母鼠营养不良导致子代在生命早期出现糖脂代谢紊乱及其机制探讨

为了探讨母鼠孕期和哺乳期营养不良对子代生命早期糖脂代谢的影响及其机制,文章对孕期和哺乳期母鼠分别喂养高脂饮食、低蛋白饮食和正常饮食,观察其子鼠断乳时(3周龄)糖脂代谢指标,并采用荧光定量PCR方法检测子鼠肝组织氧化物酶增殖物激活受体γ(PPARγ)基因的表达情况。结果表明：子鼠在3周龄时,与正常饮食组相比,低蛋白饮食组子鼠出生体重(7.36±0.91 vs 8.94±1.39,P<0.0001)较低,体长较短(12.27±0.53 vs 13.44±0.36,P<0.0001);高脂饮食组子鼠体重(9.53±0.68 vs 7.36±0.91,P<0.0001)和体长(13.22±0.35 vs 12.27±0.53,P<0.0001)均高于低蛋白饮食组;另外,高脂饮食组子鼠腹腔糖耐量实验30 min和60 min血糖明显高于正常饮食组(P<0.001),且高脂饮食组30 min血糖水平也明显高于低蛋白饮食组(P<0.001),高脂饮食组子鼠糖耐量曲线下面积明显大于正常饮食组(P<0.001)。另外,与正常饮食组相比,高脂饮食组子鼠空腹胆固醇水平明显升高(1.64±0.21 vs 1.18±0.16,P<0.01),低蛋白饮食组空腹胆固醇水平明显下降(0.96±0.09 vs 1.18±0.16,P<0.05)。荧光定量PCR结果显示,在低蛋白饮食组和高脂饮食组,其子鼠肝组织PPARγ基因表达量均明显高于正常饮食组(P<0.05)。结果显示,母鼠妊娠期和哺乳期高脂饮食与低蛋白饮食均可以诱导子鼠在发育早期出现糖脂代谢紊乱,PPARγ基因可能在其中参与了重要的调控作用。     

益生菌干预对肥胖孕鼠子代菌群及脂代谢的影响

目的分析高脂高糖饮食诱导肥胖母亲对子代菌群及脂代谢影响。方法C57BL/6J雌性小鼠30只随机分为正常对照组、肥胖组、益生菌干预组,每组10只。分别给予标准饲料、高脂高糖饲料以及高脂高糖饲料同时给予益生菌,连续喂养6周,制成肥胖母鼠模型。6周后雌、雄鼠合笼,受孕,孕期继续上述饮食。产后母乳喂养,3周后处死。留取雌性子鼠第21天粪便样本进行PCR-DGGE分析,同时酶反应比色法分析子鼠血脂情况。结果与正常对照组子代相比,肥胖母鼠子代菌群结构出现异常,益生菌干预组子代肠道菌群失调状况明显改善;肥胖母鼠子代血清总胆固醇、低密度脂蛋白含量升高,益生菌干预组子代血脂异常情况明显改善。结论高脂高糖饮食诱导肥胖母亲子代存在肠道菌群紊乱及脂代谢异常,益生菌干预母亲有利于改善子代菌群紊乱及脂代谢异常。     

芦笋对高脂饮食小鼠体质量的影响

目的探究芦笋对高脂饮食小鼠体质量的影响。方法将实验动物随机分为正常组、高脂饮食组、高脂饮食低剂量芦笋组、高脂饮食中剂量芦笋组、高脂饮食高剂量芦笋组、高脂饮食阳性对照组。其中正常组喂食正常饲料,其余组喂食高脂饲料。分别灌胃蒸馏水(正常组、高脂饮食组)、芦笋1.05g/(kg·d)(高脂饮食低剂量芦笋组)、芦笋2.10g/(kg·d)(高脂饮食中剂量芦笋组)、芦笋4.20g/(kg·d)(高脂饮食高剂量芦笋组)、降脂理肝汤1.19g/(kg·d)(高脂饮食阳性对照组),每天2次,每次0.35mL。比较分析各组小鼠的体质量变化,同时对各组之间的雌性小鼠和雄性小鼠体质量变化进行对比。结果随饲养时间的增加,服用芦笋后的三组小鼠体质量均低于高脂饮食组,但与高脂饮食组相比差异无统计学意义(P0.05)。高脂饮食低剂量芦笋组、高脂饮食中剂量芦笋组、高脂饮食高剂量芦笋组小鼠的体质量变化率低于高脂饮食组,差异无统计学意义(P0.05)。对各组之间的雌性小鼠和雄性小鼠体质量变化进行对比可以发现雄性小鼠的体质量变化大于雌性小鼠的,差异有统计学意义(P0.05)。结论芦笋能降低高脂饮食小鼠的体质量,雄性小鼠和雌性小鼠的体质量变化存在差异。     

性别对小鼠高脂血症动物模型的影响

目的观察性别对建立小鼠高脂血症动物模型的影响。方法健康成年昆明种小鼠40只,雌雄各半,随机分4组：雄性对照组、雌性对照组、雄性高脂组、雌性高脂组,按各组要求分别给予正常饲料和高脂饲料喂养。连续2周,取血测定实验小鼠血中总胆固醇（total cholesterol,TC）、甘油三酯（triglyceride,TG）、低密度脂蛋白（low density lipoprotein,LDL）、高密度脂蛋白胆固醇（high density lipoprotein cholesterol,HDL-C）含量。结果雌性对照组血脂四项指标与雄性对照组差异不显著,高脂饮食使小鼠血中TC、LDL水平明显增高（P〈0.05）,雌雄组之间差异不显著。结论性别对实验小鼠高脂血症模型的建立及效果无明显影响。     

实验性2型糖尿病心肌病大鼠模型的建立与评价

目的建立和评价2型糖尿病心肌病（DC）大鼠模型,探究高糖脂饮食在模型建立中的作用。方法将雄性Wistar大鼠随机分成正常对照组、高糖脂饮食组和高糖脂负荷小剂量STZ组。高糖高脂膳食诱导11周负荷小剂量链脲佐菌素（STZ）（30 mg/kg）腹腔注射建立DC模型,并观察糖代谢、脂代谢和心功能的变化。结果①大鼠经高糖高脂饲料诱导4周后,与正常对照组相比,胆固醇（TCH）和甘油三酯（TG）均显著增高（P〈0.05）,血糖值没有明显变化（P〉0.05）。②大鼠注射30 mg/kg STZ后72 h,血糖水平开始升高,继续以高糖高脂饲料喂养6周后,与正常对照组比较,高糖脂饮食组和高糖脂负荷小剂量STZ组大鼠TG、TCH维持高水平,差异有显著性（P〈0.05）;高糖脂负荷小剂量STZ组大鼠血糖值持续高水平,与正常对照组差异有显著性（P〈0.001）。③心功能测量结果显示,高糖脂饮食组大鼠出现温和的心脏功能异常（左心室收缩压降低,左心室舒张末压升高）;高糖脂负荷小剂量STZ组大鼠左心室收缩和舒张功能均出现异常（LVSP、每搏输出量、心排量降低,LVEDP、左心室最大舒张速率升高）,但以舒张功能异常为主。结论大鼠高糖脂饮食诱导负荷小剂量STZ可建立类似临床症状的2型DC模型,高糖脂饮食在糖脂代谢紊乱和心脏功能损伤过程中有重要作用,结合糖、脂代谢指标和心脏功能指标可以有效简便评价糖尿病心肌病模型。     

妊娠期高果糖膳食对子代胰岛素抵抗的影响

目的：探讨大鼠妊娠期高果糖膳食对子代胰岛素抵抗的影响。方法：正常饮食的成年雄性Wistar大鼠与雌性大鼠进行合笼,孕鼠随机分为5组,分别为正常对照组、正常剂量果糖组、高剂量果糖组、超高剂量果糖组和超高剂量蔗糖组,孕期每日分别给予2mL蒸馏水、2g/kg、6g/kg、18g/kg的果糖溶液以及18g/kg的蔗糖溶液灌胃,连续干预直至分娩,娩出仔鼠基础饲料喂养,并称量仔鼠体质量、检测空腹血糖。于第8周末检测空腹血糖、进行OGTT试验。于次日禁食12h后处死子代大鼠,麻醉、取血,测量血清胰岛素水平,计算胰岛素抵抗指数。结果：孕期连续干预后,娩出仔鼠出生体重：高剂量果糖组、超高剂量果糖组显著低于对照组（P＜0.05）;超高剂量果糖组娩出仔鼠空腹血糖显著高于对照组（P＜0.05）;OGTT试验：在30min处,高剂量果糖组、超高剂量果糖组以及超高剂量蔗糖组血糖值显著高于正常对照组及正常剂量果糖组（P＜0.05）,在120min处,高剂量果糖组、超高剂量果糖组及超高剂量蔗糖组血糖值显著高于正常对照组（P＜0.05）。高剂量果糖组、超高剂量果糖组及超高剂量蔗糖组的血清胰岛素含量和胰岛素抵抗指数都显著高于正常对照组和正常剂量果糖组（P＜0.05）。结论：妊娠期高果糖膳食会增加子代胰岛素抵抗及糖代谢的患病风险。     

孕期高果糖摄入对胚胎发育和胎盘血管因子的研究

目的：探讨孕期高果糖摄入对胚胎发育的影响及胎盘血管因子对其影响的机制。方法：成年雌性SD大鼠与正常饮食雄性大鼠进行交配,孕鼠随机分为5组,分别是对照组、正常剂量果糖组、高剂量果糖组、高剂量蔗糖组和超高剂量果糖组,在孕期分别给予1mL去离子水、1.6g/kg、4.8g/kg、4.5g/kg和8.0g/kg的果糖水和蔗糖水灌胃,连续干预3w,于第3w末处死孕鼠,麻醉、取血并剖取胎鼠,检查胎鼠的一般状况、着床、死胎、吸收胎、外观畸形等,制作子代内脏和骨骼标本,观察内脏和骨骼的情况;称量胎重和胎盘重,观察各组间胎盘血管内皮生长因子（VEGF）、血管内皮生长因子受体-1（sFlt-1）和一氧化氮（NO）的变化。结果：对孕鼠连续进行3w的果糖干预后,超高剂量果糖组子代出生体重显著低于对照组（P＜0.05）;高剂量果糖组、高剂量蔗糖组和超高剂量果糖组子代与对照组和正常剂量果糖组相比,死胎数和吸收胎数显著增加（P＜0.05）;但各组子代并没有发生骨骼畸形和内脏出血。超高剂量果糖组胎盘重量显著低于对照组（P＜0.05）;高剂量果糖组、高剂量蔗糖组和超高剂量果糖组胎盘中VEGF和NO水平显著低于对照组和正常剂量果糖组（P＜0.05）;胎盘中sFlt-1水平明显高于对照组和正常剂量果糖组（P＜0.05）。结论：孕期高果糖摄入可增加子代发生死胎和吸收胎等不良结局的风险,胎盘中VEGF、NO的水平降低和sFlt-1水平增高可能是导致子代发生不良结局的原因,具体机制值得深入研究。     

桂皮醛对高脂喂养小鼠糖脂代谢影响的实验研究

目的：探讨口服桂皮醛对高脂喂养小鼠（C57BL/6J 背景）糖脂代谢的影响。方法：采用雄性C57BL/6J小鼠作为研究对象,分 正常对照组（6 只）,高脂组（6 只）,高脂+ 桂皮醛（40 mg/kg,每天1 次）干预组（6 只）。桂皮醛以0.5 %羧甲基纤维素钠（CMC-Na） 溶解后口服灌胃,每天1 次;正常对照组和高脂组给予灌服等体积的CMC-Na,每天1 次,干预时间为3 月。每周观察体重、空腹血 糖,实验结束后观察胰岛素耐量（IPITT）、葡萄糖耐量（IPGTT）,观察各组小鼠的血脂水平（TC,TG,LDL-C,HDL-C）、胰岛素水 平、肠系膜脂肪重量及以HE 染色观察脂肪细胞形态。结果：在脂代谢方面,桂皮醛干预可显著防止高脂喂养小鼠的体重和血脂水 平的升高;高脂喂养小鼠肠系膜脂肪重量显著增加,HE 染色提示脂肪细胞显著增大;桂皮醛可显著防止肠系膜脂肪重量的增加 及脂肪细胞的变大。而在葡萄糖代谢方面,桂皮醛可显著降低高脂喂养小鼠血糖和胰岛素水平,改善小鼠的葡萄糖耐量和胰岛素 敏感性。结论：口服桂皮醛可显著改善高脂喂养小鼠的糖、脂代谢。     

高脂饮食对小鼠附睾内质网应激的影响及褪黑素的干预作用

目的探讨内质网应激在高脂饮食引起的ApoE基因敲除小鼠附睾损伤中的作用及褪黑素（MT）的干预机制。方法将12只ApoE基因敲除的C57BL／6J雄性小鼠随机分为高脂饮食组及MT处理组。高脂饮食组为ApoE基因敲除小鼠,给予高脂饮食;MT处理组给予高脂饲养外,并MT灌胃。以6只野生型C57BL／6J雄性小鼠作为对照组,给予普通饮食。饲养12w后,取附睾组织制片,HE染色观察附睾的病理学形态,免疫组化检测GRP78和CHOP的表达。结果HE染色显示,高脂饮食组小鼠,附睾上皮细胞形态结构不清,细胞萎缩。对照组和褪黑素处理组小鼠附睾上皮细胞形态结构完整,细胞排列整齐。免疫组化显示高脂饮食组小鼠附睾中GRP78、CHOP表达增强（P〈0．01）。MT处理组和高脂饮食组相比,附睾中GRP78、CHOP表达下调（P〈0．01）。结论内质网应激参与高脂饮食导致的附睾损伤;MT可能通过抑制附睾内质网应激,减轻高脂饮食对小鼠附睾的损伤。     

高脂饮食诱导的C57BL／6J肥胖小鼠脂肪组织RIP140基因表达水平的研究

目的：探讨高脂饮食致肥胖小鼠脂肪组织RIP140mRNA表达水平的变化及其与胰岛素抵抗的关系。方法：将C57BL／6J雄性小鼠随机分为正常饮食（NFD）组、高脂饮食（HFD）纽分别喂养14周后,测量两组小鼠体重,以NFD组小鼠体重作为对照,选取HFD组中体重大于对照组小鼠平均体重20％的小鼠作为肥胖组小鼠。对照组和肥胖组小鼠取血测甘油三酯（TG）、总胆固醇（TC）、空腹血糖（FBG）、空腹胰岛素水平（FIns）,计算稳态模型胰岛素抵抗指数（HOMA-IR）;采用RT—PCR技术检测两组小鼠附睾脂肪组织RIP140 mRNA的表达水平,并进行统计学分析。结果：HDF组小鼠中有12只符合标准计入肥胖组。肥胖组小鼠TG、TC、FBG、Fins（P〈0．05）,HOMA-1R（P〈0．01）均明显高于对照组;肥胖组小鼠脂肪组织RIP140mRNA的表达高于对照组,差异具有统计学意义（P〈0．05）;相关分析显示小鼠脂肪组织R1P140 mRNA表达水平与TG水平呈正相关（r=0．536,P〈0．05）,与胰岛素抵抗指数呈正相关（r=0．465,P〈0．05）,而与TC、FBG、Fins水平相关分析无统计学意义（P〉0．05）。结论：高脂饮食诱导的肥胖小鼠脂肪组织RIP140 mRNA表达增加,并与胰岛素抵抗程度呈正相关。     

Programmed metabolic syndrome: prenatal undernutrition and postweaning overnutrition

Maternal nutrient restriction results in intrauterine growth restriction (IUGR) newborns that develop obesity despite normal postweaning diet. The epidemic of metabolic syndrome is attributed to programmed "thrifty phenotype" and exposure to Western diets. We hypothesized that programmed IUGR newborns would demonstrate greater susceptibility to obesity and metabolic abnormalities in response to high-fat diet. From day 10 to term gestation and lactation, control pregnant rats received ad libitum (AdLib) food, whereas study rats were 50% food restricted (FR). Cross-fostering techniques resulted in three offspring groups: control (AdLib/AdLib), FR during pregnancy (FR/AdLib), and FR during lactation (AdLib/FR). At 3 weeks, offspring were weaned to laboratory chow or high-fat calorie diet (9% vs. 17% calorie as fat). Body composition, appetite hormones, and glucose and lipid profiles were determined in 9-mo-old male and female offspring. High-fat diet had no effect on body weight of AdLib/AdLib, but significantly increased weights of FR/AdLib and AdLib/FR offspring. High-fat diet significantly increased body fat, reduced lean body mass, and accentuated plasma leptin but not ghrelin levels in both sexes in all groups. In males, high-fat diet caused a significant increase in glucose levels in all three groups with increased insulin levels in AdLib/AdLib and AdLib/FR, but not in FR/AdLib. In females, high-fat diet had no effect on glucose but significantly increased basal insulin among all three groups. High-fat diet caused hypertriglyceridemia in all three groups although only food-restricted females exhibited hypercholesterolemia. Sex and offspring phenotype-associated effects of high-fat diet indicate differing pathophysiologic mechanisms that require specific therapeutic approaches.     

High-protein diet during gestation and lactation affects mammary gland mRNA abundance, milk composition and pre-weaning litter growth in mice

We evaluated the effect of a high-protein diet (HP) on pregnancy, lactational and rearing success in mice. At the time of mating, females were randomly assigned to isoenergetic diets with HP (40% w/w) or control protein levels (C; 20%). After parturition, half of the dams were fed the other diet throughout lactation resulting in four dietary groups: CC (C diet during gestation and lactation), CHP (C diet during gestation and HP diet during lactation), HPC (HP diet during gestation and C diet during lactation) and HPHP (HP diet during gestation and lactation). Maternal and offspring body mass was monitored. Measurements of maternal mammary gland (MG), kidney and abdominal fat pad masses, MG histology and MG mRNA abundance, as well as milk composition were taken at selected time points. HP diet decreased abdominal fat and increased kidney mass of lactating dams. Litter mass at birth was lower in HP than in C dams (14.8 v. 16.8 g). Dams fed an HP diet during lactation showed 5% less food intake (10.4 v. 10.9 g/day) and lower body and MG mass. On day 14 of lactation, the proportion of MG parenchyma was lower in dams fed an HP diet during gestation as compared to dams fed a C diet (64.8% v. 75.8%). Abundance of MG α-lactalbumin, β-casein, whey acidic protein, xanthine oxidoreductase mRNA at mid-lactation was decreased in all groups receiving an HP diet either during gestation and/or lactation. Milk lactose content was lower in dams fed an HP diet during lactation compared to dams fed a C diet (1.6% v. 2.0%). On days 14, 18 and 21 of lactation total litter mass was lower in litters of dams fed an HP diet during lactation, and the pups' relative kidney mass was greater than in litters suckled by dams receiving a C diet. These findings indicate that excess protein intake in reproducing mice has adverse effects on offspring early in their postnatal growth as a consequence of impaired lactational function.     

Effect of high-fat diet during gestation, lactation, or postweaning on physiological and behavioral indexes in borderline hypertensive rats

Maternal obesity is becoming more prevalent. We used borderline hypertensive rats (BHR) to investigate whether a high-fat diet at different stages of development has adverse programming consequences on metabolic parameters and blood pressure. Wistar dams were fed a high- or low-fat diet for 6 wk before mating with spontaneously hypertensive males and during the ensuing pregnancy. At birth, litters were fostered to a dam from the same diet group as during gestation or to the alternate diet condition. Female offspring were weaned on either control or "junk food" diets until about 6 mo of age. Rats fed the high-fat junk food diet were hyperphagic relative to their chow-fed controls. The junk food-fed rats were significantly heavier and had greater fat pad mass than those rats maintained on chow alone. Importantly, those rats suckled by high-fat dams had heavier fat pads than those suckled by control diet dams. Fasting serum leptin and insulin levels differed as a function of the gestational, lactational, and postweaning diet histories. Rats gestated in, or suckled by high-fat dams, or maintained on the junk food diet were hyperleptinemic compared with their respective controls. Indirect blood pressure did not differ as a function of postweaning diet, but rats gestated in the high-fat dams had lower mean arterial blood pressures than those gestated in the control diet dams. The postweaning dietary history affected food-motivated behavior; junk food-fed rats earned less food pellets on fixed (FR) and progressive (PR) ratio cost schedules than chow-fed controls. In conclusion, the effects of maternal high-fat diet during gestation or lactation were mostly small and transient. The postweaning effects of junk food diet were evident on the majority of the parameters measured, including body weight, fat pad mass, serum leptin and insulin levels, and operant performance.     

Bioactives from bitter melon enhance insulin signaling and modulate acyl carnitine content in skeletal muscle in high-fat diet-fed mice

Bioactive components from bitter melon (BM) have been reported to improve glucose metabolism in vivo, but definitive studies on efficacy and mechanism of action are lacking. We sought to investigate the effects of BM bioactives on body weight, muscle lipid content and insulin signaling in mice fed a high-fat diet and on insulin signaling in L6 myotubes. Male C57BL/6J mice were randomly divided into low-fat diet control (LFD), high-fat diet (HFD) and HFD plus BM (BM) groups. Body weight, body composition, plasma glucose, leptin, insulin and muscle lipid profile were determined over 12 weeks. Insulin signaling was determined in the mouse muscle taken at end of study and in L6 myotubes exposed to the extract. Body weight, plasma glucose, insulin, leptin levels and HOMA-IR values were significantly lower in the BM-fed HFD group when compared to the HFD group. BM supplementation significantly increased IRS-2, IR β, PI 3K and GLUT4 protein abundance in skeletal muscle, as well as phosphorylation of IRS-1, Akt1 and Akt2 when compared with HFD (P<.05 and P<.01). BM also significantly reduced muscle lipid content in the HFD mice. BM extract greatly increased glucose uptake and enhanced insulin signaling in L6 myotubes. This study shows that BM bioactives reduced body weight, improved glucose metabolism and enhanced skeletal muscle insulin signaling. A contributing mechanism to the enhanced insulin signaling may be associated with the reduction in skeletal muscle lipid content. Nutritional supplementation with this extract, if validated for human studies, may offer an adjunctive therapy for diabetes.     

Maternal essential fatty acid deficiency depresses serum leptin levels in suckling rat pups

Dietary lipid quantity and quality have recently been shown to affect serum leptin levels in adult rats. Moreover, suckling pups from dams fed a high fat diet had increased serum leptin levels. The aim of the present study was to analyze the influence of essential fatty acid (EFA) deficiency on serum leptin levels in dams and their pups during the suckling period. For the last 10 days of gestation and throughout lactation, pregnant rats were fed a control or an EFA-deficient (EFAD) diet. The levels of leptin and EFA in the serum of the dams and pups were analyzed 1, 2, and 3 weeks after delivery. In parallel, serum levels of glucose and corticosterone were analyzed in the pups. Low serum leptin levels were found in the control lactating dams during the entire lactation period compared with the age-matched nonlactating animals. The leptin concentrations in the lactating dams fed the EFAD diet were lower compared with those fed the control diet. The serum leptin levels of suckling pups from dams on the EFAD diet were markedly decreased compared with controls (P < 0.05). The reduced serum leptin levels could not be explained by nutritional restriction as evaluated by serum levels of glucose and corticosterone. These results indicate the importance of the EFA composition of the maternal diet for serum leptin levels in both dams and pups. EFA deficiency in lactating dams may cause long-term effects on the pups through dysregulation of leptin and leptin-dependent functions. -- Korotkova, M., B. Gabrielsson, L. A. Hanson, and B. Strandvik. Maternal essential fatty acid deficiency depresses serum leptin levels in suckling rat pups. J. Lipid Res. 2001. 42: 359--365.     

Impact of high-fat diet and obesity on energy balance and fuel utilization during the metabolic challenge of lactation

The effects of obesity and a high-fat (HF) diet on whole body and tissue-specific metabolism of lactating dams and their offspring were examined in C57/B6 mice. Female mice were fed low-fat (LF) or HF diets before and throughout pregnancy and lactation. HF-fed mice were segregated into lean (HF-Ln) and obese (HF-Ob) groups before pregnancy by their weight gain response. Compared to LF-Ln dams, HF-Ln, and HF-Ob dams exhibited a greater positive energy balance (EB) and increased dietary fat retention in peripheral tissues (P < 0.05). HF-Ob dams had greater dietary fat retention in liver and adipose compared to HF-Ln dams (P < 0.05). De novo synthesized fat was decreased in tissues and milk from HF-fed dams compared to LF-Ln dams (P < 0.05). However, less dietary and de novo synthesized fat was found in the HF-Ob mammary glands compared to HF-Ln (P < 0.05). Obesity was associated with reduced milk triglycerides relative to lean controls (P < 0.05). Compared to HF diet alone obesity has additional adverse affects, impairing both lipid metabolism as well as milk fat production. Growth rates of LF-Ln litters were lower than HF-Ln and HF-Ob litters (P < 0.05). Total energy expenditure (TEE) of HF-Ob litters was reduced relative to HF-Ln litters, whereas their respiratory exchange ratios (RERs) were increased (P < 0.05). Collectively these data show that consumption of a HF diet significantly affects maternal and neonatal metabolism and that maternal obesity can independently alter these responses.     

Chronic Maternal Vitamin B12 Restriction Induced Changes in Body Composition & Glucose Metabolism in the Wistar Rat Offspring Are Partly Correctable by Rehabilitation

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.