A role for lipoprotein lipase in mesolimbic function

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DESCRIPTION (provided by applicant): Metabolic factors can act directly on the brain to influence neural function and relevant behaviors. While several of these signals (e.g. leptin) are known and studied, there are likely to be many other signals in the form of metabolites. The identification of a key fat metabolic enzyme, lipoprotein lipase (LPL) in dopamine centers of the brain raises the intriguing possibility that these areas are influenced by triglycerides. This woul have implications for many behaviors influenced by dopamine, including food intake and drug addiction. Preliminary data suggests that LPL functions in the nucleus accumbens (NAc) to influence food intake. The present proposal seeks to characterize the expression and regulation of LPL in these centers while also determining the function of the lipase in both the nucleus accumbens as well as the ventral tegmental area (VTA). Both feeding and response to drugs of abuse will be measured to gain a more complete appreciation of the function of LPL in the regions. The proposed work is important for giving us an integrated picture of metabolic signaling to the brain, while also generating novel pathways for therapeutic development for obesity and addiction.