Dataset Information

Maternal low-calorie sweetener consumption rewires hypothalamic melanocortin circuits via a gut microbial co-metabolite pathway.

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.

SUBMITTER: Park S

PROVIDER: S-EPMC10322686 | biostudies-literature | 2023 May

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Maternal low-calorie sweetener consumption rewires hypothalamic melanocortin circuits via a gut microbial co-metabolite pathway.

Park Soyoung S Belfoul Amine M AM Rastelli Marialetizia M Jang Alice A Monnoye Magali M Bae Hosung H Kamitakahara Anna A Giavalisco Patrick P Sun Shan S Barelle Pierre-Yves PY Plows Jasmine J Jang Cholsoon C Fodor Anthony A Goran Michael I MI Bouret Sebastien G SG

JCI insight 20230522 10

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 ...[more]

PMID: 37014702

Similar Datasets

Project description:BackgroundMinimizing consumption of added sugars is recommended to prevent excessive weight gain among pregnant women. A common approach to lowering sugar intake is the use of low-calorie sweeteners (LCSs), yet little is known about LCS use during pregnancy or its effects on infant weight and health.ObjectiveThe aim of the study was to investigate temporal trends in LCS consumption by source (foods, beverages, or packets) among pregnant women in the United States from 1999 to 2014 and to compare recent LCS consumption patterns across sociodemographic subgroups and product categories.MethodsData were collected from pregnant women aged 20-39 y (n = 1,265) who participated in the NHANES from 1999-2000 through 2013-2014. Prevalence of LCS consumption was assessed using two 24-h dietary recalls. Analytical procedures for complex survey design were used, and sampling weights were applied to estimate national prevalence of LCS use. Rao-Scott modified chi-square tests were used to compare consumption prevalence across sociodemographic subgroups, and logistic regression was used to examine trends in LCS use over time.ResultsThe prevalence of LCS consumption among pregnant women increased by approximately 50% rising from 16.2% in 1999-2004 to 24.0% in 2007-2014, P = 0.04, with the highest prevalence observed in 2005-2006 (38.4%). This trend was driven predominantly by increases in LCS beverage use (9.9% in 1999-2004 compared with 18.3% in 2007-2014, P = 0.02). Prevalence of LCS consumption was highest among non-Hispanic white women and increased with education and income. No differences were observed based on prepregnancy weight status or trimester of pregnancy.ConclusionsApproximately one-quarter of pregnant women in the United States reported consumption of LCS during at least 1 of 2 dietary recalls. Given the widespread LCS consumption during pregnancy, research to elucidate potential effects of early life LCS exposure on taste preferences, weight trajectory, and risk of later metabolic disease is needed.

Project description:We examined the association between low-calorie sweeteners (LCS) consumption during preconception, pregnancy, and breastfeeding and child health outcomes. A systematic search of electronic databases in PubMed, Embase, Cumulated Index to Nursing and Allied Health Literature, the Cochrane Library, Scopus, Web of Science, PsycINFO, ProQuest Health and Medical, ClinicalTrials.gov, and Google Scholar was conducted up to 21 September 2023. A random effects model with restricted maximum likelihood estimation was used for the meta-analysis. Seventeen eligible studies were included. The standardised mean difference (SMD) and 95% confidence interval (CI) in birth weight between those who frequently consumed LCS (≥1 serve/day) during pregnancy and those who did not consume LCS was 0.04 (0.00, 0.08) (four cohort studies). Any LCS consumption during pregnancy compared with no consumption was not associated with birth weight [SMD (95% CI) = 0.03 (-0.03, 0.08)] (four cohort studies). Any LCS consumption during pregnancy was not associated with body mass index z-scores. The weighted mean difference (95% CI) was 0.00 (-0.05, 0.06) at birth, 0.06 (-0.29, 0.40) at 6 months, -0.04 (-0.19, 0.10) at 1 year, 0.00 (-0.16, 0.17) at 3 years, and 0.10 (-0.15, 0.34) at 7 years of the child age, compared with no intake (five cohort studies). The odds of being overweight at 1 year among children exposed to LCS during pregnancy was 1.19 (OR [95% CI]: 1.19 [0.81, 1.58]) compared with unexposed children (two cohort studies). The effect sizes were not precise for all the outcomes as the 95% CI indicated the effect estimates could range from small protective to a higher risk. The effect of LCS consumption on child behaviour and cognition was inconsistent. There is not enough evidence to confirm LCS consumption during pregnancy affects birth weight and risk of overweight in children. However, frequent consumption increased birth weight and the risk of overweight at different ages, though the effects were imprecise. More robust research evidence is required as the quality of evidence is low.

Dataset Information

Maternal low-calorie sweetener consumption rewires hypothalamic melanocortin circuits via a gut microbial co-metabolite pathway.

Publications

Maternal low-calorie sweetener consumption rewires hypothalamic melanocortin circuits via a gut microbial co-metabolite pathway.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets