Sucralose Promotes Food Intake through NPY and a Neuronal Fasting Response

Abstract

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.

Circulating glucose levels inversely correlate with Drosophila larval feeding through insulin signaling and SLC5A11

“…Moreover, hungry animals may simply eat more of the super-sweet calorie-free diet to induce satiation. A recent study showed that sucralose increases food intake in flies via a neuronal fasting response comprising the NPF system 67 .…”

Índice glicémico, carga glicémica e insulina posprandial a dos fórmulas isoglucídicas con distintos edulcorantes y fibra en adultos sanos y diabéticos tipo 2

“…Una investigación afirma que los edulcorantes artificiales, a pesar de no ser absorbidos a nivel intestinal (con nulo aporte calórico), pudieran inducir a la secreción de insulina pancreática a través del sistema nervioso central posterior a la degustación del sabor dulce del alimento (27). No obstante, son necesarios estudios clínicos en humanos.…”

Sucralose Suppresses Food Intake

“…Using radiolabeled fly food identical in composition to that used by Wang et al (2016), we found that flies ate less when the medium contained sucralose. This effect was seen on the first day (8% decrease relative to control) and, to a greater extent, on the sixth day (16% decrease relative to control) of sucralose exposure (Figure S1B).…”

“…The authors show that animals exposed to sucralose subsequently overeat when switched to sucralose-free food. Wang et al (2016) interpret this observation by suggesting that prolonged sucralose ingestion triggers a neuronal response that simulates a fasting state and promotes food intake. An untested alternative hypothesis is that flies alter their consumption of sucralose-laced food during the Exposure Phase, thereby affecting nutrient intake and potentially influencing all subsequent feeding behavior.…”

“…In a recent paper in Cell Metabolism , Wang et al (2016) tested the effect of the NNS, sucralose, on feeding behavior in Drosophila . Their experimental paradigm consisted of an Exposure Phase (of up to 6 days) on sucralose-laced food, followed by a trial period on regular, sucralose-free diet (Figure S1A).…”