Abstract
Background/objectivesMaternal obesity increases the risk of gestational diabetes mellitus (GDM), which results in fetal overgrowth and long-lasting metabolic dysfunctioning in the offspring. Previous studies show that maternal choline supplementation normalizes fetal growth and adiposity of progeny from obese mice. This study examines whether supplementation of betaine, a choline derivative, has positive effects on fetal metabolic outcomes in mouse progeny exposed to maternal obesity and GDM.MethodsC57BL/6J mice were fed either a high-fat (HF) diet or a control (normal-fat, NF) diet and received either 1% betaine (BS) or control untreated (BC) drinking water 4–6 weeks before timed-mating and throughout gestation. Maternal, placental, and fetal samples were collected for metabolite and gene-expression assays.ResultsAt E12.5, BS prevented fetal and placental overgrowth and downregulated glucose and fatty acid transporters (Glut1 and Fatp1) and the growth-promoting insulin-like growth factor 2 (Igf2) and its receptor Igf1r in the placenta of HF, glucose-intolerant dams (P < 0.05). However, these effects disappeared at E17.5. At E17.5, BS reduced fetal adiposity and prevented liver triglyceride overaccumulation in HF versus NF fetuses (P < 0.05). BS fetal livers had enhanced mRNA expression of microsomal triglyceride transfer protein (Mttp) (P < 0.01), which promotes VLDL synthesis and secretion. Although we previously reported that maternal choline supplementation downregulated mRNA expression of genes involved in de novo lipogenesis in fetal livers, such alterations were not observed with BS, suggesting differential effects of betaine and choline on fetal gene expression.ConclusionWe propose a temporal-specific mechanism by which maternal BS influences fetal growth and lipid metabolic outcomes of HF mice during prenatal development.
Highlights
Betaine (N,N,N-trimethylmethanaminium) is a methyl derivative of glycine which is formed from glycine and three methyl groups
The female mice were randomly divided into four groups: the normal diet control (NF-BC) group received a normal diet (D12450J, Research Diets, New Brunswick, NJ, USA) containing 10% kcal from fat and untreated drinking water; the NF betaine-supplemented (NF-betaine supplementation (BS)) group received the normal diet and purified drinking water supplemented with 1% betaine anhydrous; the high-fat control (HF-BC) group received a HF diet (D12492, Research Diets) containing 60% kcal from fat and untreated drinking water; and the HF betainesupplemented (HF-BS) group received the HF diet and purified drinking water supplemented with 1% betaine anhydrous (Fig. 1)
This study is a continuation of our earlier studies where we demonstrated that supplementation of choline prevents fetal overgrowth and excess adiposity in dams demonstrating phenotypes that resemble maternal obesity and GDM15, 19
Summary
Betaine (N,N,N-trimethylmethanaminium) is a methyl derivative of glycine which is formed from glycine and three methyl groups. Betaine is naturally found in foods such as shrimp, beets, and whole grains[1]. It can be derived from the semi-essential nutrient choline (N,N,Ntrimethylethanolammonium) in the body via oxidation mediated by choline dehydrogenase (CHDH). Betaine serves as an osmolyte, a methyl donor, and a lipotrope, and is primarily found in the livers of mammals. The interaction of betaine with energy and macronutrient metabolism has been revealed in multiple studies. Betaine is used as an additive to animal feed to generate a leaner carcass[2]. Betaine treatment in cells enhances mitochondrial and cellular respiration, Nutrition and Diabetes
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
