Search

Neopterin is a marker of activated immune response, but its role in hepatocarcinogenesis is unknown. The present study aims to evaluate the effects of neopterin on prooncogenic/proinflammatory, apoptotic pathways, and other molecular mechanisms in HCC. We used SNU449, Huh-7, SK-Hep-1, and HepG2 cell lines. A cell viability assay was performed with different concentrations of neopterin. RT-PCR, Western blotting, transwell migration, scratch assay, and reactive oxygen species (ROS) production assays were performed at inhibition concentration 50 of neopterin, which was 40 µM for SNU449 and 80 µM for other cell lines. There were significant changes in mTOR, STAT3, PI3K, and interleukin-6 gene expressions, which were also supported by the protein expressions. Neopterin did not affect apoptosis in SNU449, while apoptosis increased by all doses of neopterin in SK-Hep-1 and HepG2. ROS production was increased in all cell lines in response to neopterin. Cell migration was reduced in SK-Hep1 and HepG2 but did not change in SNU449 and Huh-7. Our study showed that neopterin is not just a byproduct. The results suggest that neopterin may be a paracrine factor that modulates pro-inflammatory and pro-oncogenic pathways responsible for the biological behavior of HCC in a chronic inflammatory tumor microenvironment.

BACKGROUND: A higher urinary ratio of the biologically inactive estrogen metabolite, 2-hydroxyestrone (2OHE1), to the biologically active metabolite, 16alpha-hydroxyestrone (16alphaOHE1), may be associated with a lower risk of breast cancer. High fiber intake is also associated with decreased breast cancer risk. OBJECTIVE: We investigated the effects of prunes, which are naturally rich in both soluble and insoluble fiber, on the concentrations of 2OHE1 and 16alphaOHE1 and on the ratio of 2OHE1 to 16alphaOHE1. DESIGN: Nineteen healthy premenopausal women consumed their habitual diets for 3 menstrual cycles and then consumed 100 g prunes/d for the next 3 cycles. Concentrations of urinary 2OHE1 and 16alphaOHE1 were determined during the follicular and luteal phases. RESULTS: Prune supplementation increased total and soluble fiber intakes by 4 and 2 g/d, respectively (P < 0.001). Mean (+/- SEM) luteal 2OHE1 excretion decreased from 3.92 +/- 0.79 to 2.20 +/- 0.40 nmol/mmol creatinine during the third cycle (P = 0.017). Luteal 16alphaOHE1 excretion decreased from 1.38 +/- 0.24 to 0.87 +/- 0.10 and 0.87 +/- 0.15 nmol/mmol creatinine during the first and third cycles, respectively (P = 0.018 for both values). Follicular 16alphaOHE1 excretion decreased significantly only during the first cycle (from 0.82 +/- 0.12 to 0.45 +/- 0.09 nmol/mmol creatinine; P = 0.005). The 2OHE1-16alphaOHE1 ratio did not change significantly after prune supplementation. CONCLUSIONS: Prune supplementation significantly decreased the excretion of 16alphaOHE1 during the follicular phase of the first menstrual cycle and during the luteal phases of both the first and third menstrual cycles. The 2OHE1-16alphaOHE1 ratio did not change significantly. The potential significance of the decrease in 16alphaOHE1 excretion, without a change in the 2OHE1-16alphaOHE1 ratio, on the prevention of estrogen-dependent cancers remains to be determined. Copyright © 2002 American Society for Clinical Nutrition [ABSTRACT FROM AUTHOR]

School and extracurricular sections are aim to quality development of morphological, motor skills and functional abilities of children. In order to preserve the health, well­being of the individual, but also the entire population increasingly points to the importance and necessity of active lifestyle with regular physical activity throughout the life span, both in times of childhood and adolescence and in the adult age. The purpose of the research is to analyze the preferences and frequency of physical exercise in girls aged 7-14 years with the Central Bosnia Canton. The sample was composed of 291 child, female, ages 7-14 years, various primary schools in Central Bosnia Canton. The respondents are members of the entertainment football school. The survey was conducted in 2014 in Travnik. Were determined by morphological measurements (height and weight), early in the morning, on the basis of which calculated the body mass index. After measuring the girls met the anonymous questionnaire consisted of eight questions from the questionnaire 'Fels physical activity questionnaire for children' (FPAQ). On the basis of the questionnaire were calculated indices in the field of sports (IS), leisure time (ISVs), housework (ICP) and the total score of physical activity (UTA). According to the level of physical activity according to the Likert scale, the largest proportion of girls who are mainly engaged in physical activity 167 (57.39%), while the total sample there is no proportion of girls who are in no way involved in physical activity. Today's daily habits are changing due to new forms of entertainment (TV, Internet, video games, etc.) which consequently leads to a growing number of children and adolescents with overweight and obesity. Therefore, there is a concern that new habits and a sedentary lifestyle have contributed to this phenomenon in recent years.

The radiation shielding properties of three different stainless steels have been investigated. For this purpose, linear attenuation coefficients at photon energy levels of 662 keV and 1250 keV have been measured. The obtained results showed that ferritic stainless steel was more capable in stopping the high energy photons than its non-magnetic counterpart.

In this study, the effect of cooling rate and heat treatment on the microstructural and mechanical characteristics such as microhardness of low-carbon microalloyed steel was investigated by means of optical microscopy and Vickers hardness tests. The cooling rates were controlled by introducing air-cooling, furnace-cooling, water-quenching and liquid nitrogen quenching. The obtained results showed that the difference of cooling rates and the heat treatments significantly affect the microstructure and mechanical properties of steels. These tendencies were dominant in liquid nitrogen cooled for 1073 K at 4 h and 1273 K heat treatment processes.

Polycystic ovary syndrome (PCOS) is an insulin-resistant state compensated for by the body via hyperinsulinemia. More than 50% of women with PCOS are obese and/or have metabolic syndrome. Weight loss improves both metabolic and reproductive outcomes. Energy/caloric content as well as the nutrient composition of one's diet may also be important. This article will present a series of studies from our research comparing the effects of dietary protein vs. simple carbohydrates (CHOs). The results of the acute challenge studies demonstrate that simple CHO intake causes reactive hypoglycemia in one third of women with PCOS, especially among obese and insulin-resistant individuals. Symptoms of hypoglycemia are associated with secretion of cortisol and adrenal androgens. Simple CHOs suppress the hunger signal ghrelin for a shorter period. During weight loss, women who receive protein supplementation achieve more significant weight and fat mass losses. The amino acid compositions of the protein supplements do not affect the improvements in weight and insulin resistance. It is plausible that simple CHO intake leads to weight gain, or interferes with weight loss, by causing reactive hypoglycemia, triggering adrenal steroid secretion and thus leading to snacking. Since obese women with PCOS are more susceptible to reactive hypoglycemia, a vicious cycle is established. Restriction of simple CHOs may break this cycle.

Even though polycystic ovary syndrome (PCOS) was originally defined as "amenorrhea associated with bilateral polycystic ovaries", women without PCO morphology can be included in this diagnosis. This may contribute to the clinical heterogeneity seen in PCOS. Serum anti-Mullerian hormone (AMH) correlates with the number of ovarian cysts. We investigated whether phenotyping based on serum AMH can distinguish subgroups of PCOS with different clinical and biochemical characteristics. The electronic medical records of 108 women with PCOS (Rotterdam criteria) were reviewed. The serum AMH value correlated inversely (0.03 < p < 0.0001) with age, weight, and BMI values and directly with serum total testosterone (T), free T, and bioavailable T values. When divided into quartiles based on serum AMH values, the women in the highest quartile (AMH: 18.5 ± 9.9 ng/mL; n = 27) had lower BMI (29.4 ± 6.9 vs. 34.0 ± 10.6-36.7 ± 7.2 kg/m 2 ) but higher total T (51.3 ± 27.2 vs. 26.5 ± 10.4-35.1 ± 16.3 ng/dL), free T (7.7 ± 6.0 vs. 4.4 ± 2.3-5.7 ± 3.2 ng/dL), and bioavailable T (22.1 ± 17.0 vs. 12.2 ± 6.6-16.5 ± 8.7 ng/dL) values. The combination of high AMH and high testosterone values may point to the ovaries and reproductive etiology for PCOS in this subgroup. Thus, AMH-based phenotyping may provide a practical and cost-effective tool to explore the heterogeneity in PCOS.

Objective: When glucose records from self blood glucose monitoring (SBGM) do not reflect estimated average glucose from glycosylated hemoglobin (HgBA1) or when patients' clinical symptoms are not explained by their SBGM records, clinical management of diabetes becomes a challenge. Our objective was to determine the magnitude of differences in glucose values reported by SBGM versus those documented by continuous glucose monitoring (CGM)., Methods: The CGM was conducted by a clinical diabetes educator (CDE)/registered nurse by the clinic protocol, using the Medtronic iPRO2 ™ system. Patients continued SBGM and managed their diabetes without any change. Data from 4 full days were obtained, and relevant clinical information was recorded. De-identified data sets were provided to the investigators., Results: Data from 61 patients, 27 with type 1 diabetes (T1DM) and 34 with T2DM were analyzed. The lowest, highest, and average glucose recorded by SBGM were compared to the corresponding values from CGM. The lowest glucose values reported by SBGM were approximately 25 mg/dL higher in both T1DM ( P = .0232) and T2DM ( P = .0003). The highest glucose values by SBGM were approximately 30 mg/dL lower in T1DM ( P = .0005) and 55 mg/dL lower in T2DM ( P<.0001). HgBA1c correlated with the highest and average glucose by SBGM and CGM. The lowest glucose values were seen most frequently during sleep and before breakfast; the highest were seen during the evening and postprandially., Conclusion: SBGM accurately estimates the average glucose but underestimates glucose excursions. CGM uncovers glucose patterns that common SBGM patterns cannot., Abbreviations: CDE = certified diabetes educator; CGM = continuous glucose monitoring; HgBA1c = glycosylated hemoglobin; MAD = mean absolute difference; SBGM = self blood glucose monitoring; T1DM = type 1 diabetes; T2DM = type 2 diabetes.

Androgens can have variable effects on men and women. Women may be evaluated for androgen excess for several reasons. Typically, young premenopausal women present with clinical symptoms of hirsutism, alopecia, irregular menses, and/or infertility. The most common cause of these symptoms is polycystic ovary syndrome. After menopause, even though ovaries stop producing estrogen, they continue to produce androgen, and women can have new onset of hirsutism and alopecia. Laboratory evaluation involves measurement of the major ovarian and adrenal androgens. In women, age, phase of the menstrual cycle, menopausal status, obesity, metabolic health, and sex hormone-binding proteins significantly affect total-androgen levels and complicate interpretation. This review will summarize the clinically relevant evaluation of hyperandrogenemia at different life stages in women and highlight pitfalls associated with interpretation of commonly used hormone measurements. Hypogonadism in men is a clinical syndrome characterized by low testosterone and/or low sperm count. Symptoms of hypogonadism include decreased libido, erectile dysfunction, decreased vitality, decreased muscle mass, increased adiposity, depressed mood, osteopenia, and osteoporosis. Hypogonadism is a common disorder in aging men. Hypogonadism is observed rarely in young boys and adolescent men. Based on the defects in testes, hypothalamus, and/or pituitary glands, hypogonadism can be broadly classified as primary, secondary, and mixed hypogonadism. Diagnosis of hypogonadism in men is based on symptoms and laboratory measurement. Biomarkers in use/development for hypogonadism are classified as hormonal, Leydig and Sertoli cell function, semen, genetic/RNA, metabolic, microbiome, and muscle mass-related. These biomarkers are useful for diagnosis of hypogonadism, determination of the type of hypogonadism, identification of the underlying causes, and therapeutic assessment. Measurement of serum testosterone is usually the most important single diagnostic test for male hypogonadism. Patients with primary hypogonadism have low testosterone and increased luteinizing hormone (LH) and follicle-stimulating hormone (FSH). Patients with secondary hypogonadism have low testosterone and low or inappropriately normal LH and FSH. This review provides an overview of hypogonadism in men and a detailed discussion of biomarkers currently in use and in development for diagnosis thereof., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Polycystic ovary syndrome (PCOS) is the most common endocrine disorder affecting young women. Even though the definition of PCOS has changed over the years, all diagnostic criteria include two or more of the following: oligomenorrhea/oligoovulation/anovulation, androgen excess and polycystic ovaries (PCO). Traditional method of assessing the ovarian morphology has been transvaginal pelvic ultrasound. Recent studies support that serum anti-Mullerian hormone (AMH) levels correlate with the number of ovarian follicles and cysts. Hence, measurement of AMH is adequate to make the diagnosis. Traditionally, hyperandrogenemia has been assessed by measuring total-testosterone. The literature stresses the importance of sex hormone binding globulin (SHBG) measurements and bioavailable-testosterone and free-testosterone calculations, because insulin resistance decreases SHBG, lowers total-testosterone, and leads to under-estimation of bioavailable- and free-testosterone. Since 50-60% of PCOS patients have metabolic syndrome, assessment of metabolic risk is also necessary. It is important to diagnose insulin resistance before development of glucose intolerance and diabetes. This requires measurements of not only plasma glucose but also insulin concentrations. Determination of HgBA1 can be informative as well. This review aims to present an accurate and cost-effective approach to diagnosis and management of PCOS., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Objective: Whey protein (WP) intake has been shown to reduce postprandial glycemia. Majority of WP research in type 2 diabetes (T2DM) involved acute challenge or weight loss studies. It is not known if WP supplementation can provide sustained glucose lowering. Our goal was to investigate the effects of WP on glycemia comprehensively by using continuous glucose monitoring (CGM) while avoiding the confounding effects of variable food intake through controlled feeding., Research Design and Methods: This double-blinded and placebo (PL)-controlled study included 22 patients with T2DM patients (11 male, 11 female; age 57.1±12.6 years) on diet or metformin monotherapy. First, one serving (21 g) of WP was compared with PL in parallel-armed acute challenge studies. Next, in a crossover design, each patient underwent CGM twice, over 2 consecutive weeks, 3.5 days each week. Identical diets were provided by the study during both CGM periods. During the first CGM, one serving of either WP or PL was consumed before breakfast and another before dinner. During the second CGM, participants switched to the alternate supplement. Order of the supplements was randomized., Results: During acute challenge studies, WP stimulated insulin and glucagon-like peptide (GLP)-1 secretion; suppressed ghrelin (all p<0.05), while PL had no effect. During CGM, glucose response to WP varied depending on the baseline characteristics of the patients. When evaluated using linear regression, the most predictive baseline variables were body mass index (BMI) (p=0.0006), triglycerides (p=8.3×10 -5 ) and GLP-1 (p=0.006). Lower BMI, triglyceride and GLP-1 predicted decreased glucose levels on WP. Obesity, hypertriglyceridemia and high fasting GLP-1 concentrations predicted increased glucose levels., Conclusions: Effects of WP supplementation on glycemia in T2DM depend on the baseline characteristics. Lower body weight, normal triglyceride and lower GLP-1 levels predict glucose lowering. In contrast, obesity, hypertriglyceridemia and high baseline GLP-1 predict increased glucose response., Competing Interests: Competing interests: None declared.

Background: Both fish (FO) and flaxseed oils (FLX) are n-3 polyunsaturated fatty acids (PUFA). Fish oil contains long chain while FLX contains essential n-3 PUFA. We demonstrated that FO altered insulin secretion and resistance in polycystic ovary syndrome (PCOS) women but FLX did not. Surprisingly, the effects of FO were similar to those of the n-6 PUFA-rich soybean oil (SBO). Since increased branched chain (BCAA) and aromatic amino acids (AA) affect insulin secretion and resistance, we investigated whether FO, FLX and /or SBO affect plasma metabolites, especially AA., Methods and Findings: In this six-week, randomized, 3-parallel arm, double-blinded study, 54 women received 3.5 g/day FO, FLX or SBO. In 51 completers (17 from each arm), fasting plasma metabolites were measured at the beginning and at the end. As compared to FLX, FO and SBO increased insulin response and resistance as well as several BCAA and aromatic AA. Pathway analysis indicated that FO exerted the largest biochemical impact, affecting AA degradation and biosynthesis, amine, polyamine degradation and alanine, glycine, l-carnitine biosynthesis and TCA cycle, while FLX had minimal impact affecting only alanine biosynthesis and l-cysteine degradation., Conclusion: Effects of FO and SBO on plasma AA were similar and differed significantly from those of the FLX. The primary target of dietary PUFA is not known. Dietary PUFA may influence insulin secretion and resistance directly and alter plasma AA indirectly. Alternatively, as a novel concept, dietary PUFA may directly affect AA metabolism and the changes in insulin secretion and resistance may be secondary.

Background: It has been suggested that perturbations in branched-chain amino acid (BCAA) catabolism are associated with insulin resistance and contribute to elevated systemic BCAAs. Evidence in rodents suggests dietary protein rich in BCAAs can increase BCAA catabolism, but there is limited evidence in humans., Objective: We hypothesize that a diet rich in BCAAs will increase BCAA catabolism, which will manifest in a reduction of fasting plasma BCAA concentrations., Methods: The metabolome of 27 obese women with metabolic syndrome before and after weight loss was investigated to identify changes in BCAA metabolism using GC-time-of-flight mass spectrometry. Subjects were enrolled in an 8-wk weight-loss study including either a 20-g/d whey (whey group, n = 16) or gelatin (gelatin group, n = 11) protein supplement. When matched for total protein by weight, whey protein has 3 times the amount of BCAAs compared with gelatin protein., Results: Postintervention plasma abundances of Ile (gelatin group: 637 ± 18, quantifier ion peak height ÷ 100; whey group: 744 ± 65), Leu (gelatin group: 1210 ± 33; whey group: 1380 ± 79), and Val (gelatin group: 2080 ± 59; whey group: 2510 ± 230) did not differ between treatment groups. BCAAs were significantly correlated with homeostasis model assessment of insulin resistance at baseline (r = 0.52, 0.43, and 0.49 for Leu, Ile, and Val, respectively; all, P < 0.05), but correlations were no longer significant at postintervention. Pro- and Cys-related pathways were found discriminant of whey protein vs. gelatin protein supplementation in multivariate statistical analyses., Conclusions: These findings suggest that BCAA metabolism is, at best, only modestly affected at a whey protein supplementation dose of 20 g/d. Furthermore, the loss of an association between postintervention BCAA and homeostasis model assessment suggests that factors associated with calorie restriction or protein intake affect how plasma BCAAs relate to insulin sensitivity. This trial was registered at clinicaltrials.gov as NCT00739479., (© 2015 American Society for Nutrition.)

Wingless-type MMTV integration site family member (WNT) signaling and WNT-inhibitors have been implicated in regulation of adipogenesis, insulin resistance, pancreatic function, and inflammation. Our goal was to determine serum proteins involved in WNT signaling (WNT5 and WISP2) and WNT inhibition (SFRP4 and SFRP5) as they relate to obesity, serum adipokines, insulin resistance, insulin secretion, and inflammation in humans. Study population comprised 57 insulin resistant women with polycystic ovary syndrome (PCOS) and 27 reference women. In a cross-sectional study, blood samples were obtained at fasting, during oral, and frequently sampled intravenous glucose tolerance tests. Serum WNT5, WISP2, and SFRP4 concentrations did not differ between PCOS vs. reference women. Serum WNT5 correlated inversely with weight both in PCOS and reference women, and correlated directly with insulin response during oral glucose tolerance test in PCOS women. Serum WISP2 correlated directly with fatty acid binding protein 4. Serum SFRP5 did not differ between obese (n=32) vs. nonobese (n=25) PCOS women, but reference women had lower SFRP5 (p<5×10(-6) as compared to both PCOS groups). Serum SFRP5 correlated inversely with IL-1β, TNF-α, cholesterol, and apoprotein B. These findings demonstrated that WNT5 correlated inversely with adiposity and directly with insulin response, and the WNT-inhibitor SFRP5 may be anti-inflammatory. Better understanding of the role of WNT signaling in obesity, insulin resistance, insulin secretion, lipoprotein metabolism, and inflammation is important for prevention and treatment of metabolic syndrome, diabetes and cardiovascular disease., (© Georg Thieme Verlag KG Stuttgart · New York.)

Fat accumulation is associated with the release of many novel adipokines such as retinol-binding protein 4 and fatty acid-binding protein 4. These adipokines have been linked to insulin resistance, metabolic syndrome, type 2 diabetes and cardiovascular disease. Since weight loss is the first step for the treatment of metabolic syndrome, which increases the risks for both type 2 diabetes and cardiovascular disease, we have investigated the effects of weight loss on serum retinol-binding protein 4 and fatty acid-binding protein 4 in obese individuals with this syndrome. Twenty-nine obese female subjects with metabolic syndrome, aged 18-62 years completed a 2-month weight loss diet plan. Data were collected from dual-energy X-ray absorptiometry and indirect calorimetry. Blood was taken at baseline and at 2 months and assayed for adipokines, lipids, and insulin resistance parameters. The change in circulating fatty acid-binding protein 4 levels were inversely correlated with total weight loss (p<0.02) and lean mass loss (p<0.01), but not with fat mass loss. Retinol-binding protein 4 levels did not track with any measure of body composition. Changes in leptin levels were found to correlate with weight loss (p<0.02), fat loss (p<0.03), and lean mass loss (p<0.05). Fatty acid-binding protein 4 levels increased and retinol-binding protein 4 levels did not change during moderate weight loss in obese women with metabolic syndrome; however, several other risk factors for type 2 diabetes and cardiovascular disease did improve with weight loss., (© Georg Thieme Verlag KG Stuttgart · New York.)

Free fatty acid binding protein-4 (FABP4) and retinol binding protein-4 (RBP4) contribute to metabolic syndrome. We investigated serum FABP4 and RBP4 responses to insulin sensitizing and lipid lowering therapies in polycystic ovary syndrome (PCOS). Sixty-two healthy, untreated women with PCOS (age 25.1 ± 3.6 years, BMI: 24.0 ± 4.7 kg/m(2)) were randomized to metformin (n = 24), simvastatin (n = 20) or metformin plus simvastatin (n = 18) for 3 months. Anthropometric measures, fasting blood tests and oral glucose tolerance tests (OGTT) were obtained at the baseline and the end. At the baseline serum FABP4 correlated with obesity (BMI: r = 0.63, p < 0.001), insulin resistance (fasting insulin: r = 0.44, p = 0.0002; QUICKI: r = -0.30, p = 0.02; OGTT-insulin sensitivity index: r = -0.27, p = 0.04), dyslipidemia (HDL: r = -0.26, p = 0.03) and hyperandrogenemia (free-testosterone: r = 0.23, p = 0.03; SHBG: r = -0.28, p = 0.03); while RBP4 correlated with total-cholesterol (r = 0.33, p = 0.009). Multiple regression analysis indicated that t best predictors of serum FABP4 and RBP4 were BMI (β = 1.02, p = 0.0003) and total cholesterol (β = 2326, p = 0.01), respectively. Simvastatin, alone or with metformin did not affect serum FABP4 or RBP4. Serum FABP4 related to the obesity, insulin resistance and inflammation while RBP4 related to lipids. Insulin sensitizing and lipid lowering therapies did not affect FABP4 or RBP4 levels in PCOS.

Objective: Hemoglobin A1c (A1C) ≥5.7% is now accepted as a biomarker for identifying individuals at risk for diabetes. Compared to the general population, women with polycystic ovary syndrome (PCOS) have a higher risk for diabetes. Our goal was to determine what glucose homeostasis abnormalities can be identified by A1C ≥5.7% in women with PCOS., Methods: In a cross-sectional study, nondiabetic women with PCOS (according to the National Institutes of Health [NIH] criteria) were divided into 2 groups based on A1C (<5.7% [n = 23] and ≥5.7% [n = 25]). Oral glucose tolerance tests (OGTT) and frequently sampled intravenous glucose tolerance tests (FS-IVGTT) were conducted, and body composition, cardiovascular risk factors, and sex steroid levels were assessed., Results: Compared to women with A1C <5.7%, those with A1C ≥5.7% were older (35.1 ± 1.1 years vs. 31.1 ± 1.1 years; P = .04), had higher glucose levels at fasting and during OGTT, and had a lower insulin sensitivity index (SI: 2.0 ± 0.2 vs. 4.2 ± 0.6; P = .0195) and disposition index (DI: 1,014 ± 82 vs. 1,901 ± 217; P = .011) during FS-IVGTT. They also had higher triglycerides, high-sensitivity C-reactive protein (hs-CRP), and fatty acid-binding protein 4 (FABP4) levels. There was no difference in serum androgen levels., Conclusion: A1C ≥5.7% identified the subgroup of PCOS patients with higher insulin resistance, inadequate compensatory insulin response, impaired glucose disposition, and increased cardiovascular risk factors. Thus, A1C represents an inexpensive and informative biomarker to identify PCOS patients at risk for metabolic abnormalities.

Objective: The omega-3 polyunsaturated fatty acid (n-3 PUFA) as well as lignan components of flaxseed (FLX) can have beneficial effects. In this 6-week-long, randomized, double-blinded, placebo-controlled study, we investigated the effects of FLX lignans on cardiovascular risk factors., Methods: Thirty-seven subjects (13 men and 24 women, age: 54±7 years, body mass index [BMI]: 29.7±1 kg/m2) consumed nutrition bars with similar macronutrient contents. The fatty acid composition and the lignan contents of the bars differed significantly. Two FLX bars both contained 3.0 g of alpha linolenic acid (ALA: 18:3 n-3) but different amount of lignans (0.15 g vs. 0.41 g)., Results: High-lignan FLX decreased total cholesterol (C) by 12% (p=0.044), LDL-C by 15% (p=0.022), and oxidized (Ox)-LDL by 25% (p=0.035). Regular FLX tended to increase Ox-LDL by 13% (p=0.051). The difference between the effects of high-lignan vs. regular lignan FLX on Ox-LDL was highly significant (p=0.004)., Conclusion: High-lignan FLX has the unique property of decreasing Ox-LDL, which is an independent risk factor for cardiovascular disease.

Insulin resistance is common in women with polycystic ovary syndrome (PCOS). Muscle is the major tissue utilizing glucose while excess adipose tissue relates to insulin resistance. Thus, body composition is likely to be an important regulator of insulin sensitivity. Thirty-nine PCOS patients (age: 29.9±1.0 years; BMI: 33.8±1.2 kg/m(2)) participated in a cross sectional study. Body composition was measured by dual energy x-ray absorptiometry (DEXA). Insulin resistance and secretion were assessed using oral glucose tolerance test (OGTT) and frequently sampled intravenous glucose tolerance test (FS-IVGTT). In contrast with the conventional expectations, lean mass correlated directly (P<.05) with the insulin resistance measure HOMA (r=0.440); and inversely with the insulin sensitivity index QUICKI (r=-0.522) independent of fat mass. In 11 pairs of subjects matched for fat mass (35.6±2.2 and 35.6±2.4 kg) but with discordant lean mass (52.8±1.8 vs 44.4±1.6 kg), those with higher lean mass had a higher glucose response during OGTT (AUC(Glucose); P=.034). In contrast, 17 pairs matched for lean mass (48.7±1.7 and 48.9±1.6 kg) but discordant for fat mass (43.3±2.6 vs 30.3±8.9 kg) showed no differences in insulin resistance parameters. These novel findings indicate that lean mass relates directly to insulin resistance in PCOS., (Published by Elsevier Inc.)

The objective of the study was to compare the effects of essential vs long-chain omega (n)-3 polyunsaturated fatty acids (PUFAs) in polycystic ovary syndrome. In this 6-week, prospective, double-blinded, placebo (soybean oil)-controlled study, 51 completers received 3.5 g n-3 PUFA per day (essential PUFA from flaxseed oil or long-chain PUFA from fish oil). Anthropometric variables, cardiovascular risk factors, and androgens were measured; oral glucose tolerance test (OGTT) and frequently sampled intravenous GTT (IVGTT) were conducted at baseline and 6 weeks. Between-group comparisons showed significant differences in serum triglyceride response (P = .0368), whereas the changes in disposition index also tended to differ (P = .0621). When within-group changes (after vs before intervention) were considered, fish oil and flaxseed oil lowered serum triglyceride (P = .0154 and P = .0176, respectively). Fish oil increased glucose at 120 minutes of OGTT (P = .0355), decreased the Matsuda index (P = .0378), and tended to decrease acute insulin response during IVGTT (P = .0871). Soybean oil increased glucose at 30 (P = .0030) and 60 minutes (P = .0121) and AUC for glucose (P = .0122) during OGTT, tended to decrease acute insulin response during IVGTT (P = .0848), reduced testosterone (P = .0216), and tended to reduce sex hormone-binding globulin (P = .0858). Fasting glucose, insulin, adiponectin, leptin, or high-sensitivity C-reactive protein did not change with any intervention. Long-chain vs essential n-3 PUFA-rich oils have distinct metabolic and endocrine effects in polycystic ovary syndrome; and therefore, they should not be used interchangeably., (Published by Elsevier Inc.)

α-Cyclodextrin (α-CD) is a soluble fiber derived from corn. It has previously been reported that early intervention with Mirafit fbcx, a trademarked name for α-CD, has beneficial effects on weight management in obese individuals with type 2 diabetes, and that it preferentially reduces blood levels of saturated and trans fats in the LDL receptor knockout mice. The current investigation involves overweight but not obese nondiabetic individuals and was intended to confirm the effects of α-CD on both weight management and improving blood lipid levels. Forty-one healthy adults (age: 41.4 ± 13.6 years) participated in this 2-month, double-blinded, crossover study. In 28 compliant participants (8 males and 20 females), when the active phase was compared to the control phase, there were significant decreases in body weight (-0.4 ± 0.2 kg, P < 0.05), serum total cholesterol (mean ± s.e.m., -0.295 ± 0.10 mmol/l, 5.3%, P < 0.02) and low-density lipoprotein (LDL) cholesterol (-0.23 ± 0.11 mmol/l, -6.7%, P < 0.05). Apolipoprotein B (Apo B) (-0.0404 ± 0.02 g/l, -5.6%, P = 0.06) and insulin levels also decreased by 9.5% (-0.16 ± 0.08 pmol/l, P = 0.06) while blood glucose and leptin levels did not change. These results suggest that α-CD exerts its beneficial health effects on body weight and blood lipid profile in healthy nonobese individuals, as previously reported in obese individuals with type 2 diabetes.

Objective: To determine insulin resistance and response in patients with polycystic ovary syndrome (PCOS) and normal glucose tolerance (NGT), impaired fasting glucose (IFG), impaired glucose tolerance, and combined glucose intolerance (CGI)., Research Design and Methods: In this cross-sectional study, 143 patients with PCOS (diagnosed on the basis of National Institutes of Health criteria) underwent oral glucose tolerance testing (OGTT), and 68 patients also had frequently sampled intravenous glucose tolerance tests. Changes in plasma glucose, insulin, cardiovascular risk factors, and androgens were measured., Results: Compared with patients with NGT, those with both IFG and CGI were significantly insulin resistant (homeostasis model assessment 3.3 +/- 0.2 vs. 6.1 +/- 0.9 and 6.4 +/- 0.5, P < 0.0001) and hyperinsulinemic (insulin area under the curve for 120 min 973 +/- 69 vs. 1,470 +/- 197 and 1,461 +/- 172 pmol/l, P < 0.0001). Insulin response was delayed in patients with CGI but not in those with IFG (2-h OGTT, insulin 1,001 +/- 40 vs. 583 +/- 45 pmol/l, P < 0.0001). Compared with the NGT group, the CGI group had a lower disposition index (1,615 +/- 236 vs. 987 +/- 296, P < 0.0234) and adiponectin level (11.1 +/- 1.1 vs. 6.2 +/- 0.8 ng/ml, P < 0.0096). Compared with the insulin-resistant tertile of the NGT group, those with IFG had a reduced insulinogenic index (421 +/- 130 vs. 268 +/- 68, P < 0.05). Compared with the insulin-sensitive tertile of the NGT group, the resistant tertile had higher triglyceride and high-sensitivity C-reactive protein (hs-CRP) and lower HDL cholesterol and sex hormone-binding globulin (SHBG). In the entire population, insulin resistance correlated directly with triglyceride, hs-CRP, and the free androgen index and inversely with SHBG., Conclusions: Patients with PCOS develop IFG and CGI despite having significant hyperinsulinemia. Patients with IFG and CGI exhibit similar insulin resistance but very different insulin response patterns. Increases in cardiac risk factors and free androgen level precede overt glucose intolerance.

Objective: To investigate adrenal steroid regulation in polycystic ovary syndrome., Design: Five-hour oral glucose tolerance test (OGTT) and frequently sampled-intravenous gluclose tolerance test., Setting: University research center., Patient(s): Thirty patients., Intervention(s): None., Main Outcome Measure(s): Anthropometrics, leptin, cortisol, DHEAS, glucose, insulin., Result(s): Morning cortisol correlated with sensitivity index (SI, r = .540), DHEAS correlated inversely with age (r = -.6359), body mass index (BMI, r = -.6199), fat mass (r = -0.630), and leptin (r = -0.5676). Between the second and fourth hour of OGTT, cortisol changes (Delta) exhibited three patterns: I, responders (n = 9, Delta: 10.7 +/- 1.0 microg/dL); II, nonresponders (n = 10, Delta: -3.5 +/- 0.6 microg/dL); III, intermediates (n = 11, Delta: 4.3 +/- 1.0 microg/dL). Compared with nonresponders, responders were more obese (BMI: 37.0 +/- 1.6 vs. 31.7 +/- 1.8 kg/m(2)); had higher leptin (28.9 +/- 1.7 vs. 24.1 +/- 1.1 ng/mL), and lower DHEAS (133 +/- 12 vs. 236 +/- 32 ng/mL), higher glucose at 1 h of OGTT (195 +/- 13 vs. 131 +/- 12 mg/dL), higher area under the curve (AUC)(Glucose) (332 +/- 20 vs. 265 +/- 17 mg/dL), higher AUC(Insulin) (244 +/- 50 vs. 125 +/- 30 muU/mL), and lower nadir glucose (61 +/- 2 vs. 70 +/- 2 mg/dL)., Conclusion(s): Obesity and insulin resistance are associated with lower morning cortisol and DHEAS but increased cortisol and DHEA responses after glucose ingestion. Morning steroid levels may not reflect the day-long exposure., (Published by Elsevier Inc.)

Fatty acid binding protein (FABP) 4 chaperones free fatty acids (FFAs) in the adipocytes during lipolysis. Serum FFA relates to metabolic syndrome, and serum FABP4 is emerging as a novel risk marker. In 36 overweight/obese women, serum FABP4 and FFA were measured hourly during 5-hour oral glucose tolerance test. Insulin resistance was determined using frequently sampled intravenous glucose tolerance test. Serum lipids and inflammation markers were measured at fasting. During oral glucose tolerance test, serum FABP4 decreased by 40%, reaching its nadir at 3 hours (from 45.3 +/- 3.1 to 31.9 +/- 1.6 ng/mL), and stayed below the baseline at 5 hours (35.9 +/- 2.2 ng/mL) (P < .0001 for both, compared with the baseline). Serum FFA decreased by 10-fold, reaching a nadir at 2 hours (from 0.611 +/- 0.033 to 0.067 +/- 0.004 mmol/L), then rebounded to 0.816 +/- 0.035 mmol/L at 5 hours (P < .001 for both, compared with baseline). Both fasting FABP4 and nadir FABP4 correlated with obesity. Nadir FABP4 correlated also with insulin resistance parameters from frequently sampled intravenous glucose tolerance test and with inflammation. Nadir FFA, but not fasting FFA, correlated with the metabolic syndrome parameters. In conclusion, fasting FABP4 related to metabolic risk markers more strongly than fasting FFA. Nadir FABP4 and nadir FFA measured after glucose loading may provide better risk assessment than the fasting values.

Objective: To compare the effects of protein vs. simple sugars on weight loss, body composition, and metabolic and endocrine parameters in polycystic ovary syndrome (PCOS)., Design: A 2-month, free-living, randomized, single-blinded study., Setting: University PCOS clinic., Patient(s): Thirty-three patients with PCOS., Intervention(s): To achieve a final energy reduction of 450 kcal/day, first the daily energy intake was reduced by 700 kcal; then a 240-kcal supplement containing either whey protein or simple sugars was added., Main Outcome Measure(s): Changes in weight, fat mass, fasting glucose and insulin, plasma lipoproteins, and sex steroids., Result(s): Twenty-four subjects (13 in the simple sugars group and 11 in the protein group) completed the study. The protein group lost more weight (-3.3 +/- 0.8 kg vs. -1.1 +/- 0.6 kg) and more fat mass (-3.1 +/- 0.9 kg vs. -0.5 +/- 0.6 kg) and had larger decreases in serum cholesterol (-33.0 +/- 8.4 mg/dL vs. -2.3 +/- 6.8 mg/dL), high-density lipoprotein cholesterol (-4.5 +/- 1.3 mg/dL vs. -0.4 +/- 1.3 mg/dL), and apoprotein B (-20 +/- 5 mg/dL vs. 3 +/- 5 mg/dL)., Conclusion(s): In patients with PCOS, a hypocaloric diet supplemented with protein reduced body weight, fat mass, serum cholesterol, and apoprotein B more than the diet supplemented with simple sugars.

Background: Insulin resistance, infertility, and hirsutism, common characteristics of polycystic ovary syndrome (PCOS), improve with even modest weight loss. Optimal dietary treatment for PCOS is not known., Objective: We compared the effects of acute protein administration with those of glucose challenges on hormones related to obesity and insulin resistance (ie, cortisol and insulin), hirsutism [ie, dehydroepiandosterone (DHEA) and androstenedione], and hunger (ie, ghrelin)., Design: Patients with PCOS (n = 28; aged 26 +/- 2 y) were tested with a 5-h oral-glucose-tolerance test (OGTT) and a euvolemic, euenergetic protein challenge., Results: Glucose ingestion caused larger fluctuations in blood glucose and more hyperinsulinemia than did protein (P < 0.01, overall treatment-by-time interaction). During the protein challenge, cortisol and DHEA declined over 5 h. During OGTT, cortisol and DHEA increased after the third hour and began to show significant divergence from protein from the fourth hour (P

Context: It is important to characterize the biological activity of circulating androgenic steroid hormones during the menopausal transition because these appear to impact the metabolic and cardiovascular health risk factors of women., Objective: The objective of the study was to develop and characterize a cell-based bioassay that measures the androgen receptor-mediated signal transduction in serum., Design: This was a clinically relevant experimental study nested in a sample population of a longitudinal cohort study., Setting: The study was conducted at a university laboratory., Methods: A receptor-mediated luciferase expression bioassay based on HEK 293 cells that were stably cotransfected with plasmids containing the human androgen receptor and luciferase gene was developed. In 49 samples from menstruating women aged 42-52 yr, total testosterone (T) and SHBG concentrations were measured by immunoassay; free T concentrations were calculated from the total T and SHBG concentrations., Results: Mean total T concentration of the sample was 1.15 nm (sd 0.46, range 0.57-3.86 nm). The mean bioactive androgen detected was 1.00 nm (sd 0.24, range 0.53-1.60 nm). Calculated free T (mean 0.0156 nm) was significantly lower than the levels of bioactive androgens measured by receptor-mediated bioassay. There was significant positive correlation between bioactive androgen levels and total T values in young women and polycystic ovarian disorder patients, whereas no correlation was found between the two values in middle-aged women., Conclusions: An androgen receptor-mediated bioassay can provide additional information in the evaluation of total bioactive androgens in midlife women. Our data suggest that levels of circulating SHBG may have a significant impact on the levels of total circulating bioavailable androgens.

Background: Inflammation contributes to atherogenesis. Dietary fats may be proinflammatory., Objective: The objective was to determine whether energy intake modulates the effects of low-fat, high-carbohydrate intakes on inflammatory markers., Design: Twenty-two healthy postmenopausal women with a mean (+/-SD) age of 61 +/- 11 y, who were not receiving hormone replacement therapy, were fed eucaloric diets to reduce their fat intake from 35% to 15% of energy. Next, the women consumed a 15%-fat ad libitum diet under free-living conditions. Serum highly sensitive C-reactive protein, interleukin 6, HDL serum amyloid A, and adiponectin concentrations were measured at the end of the eucaloric and ad libitum low-fat, high-carbohydrate intakes., Results: The eucaloric diet decreased adiponectin from 16.3 +/- 2.1 to 14.2 +/- 2.0 mg/L (P < 0.05) and increased triacylglycerol from 131 +/- 11 to 164 +/- 14 mg/dL (P < 0.01). The ad libitum low-fat diet caused 6 kg weight loss and decreased highly sensitive C-reactive protein from 4.3 +/- 0.6 to 2.5 +/- 0.5 mg/L (P < 0.01), decreased HDL serum amyloid A from 10.3 +/- 1.8 to 5.7 +/- 1.3 mg/L (P < 0.001), increased adiponectin from 14.2 +/- 2.0 to 16.3 +/- 1.7 mg/L (P < 0.05), and decreased triacylglycerol from 164 +/- 14 to 137 +/- 15 mg/dL (P < 0.05)., Conclusion: During the eucaloric phase, the low-fat, high-carbohydrate diet exerted unfavorable effects on the inflammatory markers. In contrast, the ad libitum low-fat, high-carbohydrate intake caused weight loss and affected inflammatory markers favorably. Thus, the energy content of a low-fat, high-carbohydrate diet determines changes in inflammatory markers.

Effects of a polyunsaturated fatty acid (PUFA)-rich diet were investigated in 17 polycystic ovary syndrome (PCOS) patients. After a 3-month habitual diet period, dietary fats were partly replaced with PUFAs for another 3 months. The PUFA-rich diet increased plasma linoleic acid from 28.36 +/- 1.00% to 33.76 +/- 1.08% (P < 0.002) and alpha-linolenic acid from 0.52 +/- 0.03% to 1.06 +/- 0.10% (P < 0.0001). Fasting glucose increased from 76 +/- 3 to 95 +/- 3 mg/dl (4.2 +/- 0.2 to 5.30.2 mmol/liter; P < 0.0001), and the area under the curve for glucose during oral glucose tolerance test increased from 421 +/- 34 to 503 +/- 31 mg/dl (23.4 +/- 1.9 to 27.9 +/- 1.7 mmol/liter; P < 0.001). Plasma insulin did not change either at fasting or during oral glucose tolerance test. Fasting plasma free fatty acids decreased from 0.596 +/- 0.048 to 0.445 +/- 0.058 mg/dl (P = 0.037), and ketone bodies decreased from 9.14 +/- 1.57 to 3.63 +/- 0.62 mg/dl (895 +/- 154 to 356 +/- 61 micromol/liter; P < 0.003). Plasma 15-deoxyprostaglandin J(2) tended to decrease (from 239 +/- 65 to 171 +/- 60 ng/ml; P = 0.053). Plasma testosterone, free testosterone, SHBG, dehydroepiandrosterone sulfate, LH, FSH, and urinary estrogen conjugates did not change. Urinary pregnanediol 3-glucuronide increased from 18.6 +/- 2.2 to 31.0 +/- 5.7 micro g/mg creatinine (P = 0.038). In conclusion, increased dietary PUFA intake can exert significant metabolic and endocrine effects in women with PCOS.

Objectives: To determine whether a very low-fat diet (<15% of energy intake) consumed ad libitum during an 8-month period can achieve weight loss of 5% to 10% of initial body weight while still providing adequate intakes of other essential nutrients., Design: Longitudinal, 8-month, ad libitum, free living, very low-fat diet trial., Subjects: Fifty-four of the sixty-four healthy postmenopausal women recruited completed the entire study (age 59+/-8 years, BMI=29.6+/-6.3). Twenty-four of these women used hormone replacement therapy, thirty women did not., Intervention: Weekly sessions aimed at teaching and reinforcing a very low-fat intake diet for eight months. MAIN: outcome measures Body weight, percent body fat, waist-to-hip ratio, resting energy expenditure, respiratory quotient, and nutrient intakes derived from 7-day food records at the beginning and at 2, 4, 6, and 8 months of the study. Statistical analysis performed Repeated measures analysis of variance and Tukey post hoc analysis were used to analyze significant differences in mean data (P<.05)., Results: Fat intake decreased from 33.2+/-7.5% to 11+/-4% over the 8-month intervention period (P<.00001). Weight loss was 6.0 kg+/- 4.2 kg (P<.000038), an 8% weight change, and decrease in percent body fat of 2.7%+/-0.2% (P< or =.000046). Weight correlated better with the self-reported fat intake (r=0.321, P<.01) than the energy intake (r=0.263, P<.05) at baseline. Fiber intake increased from 16 g+/-0.6 g to 23 g+/-0.2 g (P<.0005). All micronutrient intakes remained at or above preintervention ranges, except for a decrease in vitamin E intake from 8.1 mg+/-4.0 mg to 3.7 mg+/-1.1 mg (P<.0005) on the very low-fat diet and linoleic acid from 6.3%+/-1.5% to 2.5%+/-0.7% (P<.000001) with no significant reduction in linolenic acid. Hormone replacement was not associated with the amount of weight loss., Applications: This study demonstrates that adherence to a very low-fat diet consumed ad libitum causes weight loss in the 5% to 10% range and a reduction of body fat. These reductions, along with the observed decreases in fat intake, are associated with improved health outcomes. Because of the decreased vitamin E and n-3 fatty acid intake, emphasis on foods high in these nutrients may need to be encouraged for those consuming a very low-fat diet.

Background: Epidemiologic studies show an inverse relation between nut consumption and coronary heart disease., Objective: We determined the effects of walnut intake on plasma fatty acids, lipoproteins, and lipoprotein subclasses in patients with combined hyperlipidemia., Design: Participants sequentially adhered to the following diets: 1) a habitual diet (HD), 2) a habitual diet plus walnuts (HD+W), 3) a low-fat diet (LFD), and 4) a low-fat diet plus walnuts (LFD+W)., Results: In 13 postmenopausal women and 5 men ( +/- SD age 60 +/- 8 y), walnut supplementation did not increase body weight despite increased energy intake and the LFD caused weight loss (1.3 +/- 0.5 kg; P < 0.01). When comparing the HD with the HD+W, linoleic acid concentrations increased from 29.94 +/- 1.14% to 36.85 +/- 1.13% and alpha-linolenic acid concentrations increased from 0.78 +/- 0.04% to 1.56 +/- 0.11%. During the LFD+W, plasma total cholesterol concentrations decreased by 0.58 +/- 0.16 mmol/L when compared with the HD and by 0.46 +/- 0.14 mmol/L when compared with the LFD. LDL-cholesterol concentrations decreased by 0.46 +/- 0.15 mmol/L when compared with the LFD. Measurements of lipoprotein subclasses and particle size suggested that walnut supplementation lowered cholesterol preferentially in small LDL (46.1 +/- 1.9% compared with 33.4 +/- 4.3%, HD compared with HD+W, respectively; P < 0.01). HDL-cholesterol concentrations decreased from 1.27 +/- 0.07 mmol/L during the HD to 1.14 +/- 0.07 mmol/L during the HD+W and to 1.11 +/- 0.08 mmol/L during the LFD. The decrease was seen primarily in the large HDL particles., Conclusions: Walnut supplementation may beneficially alter lipid distribution among various lipoprotein subclasses even when total plasma lipids do not change. This may be an additional mechanism underlying the antiatherogenic properties of nut intake.

Background: Low-fat diets can increase plasma triacylglycerol and reduce HDL cholesterol. Changes in energy intake and body weight can influence the lipoprotein response., Objective: We sought to prospectively examine the effects of euenergetic and ad libitum dietary fat restriction on plasma lipoproteins in healthy postmenopausal women., Design: Participants first received a controlled euenergetic diet in which dietary fat was reduced stepwise from 35% to 25% to 15% over 4 mo. Thereafter, participants followed an ad libitum 15%-fat diet for 8 mo; 54 women completed the intervention., Results: During the controlled euenergetic diet, plasma triacylglycerol increased from 1.70 +/- 0.10 to 2.30 +/- 0.16 mmol/L, total cholesterol decreased from 5.87 +/- 0.13 to 5.53 +/- 0. 13 mmol/L, LDL cholesterol decreased from 3.41 +/- 0.10 to 2.87 +/- 0.10 mmol/L, HDL cholesterol decreased from 1.76 +/- 0.08 to 1.50 +/- 0.08 mmol/L, and apolipoprotein (apo) A-I decreased from 5.11 +/- 0.14 to 4.78 +/- 0.14 mmol/L (P < 0.0001 for all changes). Hormone replacement therapy did not affect the relative change in HDL cholesterol. Plasma glucose, insulin, hemoglobin A(1C,) free fatty acid, and apo B concentrations did not change significantly. During the ad libitum 15%-fat diet, participants lost 4.6 +/- 0.4 kg. Plasma triacylglycerol and LDL cholesterol returned to baseline values (1.77 +/- 0.12 and 3.31 +/- 0.08 mmol/L, respectively), whereas HDL cholesterol and apo A-I remained low (1.40 +/- 0.08 and 4.82 +/- 0.18 mmol/L, respectively). HDL cholesterol and apo A-I concentrations stabilized in subjects who were not receiving hormone replacement therapy but continued to decline in women who were receiving hormone therapy., Conclusions: The ad libitum 15%-fat diet resulted in significant weight loss. The euenergetic but not the ad libitum diet caused hypertriacylglycerolemia. HDL cholesterol decreased during both low-fat diets.

Background: Red wine consumption may decrease the risk of coronary heart disease through the actions of its constituent flavonoids. (+)-Catechin is an abundant flavonoid in red wine., Objective: The objective was to determine changes in plasma (+)-catechin concentrations after ingestion of a single, moderate serving of dealcoholized red wine reconstituted with either water (DRW) or water and alcohol (ARW)., Design: Nine subjects (5 men, 4 women) ingested, in random order, 120 mL DRW on one day and 120 mL ARW on another day. Both the DRW and ARW contained 35 mg (121 micromol) free (+)-catechin. Blood samples were collected at 0, 0.5, 1, 2, 3, 4, and 8 h. Plasma was analyzed by gas chromatography-mass spectrometry for (+)-catechin after enzymatic release of sulfate and glucuronide conjugates., Results: Calcium ions were needed to effectively hydrolyze (+)-catechin conjugates in plasma containing EDTA. Neither the ARW or DRW nor sex affected the area under the curve at 8 h, the maximum concentration (c(max)), or the time it took for plasma total (+)-catechin to reach maximum concentration (t(max)). Pooled mean (+/-SEM) values for the ARW and DRW were as follows: area under the curve, 306.1 +/- 29.5 nmol*h/L; c(max), 76.7 +/- 7.5 nmol/L; and t(max), 1.44 +/- 0.13 h. The half-life of (+)-catechin in plasma was significantly less (P = 0.038) after ingestion of the ARW (3.17 h) than after ingestion of the DRW (4.08 h)., Conclusions: Increases in plasma total (+)-catechin concentrations were not significantly different after single moderate servings of either the ARW or DRW. Alcohol in the ARW hastened the elimination of (+)-catechin from the plasma compartment. (+)-Catechin elimination may represent excretion or conversion to methylated derivatives.

Hypertriglyceridemia is an independent risk factor for coronary artery disease (CAD) and is also commonly associated with other coronary risk factors, ie, small, dense low-density lipoprotein (LDL) particles and low plasma levels of high-density lipoprotein cholesterol (HDL-C). Dietary fat restriction is recommended for the prevention of nutrition-related cancers. Low-fat, high-carbohydrate intake can increase plasma triglyceride (TG) and decrease HDL-C. In general, plasma TG levels are inversely related to the particle size of LDL. We investigated the effects of dietary fat restriction on the concentration and particle size of plasma lipoproteins in 14 healthy postmenopausal women (aged 61 +/- 11 years). During a 4-month period of eucaloric controlled feeding, dietary fat was reduced stepwise from a habitual intake of 33% +/- 8% to 23% and then to 14% of daily energy. Changes in the plasma lipid level and particle size of very-low-density lipoprotein (VLDL), LDL, and HDL were determined at the end of each dietary phase. Increasing carbohydrate intake without weight loss was associated with an increase in plasma TG (1.86 +/- 0.30 v 2.47 +/- 0.37 mmol/L) and decreases in total cholesterol (5.82 +/- 0.25 v 5.40 +/- 0.21 mmol/L), LDL-C (3.07 +/- 0.18 v 2.61 +/- 0.21 mmol/L), HDL-C (1.42 +/- 0.1 v 1.24 +/- 0.1 mmol/L), and apolipoprotein (apo) A1 (5.14 +/- 0.25 v 4.61 +/- 0.36 mmol/L), whereas plasma apo B did not change. The particle size of VLDL increased (42.7 +/- 1.4 v 47.0 +/- 0.9 nm). However, there was no change in either LDL (25.1 +/- 0.2 v 25.3 +/- 0.2 nm) or HDL particle size. Although at each level of dietary fat intake LDL particle size correlated inversely with plasma TG and apo B, there was no relationship between the increase in plasma TG and LDL particle size. These results show that hypertriglyceridemia caused by a eucaloric high-carbohydrate intake is not associated with a decrease in LDL particle size. Therefore, carbohydrate-induced hypertriglyceridemia may not have the same atherogenic potential as genetic hypertriglyceridemias.

Frequent coexistence of insulin resistance, central obesity, and hypertriglyceridemia in the same individual suggests an underlying common pathogenesis. Insulin resistance and hypertriglyceridemia can be induced by carbohydrate feeding in rats. Golden Syrian hamsters are believed to be resistant to the metabolic effects of dietary carbohydrates. We investigated the effects of diets containing 60% fructose or sucrose on glucose and lipid metabolism in hamsters, both in the fasting state and during an intravenous glucose tolerance test. Fructose caused obesity (weight after treatment: 131 +/- 7 gm in the control group, 155 +/- 5 gm in the fructose group, 136 +/- 7 gm in sucrose group, p < 0.04). Fructose also reduced glucose disappearance rate (KG: 2.69% +/- 0.39% in the control group, 1.45% +/- 0.18% in the fructose group, p < 0.02). Sucrose caused a marginal decrease in glucose disappearance (KG: 1.93% +/- 0.21%, p = 0.08 vs the control group). Only fructose feeding increased fasting plasma nonesterified fatty acids (0.645 +/- 0.087 mEq/L in the control group, 1.035 +/- 0.083 mEq/L in the fructose group, 0.606 +/- 0.061 mEq/L in the sucrose group, p < 0.002), plasma triglycerides (84 +/- 6 mg/dl in the control group, 270 +/- 65 mg/dl in the fructose group, 94 +/- 16 mg/dl in the sucrose group, p < 0.0002), and liver triglycerides (1.88 +/- 0.38 mg/gm liver weight in the control group, 2.35 =/- 0.24 mg/gm in the fructose group, 1.41 +/- 0.13 mg/gm in the sucrose group, p < 0.04). Previous studies in the rat have suggested that dietary carbohydrates induce insulin resistance by increasing plasma nonesterified fatty acids and triglycerides, which are preferentially used by the muscles. The present report shows that sucrose also can cause some decrease in glucose disappearance in the hamster without causing hypertriglyceridemia or increasing plasma nonesterified fatty acids. Thus other mechanisms may also contribute to the insulin resistance in the hamster. These findings suggest that hamsters provide a good model for investigation of hormonal and nutritional regulation of glucose and lipid metabolism.

Very-low-density lipoproteins (VLDLs) are the major carriers of fasting plasma triglyceride (TG). TG-enriched VLDLs become cholesterol (C)-enriched low-density lipoproteins (LDLs) through hydrolysis facilitated by lipoprotein lipase (LPL). Omega-3 fatty acid (n-3 FA) supplementation may increase LDL-C while decreasing plasma TG in hypertriglyceridemic patients. It has been proposed that n-3 FAs increase LDL-C by promoting production of TG-poor VLDL and accelerating conversion of VLDL to LDL. To study the effects of n-3 FA supplementation on in vivo lipolysis of VLDL directly, we treated 11 hypertriglyceridemic subjects with n-3 FA (3.3 g/d). Each participant was studied three times: at baseline, after a 1-month period of run-in olive oil placebo, and after 1 more month of n-3 FA supplementation. Lipolysis was induced by intravenous infusion of heparin for 2 hours. Plasma samples were obtained every 30 minutes for determination of lipids and apoproteins (apos), separation of individual lipoproteins by fast protein liquid chromatography (FPLC), and measurement of LPL and hepatic TG lipase (HTGL) levels. n-3 FA supplementation decreased fasting plasma TG (2.51 +/- 0.23 v 3.97 +/- 0.46 mmol/L), VLDL-TG (1.08 +/- 0.18 v 2.35 +/- 0.35 mmol/L), and VLDL-C (0.39 +/- 0.05 v 0.72 +/- 0.13 mmol/L) while increasing LDL-C (3.59 +/- 0.21 v 3.00 +/- 0.23 mmol/L) and plasma apo B (3.31 +/- 0.19 v 2.90 +/- 0.17 mmol/L). The absolute rate of TG lipolysis correlated with fasting TG (r = .74, P < .005) and was lower after n-3 FA supplementation (0.11 +/- 0.01 mmol/mL/min) as compared with placebo (0.19 +/- 0.01, P < .01), whereas percent decreases from baseline TG levels were similar at entry onto the study (57.4% +/- 2.5%), after placebo (58.8% +/- 2.7%), and after n-3 FA (52% +/- 3.6%).(ABSTRACT TRUNCATED AT 250 WORDS)

The n-3 fish oils initially attracted the attention of the research community because of their protective actions against coronary artery disease. However, since then, research in this field has contributed to the basic understanding of several aspects of lipid and lipoprotein metabolism.

This study was carried out on 18 albino rats. The control group, consisting of six rats, was fed a normal diet and tap water. The other rats were given a zinc-deficient diet and deionized water. Two weeks later the latter group was again divided into two into smaller groups. The first of these groups was given an given an additional 100 ppm of zinc acetate. From the fifteenth day onwards, the human growth hormone (Nanormon) was injected intra-peritoneally to each group at a dose of 80 micrograms/day for two weeks. At the end of the experiment, it was found that body weights were markedly increased in the control and zinc-added groups compared with the zinc-deficient rats. In the zinc-deficient group, serum zinc, hair zinc levels, alkaline phosphatase activity and serum protein levels were lower than those of the control and zinc-added groups. The zinc-deficient group had narrower tibial epiphyseal growth plates than those of the control group. The count of hypertrophied cells was also less in the zinc-deficient group. Based on these data, our conclusion was that the growth hormone becomes ineffective under conditions of zinc deficiency. This means that zinc deficiency has multidimensional effects on growth hormone activity.