Hypothalamic melanin concentrating hormone neurons communicate the nutrient value of sugar
Ana I Domingos,
Aylesse Sordillo,
Marcelo O Dietrich,
Zhong-Wu Liu,
Luis A Tellez,
Jake Vaynshteyn,
Jozelia G Ferreira,
Mats I Ekstrand,
Tamas L Horvath,
Ivan E de Araujo,
Jeffrey M Friedman
Affiliations
Ana I Domingos
Laboratory of Molecular Genetics, The Rockefeller University, New York, United States
Aylesse Sordillo
Laboratory of Molecular Genetics, The Rockefeller University, New York, United States
Marcelo O Dietrich
Section of Comparative Medicine, Yale University, New Haven, United States; Department of Biochemistry, Universidade Federal do Rio Grande do Sul (UFRGS), Porto Alegre, Brazil
Zhong-Wu Liu
Section of Comparative Medicine, Yale University, New Haven, United States
Luis A Tellez
Feeding Laboratory, The JB Pierce Laboratory, New Haven, United States; Department of Psychiatry, Yale University School of Medicine, New Haven, United States
Jake Vaynshteyn
Department of Neuroscience, Albert Einstein College of Medicine, New York, United States
Jozelia G Ferreira
Feeding Laboratory, The JB Pierce Laboratory, New Haven, United States; Department of Psychiatry, Yale University School of Medicine, New Haven, United States
Mats I Ekstrand
Laboratory of Molecular Genetics, The Rockefeller University, New York, United States
Tamas L Horvath
Section of Comparative Medicine, Yale University, New Haven, United States
Ivan E de Araujo
Feeding Laboratory, The JB Pierce Laboratory, New Haven, United States; Department of Psychiatry, Yale University School of Medicine, New Haven, United States
Jeffrey M Friedman
Laboratory of Molecular Genetics, The Rockefeller University, New York, United States; Howard Hughes Medical Institute, The Rockefeller University, New York, United States
Sugars that contain glucose, such as sucrose, are generally preferred to artificial sweeteners owing to their post-ingestive rewarding effect, which elevates striatal dopamine (DA) release. While the post-ingestive rewarding effect, which artificial sweeteners do not have, signals the nutrient value of sugar and influences food preference, the neural circuitry that mediates the rewarding effect of glucose is unknown. In this study, we show that optogenetic activation of melanin-concentrating hormone (MCH) neurons during intake of the artificial sweetener sucralose increases striatal dopamine levels and inverts the normal preference for sucrose vs sucralose. Conversely, animals with ablation of MCH neurons no longer prefer sucrose to sucralose and show reduced striatal DA release upon sucrose ingestion. We further show that MCH neurons project to reward areas and are required for the post-ingestive rewarding effect of sucrose in sweet-blind Trpm5−/− mice. These studies identify an essential component of the neural pathways linking nutrient sensing and food reward.
