IMPE Abstracts

Background: Healthy living, as well as treatment of overweight and obesity, includes a trend towards personalized diets. To better design these diets, predicting an individual’s metabolic response to specific nutrients is necessary and to do so we must understand how nutrients are perceived by metabolic circuits and to identify the signals involved. Moreover, as males and females respond differently to an obesogenic environment, how energy perception differs between the sexes must also be contemplated. The hypothalamus is the central integrator of metabolic signals, with this process involving both neurons and glial cells. Indeed, astrocytes process nutrients (e.g., fatty acids, glucose) and respond to metabolic signals (e.g., leptin, insulin) to release nutrients and signals to modify metabolic neurons. They are involved in the central inflammatory response and secondary complications associated with obesity. As the inflammatory response of hypothalamic astrocytes differs in response to saturated vs unsaturated fatty acids, we hypothesized that their metabolic response is also fatty-acid dependent.

Objectives: Our aims were to: 1) Determine the metabolomic profile of hypothalamic astrocytes to palmitic acid (PA) vs oleic acid (OA) and 2) Investigate whether the metabolic profile of astrocytes from males and females differ.

Materials and Methods: Primary hypothalamic astrocyte cultures from male and female mice were treated with PA (0.5 mM), OA (0.5mM) or vehicle for 24 hours. The cells were then processed for non-targeted metabolomic analysis via gas chromatography coupled to mass spectrometry.

Results: Analysis for predictive capacity resulted in a model that discriminated between PA (89.5% and control (88.9%) exposure, but not between OA and controls. The response of specific metabolites to PA and OA were strikingly different, with the citric acid cycle and other metabolic pathways being differently modulated by these two fatty acids. For example, PA decreased levels of lactic acid, malic acid, fumaric acid and oxoproline-5, with no effect of OA on these metabolites. Oxalic acid and glycerol 3-phosphate were decreased by PA but increased in response to OA. Male and female astrocytes responded similarly to these treatments, although basal levels of some metabolites were significantly different (e.g., higher oxalic acid levels in male astrocytes) and the degree of some responses differed between the sexes.

Conclusion: These results indicate that hypothalamic metabolic circuits are differentially impacted by saturated and unsaturated fatty acids and understanding the mechanisms involved will lead to new information for nutritional counseling.