Effects of choline on fetal growth and lipid accretion in gestational diabetes

胆碱对妊娠期糖尿病胎儿生长和脂质沉积的影响

• 批准号: 9272392
• 负责人: Xinyin Jiang
• 金额: $ 15.7万
• 依托单位: BROOKLYN COLLEGE
• 依托单位国家: 美国
• 财政年份: 2015
• 资助国家: 美国
• 起止时间: 2015-06-10 至 2018-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9272392
• 关键词: Address; Adverse effects; Affect; Animals; Attenuated; Blood Glucose; Blood Vessels; Body Weight; Caring; Carnitine O-Palmitoyltransferase; Catabolism; Choline; Clinical; Data; Development; Diet; Dietary Component; Dietary Intervention; Docosahexaenoic Acids; Embryo; Endocrine; Environment; Fat-Restricted Diet; Fatty Acids; Fatty Liver; Fatty acid glycerol esters; Fetal Growth; Fetal Macrosomia; Fetal Weight; Fetus; Future; Genes; Gestational Diabetes; Goals; Grant; Health; High Fat Diet; Homeostasis; Human; Incidence; Intake; Intervention; Lecithin; Life; Ligands; Lipids; Liver diseases; Longevity; Macronutrients Nutrition; Maternal Complication of Pregnancy; Measures; Medical Nutrition Therapy; Micronutrients; Mus; Non-Insulin-Dependent Diabetes Mellitus; Nutrient; Nutritional; Nutritional Support; Obesity; Outcome; PPAR alpha; Pathway interactions; Placenta; Postpartum Period; Pregnancy; Pregnancy Complications; Prevention; Process; Regulation; Research Project Grants; Risk; Stress; Subgroup; Time; Tissues; Weaning; Weight Gain; Woman; Work; acyl-CoA oxidase; adverse outcome; career development; choline supplementation; cognitive function; cost effective; diabetes control; effective intervention; fetal; improved; lipid metabolism; lipid transport; maternal hyperglycemia; mouse model; nutrition; obesity in children; obesity risk; obesogenic; offspring; postnatal; pregnant; prenatal; prenatal stress; prevent; public health relevance; pup; response; saturated fat; uptake

 DESCRIPTION (provided by applicant): Gestational diabetes mellitus (GDM), defined by maternal hyperglycemia, affects 7% of pregnancies. GDM results in fetal overgrowth, or macrosomia, which adversely influences offspring health including greater risk of obesity. Currently, medical nutrition therapy is an integral part of the GDM care process which regulates macronutrient intake and weight gain to normalize maternal blood glucose. However, attenuating maternal hyperglycemia cannot sufficiently address the increased placental lipid transfer and fetal lipid accretion, which are the major causes of macrosomia. Choline is an essential micronutrient, whose requirement increases substantially during pregnancy. The PI has previously shown that prenatal choline supplementation in humans leads to lower fetal stress and better vascular development of the placenta. Our pilot data suggests that choline supplementation in pregnant mice activates the peroxisome proliferator-activated receptor alpha pathway, which may increase fatty acid breakdown. Choline supplementation also prevents fatty liver disease in humans and animals. We hypothesize that maternal choline supplementation will prevent GDM-induced macrosomia and excessive adiposity across the lifespan of the offspring. In Aim 1, we will determine the effects of maternal choline intake on fetal growth and lipid homeostasis during gestation in a mouse model of GDM. Six-week-old C57BL/6J mice (n=6/group/time point) will be fed either a high fat diet to induce GDM during pregnancy or a control diet. Three levels of choline bitartrate (0.25, 0.5 or 1 mg/kcal of diet) will be added to he diets to generate choline deficient, control or supplemented subgroups. We will assess whether maternal choline intake decreases placental and fetal weight and reduces fat accumulation at mid-gestation and 2.5 days preterm. In Aim 2, we will determine the effects of maternal choline intake on long-term body weight regulation and adiposity in offspring affected by GDM. C57BL/6J pups (n= 2 pups/ dam/ treatment) from GDM or control dams (n=6 dams) with varied choline intake during gestation (same as Aim 1) will be fed either a low fat diet or a high fat die (obesogenic) for 6 weeks after weaning, in order to assess whether prenatal choline supplementation reduces weight gain and adiposity of the offspring in a control or obesogenic postnatal environment. At the conclusion of these studies, we will have delineated the efficacy of choline in preventing GDM macrosomia and excessive adiposity of offspring. Results of the study will lay the ground work for human studies that use choline as an innocuous and cost effective intervention for GDM.

 描述（由申请人提供）：妊娠期糖尿病 (GDM)，即母亲高血糖，影响 7% 的妊娠，导致胎儿过度生长或巨大儿，这对后代健康产生不利影响，包括更大的肥胖风险。是 GDM 护理过程的一个组成部分，它调节大量营养素的摄入和体重增加，以使母亲血糖正常化。然而，减轻母亲的高血糖并不能充分解决增加的问题。胎盘脂质转移和胎儿脂质积聚是巨大儿的主要原因，胆碱是一种必需的微量营养素，其需求在怀孕期间大幅增加。 PI 先前表明，人类产前补充胆碱可降低胎儿压力并改善血管发育。我们的试验数据表明，怀孕小鼠补充胆碱会激活过氧化物酶体增殖物激活受体α途径，这可能会增加脂肪酸分解，补充胆碱还可以预防人类和人类的脂肪肝。我们认为母体补充胆碱可以预防 GDM 引起的巨大儿和后代的过度肥胖。在目标 1 中，我们将在小鼠模型中确定母体胆碱摄入量对妊娠期间胎儿生长和脂质稳态的影响。 GDM。六周大的 C57BL/6J 小鼠（n=6/组/时间点）将在怀孕期间被喂食以诱导 GDM 或三个水平的对照饮食。将酒石酸氢胆碱（0.25、0.5 或 1 毫克/千卡饮食）添加到饮食中，以产生胆碱缺乏、对照或补充亚组。我们将评估母体胆碱摄入量是否会降低胎盘和胎儿重量并减少妊娠中期的脂肪积累。在目标 2 中，我们将确定母体胆碱摄入量对受此影响的后代的长期体重调节和肥胖的影响。来自 GDM 的 C57BL/6J 幼犬（n= 2 只幼犬/母犬/治疗）或妊娠期间胆碱摄入量不同的对照母犬（n=6 只母犬）（与目标 1 相同）将被饲喂低脂肪饮食或高脂肪饮食。断奶后 6 周进行脂肪死亡（致肥胖），以评估产前补充胆碱是否会减少对照或致肥胖产后后代的体重增加和肥胖在这些研究结束时，我们将描述胆碱在预防 GDM 巨大儿和后代过度肥胖方面的功效。研究结果将为使用胆碱作为无害且具有成本效益的干预措施的人体研究奠定基础。 GDM。

项目成果

Prenatal Choline Supplementation during High-Fat Feeding Improves Long-Term Blood Glucose Control in Male Mouse Offspring.

高脂肪喂养期间产前补充胆碱可改善雄性小鼠后代的长期血糖控制。

• 发表时间: 2020-01-04
• 影响因子: 5.9
• 作者: Korsmo, Hunter W;Edwards, Kaydine;Dave, Bhoomi;Jack;Yu, Huanling;Saxena, Anjana;Salvador, Marie;Dembitzer, Moshe;Phagoora, Jaskomal;Jiang, Xinyin
• 通讯作者: Jiang, Xinyin

Choline: Exploring the Growing Science on Its Benefits for Moms and Babies.

胆碱：探索不断发展的科学对妈妈和婴儿的好处。

• 发表时间: 2019-08-07
• 影响因子: 5.9
• 作者: Korsmo, Hunter W;Jiang, Xinyin;Caudill, Marie A
• 通讯作者: Caudill, Marie A

Prenatal Choline Supplement in a Maternal Obesity Model Modulates Offspring Hepatic Lipidomes.

母亲肥胖模型中的产前胆碱补充剂可调节后代肝脂质。

• 发表时间: 2023-02-15
• 影响因子: 5.9
• 作者: Korsmo, Hunter W;Kadam, Isma'il;Reaz, Aziza;Bretter, Rachel;Saxena, Anjana;Johnson, Caroline H;Caviglia, Jorge Matias;Jiang, Xinyin
• 通讯作者: Jiang, Xinyin

Choline Supplementation Normalizes Fetal Adiposity and Reduces Lipogenic Gene Expression in a Mouse Model of Maternal Obesity.

补充胆碱可使胎儿肥胖正常化并减少母亲肥胖小鼠模型中的脂肪生成基因表达。

• 发表时间: 2017-08-18
• 影响因子: 5.9
• 作者: Jack;Joselit, Yaelle;Nanobashvili, Khatia;Bretter, Rachel;Malysheva, Olga V;Caudill, Marie A;Saxena, Anjana;Axen, Kathleen;Gomaa, Ahmed;Jiang, Xinyin
• 通讯作者: Jiang, Xinyin

Maternal betaine supplementation affects fetal growth and lipid metabolism of high-fat fed mice in a temporal-specific manner.

母体甜菜碱补充剂以时间特异性方式影响高脂喂养小鼠的胎儿生长和脂质代谢。

• 发表时间: 2018-05-24
• 影响因子: 6.1
• 作者: Joselit, Yaelle;Nanobashvili, Khatia;Jack;Greenwald, Esther;Malysheva, Olga V;Caudill, Marie A;Saxena, Anjana;Jiang, Xinyin
• 通讯作者: Jiang, Xinyin