Nonnutritive sweetener consumption during pregnancy, adiposity, and adipocyte differentiation in offspring: evidence from humans, mice, and cells.

Autor: Azad MB; Developmental Origins of Chronic Diseases in Children Network (DEVOTION) and the Diabetes Research Envisioned and Accomplished in Manitoba (DREAM) Theme of the Children's Hospital Research Institute of Manitoba, Winnipeg, MB, Canada. meghan.azad@umanitoba.ca.; Department of Pediatrics and Child Health, University of Manitoba, Winnipeg, MB, Canada. meghan.azad@umanitoba.ca., Archibald A; Developmental Origins of Chronic Diseases in Children Network (DEVOTION) and the Diabetes Research Envisioned and Accomplished in Manitoba (DREAM) Theme of the Children's Hospital Research Institute of Manitoba, Winnipeg, MB, Canada.; Max Rady College of Medicine, University of Manitoba, Winnipeg, MB, Canada., Tomczyk MM; Developmental Origins of Chronic Diseases in Children Network (DEVOTION) and the Diabetes Research Envisioned and Accomplished in Manitoba (DREAM) Theme of the Children's Hospital Research Institute of Manitoba, Winnipeg, MB, Canada.; Department of Pharmacology and Therapeutics, University of Manitoba, Winnipeg, MB, Canada., Head A; Developmental Origins of Chronic Diseases in Children Network (DEVOTION) and the Diabetes Research Envisioned and Accomplished in Manitoba (DREAM) Theme of the Children's Hospital Research Institute of Manitoba, Winnipeg, MB, Canada.; Department of Pharmacology and Therapeutics, University of Manitoba, Winnipeg, MB, Canada., Cheung KG; Developmental Origins of Chronic Diseases in Children Network (DEVOTION) and the Diabetes Research Envisioned and Accomplished in Manitoba (DREAM) Theme of the Children's Hospital Research Institute of Manitoba, Winnipeg, MB, Canada.; Department of Pharmacology and Therapeutics, University of Manitoba, Winnipeg, MB, Canada., de Souza RJ; Department of Clinical Epidemiology & Biostatistics, McMaster University, Hamilton, ON, Canada.; Department of Nutritional Sciences, University of Toronto, Toronto, ON, Canada.; Li Ka Shing Knowledge Institute, St. Michael's Hospital, Toronto, ON, Canada., Becker AB; Developmental Origins of Chronic Diseases in Children Network (DEVOTION) and the Diabetes Research Envisioned and Accomplished in Manitoba (DREAM) Theme of the Children's Hospital Research Institute of Manitoba, Winnipeg, MB, Canada.; Department of Pediatrics and Child Health, University of Manitoba, Winnipeg, MB, Canada., Mandhane PJ; Department of Pediatrics, University of Alberta, Edmonton, AB, Canada., Turvey SE; Department of Pediatrics, BC Children's Hospital, University of British Columbia, Vancouver, BC, Canada., Moraes TJ; Department of Pediatrics, Hospital for Sick Children, University of Toronto, Toronto, ON, Canada., Sears MR; Department of Medicine, McMaster University, Hamilton, ON, Canada., Subbarao P; Department of Pediatrics, Hospital for Sick Children, University of Toronto, Toronto, ON, Canada., Dolinsky VW; Developmental Origins of Chronic Diseases in Children Network (DEVOTION) and the Diabetes Research Envisioned and Accomplished in Manitoba (DREAM) Theme of the Children's Hospital Research Institute of Manitoba, Winnipeg, MB, Canada. vdolinsky@chrim.ca.; Department of Pharmacology and Therapeutics, University of Manitoba, Winnipeg, MB, Canada. vdolinsky@chrim.ca.
Jazyk: angličtina
Zdroj: International journal of obesity (2005) [Int J Obes (Lond)] 2020 Oct; Vol. 44 (10), pp. 2137-2148. Date of Electronic Publication: 2020 May 04.
DOI: 10.1038/s41366-020-0575-x
Abstrakt: Background: Obesity often originates in early life, and is linked to excess sugar intake. Nonnutritive sweeteners (NNS) are widely consumed as "healthier" alternatives to sugar, yet recent evidence suggests NNS may adversely influence weight gain and metabolic health. The impact of NNS during critical periods of early development has rarely been studied. We investigated the effect of prenatal NNS exposure on postnatal adiposity and adipocyte development.
Methods: In the CHILD birth cohort (N = 2298), we assessed maternal NNS beverage intake during pregnancy and child body composition at 3 years, controlling for maternal BMI and other potential confounders. To investigate causal mechanisms, we fed NNS to pregnant C57BL6J mice at doses relevant to human consumption (42 mg/kg/day aspartame or 6.3 mg/kg/day sucralose), and assessed offspring until 12 weeks of age for: body weight, adiposity, adipose tissue morphology and gene expression, glucose and insulin tolerance. We also studied the effect of sucralose on lipid accumulation and gene expression in cultured 3T3-L1 pre-adipocyte cells.
Results: In the CHILD cohort, children born to mothers who regularly consumed NNS beverages had elevated body mass index (mean z-score difference +0.23, 95% CI 0.05-0.42 for daily vs. no consumption, adjusted for maternal BMI). In mice, maternal NNS caused elevated body weight, adiposity, and insulin resistance in offspring, especially in males (e.g., 47% and 15% increase in body fat for aspartame and sucralose vs. controls, p < 0.001). In cultured adipocytes, sucralose exposure at early stages of differentiation caused increased lipid accumulation and expression of adipocyte differentiation genes (e.g., C/EBP-α, FABP4, and FASN). These genes were also upregulated in adipose tissue of male mouse offspring born to sucralose-fed dams.
Conclusion: By triangulating evidence from humans, mice, and cultured adipocytes, this study provides new evidence that maternal NNS consumption during pregnancy may program obesity risk in offspring through effects on adiposity and adipocyte differentiation.
Databáze: MEDLINE
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