Effects of a Carbohydrate-restricted Diet on Emerging Plasma Markers for Cardiovascular Disease

BACKGROUND : Increasing evidence supports carbohydrate restricted diets (CRD) for weight loss and improvement in traditional markers for cardiovascular disease (CVD); less is known regarding emerging CVD risk factors. We previously reported that a weight loss intervention based on a CRD (% carbohydrate:fat:protein = 13:60:27) led to a mean weight loss of 7.5 kg and a 20% reduction of abdominal fat in 29 overweight men. This group showed reduction in plasma LDL-cholesterol and triglycerides and elevations in HDL-cholesterol as well as reductions in large and medium VLDL particles and increases in LDL particle size. In this study we report on the effect of this intervention with and without fiber supplementation on plasma homocysteine, lipoprotein (a) [Lp(a)], C-reactive protein (CRP), interleukin-6 (IL-6), and tumor necrosis factor alpha (TNF-alpha). METHODS : Twenty nine overweight men [body mass index (BMI) 25-35 kg/m2] aged 20-69 years consumed an ad libitum CRD (% carbohydrate:fat:protein = 13:60:27) including a standard multivitamin every other day for 12 wk. Subjects were matched by age and BMI and randomly assigned to consume 3 g/d of either a soluble fiber supplement (n = 14) or placebo (n = 15). RESULTS : There were no group or interaction (fiber x time) main effects, but significant time effects were observed for several variables. Energy intake was spontaneously reduced (-30.5%). This was accompanied by an increase in protein intake (96.2 +/- 29.8 g/d to 107.3 +/- 29.7 g/d) and methionine intake (2.25 +/- 0.7 g/d, to 2.71 +/- 0.78 g/d; P < 0.001). Trans fatty acid intake was significantly reduced (-38.6%) while dietary folate was unchanged, as was plasma homocysteine. Bodyweight (-7.5 +/- 2.5 kg) was reduced as was plasma Lp(a) (-11.3%). Changes in plasma Lp(a) correlated with reductions in LDL-cholesterol (r = .436, P < 0.05) and fat loss (r = .385, P < 0,05). At wk 12, both CRP (-8.1%) and TNF-alpha (-9.3%) were reduced (P < 0.05) independently of weight loss. IL-6 concentrations were unchanged. CONCLUSION : A diet based on restricting carbohydrates leads to spontaneous caloric reduction and subsequent improvement in emerging markers of CVD in overweight/obese men who are otherwise healthy.

SOCIAL, ATTITUDINAL AND BEHAVIORAL CORRELATES OF WEIGHT CHANGE AMONG MEXICAN AMERICAN WOMEN (OBESITY, DIET, TEXAS)

In industrialized countries the prevalence of obesity among women decreases with increasing socioeconomic status. While this relation has been amply documented, its explanation and implications for other causal factors of obesity has received much less attention. Differences in childbearing patterns, norms and attitudes about fatness, dietary behaviors and physical activity are some of the factors that have been proposed to explain the inverse relation.^ The objectives of this investigation were to (1) examine the associations among social characteristics and weight-related attitudes and behaviors, and (2) examine the relations of these factors to weight change and obesity. Information on social characteristics, weight-related attitudes, dietary behaviors, physical activity and childbearing were collected from 304 Mexican American women aged 19 to 50 living in Starr County, Texas, who were at high risk for developing diabetes. Their weights were recorded both at an initial physical examination and at a follow-up interview one to two and one-half years later, permitting the computation of current Body Mass Index (weight/height('2)) and weight change during the interval for each subject. Path analysis was used to examine direct and indirect relations among the variables.^ The major findings were: (1) After controlling for age, childbearing was not an independent predictor of weight change or Body Mass Index. (2) Neither planned exercise nor total daily physical activity were independent predictors of weight change. (3) Women with higher social characteristics scores reported less frequent meals and less use of calorically dense foods, factors associated with lower risk for weight gain. (4) Dietary intake measures were not significantly related to Body Mass Index. However, dietary behaviors (frequency of meals and snacks, use of high and low caloric density foods, eating restraint and disinhibition of restraint) did explain a significant portion (17.4 percent) of the variance in weight change, indicating the importance of using dynamic measures of weight status in studies of the development of obesity. This study highlights factors amenable to intervention to reverse or to prevent weight gain in this population, and thereby reduce the prevalence of diabetes and its sequelae. ^

Targeting AKT/mTOR Signaling Pathways During Murine Skin Tumor Promotion and the Impact of Dietary Energy Balance Manipulation

The prevalence of obesity has continued to rise over the last several decades in the United States lending to overall increases in risk for chronic diseases including many types of cancer. In contrast, reduction in energy consumption via calorie restriction (CR) has been shown to be a potent inhibitor of carcinogenesis across a broad range of species and tumor types. Previous data has demonstrated differential signaling through Akt and mTOR via the IGF-1R and other growth factor receptors across the diet-induced obesity (DIO)/CR spectrum. Furthermore, mTORC1 is known to be regulated directly via nutrient availability, supporting its role in the link between epithelial carcinogenesis and diet-induced obesity. In an effort to better understand the importance of mTORC1 in the context of both positive and negative energy balance during epithelial carcinogenesis, we have employed the use of specific pharmacological inhibitors, rapamycin (mTORC1 inhibitor) and metformin (AMPK activator) to target mTORC1 or various components of this pathway during skin tumor promotion. Two-stage skin carcinogenesis studies demonstrated that mTORC1 inhibition via rapamycin, metformin or combination treatments greatly inhibited skin tumor development in normal, overweight and obese mice. Furthermore, mechanisms by which these chemopreventive agents may be exerting their anti-tumor effects were explored. In addition, the effect of these compounds on the epidermal proliferative response was analyzed and drastic decreases in epidermal hyperproliferation and hyperplasia were found. Rapamycin also inhibited dermal inflammatory cell infiltration in a dose-dependent manner. Both compounds also blocked or attenuated TPA-induced signaling through epidermal mTORC1 as well as several downstream targets. In addition, inhibition of this pathway by metformin appeared to be, at least in part, dependent on AMPK activation in the skin. Overall, the data indicate that pharmacological strategies targeting this pathway offset the tumor-enhancing effects of DIO and may serve as possible CR mimetics. They suggest that mTORC1 contributes significantly to the process of skin tumor promotion, specifically during dietary energy balance effects. Exploiting the mechanistic information underlying dietary energy balance responsive pathways will help translate decades of research into effective strategies for prevention of epithelial carcinogenesis.

Acceleration of the PanIN Development in Mice Expressing Oncogenic K-Ras Due to a High Fat Diet

Obesity is postulated to be one of the major risk factors for pancreatic cancer, and recently it was indicated that an elevated body mass index (BMI correlates strongly with a decrease in patient survival. Despite the evident relationship, the molecular mechanisms involved are unclear. Oncogenic mutation of K-Ras is found early and is universal in pancreatic cancer. Extensive evidence indicates oncogenic K-Ras is not entirely active and it requires a triggering event to surpass the activity of Ras beyond the threshold necessary for a Ras-inflammation feed-forward loop. We hypothesize that high fat intake induces a persistent low level inflammatory response triggering increased K-Ras activity and that Cox-2 is essential for this inflammatory reaction. To determine this, LSL-K-Ras mice were crossed with Ela-CreER (Acinar-specific) or Pdx-1-Cre (Pancreas-specific) to “knock-in” oncogenic K-Ras. Additionally, these animals were crossed with Cox-2 conditional knockout mice to access the importance of Cox-2 in the inflammatory loop present. The mice were fed isocaloric diets containing 60% energy or 10% energy from fat. We found that a high fat diet increased K-Ras activity, PanIN formation, and fibrotic stroma significantly compared to a control diet. Genetic deletion of Cox-2 prevented high fat diet induced fibrosis and PanIN formation in oncogenic K-Ras expressing mice. Additionally, long term consumption of high fat diet, increased the progression of PanIN lesions leading to invasive cancer and decreased overall survival rate. These findings indicate that a high fat diet can stimulate the activation of oncogenic K-Ras and initiate an inflammatory feed forward loop requiring Cox-2 leading to inflammation, fibrosis, and PanINs. This mechanism could explain the relationship between a high fat diet and elevated risk for pancreatic cancer.

Radiative properties for warm and hot dense matter

We will present calculations of opacities for matter under LTE conditions. Opacities are needed in radiation transport codes to study processes like Inertial Confinement Fusion and plasma amplifiers in X-ray secondary sources. For the calculations we use the code BiGBART, with either a hydrogenic approximation with j-splitting or self-consistent data generated with the atomic physics code FAC. We calculate the atomic structure, oscillator strengths, radiative transition energies, including UTA computations, and photoionization cross-sections. A DCA model determines the configurations considered in the computation of the opacities. The opacities obtained with these two models are compared with experimental measurements.

Equation of state for hot dense matter using a relativistic screened hydrogenic model

The study of matter under conditions of high density, pressure, and temperature is a valuable subject for inertial confinement fusion (ICF), astrophysical phenomena, high-power laser interaction with matter, etc. In all these cases, matter is heated and compressed by strong shocks to high pressures and temperatures, becomes partially or completely ionized via thermal or pressure ionization, and is in the form of dense plasma. The thermodynamics and the hydrodynamics of hot dense plasmas cannot be predicted without the knowledge of the equation of state (EOS) that describes how a material reacts to pressure and how much energy is involved. Therefore, the equation of state often takes the form of pressure and energy as functions of density and temperature. Furthermore, EOS data must be obtained in a timely manner in order to be useful as input in hydrodynamic codes. By this reason, the use of fast, robust and reasonably accurate atomic models, is necessary for computing the EOS of a material.

Equation of State and Opacities for Warm Dense Matter.

We will present recent developments in the calculation of opacity and equation of state tables suitable for including in the radiation hydrodynamic code ARWEN [1] to study processes like ICF or X-ray secondary sources. For these calculations we use the code BiG BART to compute opacities in LTE conditions, with self-consistent data generated with the Flexible Atomic Code (FAC) [2]. Non-LTE effects are approximately taken into account by means of the improved RADIOM model [3], which makes use of existing LTE data tables. We use the screened-hydrogenic model [4] to derive the Equation of State using the population and energy of the levels avaliable from the atomic data

Apparent digestibility and metabolizable energy content of lipid sources in poultry

A trial was conducted to determine the apparent digestibility (ATTD) and AME content of different lipid sources in 21d-old broilers. There were a control diet based on corn and soybean meal without any supplemental fat and 6 additional diets forming a 3x2 factorial with 3 sources of fat (soy oil, SBO; reconstituted monoglyceride oil, RMG; and reconstituted triglyceride oil, RTG) included in the diet (3 or 6%) at expenses (wt:wt) of the basal diet.

Effect of different exercise modalities plus a hypocaloric diet on inflammation markers in overweight patients

Summary Background & aims Inflammation markers (IM) have been associated with the development of chronic diseases. This study compares the effects on IM of three exercise programs combined with a hypocaloric diet. Methods 119 overweight participants (73 women, 46 men) aged 18–50 years were randomised into four treatment groups: strength training (S; n = 30), endurance training (E; n = 30), combined S + E (SE; n = 30), and a diet and physical activity recommendations group (D; n = 29). Energy intake, anthropometric variables (AV), training variables (VO2peak, strength index, dynamometric strength index [DSI]) and plasma IM were recorded at baseline and after 22 weeks of treatment. Results 84 participants completed the study. At 22 weeks, all groups showed a significantly reduced energy intake (P < 0.001) and improved AV (P < 0.001). VO2peak significantly increased in all groups (P < 0.01). DSI increased in the exercise groups only (P < 0.05). Plasma leptin fell significantly (P < 0.001) in the S and E groups, but not significantly in the SE group (P = 0.029) (no significant differences between these groups). Tumour necrosis factor-α (TNF-α), and C-reactive protein (CRP) concentrations decreased in all groups when examined together, but not when examined separately. No significant differences were seen in interleukin-6 (IL-6). Conclusions Combining strength or endurance training with a hypocaloric diet improved AV and reduced plasma leptin concentrations. No differences were seen between groups in terms of TNF-α, IL-6 or CRP reduction. This trial was registered at clinical trials.gov as NCT01116856. http://clinicaltrials.gov/.

Inluence of source and level of glycerin in the diet on growth performance, liver characteristics, and nturient digestibility in broilers from hatching to 21 days of age

The influence of source and level of inclusion of raw glycerin (GLYC) in the diet on growth performance, digestive traits, total tract apparent retention (TTAR), and apparent ileal digestibility of nutrients was studied in broilers from 1 to 21 d of age. There was a control diet based on corn and soybean meal and 8 additional diets that formed a 2 × 4 factorial with 2 sources of GLYC and 4 levels of inclusion (2.5, 5.0, 7.5, and 10%). The GLYC used were obtained from the same original batch of soy oil that was dried under different processing conditions and contained 87.5 or 81.6% glycerol, respectively. Type of processing of the GLYC did not affect any of the variables studied except DM and organic matter retention (P < 0.05) that was higher for the 87.5% glycerol diet. From d 1 to 21, feed conversion ratio (FCR) improved linearly (L, P ≤ 0.01) as the GLYC content of the diet increased, but ADG was not affected. On d 21, the relative weight (% BW) of the liver and the digestive tract increased (L, P < 0.01) as the level of GLYC in the diet increased, but lipid concentration in the liver was not affected. The TTAR of DM and organic matter increased quadratically (Q, P < 0.05) and the AMEn content of the diet increased linearly (L, P < 0.01) with increases in dietary GLYC. Also, the apparent ileal digestibility of DM (L, P < 0.05; Q, P = 0.07) and gross energy (L, P < 0.01) increased as the GLYC content of the diet increased. It is concluded that raw GLYC from the biodiesel industry can be used efficiently, up to 10% of the diet, as a source of energy for broilers from 1 to 21 d of age and that the energy content of well-processed raw GLYC depends primarily on its glycerol content.

Dietary xylanase increases hepatic vitamin E concentration of chickens fed wheat based diet

The study examined the effect of xylanase supplementation on apparent metabolizable energy (AME) and hepatic vitamin E and carotenoids in broiler chickens fed wheat based diets. A total of one hundred forty four male Ross 308 chickens were used in this study. Birds were randomly assigned to 3 dietary treatments (8 cages per treatment of 6 male broilers each) for 14 days from 7 to 21 day old. The control treatment was based on wheat-soyabean meal and was either unsupplemented or supplemented with either 1000 or 2000 xylanase units per kg diet. Orthogonal polynomial contrasts were used to test linear response to dietary xylanase activity. There was a positive linear relationship (P < 0.05) between dietary AME and doses of supplementary xylanase. A linear relationship (P < 0.05) was also observed between dosage of xylanase supplementation and hepatic vitamin E concentration and retention. In conclusion, xylanase supplementation improved dietary AME and increased hepatic vitamin E concentration which may have positive effects on the antioxidative status of the birds.

Partioning of dietary energy of chickens fed maize or wheat-based diets with and without a commercial blend of phytogenic feed additives

The aim of the study was to investigate the effects of a standardized mixture of a commercial blend of phytogenic feed additives containing 5% carvacrol, 3% cinnamaldehyde, and 2% capsicum on utilization of dietary energy and performance in broiler chickens. Four experimental diets were offered to the birds from 7 to 21 d of age. These included 2 basal control diets based on either wheat or maize that contained 215 g CP/kg and 12.13 MJ/kg ME and another 2 diets using the basal control diets supplemented with the plant extracts combination at 100 mg/kg diet. Each diet was fed to 16 individually penned birds following randomization. Dietary plant extracts improved feed intake and weight gain (P < 0.05) and slightly (P < 0.1) improved feed efficiency of birds fed the maize-based diet. Supplementary plant extracts did not change dietary ME (P > 0.05) but improved (P < 0.05) dietary NE by reducing the heat increment (P < 0.05) per kilogram feed intake. Feeding phytogenics improved (P < 0.05) total carcass energy retention and the efficiency of dietary ME for carcass energy retention. The number of interactions between type of diet and supplementary phytogenic feed additive suggest that the chemical composition and the energy to protein ratio of the diet may influence the efficiency of phytogenics when fed to chickens. The experiment showed that although supplementary phytogenic additives did not affect dietary ME, they caused a significant improvement in the utilization of dietary energy for carcass energy retention but this did not always relate to growth performance.

Productive performance of brown-egg laying pullets from hatching to 5 weeks of age as affected by fiber inclusion, feed form, and energy concentration of the diet1

The effects of fiber inclusion, feed form, and energy concentration of the diet on the growth performance of pullets from hatching to 5 wk age were studied in 2 experiments. In Experiment 1, there was a control diet based on cereals and soybean meal, and 6 extra diets that included 2 or 4% of cereal straw, sugar beet pulp (SBP), or sunflower hulls (SFHs) at the expense (wt/wt) of the whole control diet. From hatching to 5 wk age fiber inclusion increased (P < 0.05) ADG and ADFI, and improved (P < 0.05) energy efficiency (EnE; kcal AMEn/g ADG), but body weight (BW) uniformity was not affected. Pullets fed SFH tended to have higher ADG than pullets fed SBP (P = 0.072) with pullets fed straw being intermediate. The feed conversion ratio (FCR) was better (P < 0.05) with 2% than with 4% fiber inclusion. In Experiment 2, 10 diets were arranged as a 2×5 factorial with 2 feed forms (mash vs. crumbles) and 5 levels of AMEn (2,850, 2,900, 2,950, 3,000, and 3,050 kcal/kg). Pullets fed crumbles were heavier and had better FCR than pullets fed mash (P < 0.001). An increase in the energy content of the crumble diets reduced ADFI and improved FCR linearly, but no effects were detected with the mash diets (P < 0.01 and P < 0.05 for the interactions). Feeding crumbles tended to improve BW uniformity at 5 wk age (P = 0.077) but no effects were detected with increases in energy concentration of the diet. In summary, the inclusion of moderate amounts of fiber in the diet improves pullet performance from hatching to 5 wk age. The response of pullets to increases in energy content of the diet depends on feed form with a decrease in feed intake when fed crumbles but no changes when fed mash. Feeding crumbles might be preferred to feeding mash in pullets from hatching to 5 wk age.

Effect of level of fiber of the rearing phase diets on egg production, digestive tract traits, and body measurements of brown egg-laying hens fed diets differing in energy concentration

This research studied the effects of additional fiber in the rearing phase diets on egg production, gastrointestinal tract (GIT) traits, and body measurements of brown egg-laying hens fed diets varying in energy concentration from 17 to 46 wk of age. The experiment was completely randomized with 10 treatments arranged as a 5 × 2 factorial with 5 rearing phase diets and 2 laying phase diets. During the rearing phase, treatments consisted of a control diet based on cereals and soybean meal and 4 additional diets with a combination of 2 fiber sources (cereal straw and sugar beet pulp, SBP) at 2 levels (2 and 4%). During the laying phase, diets differed in energy content (2,650 vs. 2,750 kcal AMEn/kg) but had the same amino acid content per unit of energy. The rearing diet did not affect any production trait except egg production that was lower in birds fed SBP than in birds fed straw (91.6 and 94.1%, respectively; P < 0.05). Laying hens fed the high energy diet had lower feed intake (P < 0.001), better feed conversion (P < 0.01), and greater BW gain (P < 0.05) than hens fed the low energy diet but egg production and egg weight were not affected. At 46 wk of age, none of the GIT traits was affected by previous dietary treatment. At this age, hen BW was positively related with body length (r = 0.500; P < 0.01), tarsus length (r = 0.758; P < 0.001), and body mass index (r = 0.762; P < 0.001) but no effects of type of diet on these traits were detected. In summary, the inclusion of up to 4% of a fiber source in the rearing diets did not affect GIT development of the hens but SBP reduced egg production. An increase in the energy content of the laying phase diet reduced ADFI and improved feed efficiency but did not affect any of the other traits studied.

Electrostatic interaction between helical macromolecules in dense aggregates: An impetus for DNA poly- and meso-morphism

DNA exhibits a surprising multiplicity of structures when it is packed into dense aggregates. It undergoes various polymorphous transitions (e.g., from the B to A form) and mesomorphous transformations (from hexagonal to orthorhombic or monoclinic packing, changes in the mutual alignment of nearest neighbors, etc). In this report we show that such phenomena may have their origin in the specific helical symmetry of the charge distribution on DNA surface. Electrostatic interaction between neighboring DNA molecules exhibits strong dependence on the patterns of molecular surface groups and adsorbed counter-ions. As a result, it is affected by such structural parameters as the helical pitch, groove width, the number of base pairs per helical turn, etc. We derive expressions which relate the energy of electrostatic interaction with these parameters and with the packing variables characterizing the axial and azimuthal alignment between neighboring macromolecules. We show, in particular, that the structural changes upon the B-to-A transition reduce the electrostatic energy by ≈kcal/mol per base pair, at a random adsorption of counter ions. Ion binding into the narrow groove weakens or inverts this effect, stabilizing B-DNA, as it is presumably the case in Li+-DNA assemblies. The packing symmetry and molecular alignment in DNA aggregates are shown to be affected by the patterns of ion binding.