Separate gut-brain circuits for fat and sugar reinforcement combine to promote overeating.
Molly McDougle, Alan de Araujo, Arashdeep Singh, Mingxin Yang, Isadora Braga, Vincent Paille, Rebeca Mendez-Hernandez, Macarena Vergara, Lauren N Woodie, Abhishek Gour, Abhisheak Sharma, Nikhil Urs, Brandon Warren, Guillaume de Lartigue
Author Information
Molly McDougle: Department of Pharmacodynamics, University of Florida, Gainesville, FL, USA; Center for Integrative Cardiovascular and Metabolic Disease, University of Florida, Gainesville, FL, USA; Department of Neuroscience, University of Pennsylvania, Philadelphia, PA, USA.
Alan de Araujo: Department of Pharmacodynamics, University of Florida, Gainesville, FL, USA; Center for Integrative Cardiovascular and Metabolic Disease, University of Florida, Gainesville, FL, USA.
Arashdeep Singh: Department of Pharmacodynamics, University of Florida, Gainesville, FL, USA; Center for Integrative Cardiovascular and Metabolic Disease, University of Florida, Gainesville, FL, USA; Monell Chemical Senses Center, Philadelphia, PA, USA; Department of Neuroscience, University of Pennsylvania, Philadelphia, PA, USA.
Mingxin Yang: Department of Pharmacodynamics, University of Florida, Gainesville, FL, USA; Center for Integrative Cardiovascular and Metabolic Disease, University of Florida, Gainesville, FL, USA; Monell Chemical Senses Center, Philadelphia, PA, USA; Department of Neuroscience, University of Pennsylvania, Philadelphia, PA, USA.
Isadora Braga: Department of Pharmacodynamics, University of Florida, Gainesville, FL, USA; Monell Chemical Senses Center, Philadelphia, PA, USA; Department of Neuroscience, University of Pennsylvania, Philadelphia, PA, USA.
Vincent Paille: Monell Chemical Senses Center, Philadelphia, PA, USA; Department of Neuroscience, University of Pennsylvania, Philadelphia, PA, USA; UMR1280 Physiopathologie des adaptations nutritionnelles, INRAE, Institut des maladies de l'appareil digestif, Université de Nantes, Nantes, France.
Rebeca Mendez-Hernandez: Monell Chemical Senses Center, Philadelphia, PA, USA; Department of Neuroscience, University of Pennsylvania, Philadelphia, PA, USA.
Macarena Vergara: Department of Pharmacodynamics, University of Florida, Gainesville, FL, USA; Center for Integrative Cardiovascular and Metabolic Disease, University of Florida, Gainesville, FL, USA.
Lauren N Woodie: Institute for Diabetes, Obesity and Metabolism, University of Pennsylvania, Philadelphia, PA, USA.
Abhishek Gour: Department of Pharmaceutics, University of Florida, Gainesville, FL, USA.
Abhisheak Sharma: Department of Pharmaceutics, University of Florida, Gainesville, FL, USA.
Nikhil Urs: Department of Pharmacology, University of Florida, Gainesville, FL, USA.
Brandon Warren: Department of Pharmacodynamics, University of Florida, Gainesville, FL, USA.
Guillaume de Lartigue: Department of Pharmacodynamics, University of Florida, Gainesville, FL, USA; Center for Integrative Cardiovascular and Metabolic Disease, University of Florida, Gainesville, FL, USA; Monell Chemical Senses Center, Philadelphia, PA, USA; Department of Neuroscience, University of Pennsylvania, Philadelphia, PA, USA. Electronic address: gdelartigue@monell.org.
Food is a powerful natural reinforcer that guides feeding decisions. The vagus nerve conveys internal sensory information from the gut to the brain about nutritional value; however, the cellular and molecular basis of macronutrient-specific reward circuits is poorly understood. Here, we monitor in vivo calcium dynamics to provide direct evidence of independent vagal sensing pathways for the detection of dietary fats and sugars. Using activity-dependent genetic capture of vagal neurons activated in response to gut infusions of nutrients, we demonstrate the existence of separate gut-brain circuits for fat and sugar sensing that are necessary and sufficient for nutrient-specific reinforcement. Even when controlling for calories, combined activation of fat and sugar circuits increases nigrostriatal dopamine release and overeating compared with fat or sugar alone. This work provides new insights into the complex sensory circuitry that mediates motivated behavior and suggests that a subconscious internal drive to consume obesogenic diets (e.g., those high in both fat and sugar) may impede conscious dieting efforts.
