Sucralose uses reward pathways to promote acute caloric intake

Qiao-Ping Wang; An-Qi Li; Bei Wang; Xin-Yuan Zhao; Sha-Sha Li; Herbert Herzog; G Gregory Neely

doi:10.1016/j.npep.2025.102502

Sucralose uses reward pathways to promote acute caloric intake

Neuropeptides. 2025 Jan 6:110:102502. doi: 10.1016/j.npep.2025.102502. Online ahead of print.

Authors

Qiao-Ping Wang¹, An-Qi Li², Bei Wang³, Xin-Yuan Zhao³, Sha-Sha Li³, Herbert Herzog⁴, G Gregory Neely⁵

Affiliations

¹ Lab of Metabolism and Aging, School of Pharmaceutical Sciences (Shenzhen), Shenzhen Campus of Sun Yat-sen University, Shenzhen 518107, China; Guangdong Provincial Key Laboratory of Diabetology, Guangzhou Key Laboratory of Mechanistic and Translational Obesity Research, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou 510630, China. Electronic address: [email protected].
² Lab of Metabolism and Aging, School of Pharmaceutical Sciences (Shenzhen), Shenzhen Campus of Sun Yat-sen University, Shenzhen 518107, China; Department of Pharmacy, The Third Affiliated Hospital, Sun Yat-Sen University, Guangzhou 510630, China.
³ Lab of Metabolism and Aging, School of Pharmaceutical Sciences (Shenzhen), Shenzhen Campus of Sun Yat-sen University, Shenzhen 518107, China.
⁴ St Vincent's Center for Applied Medical Research, Darlinghurst, Sydney, Australia.
⁵ The Dr. John and Anne Chong Laboratory for Functional Genomics, Charles Perkins Centre and School of Life & Environmental Sciences, The University of Sydney, Sydney, NSW 2006, Australia. Electronic address: [email protected].

PMID: 39793271
DOI: 10.1016/j.npep.2025.102502

Abstract

Non-nutritive sweeteners (NNSs) are used to reduce caloric intake by replacing sugar with compounds that are sweet but contain little or no calories. In this study, we investigate how non-nutritive sweetener sucralose to promote acute food intake in the fruit fly Drosophila melanogaster. Our results showed that acute exposure to NNSs sweetness induces a robust hyperphagic response in flies. Cellular and molecular dissection of this acute effect revealed the requirement of a reward pathway comprising of sweet taste neurons, octopaminergic neurons, and NPF neurons which drive increased food intake in response to sucralose. These data provide mechanistic insight into how NNSs can increase food intake, information that may help us better understand how artificially sweeteners may impact our physiology.

Keywords: Drosophila; Food intake; Non-nutritive sweeteners; Reward pathway; Sucralose.