Journal article
Maternal low-calorie sweetener consumption rewires hypothalamic melanocortin circuits via a gut microbial co-metabolite pathway
JCI insight, Vol.8(10), e156397
05/22/2023
DOI: 10.1172/jci.insight.156397
PMID: 37014702
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.
Details
- Title: Subtitle
- Maternal low-calorie sweetener consumption rewires hypothalamic melanocortin circuits via a gut microbial co-metabolite pathway
- Creators
- Soyoung Park - University of Southern CaliforniaAmine M. Belfoul - InsermMarialetizia Rastelli - InsermAlice Jang - University of Southern CaliforniaMagali Monnoye - AgroParisTechHosung Bae - University of California, IrvineAnna Kamitakahara - University of Southern CaliforniaPatrick Giavalisco - Max Planck Institute for Metabolism ResearchShan Sun - University of North Carolina at CharlottePierre-Yves Barelle - InsermJasmine Plows - University of Southern CaliforniaCholsoon Jang - University of California, IrvineAnthony Fodor - University of North Carolina at CharlotteMichael I. Goran - University of Southern CaliforniaSebastien G. Bouret - Inserm
- Resource Type
- Journal article
- Publication Details
- JCI insight, Vol.8(10), e156397
- DOI
- 10.1172/jci.insight.156397
- PMID
- 37014702
- NLM abbreviation
- JCI Insight
- ISSN
- 2379-3708
- eISSN
- 2379-3708
- Publisher
- American Society for Clinical Investigation
- Grant note
- ANR-22-CE16-0007 / ; to SGB / ; NA / Edward Mallinckrodt Jr. Foundation Award AASLDF 50028 / American Association for the Study of Liver Diseases
- Language
- English
- Date published
- 05/22/2023
- Academic Unit
- Internal Medicine
- Record Identifier
- 9985217133802771
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