Colleen Novak, Ph.D.
Endocrine Research Unit
Mayo Clinic, Rochester, MN
Obesity is a growing health concern. As obesity has increased, the amount of physical activity in the population has decreased. In our sedentary society, low levels of physical activity have an important impact on weight gain. Whereas the neural, hormonal, molecular, and genetic mechanisms of energy intake are well studied, little is known about the mechanisms that regulate energy expenditure through physical activity. Non-exercise activity thermogenesis (NEAT) in humans is comprised of the energy expenditure of all physical activity outside of volitional exercise; NEAT contributes significantly to the ability to resist weight gain in the face of overfeeding. We have previously demonstrated that obese rats show decreased NEAT. Moreover, the sensitivity to central NEAT-promoting peptides also decreases with obesity. We do not know the mechanisms through which energy intake or storage alters the brain mechanisms of NEAT, however.
Here, we propose to systematically examine the actions of the intestinal hormone oxyntomodulin on NEAT. Oxyntomodulin (OXM) is a satiety signal released in reponse to food intake. Our preliminary data suggest that OXM increases physical activity when microinjected into the paraventricular nucleus of the hypothalamus (PVN). We hypothesize that OXM is one hormone that increases NEAT in response to positive energy balance.
In our first study, we hypothesize that systemic injections of OXM will increase physical activity and NEAT in a dose-dependent manner relative to vehicle controls. Second, we will determine if microinjections of OXM into the PVN and arcuate nucleus increase NEAT compared to vehicle-injected controls. Lastly, we hypothesize that OXM increases NEAT through its actions on GLP-1 receptors in the arcuate nucleus of the hypothalamus.
We will microinject a GLP-1 receptor antagonist into the arcuate nucleus and we predict that it will decrease OXM-induced NEAT. With these studies, we hope to delineate the neural mechanisms of OXM actions on physical activity and NEAT. Understanding the mechanisms through which changes in energy intake affect NEAT could be a critical step in developing effective behavioral and pharmacological strategies to combat obesity.
ZEB1 and the Development of Obesity
Oxyntomodulin and the Regulation of Non-Exercise Activity Thermogenesis
Hypothalamic Acyl-CoA Metabolism and Food Intake Regulation
Parents as the Agent of Change for Childhood Obesity
Identifying Novel Roles of Lipocalin 2 in Insulin Action and Glucose Metabolism
GIRK$: A New Obesity Gene?
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