We have previously shown that dietary inositol hexakisphosphate (IP6) and myo-inositol prevent fatty liver in rats fed a casein-based diet containing 1,1,1-trichloro-2,2-bis (p-chlorophenyl) ethane (DDT). This study was performed to examine the comparative effects of dietary equimolar amounts of sodium IP6 (1.02%) and myo-inositol (0.2%) on the development of DDT-induced fatty liver and hypercholesterolemia in rats fed 20% casein-type amino acid mixtures designed to exclude a possible myo-inositol contaminant in casein. Thirty-six male Wistar rats were divided into 6 groups of 6 rats each for: a control group, myo-inositol-supplemented group, IP6-supplemented group, DDT-treated group, DDT + myo-inositol-supplemented group, and a DDT + IP6-supplemented group. Dietary IP6 clearly suppressed the rises in serum concentrations of cholesterol and phospholipids because of DDT feeding, but myo-inositol had no significant influence on such elevations. Dietary IP6, but not myo-inositol, caused significant body weight gain with or without DDT intake. Supplemental IP6 and myo-inositol significantly increased hepatic-free myo-inositol regardless of DDT intake and prevented fatty liver in rats fed DDT. In conclusion, dietary IP6 and myo-inositol exert similar effects on DDT-induced fatty liver and myo-inositol status but distinct effects on DDT-induced hypercholesterolemia and growth rate in rats fed casein-type amino acid mixtures.
In vitro and animal studies indicate that n-3 polyunsaturated fatty acids (PUFAs) suppress carcinogenesis. This study presents a new insight on effectiveness of marine phospholipids for suppression of colon carcinogenesis. The purpose of this study was to investigate growth inhibition and apoptosis inducing effects of n-3 PUFA in the form of marine phosphatidylcholine (PC) on chemically induced (1,2-dimethylhydrazine) colon cancer in rats. Growth inhibition of Caco-2 cells was determined by colorimetric sodium 2-(4-iodophenyl)-3-(4-nitrophenyl)-5-(2,4-disulfophenyl)-2H-tetrazolium (WST-1) dye reduction assay. For animal studies, the rats were fed 5 different diets containing docosahexaenoic acid (DHA)-ethyl ester, eicosapentaenoic acid (EPA)-ethyl ester, squid meal PC (rich in DHA), starfish PC (rich in EPA), and corn oil. The 1,2-dimethylhydrazine (30 mg/kg) or saline was injected 48 hours before the experiment. Rats were anesthetized, and apoptotic as well as mitotic cells in crypt were counted based on morphological criteria in isolated crypts. Squid meal and starfish PC potently inhibited the growth of Caco-2 cells. The experimental diets containing n-3 PUFA suppressed colon cancer in rats. Rats that consumed diets containing DHA-ethyl ester, EPA-ethyl ester, squid meal PC, and starfish PC showed increased apoptosis (P < .01) and suppressed proliferation. These results suggest that marine PC-containing diets might be an effective dietary protective factor against colon cancer.
Identification and characterization of compounds that enhance the growth, development, and health of infants who are not breastfed continues to be a goal for nutritional science. This study explored the effects of one dietary component, (1,3/1,6)-β-d-glucan (Wellmune WGP), on lung immune development in the neonatal piglet. The hypothesis was that supplementation with WGP, a pathogen-associated molecular pattern, would enhance pathogen-responsive elements of the immune system, for instance, by increasing the size of the cytotoxic T-cell population or the expression of inflammatory cytokines. Piglets were fed a control formula or formula plus WGP at 1.8, 18, or 90 mg/kg body weight per day. Serum, thoracic lymph nodes (TLNs), mediastinal lymph nodes, and lung were collected at days 7 or 21. Immune parameters including tissue messenger RNA (mRNA) expression and T-cell phenotypes were analyzed. Normal developmental changes were observed, with a decrease in T-helper cells and an increase in cytotoxic T cells in both TLN and mediastinal lymph node, but there was no effect of WGP. Dietary WGP reduced the mRNA expression of transforming growth factor (TGF) β2 and tended to reduce the mRNA expression of TGF-β1 in lung tissue. With the exception of reducing TGF-β mRNA in the lung and tending to decrease the ratio of T helper to cytotoxic T cell in the TLN, dietary WGP did not affect lung-associated adaptive immunity in piglets.
Previous reports have demonstrated that conjugated linoleic acid (CLA) acts on body fat accumulation in a variety of animal models. The aim of the present study was to investigate the effect of cis (c)-9,trans (t)-11 and t10,c12 CLA isomers on the number and size of adipocytes from the inguinal and retroperitoneal fats in Wistar male rats. A 5.1% palm oil-based diet was supplemented with CLA isomers as follows: 0.6% of c9,t11, 0.6% of t10,c12, 1.3% of c9,t11 and t10,c12 isomers in mixture, and a control nonsupplemented group for comparative purposes. Fat tissues were prepared on microscope slides for histologic examination using an image-analysis software to count the number of adipocytes and measure cell sizes. The results showed that CLA isomers did not affect (P > .05) either final body and fat depot weights or serum lipids (with the exception of triacylglycerols) and adipocytokines (leptin and adiponectin). Animals fed the c9,t11 CLA isomer diet showed larger adipocytes when compared to other groups. Independently of the CLA dietary treatment, retroperitoneal fat showed larger adipocytes (3319 microm(2)) and therefore a smaller number of adipocytes per unit of area, compared to inguinal fat (3055 microm(2)). Taken together, the data suggest that a palm oil-based diet supplemented with the c9,t11 CLA isomer in Wistar rats, in contrast to the t10,c12 isomer and the mixture of both isomers, increases adipocyte dimensions in inguinal and retroperitoneal fat depots, while having a minor effect in serum lipids and adipocytokines.
Prenatal undernutrition affects offspring phenotype via changes in the epigenetic regulation of specific genes. We hypothesized that pregnant females that were fed a calcium (Ca)-deficient diet would have offspring with altered hepatic glucocorticoid-related gene expression and altered epigenetic gene regulation. Female Wistar rats ate either a Ca-deficient or control diet from 3 weeks before conception to 21 days after parturition. Pups were allowed to nurse from their original mothers and then euthanized on day 21. Methylation of individual cytosine-guanine dinucleotides in the phosphoenolpyruvate carboxykinase (Pck1), peroxisome proliferator-activated receptor α (Ppara), glucocorticoid receptor (Nr3c1), 11β-hydroxysteroid dehydrogenase-1 (Hsd11b1), and 11β-hydroxysteroid dehydrogenase-2 (Hsd11b2) promoters was measured in liver tissue using pyrosequencing. For each gene, quantitative real-time polymerase chain reaction was used to assess mRNA levels in liver tissue. Overall Hsd11b1 methylation was lower in the Ca-deficient group than in the control group; however, overall methylation of each other gene did not differ between groups. Serum corticosterone levels in male pups from Ca-deficient dams were higher than those in control pups. Expression of Pck1 and Nr3c1 was lower in the Ca-deficient group than in the control group. A Ca-deficient diet for a dam during gestation and early nursing may alter glucocorticoid metabolism and lead to higher intracellular glucocorticoid concentrations in the hepatic cells of her offspring; moreover, this abnormal glucocorticoid metabolism may induce the metabolic complications that are associated with Ca deficiency. These findings indicated that prenatal nutrition affected glucocorticoid metabolism in offspring in part by affecting the epigenome of offspring.
In recent decades, diets have changed rapidly in the Kingdom of Saudi Arabia (KSA) because the Western diet is replacing the traditional Arabic diet. This has resulted in an alarming increase in the number of overweight and obese children and adolescents in KSA. It is well documented that lifestyle is strongly associated with the development of obesity. Nevertheless, this remains to be demonstrated in adolescents from a rapidly developing country in the Middle East such as Saudi Arabia. This study tested the hypothesis that the new current dietary habits are related to the increase in overweight and obese Saudi Arabian adolescents. In 2006, a cross-sectional study was conducted among 239 adolescents (13-18 years old) who were selected by cluster sampling from schools in Jeddah, KSA. The nutritional status was assessed by anthropometric and biochemical parameters at the Saudi German Hospitals Group, Jeddah. Dietary habits were evaluated by a 3-day dietary recall (food diary) and a food frequency questionnaire. The mean age of the participants was 15.5 ± 2.5 years. The mean body mass index was 27.43 ± 4.61 kg/m(2). A total of 44.6% of the adolescents were overweight, and 56.6%, 30.5%, and 13.0% of energy was derived from carbohydrates, fats, and proteins, respectively. Compared with the Dietary Reference Intake, carbohydrate and fat intakes were higher, and calcium, iron, and zinc intakes were lower. Higher cholesterol and lower hemoglobin levels were found in 30.5% and 53.6% of the adolescents, respectively. In summary, increased weight status of 13- to 18-year-old Saudi adolescents was related to their inadequate dietary habits. This indicates the importance of rapidly promoting a healthier lifestyle among Saudi Arabian adolescents.
Studies examining an association between consumption of added sugars (AS) and weight measures in children are inconclusive. This study examined the association between intake of AS and 5 measures of weight or adiposity using a nationally recent representative sample of children. National Health and Nutrition Examination Surveys 2003-2006 24-hour recall data from children 6 to 18 years (n = 3136) were used. United States Department of Agriculture's definition of AS and MyPyramid Equivalents Database were used to estimate daily intake. Multiple linear regression and squared partial correlation coefficients were used to estimate the strength of association between weight, body mass index (BMI), BMI Z scores, waist circumference, and triceps and subscapular skinfolds as dependent variables with AS as the independent variable. Covariates were age, sex, race/ethnicity, poverty income ratio, total energy intake (kJ), and physical activity. Mean intake of AS was 23 ± 0.55 teaspoons (tsp) (21 tsp for 6-11 years and 25 tsp for 12-18 years) accounting for 17% of total energy intake for both groups. The percent variance explained in BMI Z scores was 3.9% in children 6 to 11 years, with AS contributing only 0.03%. In children 12 to 18 years, the percent variance explained in the BMI Z scores was 6.5% with 0.18% coming from AS. No significant associations were observed between intake of AS and weight or adiposity measures. Consumption of AS did not contribute significantly to BMI Z scores in children 6 to 18 years. Longitudinal studies using more robust and precise measures of dietary intake are needed to further investigate the role of AS and weight in children.
The purpose of this study was to determine the association of out-of-hand nut (OOHN) consumption with nutrient intake, diet quality, and the prevalence of risk factors for cardiovascular disease and metabolic syndrome. Data from 24-hour recalls from individuals aged 2+ years (n = 24,385) participating in the 1999-2004 National Health and Nutrition Examination Survey were used. The population was divided into children aged 2 to 11, 12 to 18, and adults 19+ years, and each group was dichotomized into OOHN consumers and nonconsumers. Out-of-hand nut consumers were defined as those individuals consuming ¼ oz of nuts or more per d. Means, standard errors, and covariate-adjusted analyses of variance were determined using appropriate sample weights. Diet quality was determined using the Healthy Eating Index-2005. Significance was set at P < .05. The percent of OOHN consumers increased with age: 2.1% ± 0.3%, 2.6% ± 0.3%, 6.5% ± 0.5%, and 9.6% ± 0.5% those aged 2 to 11, 12 to 18, 19 to 50, and 51+ years, respectively. The 2 latter groups were combined into a single group of consumers aged 19+ years for subsequent analyses. Consumers of OOHN from all age groups had higher intakes of energy, monounsaturated and polyunsaturated fatty acids, dietary fiber, copper, and magnesium and lower intakes of carbohydrates, cholesterol, and sodium than did nonconsumers. Diet quality was higher in OOHN consumers of all age groups. In children aged 2 to 11 years, consumers had a higher prevalence of overweight/obesity. In those aged 12 to 18 years, weight and percent overweight were lower in consumers. Adult consumers had higher high-density lipoprotein cholesterol, red blood cell folate, and serum folate levels and lower insulin, glycohemoglobin, and C-reactive protein levels than did nonconsumers. Adult consumers also had a 19% decreased risk of hypertension and a 21% decreased risk of low high-density lipoprotein cholesterol levels. Data suggested that OOHN consumption was associated with improved nutrient intake, diet quality, and, in adults, a lower prevalence of 2 risk factors for metabolic syndrome. Consumption of OOHN, as part of a healthy diet, should be encouraged by health professionals.
Consumption of lean meat is a valuable addition to a healthy diet because it provides complete protein and is a rich source of vitamin B(12), iron, and zinc. The objective of this study was to examine the nutritional contribution of total beef and lean beef (LB) to the American diet using the USDA definition of LB as defined in MyPyramid. Twenty-four-hour dietary recall data from adults 19 to 50 years of age (n = 7049) and 51+ years (n = 6243) participating in the National Health and Nutrition Examination Survey 1999-2004 were assessed. Lean beef was defined as beef with <9.28 g fat per 100 g (excess was discretionary fat). Fifty percent of adults 19 to 50 years and 41% of adults 51+ years consumed beef on the day of the dietary recall. Total beef consumed among adults 19 to 50 and 51+ years was 49.3 +/- 1.4 g (1.74 oz/d) and 37.1 +/- 1.2 g (1.31 oz/d), respectively. In adults 19 to 50 and 51+ years, LB contributed 3.9% and 3.7% to total energy; 4.5% and 4.1% to total fat, 3.8% and 3.6% to saturated fatty acids; 13% and 11% to cholesterol intake; 15% and 14% to protein; 25% and 20% to vitamin B(12); 23% and 20% to zinc; and 8% and 7% to iron, respectively. Beef was also an important food source of many other nutrients, including niacin, vitamin B(6), phosphorus, and potassium. In addition, beef provided only 1% of total sodium intake. Consumption of beef contributed significantly to intake of protein and other key nutrients by US adults.
This study examined the association of whole grain consumption with body weight measures and prevalence of overweight/obesity in a recent, nationally representative sample of adults. A secondary analysis of 1999-2004 National Health and Nutrition Examination Survey (NHANES) data was conducted using adults 19 to 50 years of age (y) (n = 7,039) and 51+ y (n = 6,237). Participants were categorized by whole grain consumption: ≥ 0 to <0.6, ≥ 0.6 to <1.5, ≥ 1.5 to <3.0, and ≥ 3.0 servings/day. Main outcome measures included body mass index (BMI), waist circumference (WC), and prevalence of overweight/obesity. Sample weights were applied and the number and percentages of adults in whole grain consumption groups were determined. Least-square means and standard errors were calculated for body weight measures. Two regression models were developed and compared. Model 1 covariates included age, gender, ethnicity, and total energy intake; Model 2 was extended to include cereal fiber. Trend analysis was conducted to test for differences between least-square means. Significance was set at P ≤ .05. Adults 19-50 and 51+ y consumed a mean of 0.63 and 0.77 servings of whole grains/day, respectively. A significant trend was observed in both age groups for increased consumption of whole grains with lower BMI, WC, and percentage overweight/obese (Model 1); however, a significant trend was not observed when cereal fiber was added as a covariate (Model 2). Results confirm overall whole grain intake well below recommendations, and adults who consumed the most servings of whole grains had lower body weight measures. Results also suggest that fiber in whole grain foods may mediate associations with weight measures in adults. Intake of whole grain foods should be encouraged by health professionals.
There is limited research examining the relationship of candy consumption by adults on diet and health. The purpose of this study was to determine total, chocolate, or sugar candy consumption and their effect on energy, saturated fatty acid and added sugar intake, weight, risk factors for cardiovascular disease, metabolic syndrome (MetS), and diet quality in adults 19 years and older (n = 15,023) participating in the 1999-2004 National Health and Nutrition Examination Survey. Twenty-four-hour dietary recalls were used to determine intake. Covariate-adjusted means ± SE and prevalence rates were determined for candy consumption groups. Odds ratios were used to determine the likelihood of cardiovascular risk factors and MetS. A total of 21.8%, 12.9%, and 10.9% of adults consumed total, chocolate, and sugar candy, respectively. Mean daily per capita intake of total, chocolate, and sugar candy was 9.0 ± 0.3, 5.7 ± 0.2, and 3.3 ± 0.2 g, respectively; intake in consumers was 38.3 ± 1.0, 39.9 ± 1.1, and 28.9 ± 1.3 g, respectively. Energy (9973 ± 92 vs 9027 ± 50 kJ; P < .0001), saturated fatty acid (27.9 ± 0.26 vs 26.9 ± 0.18 g; P = .0058), and added sugar (25.7 ± 0.42 vs 21.1 ± 0.41 g; P < .0001) intake were higher in candy consumers than nonconsumers. Body mass index (27.7 ± 0.15 vs 28.2 ± 0.12 kg/m(2); P = .0092), waist circumference (92.3 ± 0.34 vs 96.5 ± 0.29 cm; P = .0051), and C-reactive protein (0.40 ± 0.01 vs 0.43 ± 0.01 mg/dL; P = .0487) levels were lower in candy consumers than nonconsumers. Candy consumers had a 14% decreased risk of elevated diastolic blood pressure (P = .0466); chocolate consumers had a 19% decreased risk of lower high-density lipoprotein cholesterol (P = .0364) and a 15% reduced risk of MetS (P = .0453). Results suggest that the current level of candy consumption was not associated with health risks.
Epidemiological studies examining potential associations between dried fruit consumption, diet quality, and weight status are lacking. The goal of this study was to examine the association of dried fruit consumption with nutrient intake, diet quality, and anthropometric indicators of overweight/obesity. A secondary analysis of dietary and anthropometric data collected from adult (19+ years) participants (n = 13 292) of the 1999-2004 National Health and Nutrition Examination Survey was conducted. Dried fruit consumers were defined as those consuming amounts ⅛ cup-equivalent fruit per day or more and identified using 24-hour recalls. Diet quality was measured using the Healthy Eating Index 2005. Covariate-adjusted means, SEs, prevalence rates, and odds ratios were determined to conduct statistical tests for differences between dried fruit consumers and nonconsumers. Seven percent of the population consumed dried fruit. Mean differences (P < .01) between consumers and nonconsumers in adult shortfall nutrients were dietary fiber (+6.6 g/d); vitamins A (+173 μg retinol activity equivalent per day), E (+1.5 mg α-tocopherol per day), C (+20 mg/d), and K (+20 mg/d); calcium (+103 mg/d); phosphorus (+126 mg/d); magnesium (+72 mg/d); and potassium (+432 mg/d). Dried fruit consumers had improved MyPyramid food intake, including lower solid fats/alcohol/added sugars intake, and a higher solid fats/alcohol/added sugars score (11.1 ± 0.2 vs 8.2 ± 0.1) than nonconsumers. The total Healthy Eating Index 2005 score was significantly higher (P < .01) in consumers (59.3 ± 0.5) than nonconsumers (49.4 ± 0.3). Covariate-adjusted weight (78.2 ± 0.6 vs 80.7 ± 0.3 kg), body mass index (27.1 ± 0.2 vs 28.1 ± 0.2), and waist circumference (94.0 ± 0.5 vs 96.5 ± 0.2 cm) were lower (P < .01) in consumers than nonconsumers, respectively. Dried fruit consumption was associated with improved nutrient intakes, a higher overall diet quality score, and lower body weight/adiposity measures.
Recently, phosphatidylserine (PS) has received attention for its anti-inflammatory effect; however, the molecular mechanisms of its action have not been fully understood. Thus, we hypothesized that PS might have antiarthritic and anti-inflammatory effects. To test this hypothesis, the in vitro anti-inflammatory effect of soybean-derived PS was tested on interleukin (IL)-1β-stimulated fibroblast-like synoviocytes from rheumatoid arthritis patients (RA-FLS) by measuring the levels of IL-6, IL-8, prostaglandin E2, and vascular endothelial growth factor by enzyme-linked immunosorbent assay. The analgesic and antiarthritic activities of PS were investigated in rat models of carrageenan-induced acute paw pain and arthritis. The former was evaluated with a paw pressure test; the latter, by measuring paw volume and weight distribution ratio. In addition, the participation of mitogen-activated protein kinase signaling in the anti-inflammatory and antiarthritic effects of PS was investigated in RA-FLS. Phosphatidylserine inhibited the production of inflammatory mediators IL-6; IL-8; vascular endothelial growth factor; and, in particular, prostaglandin E2 in IL-1β-stimulated RA-FLS. These effects were associated with abrogation of inhibitor of nuclear factor-κBα phosphorylation and suppression of p38 and c-jun amino terminal kinase but not extracellular signal-regulated kinase 1/2 phosphorylation. In rats, PS also showed a significant inhibitory effect on arthritic and nociceptive symptoms induced by carrageenan. These findings suggest that PS has anti-inflammatory and antiarthritic effects in vitro and in in vivo animal models; thus, PS should be further studied to determine its potential use as either a pharmaceutical or dietary supplement for alleviating arthritic symptoms.
Few studies have explored the relationship between sugar content in cereal and health outcome among children and adolescents. This study was designed to investigate the associations between ready-to-eat cereals, categorized by sugar content, with weight indicators and nutrient intake profiles. Data collected from 6- to 18-year-old US children and adolescents (N = 9660) in the National Health and Nutrition Examination Survey 2001-06 were used to analyze cereal consumption. Body mass index (BMI), BMI-for-age, waist-to-height ratio, percent overweight or obese, mean day-1 intake, and usual daily intake of macronutrients and micronutrients were the dependent variables; day-1 cereal intake, categorized by tertiles of sugar content, was the main independent variable. Weighted regression with adjustment for the survey design was used to model the dependent variables as a function of day-1 cereal intake, adjusting for age group, sex, race/ethnicity, total day-1 intake of energy, calcium and sugar, the Healthy Eating Index-2005 total score, and household income. For all tertiles of sugar classifications of cereal, children who consumed cereal had significantly lower BMI compared with children who consumed no cereal (P's < .05). Similarly, when compared with children who consumed no cereal, those who ate cereal consumed significantly less fat and cholesterol and significantly more carbohydrates, sugar, whole grains, vitamin A, thiamin, riboflavin, niacin, vitamin B(6), folic acid, vitamin B(12), vitamin C, calcium, magnesium, iron, and zinc. Lower weight and positive nutrient profiles were associated with cereal consumption regardless of sugar content.
We tested the hypothesis that racial differences in vitamin D levels are associated with racial disparities in insulin resistance between blacks and whites. Among 3628 non-Hispanic black and white adults in the National Health and Nutrition Examination Survey from 2001 to 2006, we examined the association between race and insulin resistance using the homeostasis assessment model for insulin resistance. We conducted analyses with and without serum 25-hydroxyvitamin D (25[OH]D). We adjusted for age, sex, educational level, body mass index, waist circumference, physical activity, alcohol intake, smoking, estimated glomerular filtration rate, and urinary albumin/creatinine ratio. Blacks had a lower mean serum 25(OH)D level compared with whites (14.6 [0.3] ng/mL vs 25.6 [0.4] ng/mL, respectively; P < .0001). Blacks had a higher odds ratio (OR) for insulin resistance without controlling for serum 25(OH)D levels (OR, 1.67; 95% confidence interval, 1.26-2.20). The association was not significant (OR, 1.28; 95% confidence interval, 0.90-1.82) after accounting for serum 25(OH)D levels. The higher burden of insulin resistance in blacks compared with whites may be partially mediated by the disparity in serum 25(OH)D levels.
Type 2 diabetes has been shown to occur in response to environmental and genetic influences, among them nutrition; food intake patterns; sedentary lifestyle; body mass index; and exposure to persistent organic pollutants, such as polychlorinated biphenyls (PCBs). Nutrition is essential in the prevention and management of type 2 diabetes and has been shown to modulate the toxicity of PCBs. Serum carotenoid concentrations, considered a reliable biomarker of fruit and vegetable intake, are associated with the reduced probability of chronic diseases, such as type 2 diabetes and cardiovascular disease. Our hypothesis is that fruit and vegetable intake, reflected by serum carotenoid concentrations, is associated with the reduced probability of developing type 2 diabetes in US adults with elevated serum concentrations of PCBs 118, 126, and 153. This cross-sectional study used the Center for Disease Control and Prevention database, National Health and Nutrition Examination Survey 2003-2004, in logistic regression analyses. Overall prevalence of type 2 diabetes was approximately 11.6% depending on the specific PCB. All 3 PCBs were positively associated with the probability of type 2 diabetes. For participants at higher PCB percentiles (eg, 75th and 90th) for PCB 118 and 126, increasing serum carotenoid concentrations were associated with a smaller probability of type 2 diabetes. Fruit and vegetable intake, as reflected by serum carotenoid concentrations, predicted notably reduced probability of dioxin-like PCB-associated risk for type 2 diabetes.
Because dairy products provide shortfall nutrients (eg, calcium, potassium, and vitamin D) and other important nutrients, this study hypothesized that it would be difficult for Americans to meet nutritional requirements for these nutrients in the absence of dairy product consumption or when recommended nondairy calcium sources are consumed. To test this hypothesis, MyPyramid dietary pattern modeling exercises and an analyses of data from the National Health and Nutrition Examination Survey 2003-2006 were conducted in those aged at least 2 years (n = 16 822). Impact of adding or removing 1 serving of dairy, removing all dairy, and replacing dairy with nondairy calcium sources was evaluated. Dietary pattern modeling indicated that at least 3 servings of dairy foods are needed to help individuals meet recommendations for nutrients, such as calcium and magnesium, and 4 servings may be needed to help some groups meet potassium recommendations. A calcium-equivalent serving of dairy requires 1.1 servings of fortified soy beverage, 0.6 serving of fortified orange juice, 1.2 servings of bony fish, or 2.2 servings of leafy greens. The replacement of dairy with calcium-equivalent foods alters the overall nutritional profile of the diet and affects nutrients including protein, potassium, magnesium, phosphorus, riboflavin, vitamins A, D and B(12). Similar modeling exercises using consumption data from the National Health and Nutrition Examination Survey also demonstrated that nondairy calcium replacement foods are not a nutritionally equivalent substitute for dairy products. In conclusion, although it is possible to meet calcium intake recommendations without consuming dairy foods, calcium replacement foods are not a nutritionally equivalent substitute for dairy foods and consumption of a calcium-equivalent amount of some nondairy foods is unrealistic.
Whole grain (WG) foods have been shown to reduce chronic disease risk and overweight. Total dietary fiber is associated with WG and its health benefits. The purpose was to determine whether associations exist between WG intake (no-WG intake, 0 ounce equivalent [oz eq]; low, >0-<3 oz eq; high, ≥3 oz eq) and total dietary fiber intake among Americans 2 years and older. One-day food intake data from the US National Health and Nutrition Examination Survey 2009 to 2010 (n = 9042) showed that only 2.9% and 7.7% of children/adolescents (2-18 years) and adults (≥19 years) consumed at least 3 WG oz eq/d, respectively. For children/adolescents and adults, individuals in the high WG intake group were 59 and 76 times more likely to fall in the third fiber tertile, respectively, compared with those with no-WG intake. Total dietary fiber intake from food sources varied by WG intake group for children/adolescents and adults with more total dietary fiber consumed from ready-to-eat (RTE) and hot cereals and yeast breads/rolls in the high WG intake group compared with the no-WG intake group. Major WG sources for children/adolescents and adults included yeast bread/rolls (24% and 27%, respectively), RTE cereals (25% and 20%, respectively), and oatmeal (12% and 21%, respectively). Among those with the highest WG intake, WG RTE cereal with no added bran was the greatest contributor to total dietary fiber compared with other RTE cereal types. Whole grain foods make a substantial contribution to total dietary fiber intake and should be promoted to meet recommendations.
The 2010 US Dietary Guidelines recommended limiting intake of sodium to 1500 mg/d for people older than 50 years, African Americans, and those suffering from chronic disease. The guidelines recommended that all other people consume less than 2300 mg sodium and 4700 mg of potassium per day. The theoretical feasibility of meeting the sodium and potassium guidelines while simultaneously maintaining nutritional adequacy of the diet was tested using food pattern modeling based on linear programming. Dietary data from the National Health and Nutrition Examination Survey 2001-2002 were used to create optimized food patterns for 6 age-sex groups. Linear programming models determined the boundary conditions for the potassium and sodium content of the modeled food patterns that would also be compatible with other nutrient goals. Linear programming models also sought to determine the amounts of sodium and potassium that both would be consistent with the ratio of Na to K of 0.49 and would cause the least deviation from the existing food habits. The 6 sets of food patterns were created before and after an across-the-board 10% reduction in sodium content of all foods in the Food and Nutrition Database for Dietary Studies. Modeling analyses showed that the 2010 Dietary Guidelines for sodium were incompatible with potassium guidelines and with nutritionally adequate diets, even after reducing the sodium content of all US foods by 10%. Feasibility studies should precede or accompany the issuing of dietary guidelines to the public.
Water-soluble black Chinese (Pu-Erh) tea extract (BTE), which contains high gallic acid content, has been demonstrated to elicit antiobese effects in animals. Because gallic acid is related with the reduction of visceral fat and cholesterol contents and improvement of obesity in animals, we investigated the effects of BTE intake on 36 preobese Japanese adults (body mass index [BMI], >25- <30 kg/m(2)) in a 12-week double-blind, randomized, placebo-controlled group comparison study using powdered barley tea with or without (placebo) BTE. A follow-up 4-week period after BTE intake termination was monitored to observe the withdrawal effect. All subjects ingested barley tea with or without BTE (333 mg) before each of the 3 daily meals. In the BTE-treated group, the mean pretreament values of body weight and BMI significantly decreased after intake and after BTE withdrawal. However, the corresponding values scored significant differences only from 8 weeks after intake (vs the placebo-treated group). The mean values of the waist circumference indicated a similar tendency. Furthermore, coronal navel section (same anatomical position) images of computed tomography of all BTE- and non-BTE-treated subjects revealed that the visceral fat areas (cm(2)) were significantly (P < .05) less in the former 12 weeks after BTE ingestion. Measured biochemical parameters did not indicate significant differences, and BTE-treated subjects did not complain of any adverse effects (abdominal distension, etc). Ingestion of BTE exhibited significant effects in reducing the mean waist circumference, BMI, and visceral fat values and might be useful for weight control and prevention of obesity development (or metabolic syndrome) in humans.
This study was designed to monitor the metabolic differences after feeding starch, galactose and fructose diets with adequate or marginal copper levels to normal male rats over a period of 9-21 months. Two hundred and forty-five weanling male Sprague-Dawley rats weighing approximately 50-60 g were randomly divided into one of the eight dietary groups. All diets were either Cu marginal (1.5 &mgr;g/g diet) or adequate (5-6 &mgr;g/g) with 627 carbohydrate (g/kg diet) as starch; 500 galactose and 127 starch; 500 fructose and 127 starch; or 400 galactose and 227 fructose. Glycated hemoglobin, ceruloplasmin oxidase activity, hematocrit, and plasma glucose, cholesterol, and triglyceride were measured in 72 rats after nine months. Galactose-fed rats had the lowest (P < 0.0001) body weights. Severe mortality rates were found in galactose-fructose-marginal Cu-fed rats. Marginal Cu deficiency significantly (P < 0.0001) reduced hepatic copper and increased hepatic Fe in all carbohydrate groups. Ceruloplasmin activity of the rats fed the marginal Cu and fructose-containing diets declined to undetectable levels and plasma cholesterol levels increased. Glycated hemoglobin was significantly (P < 0.001) increased in the galactose-fed rats compared to fructose or starch-fed rats regardless of dietary copper concentration. The data suggest that dietary galactose and fructose exacerbate effects of long term marginal Cu intake including hypertrophy of liver, heart and kidney, hyperlipidemia, and increased mortality.
Interleukin-23 (IL-23), a cytokine produced primarily by dendritic cells, is involved in host defense against gut pathogens and promotes innate immunity and inflammatory responses through the IL-23/interleukin-17 axis. We previously reported that extracts from edible mushrooms enhanced antimicrobial α-defensin production n HL60 cells. Because IL-23 is involved in defensin production, we hypothesized that edible mushrooms may modulate its secretion and gut inflammation. Eight-week-old C57BL/6 mice were fed the AIN76 diet or the same diet supplemented with 5% white button (WBM), portabella, or shiitake mushrooms. To assess in vivo and in vitro cytokine secretion, 7 to 8 mice per group received 3% dextran sodium sulfate (DSS) in drinking water during the last 5 days of the 6-week feeding period. To delineate the mechanisms by which mushrooms alter IL-23 secretion, J.744.1 cells were incubated with (100 μg/mL) WBM, portabella, and shiitake extracts without and with 100 μg/mL curdlan (a dectin-1 agonist) or 1 mg/mL laminarin (a dectin-1 antagonist). The dectin-1 receptor is a pattern-recognition receptor found in phagocytes, and its activation promotes antimicrobial innate immunity and inflammatory responses. In DSS-untreated mice, mushrooms significantly increased IL-23 plasma levels but decreased those of interleukin-6 (IL-6) (P < .05). In DSS-treated mice, mushroom-supplemented diets increased IL-6 and IL-23 levels (P < .05). Mushroom extracts potentiated curdlan-induced IL-23 secretion, and mushroom-induced IL-23 secretion was not blocked by laminarin in vitro, suggesting the involvement of both dectin-1-dependent and dectin-1-independent pathways. Although all mushrooms tended to increase IL-6 in the colon, only WBM and shiitake tended to increase IL-23 levels. These data suggest that edible mushrooms may enhance gut immunity through IL-23.
alpha-Lipoic acid (LA), a naturally occurring molecule in animal and plant cells, is a potent antioxidant that reportedly exerts beneficial effects on cell proliferation and apoptosis in various cancer cell lines. However, the molecular mechanisms behind the antimetastatic property of LA are not well understood. The present study investigates the effect of LA on metastasis in a cell system. Our hypothesis is that LA inhibits metastasis via inhibition of matrix metalloproteinase (MMP) in vitro. MDA-MB-231 cells, a human breast cancer cell line, were treated with various concentrations of LA (0, 250, 500, or 1000 mumol/L) to measure metastasis, MMP activity, and mRNA expression. The viability of cells was examined by the 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide assay. The effect of LA on metastasis was evaluated using the motility, migration, and invasion assay in vitro. The activity and mRNA expression of MMP-2 and MMP-9 were measured. After LA treatment, cell motility and cell migration were significantly decreased (P < .05). alpha-Lipoic acid also reduced cell invasion through a Matrigel-coated chamber (P < .05). Activities of MMP-2 and MMP-9 were decreased by LA treatment in a dose-dependent manner. RT-PCR analysis confirmed the reduction in mRNA expression level of MMP-2 and MMP-9 by LA treatment. We conclude that in this cell culture model, LA treatment inhibits cancer metastasis, and this inhibition is likely due to the decrease in the activity and mRNA expression levels of MMP-2 and MMP-9 caused by LA.
We hypothesized that consuming eggs for breakfast would significantly lower postprandial satiety and energy intake throughout the day. Using a crossover design, 21 men, 20 to 70 years old, consumed 2 isoenergetic test breakfasts, in a random order separated by 1 week. The macronutrient composition of the test breakfasts were as follows: (EGG, % CHO/fat/protein = 22:55:23) and (BAGEL, % CHO/fat/protein = 72:12:16). Fasting blood samples were drawn at baseline before the test breakfast and at 30, 60, 120, and 180 minutes after breakfast. After 180 minutes, subjects were given a buffet lunch and asked to eat until satisfied. Subjects filled out Visual Analog Scales (VAS) during each blood draw and recorded food intake the days before and after the test breakfasts. Plasma glucose, insulin, and appetite hormones were analyzed at each time point. Subjects consumed fewer kilocalories after the EGG breakfast compared with the BAGEL breakfast (P< .01). In addition, subjects consumed more kilocalories in the 24-hour period after the BAGEL compared with the EGG breakfast (P < .05). Based on VAS, subjects were hungrier and less satisfied 3 hours after the BAGEL breakfast compared with the EGG breakfast (P < .01). Participants had higher plasma glucose area under the curve (P < .05) as well as an increased ghrelin and insulin area under the curve with BAGEL (P < .05). These findings suggest that consumption of eggs for breakfast results in less variation of plasma glucose and insulin, a suppressed ghrelin response, and reduced energy intake.
Infants between 6 and 24 months of age are at the highest risk of development of iron deficiency anemia (IDA) in developing countries. Consuming unmodified cow's milk, delayed introduction of solid foods after 6 months, and high birth order could be predictors of the presence of IDA. Three hundred infants between the ages of 6 and 24 months (mean, 13.94 ± 6.17 months) from Ain Shams University Children's Hospital were enrolled in the study. Data collected included demographic information and dietary assessment including the type of milk feeding, introduction of solid foods, and daily iron intake. The infants were examined, and anthropometric measurements were recorded. Anemic infants (hemoglobin level <11 g/dL) were further evaluated by complete blood count, hemoglobin electrophoresis, and iron profile. Anemia was diagnosed among 198 infants (66%), of whom 129 (43%) had IDA. Red cell distribution width at a cutoff value of 15.8% was 86% sensitive and 74% specific in predicting IDA. The main risk factors for IDA included being between 6 and 18 months of age, of the male sex, birth order above the second order, consuming cow's milk, predominant breast-feeding beyond 6 months of age, and low daily iron intake. We conclude that IDA is the most common cause of anemia among Egyptian infants 6 to 24 months old of low socioeconomic standard. Independent clinical predictors were consuming cow's milk during the first 6 months, delayed introduction of solid foods after 6 months, and birth order beyond the second order.
This secondary analysis investigated the influence of body mass index (BMI) category and sex on reporting accuracy during multiple 24-hour dietary recalls. On three occasions, each of 79 children (40 girls) was observed eating school meals and interviewed the next morning about the previous day's intake, with ≥ 25 days between any two consecutive occasions for a child. Using age/sex BMI percentiles, we categorized 48 children as healthy weight (≥ 5(th) percentile <85(th)), 14 as at risk of overweight (≥ 85(th) percentile <95(th)), and 17 as overweight (≥95(th) percentile). A repeated-measures analysis was conducted for each of five outcomes (number of items observed eaten, number of items reported eaten, omission rate, intrusion rate, total inaccuracy). For items observed, BMI category x trial was marginally significant (P=0.079); over trials, this outcome was stable for healthy-weight children, decreased and stabilized for at-risk-of-overweight children, and was stable and decreased for overweight children. This outcome was greatest for overweight children and least for healthy-weight children (P=0.015). For items reported, no significant effects were found. For omission rate (P=0.028) and intrusion rate (P=0.083), BMI category x trial was significant and marginally significant; over trials, both decreased for healthy-weight children, decreased and stabilized for at-risk-of-overweight children, and increased and stabilized for overweight children. Total inaccuracy decreased slightly over trials (P=0.076); this outcome was greater for boys than for girls (P=0.049). Results suggest that children's dietary reporting accuracy over multiple recalls varies by BMI category. Validation studies with adequate samples for each BMI category, sex, and race are needed.
N-3 polyunsaturated fatty acids (PUFAs) are known to have antihypertensive properties, but the association between 24-hour ambulatory blood pressure and the tissue content of n-3 PUFA remains controversial. The purpose of the present study was to investigate the hypothesis that the level of erythrocyte n-3 PUFA is inversely related with 24-hour ambulatory blood pressure after adjustment for relevant confounders. Fifty-one male and 49 female Korean patients were included in this study. Twenty-seven of the patients were defined as having hypertension. There were significant differences in age, body mass index, sex, marital status, and family history of hyperlipidemia between hypertensive and nonhypertensive subjects, and these factors were therefore considered to be confounding factors. Multivariate-adjusted regression analysis showed that erythrocyte fatty acids were not significantly associated with the risk of hypertension after adjusting for confounders. However, Pearson correlation analysis showed that 24-hour ambulatory systolic blood pressure (SBP) was significantly and negatively correlated with n-3 PUFA (r = -0.228, P = .027) and eicosapentaenoic acid (r = -0.270, P = .008), but not with docosahexaenoic acid (r = -0.156, P = .131). Multivariate-adjusted regression analysis also showed that intake of protein, vitamin B(2), vitamin E, and cholesterol increased the risk of hypertension after adjusting for confounders. In addition, Pearson correlation analysis showed that fat and cholesterol consumption was positively correlated with SBP, but carbohydrate intake was negatively correlated with SBP. In conclusion, erythrocyte n-3 PUFA did not reduce the risk of hypertension but were negatively correlated with 24-hour ambulatory SBP in the Korean population.
Cancer cachexia syndrome contributes to wasting and weight loss leading to inefficacy of anticancer therapy. In this study, the anticatabolic agent beta-hydroxy-beta-methylbutyrate (HMB) was supplemented to adult Walker 256 tumor-bearing rats during 8 weeks aiming to determine if tumor burden could be reduced. Male Wistar rats were randomly assigned to nontumor and tumor-bearing groups and fed regular chow or regular chow plus HMB supplemented (76 mg/kg body weight). Beta-hydroxy-beta-methylbutyrate supplementation induced a lower tumor weight and tumor cell proliferation ex vivo, totally prevented glycemia reduction, as well as blunted the increase in the serum lactate concentrations and also preserved glycogen stores in tumor-bearing rats. Reduction in tumor cell proliferation ex vivo was accompanied by increased nuclear factor-kappaB inhibitor-alpha content by more than 100%. In contrast, nuclear factor-kappaB p65 subunit content was suppressed by 17% with HMB supplementation. In conclusion, HMB supplementation, at a similar dose used in humans to increase muscle mass, caused antitumor and anticachectic effects, with tumor-cell nuclear factor-kappaB pathway participation, which might be a potential nutritional strategy in cancer therapy.
We investigated whether lipid extract from a blue-green alga, N commune, modulates proinflammatory gene expression in RAW 264.7 macrophages. The cells were incubated with N commune lipid extract (0-100 microg/mL) and subsequently activated by LPS (100 ng/mL). Quantitative real-time PCR analysis showed that mRNA abundance of proinflammatory mediators, including TNF-alpha, COX-2, IL-1beta, IL-6, and iNOS, was significantly reduced by N commune lipid extract in a dose-dependent manner. Secretion of TNF-alpha and IL-1beta into cell culture medium was also significantly decreased by N commune lipid extract. Thin-layer chromatography-densitometry analysis showed that N commune lipid extract contained approximately 15% of fatty acids. To determine whether the inhibition of proinflammatory mediator production by N commune lipid extract is primarily conferred by fatty acids in the lipid extract, macrophages were incubated with 100 microg/mL of N commune lipid extract or 15 microg/mL of a fatty acid mixture, which was formulated to reflect the fatty acid composition of N commune lipid extract. The fatty acid mixture significantly reduced RNA abundance of TNF-alpha and COX-2, but to a lesser extent than did the N commune lipid extract, suggesting the presence of additional bioactive compounds with an antiinflammatory property in the lipid extract. As NF-kappaB is a major regulator for the proinflammatory gene expression, we measured its DNA-binding activity. DNA-binding activity of NF-kappaB was significantly reduced by N commune lipid extract. In conclusion, our study suggests that N commune lipid extract represses the expression of proinflammatory genes in RAW 264.7 macrophages, at least in part, by inhibiting the activation of NF-kappaB pathway.
It was hypothesized that d-aspartic acid (D-ASP) supplementation would not increase endogenous testosterone levels or improve muscular performance associated with resistance training. Therefore, body composition, muscle strength, and serum hormone levels associated with the hypothalamo-pituitary-gonadal axis were studied after 28 days of resistance training and D-ASP supplementation. Resistance-trained men resistance trained 4 times/wk for 28 days while orally ingesting either 3 g of placebo or 3 g of D-ASP. Data were analyzed with 2 × 2 analysis of variance (P < .05). Before and after resistance training and supplementation, body composition and muscle strength, serum gonadal hormones, and serum D-ASP and d-aspartate oxidase (DDO) were determined. Body composition and muscle strength were significantly increased in both groups in response to resistance training (P < .05) but not different from one another (P > .05). Total and free testosterone, luteinizing hormone, gonadotropin-releasing hormone, and estradiol were unchanged with resistance training and D-ASP supplementation (P > .05). For serum D-ASP and DDO, D-ASP resulted in a slight increase compared with baseline levels (P > .05). For the D-ASP group, the levels of serum DDO were significantly increased compared with placebo (P < .05). The gonadal hormones were unaffected by 28 days of D-ASP supplementation and not associated with the observed increases in muscle strength and mass. Therefore, at the dose provided, D-ASP supplementation is ineffective in up-regulating the activity of the hypothalamo-pituitary-gonadal axis and has no anabolic or ergogenic effects in skeletal muscle.
Tomato product consumption is inversely related to prostate cancer incidence, and lycopene (LYC) has been implicated in reduced prostate cancer risk. The contribution of other tomato carotenoids, phytoene (PE) and phytofluene (PF), towards prostate cancer risk has not been adequately studied. The relative uptake and tissue distribution of tomato carotenoids are not known. We hypothesize that PE and PF are bioavailable from a tomato powder diet or from a purified source and accumulate in androgen-sensitive tissues. In this study, 4 wk old male Fisher 344 rats were pre-fed an AIN-93G powder diet composed of 10% tomato powder containing PE, PF, and LYC (0.015, 0.012, and 0.011 g/kg diet, respectively). After 30 d tomato powder feeding, hepatic PF concentrations (168 ± 20 nmol/g) were higher than PE or LYC (104 ± 13 and 104 ± 13 nmol/g, respectively). In contrast, LYC, followed by PF, had the highest accumulation of the measured carotenoids in the prostate lobes and seminal vesicles. When tomato powder-fed rats received a single oral dose of either ∼2.7 mg PE or PF, an increase in the dosed carotenoid concentration was observed in all measured tissues, except the adrenal. Percent increases of PF were greater than that of PE in liver, serum, and adipose (37, 287 and 49% versus 16, 179 and 23%, respectively). Results indicate that the relative tomato carotenoid biodistribution differs in liver and androgen-sensitive tissues, suggesting that minor changes in the number of sequential double bonds in carotenoid structures alter absorption and/or metabolism of tomato carotenoids.
Uncoupling protein 1 (UCP1) plays an important role in thermogenesis in brown adipose tissue. Previously, we reported an association between -3826 A/G single-nucleotide polymorphism (SNP) in the promoter of UCP1 gene and lower thermogenesis in young women, suggesting this SNP has an adverse effect on the regulation of energy balance. Based on the hypothesis that this SNP (G allele) may have resistance against diet-induced weight loss, we examined its effects on anthropometric and metabolic responses to short-term, controlled-energy diet in young women. Seventeen lean women (20.9 ± 0.2 years; body mass index, 22.1 ± 0.5 kg/m(2)) were fed a controlled-energy diet (5.0 MJ/d, 62% carbohydrate, 19% protein, and 19% fat) administered by dietitians for 2 weeks. Clinical measurements were determined at baseline and after the dietary intervention. The subjects' physical activity was obtained using pedometers and self-reporting. The thermoregulatory sympathetic nervous system was evaluated using heart rate variability power spectral analysis. Upon the completion of the intervention, subjects were genotyped using an allele-specific DNA primer assay and results compared with their clinical measurements focusing on with or without the G allele. After dietary intervention, G allele subjects (A/G + G/G, n = 10) showed significantly smaller changes in body weight, body mass index, and waist circumference compared with A/A genotype subjects (n = 7). Similar changes were observed in parameters regarding glucose or lipid metabolism in both groups. These results suggest that the UCP1 gene -3826 G allele may result in smaller weight loss after a short-term, controlled-energy diet in young, lean women.
β-Hydroxy-β-methylbutyrate (HMB) prevents deleterious muscle responses under pathological conditions, including tumor- and chronic steroid therapy-related muscle losses. Here, we investigated the hypothesis that HMB may modulate the balance between protein synthesis and degradation in the PI3K/Akt-mediated mammalian target of rapamycin (mTOR) and FoxO1/FoxO3a-dependent mechanisms in differentiated C2C12 muscle cells. We also tested the effect of HMB on the expression of MuRF-1 and atrogin-1 in response to the inflammatory stress. β-Hydroxy-β-methylbutyrate up-regulated phosphorylation of Akt and mTOR, and these effects were completely abolished in the presence of PI3K inhibitor LY294002. β-Hydroxy-β-methylbutyrate also up-regulated FoxO1 and FoxO3a phosphorylation, and these changes were inhibited by LY294002. Although, unexpectedly, HMB failed to reduce the expressions of atrophy-related atrogin-1 messenger RNA and the protein response to the proinflammatory cytokines tumor necrosis factor α plus interferon γ, HMB did attenuate the MuRF-1 expression. Thus, HMB appears to restore the balance between intracellular protein synthesis and proteolysis, likely via activation of the PI3K/Akt-dependent mTOR and FoxO1/FoxO3a signaling pathway and the reduction of tumor necrosis factor α/interferon γ-induced MuRF-1 expression, thereby ameliorating aging-related muscle atrophy.
We have previously shown that mulberry leaf extract (MA) causes blood glucose levels to decrease in rats with streptozotocin-induced diabetes while enhancing glucose uptake by isolated fat cells. We hypothesized that the antidiabetic activity of MA is mediated via enhancement of adiponectin secretion and adipogenesis, which consequently decreases blood glucose. In the present study, we aimed to elucidate the molecular basis for the observed antidiabetic activity using murine 3T3-L1 preadipocyte cultures. We found that treatment of differentiating 3T3-L1 cells with MA at concentrations of 5, 15, and 45 μg/mL increased expression of adiponectin messenger RNA from 1.4-fold (control) to 1.5-, 1.95-, and 2.2-fold above basal values, respectively, while causing adiponectin secretion to increase from 70 ± 7.4 ng/mL to 100 ± 1.4, 138 ± 2.0, and 176 ± 21.4 ng/mL, respectively. Furthermore, we observed an increase in both lipid accumulation and messenger RNA expression of transcription factors, such as CCAAT/enhancer-binding protein α and peroxisome proliferator-activated receptor γ; and of the fatty acid-binding protein aP2 in differentiated 3T3-L1 cells pretreated with MA. Our findings indicate that the stimulatory effects of mulberry leaf extract on adipocyte proliferation and differentiation likely occur through up-regulation of adipogenic transcription factors and downstream gene expression. Such effects of mulberry leaf extract on adiponectin secretion and adipocyte activity may account for, at least in part, the antidiabetic effects of consumption of beverages containing mulberry leaves.
Fructose- or sucrose-rich diets can cause insulin resistance and increase the risk of cardiovascular disease. Adipokines are correlated with the development of these diseases in obesity. We hypothesize that fructose and sucrose induce insulin resistance via effects on adipokine gene expression in adipocytes. This study analyzed the effect of fructose or glucose on adiponectin, haptoglobin, and angiotensinogen gene expression in 3T3-L1 adipocytes. Ten days after differentiation, the cells were pretreated with serum- and glucose-free medium. Twenty-four hours later, fructose or glucose (0, 5, 10, or 20 mmol) was added into the medium, and the cells were collected after a further 24 hours. Adiponectin, haptoglobin, and angiotensinogen gene expression were determined. Adiponectin gene expression increased when 10 or 20 mmol glucose was added compared with that observed for the non-hexose-treated cells. A similar effect occurred when 5 mmol fructose was added. Glucose (10 mmol) and fructose (20 mmol) stimulated haptoglobin gene expression in 3T3-L1 adipocytes compared with 0 mmol, with glucose producing a more pronounced effect. Although 20 mmol fructose caused an increase in angiotensinogen gene expression, glucose did not. In conclusion, in this study of 2 hexoses revealed an increase in adiponectin gene expression, suggesting that the effect of a glucose-rich diet on the development of insulin resistance is not related to the effect of these hexoses on adipocyte adiponectin gene expression. However, insulin resistance and cardiovascular disease promoted by fructose-rich diets could be partially related to the effect of fructose on adiponectin and angiotensinogen gene expression.
The purpose of our research was to test the hypothesis that silk protein hydrolysate increases glucose uptake in cultured murine embryonic fibroblasts. Insulin sensitizing activity was observed in a cell-based glucose uptake assay using 3T3-L1 embryonic fibroblasts. The treatment of 1 mg/mL of silk peptide E5K6 plus 0.2 nM insulin was associated with a significant increase in glucose uptake (124.0% ± 2.5%) compared to treatment with 0.2 nM insulin alone. When the 3T3-L1 cells were induced to differentiate into fibroblasts, fat droplets formed inside the cells. Silk peptide E5K6 reduced the formation of fat droplets at the 1-mg/mL dosage (86.1% ± 2.5%) when compared to the control (100.0% ± 5.8%). A 1 mg/mL dose of silk peptide E5K6 significantly increased GLUT 4 expression (131.5% ± 4.0%). The treatment of 1 mg/mL of silk peptide E5K6 did not present any changes for adipogenic expressed genes, but leptin expression was significantly increased by silk peptide E5K6 supplementation (175.9% ± 11.1%). From these results, silk peptide E5K6 increased glucose uptake via up-regulation of GLUT 4 and decreased fat accumulation via the up-regulation of leptin.
We previously reported that grape skin ethanol extract (GSE) decreases adipogenic transcription factor gene expression, inhibiting triglyceride accumulation in 3T3-L1 adipocytes. In this study, we hypothesized that GSE may induce differential expression profiles in adipocytes, thus providing protection against obesity. Thirty-five genes involved in the peroxisome proliferator-activated receptor-γ (PPARγ) signaling pathway, lipid metabolism, or adipogenesis were identified through microarray analysis of adipocytes treated with GSE. Expression of the genes involved in PPARγ signaling, Adipoq, Scd1, Nr1h3, Fabp5, Scd2, and Pparg decreased with GSE treatment, whereas expression of Ppargc1a increased. Lipid metabolism-associated genes Mlxp1, Stat5a, Hsl, Plin1, and Vdr were down-regulated. Interestingly, GSE also affected expression of genes related to the mitogen-activated protein kinases pathway. GSE extract treatment decreased expression of aP2, Fas, and Tnfa, known markers of adipogenesis, as measured by real-time polymerase reaction. These findings demonstrate the antiadipogenic effects of GSE on 3T3-L1 adipocytes at the genetic level, primarily on the PPARγ signaling pathway.
Anthocyanins are naturally occurring polyphenolic pigments in plants that have been shown to decrease weight gain and insulin resistance in mice-fed high-fat diets. We investigated the effects of anthocyanins on cell growth, differentiation, and lipolysis in 3T3-L1 cells to test our hypothesis that anthocyanins could reduce adipose tissue mass by acting directly on adipocytes. Anthocyanin extracts from black soybeans were used and composed of 3 of the following major anthocyanins: cyanidine-3-O-glucoside (68.3%), delphinidin-3-O-glucoside (25.2%), and petunidin-3-O-glucoside (6.5%). Treatment with 12.5 and 50 μg/mL of black soybean anthocyanins exhibited inhibitory effects on the proliferation of both preconfluent preadipocytes (P < .01) and maturing postconfluent adipocytes (P < .01). In fully differentiated adipocytes, the number of viable cells was reduced by black soybean anthocyanins (P < .01). Treatment with 50 μg/mL of black soybean anthocyanins slightly increased epinephrine-induced lipolysis but decreased the basal lipolysis of fully differentiated adipocytes (P < .05). Black soybean anthocyanins also reduced lipid accumulation and suppressed the expression of the peroxisome proliferator-activated receptor γ, a major transcription factor for the adipogenic gene (P < .01). These results suggest that black soybean anthocyanins inhibit adipocyte differentiation and basal lipolysis, which may contribute to their antiobesity and antidiabetic properties.
Oleanolic acid is a triterpenoid compound that is widely present in vegetables, medicinal herbs, and other plants and has potent antioxidant and antiinflammatory properties. However, the potential of oleanolic acid to offset obesity is not clear. This study tested the hypothesis that oleanolic acid suppresses the differentiation of 3T3-L1 adipocytes by downregulating cellular induction of peroxisome proliferators-activated receptor γ (PPARγ) and cytidine-cytidine-adenosine-adenosine-thymidine (CCAAT) enhancer binding protein α (C/EBPα). The 3T3-L1 adipocytes were cultured and differentiated in Dulbecco modified Eagle medium containing 10% fetal bovine serum for 6 to 8 days in the absence and presence of 1 to 25 μmol/L oleanolic acid according to differentiating protocols. Nontoxic oleanolic acid, at 25 μmol/L or less, dose-dependently attenuated lipid accumulation in differentiated adipocytes as evidenced by Oil Red O staining. Western blot analysis showed that the induction of PPARγ and C/EBPα was markedly attenuated in differentiated and oleanolic acid-treated adipocytes at their transcriptional messenger RNA levels. Furthermore, this study examined whether oleanolic acid dampened the induction of visfatin, a proinflammatory and visceral fat-specific adipokine expressed in adipocytes. Visfatin expression was inhibited in differentiated adipocytes exposed to a PPARγ inhibitor GW9662. In addition, the visfatin production was significantly repressed in 25 μmol/L oleanolic acid-treated adipocytes, possibly through blocking PPARγ activation. These results demonstrate that oleanolic acid may be a promising agent to disturb adipocyte differentiation and suppress obesity-associated inflammation.