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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