Hypothalamic melanin concentrating hormone neurons communicate the nutrient value of sugar.

Jeffrey M Friedman,Ana I Domingos,Aylesse Sordillo,Marcelo O Dietrich,Tamas L Horvath,Jozelia G Ferreira,Luis A Tellez,Mats I Ekstrand,Ivan E De Araujo,Jake Vaynshteyn,Zhong-Wu Liu

doi:10.7554/elife.01462

Abstract

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. DOI: http://dx.doi.org/10.7554/eLife.01462.001.

Highlights

Animals and humans generally prefer sugars containing glucose, such as sucrose, compared to nonnutritive sweeteners such as sucralose (Smiciklas-Wright et al, 2002; Jacobson, 2005; Domingos et al, 2011; Sicher, 2011) as a result of the post-ingestive rewarding effect of sucrose (Domingos et al, 2011)
Spike attenuation (Figure 1D, inset) during optogenetic stimulation was similar to what has been previously reported for glucose-triggered responses (Burdakov et al, 2005; Kong et al, 2010) in melanin-concentrating hormone (MCH) neurons, and changes in membrane potential were resilient to optical stimulation (Figure 1—figure supplement 1B)
We report that MCH neurons are necessary and sufficient for establishing a preference for sucrose vs sucralose, an artificial sweetener

Summary

Introduction

Animals and humans generally prefer sugars containing glucose, such as sucrose, compared to nonnutritive sweeteners such as sucralose (Smiciklas-Wright et al, 2002; Jacobson, 2005; Domingos et al, 2011; Sicher, 2011) as a result of the post-ingestive rewarding effect of sucrose (Domingos et al, 2011). These studies have indicated that the nutrient value of sucrose is sensed and in turn establishes a preference for nutritive sugars (Ren et al, 2010; de Araujo et al, 2010; Sclafani et al, 2011; Fernstrom et al, 2012) These data further indicate that the post-ingestive rewarding effect plays an important role in driving nutrient choice (in addition to sweet taste). Despite the substantial evidence that they play a major, perhaps dominant, role in driving food intake

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Conclusion