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. (2016). Sucralose Promotes Food Intake through NPY and a Neuronal Fasting Response.  Cell Metab. 24(1): 75--90.

FBrf0234991

Research paper

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.