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The lasting effect of maternal choline supplementation on lipid metabolism in mouse progeny affected by maternal obesity and gestational diabetes mellitus

Award Number: SC3GM132010
ORGANIZATION: NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

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The lasting effect of maternal choline supplementation on lipid metabolism in mouse progeny affected by maternal obesity and gestational diabetes mellitus - Project summary Maternal obesity affects more than one third of pregnant women in the U.S. and increases the risk of gestational diabetes mellitus (GDM), defined by high blood glucose during pregnancy. Both maternal obesity and GDM lead to fetal overgrowth, which subsequently increases the risk of obesity and cardio-metabolic diseases of the offspring later in life. Despite the increase in overall adiposity, GDM-affected babies demonstrate a paradoxical decrease in long-chain polyunsaturated fatty acids (LC-PUFAs) such as docosahexaenoic acid (DHA) content in the cord blood, which likely affects DHA incorporation into the brain and cognitive development. Choline is a semi-essential nutrient that affects different pathways of lipid metabolism, such as mediating lipid transport and epigenetic control of lipid metabolic genes. Our prior studies have demonstrated that maternal choline supplementation (MCS) prevented fetal overgrowth and enhanced the expression of a LC-PUFA transporter in the placenta of mouse embryos from obese and GDM dams. In the current study, we hypothesize that MCS in obese/GDM mice persistently reduces ectopic fat accumulation in different organs while restoring LC-PUFA status in mouse progeny, thereby maintaining their metabolic health later in life. Aim 1 will determine the persisting influence of MCS on lipid homeostasis in key organs regulating metabolism. C57BL/6J female mice will be fed either a 60% high-fat (HF) diet to induce obesity and GDM or a 10% normal fat (NF) diet. Mice will be either supplemented with 25mM choline chloride in water or given control plain drinking water 4 weeks prior to timed-mating until weaning of pups. We will dissect pups either at weaning or after 6 weeks of post-weaning HF feeding (n=2 females and 2 males/dam and 10 dams/group) and quantify lipoprotein-cholesterol, triglyceride, and fatty acid contents as well as lipid metabolic gene expression in the liver, blood, skeletal muscle and gonadal fat pad. Aim 2 will determine the differential effect of MCS on the metabolism of individual fatty acids, especially LC-PUFA in the offspring. A lipidomics approach will be used to scan all fatty acid species. Aim 3 will delineate which pathway of choline metabolism participates in the regulation of lipid homeostasis. We will use a deuterium labeled choline tracer to trace the metabolic fate of choline in the body. We anticipate that MCS has long-lasting effects on promoting lipid catabolism and export, while preserving LC-PUFA status in the offspring from obese/GDM dams and preventing them from HF diet- induced obesity, fatty liver, and diabetes. This study will comprehensively determine the mechanism by which MCS influences the lipid profile, distribution, and metabolism in mouse progeny affected by maternal obesity/GDM. Results will provide insights into a cost-effective nutritional approach to counteract the lasting adverse influence of maternal obesity /GDM on lipid homeostasis and metabolic health of the offspring.


Issue Date FY	Funding FY	Legal Entity Name	Legal Entity Address	Legal Entity City	Legal Entity State	Legal Entity Zip Code	Legal Entity COUNTY	Legal Entity COUNTRY	Assistance Listing	Award Code	Budget Year	Action Date	Action Type	Action Amount

Issue Date FY: 2024 ( Subtotal = -$1 )
2024	2022	RESEARCH FOUNDATION OF THE CITY UNIVERSITY OF NEW YORK	2900 BEDFORD AVE	BROOKLYN	NY	11210	KINGS	USA	Biomedical Research and Research Training	001	4	2/25/2024	NON-COMPETING CONTINUATION	-$1
2024	2022	RESEARCH FOUNDATION OF THE CITY UNIVERSITY OF NEW YORK	2900 BEDFORD AVE	BROOKLYN	NY	11210	KINGS	USA	Biomedical Research and Research Training	000	4	11/10/2023	NON-COMPETING CONTINUATION	$0
														Subtotal = -$1

Issue Date FY: 2022 ( Subtotal = $117,750 )
2022	2022	RESEARCH FOUNDATION OF THE CITY UNIVERSITY OF NEW YORK	2900 BEDFORD AVE STE 1	BROOKLYN	NY	11210	KINGS	USA	Biomedical Research and Research Training	001	4	6/27/2022	NON-COMPETING CONTINUATION	$11,775
2022	2022	RESEARCH FOUNDATION OF THE CITY UNIVERSITY OF NEW YORK	2900 BEDFORD AVE STE 1	BROOKLYN	NY	11210	KINGS	USA	Biomedical Research and Research Training	000	4	2/9/2022	NON-COMPETING CONTINUATION	$105,975
														Subtotal = $117,750

Issue Date FY: 2021 ( Subtotal = $117,750 )
2021	2021	RESEARCH FOUNDATION OF THE CITY UNIVERSITY OF NEW YORK	2900 BEDFORD AVE STE 1	BROOKLYN	NY	11210	KINGS	USA	Biomedical Research and Research Training	000	3	2/24/2021	NON-COMPETING CONTINUATION	$117,750
														Subtotal = $117,750

Issue Date FY: 2020 ( Subtotal = $117,750 )
2020	2020	RESEARCH FOUNDATION OF THE CITY UNIVERSITY OF NEW YORK	2900 BEDFORD AVE STE 1	BROOKLYN	NY	11210	KINGS	USA	Biomedical Research and Research Training	000	2	2/20/2020	NON-COMPETING CONTINUATION	$117,750
														Subtotal = $117,750

Issue Date FY: 2019 ( Subtotal = $117,750 )
2019	2019	RESEARCH FOUNDATION OF THE CITY UNIVERSITY OF NEW YORK	2900 BEDFORD AVE STE 1	BROOKLYN	NY	11210	KINGS	USA	Biomedical Research and Research Training	000	1	3/29/2019	NEW	$117,750
														Subtotal = $117,750

Grand Total All Awards = $470,999

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The lasting effect of maternal choline supplementation on lipid metabolism in mouse progeny affected by maternal obesity and gestational diabetes mellitus

Award Number: SC3GM132010

ORGANIZATION: NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

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