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母体长期维生素B12限制诱导Wistar大鼠后代身体成分和葡萄糖代谢发生变化,部分变化可通过康复纠正。

Chronic maternal vitamin B12 restriction induced changes in body composition & glucose metabolism in the Wistar rat offspring are partly correctable by rehabilitation.

作者信息

Kumar Kalle Anand, Lalitha Anumula, Reddy Umakar, Chandak Giriraj Ratan, Sengupta Shantanu, Raghunath Manchala

机构信息

Division of Endocrinology and Metabolism, National Institute of Nutrition, Indian Council of Medical Research (ICMR), Hyderabad, Telangana, India.

Centre for Cellular and Molecular Biology (CCMB), Council of Scientific and Industrial Research (CSIR), Hyderabad, Telangana, India.

出版信息

PLoS One. 2014 Nov 14;9(11):e112991. doi: 10.1371/journal.pone.0112991. eCollection 2014.

Abstract

Maternal under-nutrition increases the risk of developing metabolic diseases. We studied the effects of chronic maternal dietary vitamin B12 restriction on lean body mass (LBM), fat free mass (FFM), muscle function, glucose tolerance and metabolism in Wistar rat offspring. Prevention/reversibility of changes by rehabilitating restricted mothers from conception or parturition and their offspring from weaning was assessed. Female weaning Wistar rats (n = 30) were fed ad libitum for 12 weeks, a control diet (n = 6) or the same with 40% restriction of vitamin B12 (B12R) (n = 24); after confirming deficiency, were mated with control males. Six each of pregnant B12R dams were rehabilitated from conception and parturition and their offspring weaned to control diet. While offspring of six B12R dams were weaned to control diet, those of the remaining six B12R dams continued on B12R diet. Biochemical parameters and body composition were determined in dams before mating and in male offspring at 3, 6, 9 and 12 months of their age. Dietary vitamin B12 restriction increased body weight but decreased LBM% and FFM% but not the percent of tissue associated fat (TAF%) in dams. Maternal B12R decreased LBM% and FFM% in the male offspring, but their TAF%, basal and insulin stimulated glucose uptake by diaphragm were unaltered. At 12 months age, B12R offspring had higher (than controls) fasting plasma glucose, insulin, HOMA-IR and impaired glucose tolerance. Their hepatic gluconeogenic enzyme activities were increased. B12R offspring had increased oxidative stress and decreased antioxidant status. Changes in body composition, glucose metabolism and stress were reversed by rehabilitating B12R dams from conception, whereas rehabilitation from parturition and weaning corrected them partially, highlighting the importance of vitamin B12 during pregnancy and lactation on growth, muscle development, glucose tolerance and metabolism in the offspring.

摘要

母体营养不足会增加患代谢性疾病的风险。我们研究了母体长期饮食中维生素B12限制对Wistar大鼠后代瘦体重(LBM)、去脂体重(FFM)、肌肉功能、葡萄糖耐量和代谢的影响。评估了从受孕或分娩时使受限母体恢复正常饮食以及从断奶时使后代恢复正常饮食对这些变化的预防/可逆性。雌性断奶Wistar大鼠(n = 30)自由采食12周,一组给予对照饮食(n = 6),另一组给予维生素B12限制40%的相同饮食(B12R)(n = 24);确认维生素B12缺乏后,与对照雄性大鼠交配。每组6只怀孕的B12R母鼠从受孕和分娩时开始恢复正常饮食,其后代断奶后给予对照饮食。而另外6只B12R母鼠的后代断奶后继续给予B12R饮食。在母鼠交配前以及雄性后代3、6、9和12月龄时测定生化参数和身体组成。饮食中维生素B12限制增加了母鼠的体重,但降低了LBM%和FFM%,但未改变组织相关脂肪百分比(TAF%)。母体B12R降低了雄性后代的LBM%和FFM%,但它们的TAF%、膈肌基础葡萄糖摄取和胰岛素刺激的葡萄糖摄取未改变。在12月龄时,B12R后代的空腹血糖、胰岛素、HOMA-IR较高,葡萄糖耐量受损。它们的肝脏糖异生酶活性增加。B12R后代的氧化应激增加,抗氧化状态降低。从受孕时使B12R母鼠恢复正常饮食可逆转身体组成、葡萄糖代谢和应激的变化,而从分娩和断奶时恢复正常饮食只能部分纠正这些变化,突出了孕期和哺乳期维生素B12对后代生长、肌肉发育、葡萄糖耐量和代谢的重要性。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b517/4232526/bab2fce474c1/pone.0112991.g001.jpg

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