Neuroendocrine Control of Energy Balance
Our laboratory’s overarching goal seeks to understand the neuroendocrine systems regulating energy balance and motivated behaviors. Using multiple approaches from the cell to the whole organism and extensively examine the role of various neuroendocrine signaling systems (e.g., GLP-1, leptin, amylin, CCK, serotonin, glutamate, and dopamine) in peripheral and central control of food intake and body weight regulation.
Overall, our research program takes a novel systems-neuroscience approach aimed at enhancing the development of realistic pharmacological-based therapeutics to treat obesity and associated comorbidities (e.g. obesity, eating disorders, diabetes, drug addiction and nausea / malaise).
Amylin Modulates a Ventral Tegmental Area-to-Medial Prefrontal Cortex Circuit to Suppress Food Intake and Impulsive Food-Directed Behavior
The VTA and mPFC are implicated in behaviors related to reward seeking, impulsivity, and attention around feeding and other hedonic stimuli. This is the first study to investigate how a satiation hormone affects mesocortical pathway activity and food reward–directed behaviors. Using multiple behavioral, pharmacological, and genetic approaches, we demonstrated that amylin signaling in the VTA reduced palatable food intake, impulsive behavior for a food reward, and mPFC dopamine release, likely through activation of local VTA GABA neurotransmission and inhibition of VTA-to-mPFC projecting dopamine neurons.
Metabolic hormone action in the VTA: Reward-directed behavior and mechanistic insights
This review provides a comprehensive update of the regulation of midbrain dopamine circuits by peripheral feeding hormones, cataloging what is currently known about the mechanisms by which these hormones influence VTA activity and how these actions regulate food intake and behavior around drugs of abuse. Better understanding of the reward-modulating effects of these hormone systems will help develop more effective treatments for obesity and addictive disorders.
Tirzepatide suppresses palatable food intake by selectively reducing preference for fat in rodents
In collaboration with Eli Lilly, we showed that the dual GLP-1/GIP agonist Tirzepatide robustly decreases preference for palatable foods by selectively decreasing lipid consumption. Our preclinical findings highlight that promoting healthier food options may contribute to the weight-loss success of therapeutic Tirzepatide use for patients.