Thursday, February 2, 2017

An update from the Buettner Lab

The interests and goals of Dr. Christoph Buettner’s laboratory are to study the regulation of metabolism through the central nervous system. Laboratory researchers employ integrated physiology approaches to understand a role of the brain in regulating metabolism throughout the body (orchestrating organ crosstalk such as nutrient flux between adipose tissue and the liver and its relevance in regulating insulin action). It turns out that the brain controls
metabolism and diseases that affect the brain such as Alzheimer’s and other psychiatric diseases, alcohol consumption and stress impair the ability of the brain to control metabolism. In obesity and diabetes, the ability of the brain to process important signals from the periphery such as sensing hormones and nutrients are similarly impaired. The Buettner laboratory tries to understand how the brain achieves this control and how to restore metabolic control by the brain. The group has found that the brain controls inflammation by
controlling lipid metabolism.

A commonly used approach in the Buettner laboratory is to study nutrient partitioning using
metabolic tracers during clamps in rodents that allow the simultaneous assessment of lipid, glucose and amino acid fluxes. These physiological study techniques are complemented by transcriptional, proteomic and metabolomic techniques to arrive at a molecular understanding of how the brain controls nutrient fluxes in peripheral organs such as liver and adipose tissue. The Buettner lab has established that hypothalamic leptin and insulin signaling play important roles in the regulation of adipose tissue lipolysis and lipogenesis. Further, our results obtained to date indicate that hypothalamic insulin and leptin play important roles in regulating hepatic glucose production, VLDL (very low density lipoprotein) secretion, amino acid metabolism and systemic inflammation. In obesity and diabetes, hypothalamic insulin action is impaired, in part through increased endocannabinoid tone in the brain, resulting in dysregulated
nutrient partitioning and a pro-inflammatory state.