ArticleJCI insight2023
Maternal low-calorie sweetener consumption rewires hypothalamic melanocortin circuits via a gut microbial co-metabolite pathway.
Article in JCI insight, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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Who cites it
14 citing papers in PubMed, 24 citations in OpenAlex.
- Beyond satiety: unraveling the complex roles of POMC neurons in behavior and metabolism.Reviews in endocrine & metabolic disorders · 2026Review
- Comparative study of rebaudioside A and rebaudioside Aα: physicochemical properties and in vivo metabolism.NPJ science of food · 2025Article
- The long-term impact of obesity in pregnancy on offspring hypothalamic feeding pathways.Royal Society open science · 2025Review
- Sex differences in fecal metabolic profiles of major depressive disorder: unveiling sex-specific metabolomic panel.BMC psychiatry · 2025Article
- Rebaudioside D and M, the next-generation sugar substitutes, do not exacerbate metabolic dysfunction in high-fat diet mice.Food chemistry: X · 2025Article
- Gestational saccharin consumption disrupts gut-brain axis glucose homeostasis control in adolescent offspring rats in a sex-dependent manner.Biology of sex differences · 2025Article
- AgRP neurons mediate activity-dependent development of oxytocin connectivity and autonomic regulation.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- Intestinal gluconeogenesis controls the neonatal development of hypothalamic feeding circuits.Molecular metabolism · 2024Article
- Effects of high dose aspartame-based sweetener on the gut microbiota and bone strength in young and aged mice.JBMR plus · 2024Article
- Determinants of obesity in Latin America.Nature metabolism · 2024 · on this mapReview
- Effects of long-term high dose aspartame on body mass, bone strength, femoral geometry, and microbiota composition in a young and aged cohort of male and female mice.bioRxiv : the preprint server for biology · 2024Article
- Scarring the early-life microbiome: its potential life-long effects on human health and diseases.BMB reports · 2023Review
- Maternal emulsifier consumption programs offspring metabolic and neuropsychological health in mice.PLoS biology · 2023Article
- Emulsifiers during gestation: The risks of ultra-processed food revealed in mice.PLoS biology · 2023Article
Corrections and comments
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Authors and funding
15 authors at 6 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The prevalence of obesity and type 2 diabetes is growing at an alarming rate, including among pregnant women. Low-calorie sweeteners (LCSs) have increasingly been used as an alternative to sugar to deliver a sweet taste without the excessive caloric load. However, there is little evidence regarding their biological effects, particularly during development. Here, we used a mouse model of maternal LCS consumption to explore the impact of perinatal LCS exposure on the development of neural systems involved in metabolic regulation. We report that adult male, but not female, offspring from both aspartame- and rebaudioside A-exposed dams displayed increased adiposity and developed glucose intolerance. Moreover, maternal LCS consumption reorganized hypothalamic melanocortin circuits and disrupted parasympathetic innervation of pancreatic islets in male offspring. We then identified phenylacetylglycine (PAG) as a unique metabolite that was upregulated in the milk of LCS-fed dams and the serum of their pups. Furthermore, maternal PAG treatment recapitulated some of the key metabolic and neurodevelopmental abnormalities associated with maternal LCS consumption. Together, our data indicate that maternal LCS consumption has enduring consequences on the offspring's metabolism and neural development and that these effects are likely to be mediated through the gut microbial co-metabolite PAG.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.