Sucralose Promote Food Intake Through NPY and A Neuronal Fasting Response

Non-nutritive sweeteners like sucralose are consumed by billions of people. While animal and human studies have demonstrated a link between synthetic sweetener consumption and metabolic dysregulation, the mechanisms responsible remain unknown. Here we use a diet supplemented with sucralose to investigate the long-term effects of sweet/energy imbalance. In flies, chronic sweet/energy imbalance promoted hyperactivity, insomnia, glucose intolerance, enhanced sweet taste perception and a sustained increase in food and calories consumed, effects that are reversed upon sucralose removal. Mechanistically, this response was mapped to the ancient insulin, catecholamine, and NPF/NPY systems and the energy sensor AMPK, which together comprise a novel neuronal starvation response pathway. Interestingly, chronic sweet/energy imbalance promoted increased food intake in mammals as well, and this also occurs through an NPY-dependent mechanism. Together our data show that chronic consumption of a sweet/energy imbalanced diet triggers a conserved neuronal fasting response and increases the motivation to eat. Overall design: RNA-seq on Drosophila head samples fed control and sucralose diet

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Wang QP, Lin YQ, Zhang L, Wilson YA, Oyston LJ, Cotterell J, Qi Y, Khuong TM, Bakhshi N, Planchenault Y, Browman DT, Lau MT, Cole TA, Wong AC, Simpson SJ, Cole AR, Penninger JM, Herzog H, Neely GG