation on the unique physiological adaptations in hibernators to underserved K-5 students. Hibernating mammals demonstrate remarkable resilience by having evolved physiological mechanisms that allow them to survive extreme physiological and environmental conditions for prolonged periods of time. Physical inactivity, obesity, and anorexia are well known to negatively impact bone metabolism and structure in non-hibernating animals. However, the physical inactivity, obesity, and anorexia that occur during hibernation do not negatively affect bone in marmots. The research will investigate the role of the endocannabinoid system in preventing bone loss in hibernating marmots. The research will test the general hypothesis that the endocannabinoid system regulates bone metabolism during hibernation to prevent bone loss. The project will undertake an interdisciplinary approach to understanding the role of paracrine signaling from bone marrow adipocytes in endocannabinoid regulated bone metabolism during hibernation. Novel targeted mass spectrometry methodology to measure tissue levels of endocannabinoid ligands, with greater sensitivity than previously reported, will be used to measure endocannabinoid levels in marmot serum, bone, and adipose tissue. Pharmacological blocking will be used to assess the role of specific components of the endocannabinoid system in regulating bone remodeling and structure during hibernation. Additionally, the methodology and results from the study will provide the conceptual framework for modeling how the endocannabinoid system regulates metabolism in other physiological systems during the extreme conditions of hibernation.