High multivitamin (10-fold AIN-93G, HV) diets fed during pregnancy to Wistar rats increase characteristics of metabolic syndrome in offspring when weaned to the recommended vitamin (RV) diet.
To ...determine whether the effects of HV gestational diets on obesogenic phenotypes in the offspring arise as a consequence of altered hypothalamic control of feeding behavior and if their increased food intake could be prevented by feeding them HV or high folate (10-fold folate, HFol) diets.
Male offspring of dams fed HV diet during pregnancy weaned to RV, HV or HFol diets were compared with those born to RV dams and weaned to RV diet for 29 weeks. Food intake over 72 h and body weight were measured bi-weekly and weekly, respectively. Glucose response to a glucose load was measured at 18 weeks post weaning. Hypothalamic gene expression of feeding-related neuropeptides including neuropeptide Y, pro-opiomelanocortin (POMC), insulin receptor, leptin receptor, brain-derived neurotrophic factor (BDNF), receptors for dopamine (DopaR1/2/5) and serotonin (SeroR1A/2A/2C), as well as global DNA methylation and brain and plasma folate concentrations were measured at 29 weeks post weaning.
HV or HFol pup diets increased brain and plasma folate concentrations and prevented the increase in food intake (5%, P=0.03), body weight (8%, P=0.0006) and glucose response to a glucose load (36%, P=0.02) found in those fed the RV diet. Expression of anorexigenic POMC (P=0.004) and BDNF (P=0.02) was higher, and DopaR1 was lower (P=0.06) in pups fed the HV diet. The HFol pup diet partially brought BDNF to the control level (P=0.02) and lowered SeroR2A (P=0.008). Expression of other genes was unaffected. Global DNA methylation was similar among the diet groups.
The obesogenic phenotype in offspring from HV-fed dams is prevented by feeding HV or HFol pup diets, possibly due to post-weaning modulation of food intake regulatory mechanisms.
Vitamin consumption prior to and during pregnancy has increased as a result of proactive recommendations by health professionals, wide availability of vitamin supplements, and liberal ...food-fortification policies. Folic acid, alone or in combination with other B vitamins, is the most recommended vitamin consumed during pregnancy because deficiency of this vitamin leads to birth defects in the infant. Folic acid and other B vitamins are also integral components of biochemical processes that are essential to the development of regulatory systems that control the ability of the offspring to adapt to the external environment. Although few human studies have investigated the lasting effects of high vitamin intakes during pregnancy, animal models have shown that excess vitamin supplementation during gestation is associated with negative metabolic effects in both the mothers and their offspring. This research from animal models, combined with the recognition that epigenetic regulation of gene expression is plastic, provides evidence for further examination of these relationships in the later life of pregnant women and their children.
Maternal intake of multivitamins or folic acid above the basal dietary requirement alters the growth and metabolic trajectory of rat offspring. We hypothesized that a modest increase in the folic ...acid content of maternal diets would alter the offspring’s metabolic phenotype, and that these effects could be corrected by matching the folic acid content of the offspring’s diet with that of the maternal diet. Female Sprague–Dawley rats were placed on a control or a 2.5× folic acid-supplemented diet prior to mating and during pregnancy and lactation. At weaning, pups from each maternal diet group were randomized to the control or to the 2.5× folic acid-supplemented diet for 25 weeks. Male pups from dams fed the folic acid-supplemented diet were 3.7% heavier than those from control-fed dams and had lower mRNA expression for leptin receptor Obrb isoform (Lepr) (11%) and Agouti-related protein (Agrp) (14%). In contrast, female pups from folic acid-supplemented dams were 5% lighter than those from control-fed dams and had lower proopiomelanocortin (Pomc) (42%), Lepr (32%), and Agrp (13%), but higher neuropeptide Y (Npy) (18%) mRNA expression. Folic acid supplementation ameliorated the alterations induced by maternal folic acid supplementation in male pups and led to the lowest insulin resistance, but the effects were smaller in female pups and led to the highest insulin resistance. In conclusion, maternal folic acid supplementation at 2.5× the control level was associated with alterations in body weight and hypothalamic gene expression in rat offspring in a sex-specific manner, and some of these effects were attenuated by postweaning folic acid supplementation.
Obesity is associated with increased consumption and preference for dietary fat. Experimental models of fat-induced obesity use either lard or vegetable shortening. Yet, there are no direct ...comparisons of these commonly used fat sources, or the influence of their fatty acid composition, on the development of diet-induced obesity.
To compare the effects of lard and hydrogenated vegetable-shortening diets, which differ in their fatty acid composition, on weight gain and the development of obesity and insulin resistance in rats.
Male Wistar rats were fed ad libitum for 14 weeks high-fat diets containing either (1) high vegetable fat (HVF, 60 kcal% from vegetable shortening) or (2) high lard fat (HLF, 60 kcal% from lard). Rats fed normal-fat (NF, 16 kcal% from vegetable shortening) diet served as control. Body weight, food intake, adipose tissue mass, serum 25OHD3, glucose, insulin and fatty acid composition of diets were measured.
Rats fed either of the two high-fat diets had higher energy intake, weight gain and fat accretion than rats fed normal-fat diet. However, rats fed the HLF diet consumed more calories and gained more weight and body fat with greater increases of 32% in total (158.5±8.2 vs 120.2±6.6 g, P<0.05), 30% in visceral (104.4±5.2 vs 80.3±4.2 g, P<0.05) and 36% in subcutaneous fat mass (54.1±3.6 vs 39.9±3.1 g, P<0.05), compared with rats fed the HVF diet. Higher visceral adiposity was positively correlated with serum insulin (r=0.376, P<0.05) and homeostatic model assessment insulin resistance (r=0.391, P<0.05).
We conclude that lard-based high-fat diets accentuate the increase in weight gain and the development of obesity and insulin resistance more than hydrogenated vegetable-shortening diets. These results further point to the importance of standardizing fatty acid composition and type of fat used in determining outcomes of consuming high-fat diets.
Scope
High multivitamin (HV, tenfold AIN‐93G) gestational diets fed to Wistar rats increase food intake, obesity, and characteristics of metabolic syndrome in the offspring. We hypothesized that ...methyl vitamins, and specifically folate, in the HV gestational diet contribute to the obesogenic phenotypes consistent with their epigenetic effects on hypothalamic food intake regulatory mechanisms.
Methods and results
Male offspring of dams fed the AIN‐93G diet with high methyl vitamins (HMethyl; tenfold folate, vitamins B12, and B6) (Study 1) and HV with recommended folate (HVRF) (Study 2) were compared with those from HV and recommended vitamin (RV) fed dams. All offspring were weaned to a high fat diet for 8 wks. HMethyl diet, similar to HV, and compared to RV, resulted in higher food intake, body weight, and metabolic disturbances. Removing folate additions to the HV diet in HVRF offspring normalized the obesogenic phenotype. Methyl vitamins, and folate in HV diets, altered hypothalamic gene expression toward increased food intake concurrent with DNA methylation and leptin and insulin receptor signaling dysfunction.
Conclusion
Methyl vitamins in HV gestational diets contribute to obesogenic phenotypes and epigenetic alterations in the hypothalamic feeding pathways in the offspring. Folate alone accounts for many of these effects.
The objective was to compare the effect of dairy and nondairy beverages when consumed with carbohydrate at breakfast on subjective appetite, food intake (FI), and postprandial glycemia (PPG) in ...healthy young adults. Twenty-six healthy males and females (13 males and 13 females; 23.0 ± 2.6 years; BMI: 22.3 ± 1.5 kg/m
2
) participated in a randomized crossover study. They consumed nonisocaloric amounts (250 mL) of almond beverage, soy beverage, 1% fat milk, yogurt beverage, and water (control) with cereal and 120 min later, an ad libitum meal. Subjective appetite, PPG, and insulin were measured at baseline and at intervals before and after the meal at which FI was measured. Post-treatment blood glucose was lowest following soy beverage compared with all treatments but was not different from milk (p = 0.0002). There were no differences between any other treatments. However, over the first hour, PPG for all treatments was 27% lower compared with water (p < 0.0001). Milk and yogurt beverage led to the highest insulin concentrations post-treatment (p < 0.0001) but there were no differences between treatments postmeal. All treatments reduced appetite and led to lower FI at the meal compared with water, but FI was lower after milk compared with all treatments except yogurt beverage (p < 0.0001). Both dairy and nondairy beverages consumed with a high glycemic cereal at breakfast increased satiety and decreased FI compared with water with cereal. Despite higher carbohydrate content, all beverages led to similar or lower PPG than the water breakfast, but dairy beverages increased insulin more than nondairy beverages.
Abstract Recent research shows a link between vitamin intake during pregnancy and offspring health. Inadequate intakes of water-soluble vitamins during pregnancy lead to obesity and characteristics ...of the metabolic syndrome, concurrent with altered developments in food intake regulatory pathways. Few studies, however, have reported on the effects of fat-soluble vitamins (A, D, E, and K) on the development of food intake regulatory pathways. The majority of studies to date have focused on associations between inadequate and high intakes of folic acid and vitamin D and neurocognitive development of the offspring. Hence, the objective of this review is to present an evaluation of the role of maternal vitamins A, D, E, and K in brain development and function of neural pathways that regulate feeding behaviors. PubMed and Google Scholar were searched from 1975 through September, 2016. Most studies supporting a role for fat-soluble vitamins in regulating brain development and associated behaviors have been conducted in animal and cell models, leaving uncertain their relevance to neurocognitive development and function in humans. Nevertheless, although current research on defining the role of maternal fat-soluble vitamins in offspring's brain development is limited, it is sufficient to warrant further investigations on their impact when intake amounts during pregnancy are not only inadequate but also exceed requirements.
•High multi- and methyl-vitamin diets were fed to Wistar rats during pregnancy alone.•Dams were exposed to a high fat diet for 16 weeks post-weaning.•High vitamin diets during pregnancy increased ...maternal post-weaning weight gain.•No common mechanism was found to explain their similar effects on weight gain.•Methyl vitamins alone do not account for all of the high multivitamin diet effects.
High multivitamin (10-fold, HV) and high folic acid (Fol) diets fed to pregnant Wistar rats increase body weight and characteristics of the metabolic syndrome in their offspring. Our objective was to determine the effects of a HV maternal diet on dams and whether methyl vitamins contribute to these effects. Pregnant Wistar rats were fed AIN-93G diets containing either (1) recommended multivitamins (RV, control), (2) HV, (3) HV with recommended Fol (HVRF; 1-fold Fol), or (4) RV with high methyl group vitamins (HMethyl; 10-fold Fol, vitamin B12 and B6). All groups were fed a RV diet during lactation until weaning and a RV high fat (HF; 60% fat) diet for 16 weeks post-weaning. The HV, HVRF and HMethyl diet fed dams gained 45% more weight from 2 to 15 weeks post-weaning and their weight gain (WG) was positively associated with cumulative post-weaning food intake (FI). However, only HV dams had a reduced preference for a sucrose solution, lower mesolimbic dopamine (DA) turnover in the nucleus accumbens (NAc), and higher expression of several genes involved in FI regulation in the arcuate nucleus of the hypothalamus (ARC). Energy conserving peroxisome proliferator-activated receptor (Ppar)-γ in adipose and -α in liver was also greater in these dams consistent with their WG. In conclusion, HV, HVRF and HMethyl maternal diets exacerbate maternal WG when dams are exposed to a HF diet post-weaning. However, the diets differed in their effects on central and peripheral regulatory systems of energy balance.
Excess vitamins, especially folate, are consumed during pregnancy but later-life effects on the offspring are unknown. High multivitamin (10-fold AIN-93G, HV) gestational diets increase ...characteristics of metabolic syndrome in Wistar rat offspring. We hypothesized that folate, the vitamin active in DNA methylation, accounts for these effects through epigenetic modification of food intake regulatory genes. Male offspring of dams fed 10-fold folate (HFol) diet during pregnancy and weaned to recommended vitamin (RV) or HFol diets were compared with those born to RV dams and weaned to RV diet for 29 weeks. Food intake and body weight were highest in offspring of HFol dams fed the RV diet. In contrast, the HFol pup diet in offspring of HFol dams reduced food intake (7%, p = 0.02), body weight (9%, p = 0.03) and glucose response to a glucose load (21%, p = 0.02), and improved glucose response to an insulin load (20%, p = 0.009). HFol alone in either gestational or pup diet modified gene expression of feeding-related neuropeptides. Hypomethylation of the pro-opiomelanocortin (POMC) promoter occurred with the HFol pup diet. POMC-specific methylation was positively associated with glucose response to a glucose load (r = 0.7, p = 0.03). In conclusion, the obesogenic phenotype of offspring from dams fed the HFol gestational diet can be corrected by feeding them a HFol diet. Our work is novel in showing post-weaning epigenetic plasticity of the hypothalamus and that in utero programming by vitamin gestational diets can be modified by vitamin content of the pup diet.
The AIN-93G diets based on soya protein or casein were fed to pregnant Wistar rats from day 3 of gestation and compared for their effects on characteristics of the metabolic syndrome in male ...offspring. Pregnant rats were randomised to either a casein (C) or soya protein (S) diet (n 12) during gestation only (Expt 1) or during gestation and lactation (Expt 2). Male offspring were weaned to either a C or S diet for 9 weeks (Expt 1) or 15 weeks (Expt 2). In Expt 1, pups born to S-fed dams had higher fasting blood glucose (BG), systolic blood pressure (SBP) and diastolic blood pressure (DBP) at week 4, higher blood glucose (BG) response to a glucose administration (P < 0·001) and higher body weight (BW) at week 8 (P < 0·05). In Expt 2, consumption of the S diet throughout gestation and lactation resulted in higher BW (P < 0·05), DBP (P < 0·005) and SBP (P < 0·005) in the offspring. They also had higher homeostasis model assessment of insulin resistance (HOMA-IR; P < 0·05) and plasma homocysteine (P < 0·05) at weaning, higher fasting BG and glucose response to glucose administration (P < 0·005) at week 12 and higher HOMA-IR (P < 0·01) at week 15. Although composition of the weaning diets interacted with the diet of the dams, the latter was the dominant factor in determining metabolic outcomes in the offspring. In conclusion, the S diet, compared with the C diet, when consumed during gestation or throughout gestation and lactation increased the presence of characteristics of the metabolic syndrome in the offspring.
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