Clara E. Cho

Effect of premeal consumption of whey protein and its hydrolysate on food intake and postmeal glycemia and insulin responses in young adults.

BACKGROUND Dairy protein ingestion before a meal reduces food intake and, when consumed with carbohydrate, reduces blood glucose. OBJECTIVE The objective was to describe the effect of whey protein (WP) or its hydrolysate (WPH) when consumed before a meal on food intake, pre- and postmeal satiety, and concentrations of blood glucose and insulin in healthy young adults. DESIGN Two randomized crossover studies were conducted. WP (10-40 g) in 300 mL water was provided in experiment 1, and WP (5-40 g) and WPH (10 g) in 300 mL water were provided in experiment 2. At 30 min after consumption, the subjects were fed an ad libitum pizza meal (experiment 1) or a preset pizza meal (12 kcal/kg, experiment 2). Satiety, blood glucose, and insulin were measured at baseline and at intervals both before and after the meals. RESULTS In experiment 1, 20-40 g WP suppressed food intake (P < 0.0001) and 10-40 g WP reduced postmeal blood glucose concentrations and the area under the curve (AUC) (P < 0.05). In experiment 2, 10-40 g WP, but not WPH, reduced postmeal blood glucose AUC and insulin AUC in a dose-dependent manner (P < 0.05). The ratio of cumulative blood glucose to insulin AUCs (0-170 min) was reduced by > or =10 g WP but not by 10 g WPH. CONCLUSIONS WP consumed before a meal reduces food intake, postmeal blood glucose and insulin, and the ratio of cumulative blood glucose to insulin AUCs in a dose-dependent manner. Intact WP, but not WPH, contributes to blood glucose control by both insulin-dependent and insulin-independent mechanisms. This trial was registered at clinicaltrials.gov as NCT00988377 and NCT00988182.

Cesarean section and development of the immune system in the offspring

This review examines the relation between the mode of delivery and development of the immune system in the offspring. Recent epidemiological studies provide evidence that elective cesarean section (CS) is associated with aberrant short-term immune responses in the newborn infant, and a greater risk of developing immune diseases such as asthma, allergies, type 1 diabetes, and celiac disease. However, it is still unknown whether CS causes a long-term effect on the immune system of the offspring that contributes to compromised immune health. With the dramatic increase in the rate of CS today, a greater emphasis should be placed on the discussion among both professionals and childbearing women on potential consequences of CS on the health of the offspring.

Relation between estimates of cornstarch digestibility by the Englyst in vitro method and glycemic response, subjective appetite, and short-term food intake in young men

BACKGROUND Starch composition and rate of digestion are determinants of blood glucose concentrations and food intake (FI). OBJECTIVE Our objective was to describe relations between estimates of digestibility of starches by the in vitro Englyst method and their effect on blood glucose concentrations, subjective appetite, and FI in young men. DESIGN Subjects consumed 5 soups containing 50 g maltodextrin, whole-grain, high-amylose, regular cornstarch, or no added starch at 1-wk intervals. Ad libitum FI was measured at 30 min (experiment 1) or 120 min (experiment 2) later, which were the estimated times of digestion of a rapidly digestible starch (RDS) and slowly digestible starch, respectively. Blood glucose concentrations and appetite were measured pre- and postmeal. RESULTS At 30 min, FI was reduced by maltodextrin only [86% RDS, 12% resistant starch (RS); P < 0.05], but at 120 min FI was reduced by whole-grain (24% RDS, 66% RS), high-amylose corn (40% RDS, 48% RS), and regular corn (27% RDS, 39% RS) (P < 0.0001). The premeal blood glucose concentration at 30 and 120 min was highest and lowest after maltodextrin treatment, respectively (P < 0.0001). After the meal, the blood glucose area under the curve at 30 min was lower after all starch treatments (P < 0.05), but at 120 min the blood glucose area under the curve was lower only after the regular cornstarch treatment (P < 0.05). Premeal appetite decreased by all treatments (P < 0.05). CONCLUSION The in vitro estimates of starch digestibility by the Englyst method predicted the effects of starch composition on blood glucose concentrations and FI in young men 30 and 120 min after consumption. This trial was registered at clinicaltrials.gov as NCT00980941 for experiment 1 and NCT00988689 for experiment 2.

High folate gestational and post-weaning diets alter hypothalamic feeding pathways by DNA methylation in Wistar rat offspring.

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.

Methyl vitamins contribute to obesogenic effects of a high multivitamin gestational diet and epigenetic alterations in hypothalamic feeding pathways in Wistar rat offspring.

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.

A comparison of effects of lard and hydrogenated vegetable shortening on the development of high-fat diet-induced obesity in rats

Background: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.Objective: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.Methods and design: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 25[OH]D3, glucose, insulin and fatty acid composition of diets were measured.Results: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).Conclusion: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.

High Folic Acid Intake during Pregnancy Lowers Body Weight and Reduces Femoral Area and Strength in Female Rat Offspring

Rats fed gestational diets high in multivitamin or folate produce offspring of altered phenotypes. We hypothesized that female rat offspring born to dams fed a gestational diet high in folic acid (HFol) have compromised bone health and that feeding the offspring the same HFol diet attenuates these effects. Pregnant rats were fed diets with either recommended folic acid (RFol) or 10-fold higher folic acid (HFol) amounts. Female offspring were weaned to either the RFol or HFol diet for 17 weeks. HFol maternal diet resulted in lower offspring body weights (6%, P = 0.03) and, after adjusting for body weight and femoral length, smaller femoral area (2%, P = 0.03), compared to control diet. After adjustments, HFol pup diet resulted in lower mineral content (7%, P = 0.01) and density (4%, P = 0.002) of lumbar vertebra 4 without differences in strength. An interaction between folate content of the dam and pup diets revealed that a mismatch resulted in lower femoral peak load strength (P = 0.01) and stiffness (P = 0.002). However, the match in folate content failed to prevent lower weight gain. In conclusion, HFol diets fed to rat dams and their offspring affect area and strength of femurs and mineral quantity but not strength of lumbar vertebrae in the offspring.

Role of maternal vitamins in programming health and chronic disease

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.

A high multivitamin diet fed to Wistar rat dams during pregnancy increases maternal weight gain later in life and alters homeostatic, hedonic and peripheral regulatory systems of energy balance

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.

Increasing vitamin A in post-weaning diets reduces food intake and body weight and modifies gene expression in brains of male rats born to dams fed a high multivitamin diet.

High multivitamin gestational diets (HV, 10-fold AIN-93G levels) increase body weight (BW) and food intake (FI) in rat offspring weaned to a recommended multivitamin (RV), but not to a HV diet. We hypothesized that high vitamin A (HA) alone, similar to HV, in post-weaning diets would prevent these effects of the HV maternal diet consistent with gene expression in FI and reward pathways. Male offspring from dams fed HV diets were weaned to a high vitamin A (HA, 10-fold AIN-93G levels), HV or RV diet for 29 weeks. BW, FI, expression of genes involved in regulation of FI and reward and global and gene-specific DNA methylation of pro-opiomelanocortin (POMC) in the hypothalamus were measured. Both HV and HA diets slowed post-weaning weight gain and modified gene expression in offspring compared to offspring fed an RV post-weaning diet. Hypothalamic POMC expression in HA offspring was not different from either HV or RV, and dopamine receptor 1 was 30% (P<.05) higher in HA vs. HV, but not different from RV group. Hippocampal expression of serotonin receptor 1A (40%, P<.01), dopamine receptor 2 (40%, P<.05) and dopamine receptor 5 (70%, P<.0001) was greater in HA vs. RV fed pups and is 40% (P<.01), 50% (P<.05) and 40% (P<.0001) in HA vs. HV pups, respectively. POMC DNA methylation was lower in HA vs. RV offspring (P<.05). We conclude that high vitamin A in post-weaning diets reduces post-weaning weight gain and FI and modifies gene expression in FI and reward pathways.