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Publication : Separate gut-brain circuits for fat and sugar reinforcement combine to promote overeating.

First Author  McDougle M Year  2024
Journal  Cell Metab Volume  36
Issue  2 Pages  393-407.e7
PubMed ID  38242133 Mgi Jnum  J:346160
Mgi Id  MGI:7613891 Doi  10.1016/j.cmet.2023.12.014
Citation  McDougle M, et al. (2024) Separate gut-brain circuits for fat and sugar reinforcement combine to promote overeating. Cell Metab 36(2):393-407.e7
abstractText  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.
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