Circulating Triglycerides and The Brain’s Reward Circuit

Following a lipid rich meal, circulating triglyceride levels increase and some level of reward is experienced. We suspect that a dietary triglyceride processing enzyme known as lipoprotein lipase (LPL) is the sensor involved in triglyceride sensing in the mesolimbic brain. We also believe that circulating triglycerides in the brain increase activity of the reward circuit, signaling positive reinforcement and in cases of overexposure, promoting neuroadaptations similar to those seen in individuals addicted to substances of abuse. Using fluorescent in-situ hybridization we found that LPL’s expression was specific to specific cell types within mesolimbic circuitry, namely dopaminergic and medium spiny neurons. By chronically catheterizing the carotid artery of mice, we were able to directly infuse triglycerides to the brain via catheter in order to emulate post-meal neurophysiology. We performed lipid profile analyses of mice that had received brain triglyceride delivery (BTGD) and found significant changes in striatal glycerolipid, free fatty acid, and eicosanoid species, validating our approach to examining post-meal neurophysiology and pointing to activation of the pro-inflammatory lipoxygenase (LOX) pathway. Using immunohistochemistry following BTGD, we found that circulating triglycerides may upregulate markers of neural activity in mesolimbic and basal ganglia circuitry. Lastly, we assayed the effects that circulating triglycerides may have on anxiety, and found mice that received BTGD exhibited a more anxious behavioral phenotype. We therefore have further reason to believe in the ability of palatable foods to act as an addictive substance, and in the role of LPL as a lipid sensor in the mesolimbic brain