Differential sympathetic activity to adipose tissue, Implications in energy homeostasis and weight loss

Sipe, Laura, Biology - Graduate School of Arts and Sciences, University of Virginia
Deppmann, Christopher, Department of Biology, University of Virginia

In order to provide precise control of energy homeostasis, the sympathetic nervous system (SNS) activity is differentially regulated to specific adipose depots. Throughout calorie restriction, the SNS activity toward each adipose depot is unique in timing, pattern of activation, and habituation with the most dramatic contrast between the visceral and subcutaneous adipose depots. Sympathetic drive toward visceral gonadal adipose is more than doubled early in weight loss and then suppressed later in the diet when weight loss has plateaued. Coincident with the decline in SNS activity toward visceral adipose is an increase in activity toward subcutaneous depots indicating a switch in lipolytic sources. The SNS activity was necessary for adipose loss, as a pharmacological blockage of sympathetic activity on adipose tissue suppressed loss of visceral adipose tissue. This pattern of sympathetic activation is required for energy liberation and loss of adipose tissue in response to a calorie restricted diet.
Although, SNS activity to adipose depots is differentially regulated in response to calorie restriction, the importance of this observation is unknown. To determine the consequence of disrupting the preferential sympathetic drive to adipose depots, we analyzed the p75 Neurotrophin Receptor (p75NTR) deficient mice. p75NTR deficient mice are resistant to body weight loss during calorie restriction independent of changes in starting body weight or food intake. p75NTR deficient mice lost significantly less visceral adipose mass following calorie restriction. The sympathetic drive to adipose tissue is essential for adipose tissue loss and p75NTR deficient mice exhibited decreased sympathetic drive to white adipose tissue following calorie restriction. One mechanism behind the decrease in sympathetic drive could be the increase in synapses during development at the sympathetic ganglia, which would lead to altered differential sympathetic outflow to adipose tissue. We have begun to elucidate the cell autonomous role of p75NTR in the SNS and cement the importance of differential sympathetic activity to adipose tissue throughout calorie restriction.
We established that differential sympathetic drive is essential for adipose loss from calorie restriction. Future work will address how differential sympathetic drive to adipose tissue regulated, which will lead to advances in metabolic health and the understanding of energy homeostasis.

PHD (Doctor of Philosophy)
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