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Sucralose promotes 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.

Type Journal
Authors Wang, Q. P.; Lin, Y. Q.; Zhang, L.; Wilson, Y. A.; Oyston, L. J.; Cotterell, J.; Qi, Y.; Khuong, T. M.; Bakhshi, N.; Planchenault, Y.; Browman, D. T.; Lau, M. T.; Cole, T. A.; Wong, A. C.; Simpson, S. J.; Cole, A. R.; Penninger, J. M.; Herzog, H.; Neely, G. G.
Publisher Name Cell Metabolism
Published Date 2016-07-12
Published Volume 24
Published Issue 1
Published Pages 75-90
Status Published in-print
DOI 10.1016/j.cmet.2016.06.010
URL link to publisher's version
OpenAccess link to author's accepted manuscript version