Search

With the approval for use in foods in Japan and the United States, the use of diacylglycerol (DAG) oil in fat-based products may become extensive due to equivalent physicochemical properties to conventional triacylglycerol (TAG) oil. The objective of the present study was to compare the effects of high-dose consumption of DAG oil in humans with that of TAG oil. In a double-blind controlled parallel trial, moderately lean men (n=42) and women (n=39) consumed either DAG or TAG at a dose of approximately 0.5 g/kg body weight/day as part of their diet for 12 weeks. All subjects completing the study tolerated the test oils well and showed no overt effects. Total caloric and fat intake remained constant and showed no significant differences between the groups. There was no significant difference in the occurrence of clinical signs and physical complaints related to test oil consumption. Although some statistically significant effects were reported in hematological and serum chemistry parameters in both DAG and TAG groups, none of these reported changes were considered biologically significant. Overall, this 12-week clinical study revealed no significant or treatment-related adverse effects of DAG oil consumed at a dose of 0.5 g/kg of body weight/day as part of the diet.

The science and policy underlying food labeling and food fortification have evolved over the past 30 years to a point where dietary guidance and nutrition labeling now provide consumers with highly sophisticated, very specific information about links between diet and health. The focus was once on prevention of nutrient deficiency diseases, but today it is on reducing the risk of chronic diseases and health-related conditions. The Nutrition Labeling and Education Act of 1990, with its provisions for authorization of health claims on food labels, has provided a gateway through which a broader realm of nutrition and health information can be made available to consumers. However, the interpretation and implementation of the health claim provisions must evolve, based on a strong foundation of supporting science, so that industry may more readily make health information available to consumers in a form that is easily understood and effectively used in making their dietary choices. We must develop a database to support claims of beneficial effects of food components. We must be assured that the beneficial effects are not outweighed by safety concerns. And we must develop an environment that is conducive to conducting the research to develop these data. This can only be accomplished through the collaborative efforts of industry, academia, consumers and public health agencies.

Glycogen metabolism was studied in the isolated perfused liver of the monkey conceptus at 90% of gestation using an in situ recirculating perfusion system. Net uptake of glucose and galactose and the activities of the enzymes, glycogen synthetase and phosphorylase, were studied in response to varied perfusate composition. Synthetase activity was expressed as %I. the percentage of total synthetase activity in the active form. Perfusate glucose concentrations as high as 700 mg/100 ml did not lead to net glucose uptake of to an increase in the baseline %I synthetase (4 +/- 1, mean +/- SEM). In the presence of 300 mg/100 ml glucose, insulin at 10(-7) M in creased %I to 8 +/- 2, and galactose greater than 75 mg/100 ml increased %I to 8 +/- 1. The combination of galactose, glucose, and insulin increased %I to 40 +/- 5. With this latter combination, synthetase activity was proportional to perfusate glucose concentration above 100 mg/100 ml. Phosphorylase activity was diminished by either galactose or insulin, and phosphorylase activity was lowest in the group receiving galactose, glucose, and insulin. Galactose was taken up by all livers, but net glucose uptake was not observed under any condition; net hexose uptake was observed in perfusions with galactose. Glycogen levels did not vary significantly with varied perfusate composition during the 30-min perfusion periods.

With heat treatment (20 degrees C for 30 min), the glucocorticoid-receptor complex becomes 'activated' and undergoes an increase in affinity for DNA. A two-stage procedure was used to separate sequentially the rat liver glucocorticoid-receptor complex from proteins with high and low affinity for DNA. DNA-cellulose column chromatography of unheated cytosol resulted in the retention of DNA-binding proteins, but not the unactivated receptor complex. Heat treatment of the column eluate resulted in increased affinity of the receptor complex to DNA, and chromatography on DNA-cellulose then yielded receptor complex free from proteins with low affinity for DNA. Removal of DNA-binding proteins during the first chromatographic step was critically dependent on ionic conditions and the ratio of cytosol chromatographed to DNA-cellulose. A purification of 11000-fold (85% yield) was achieved by this procedure. The partially purified receptor complex was taken up by rat liver nuclei.

Near term fetal monkey livers were perfused with a closed recirculating system and a defined perfusion medium. Livers from normal fetal animals were able to release glucose rapidly into the perfusate when they were exposed to glucagon, cyclic AMP, or an aglycemic perfusate, but they did not remove glucose rapidly from the perfusate, synthesize glycogen, or activate liver glycogen synthetase in response to hyperglycemia (Figs. 1,2, and 3; Table 1). Insulin decreased glucose mobilization in response to aglycemia, but did not stimulate glucose uptake during hyperglycemia; insulin activated glycogen synthetase (Table 1; Figs. 1 and 3). Livers from fetuses of streptozotocin-treated mothers and livers from 2-week-old neonates released more glucose into the perfusate in response to aglycemia then did livers from normal fetal monkeys (Fig. 4). These observations support the possibility that neonatal monkey liver is capable of rapidly mobilizing glucose during periods of hypoglycemia but is unable to take up glucose and store glycogen rapidly during periods of hyperglycemia.

Partially purified rabbit skeletal muscle phosphorylase phosphatase (EC 3.1.3.17; phosphoprotein phosphohydrolase) was inactivated when it was incubated with exogenous cyclic AMP-dependent protein kinase (EC 2.7.1.37; ATP:protein phosphotransferase), cyclic AMP, and ATP-Mg. Subsequent separation of the phosphatase by acrylamide gel electrophoresis or sucrose density centrifugation resulted in reactivation of the enzyme. The phosphatase decreased in molecular weight from approximately 70,000 to 52,000, and a phosphorylated inhibitor with molecular weight of 26,000 was found. Reactivation of phosphatase also occurred when it was incubated with MnCl2 or trypsin. The inhibitor was effective at less than 10(-8) M and was relatively heat stable. Its activity was destroyed by tryptic digestion and by dephosphorylation by a Mn-stimulated phosphatase. These observations support the possibility that phosphorylase phosphatase activity is controlled by cyclic AMP-dependent protein kinase and a Mn-stimulated phosphatase by a reaction involving phosphorylation and dephosphorylation of a protein phosphatase inhibitor.

A critical review composed of two parts: estimates of present levels of sugars intake and of recent trends in nutritive carbohydrate sweetener content of the food supply and a review of recent scientific literature addressing potentially adverse health effects associated with sugars consumption. The review contains an executive summary, an appendix with 75 tables summarizing the estimation of sugars intake of U.S. population groups, and over one thousand citations.

In fetal rat liver in utero, an increase in glycogen and the glycogen synthetic enzyme glycogen synthetase (EC 2.4.1.11) occurs between gestational days 17 and 19. We used an organ culture system for finding the stimulus for increased enzyme activity and defining the relationship of this increase to glycogen synthesis. In fetal-liver explants from an earlier period (gestational day 16), hydrocortisone causes an elevation in total glycogen synthetase activity. This effect, which can be blocked by actinomycin D, is strikingly similar in time course and magnitude to the normal increase in utero. However, in order for glycogen synthesis to proceed after hydrocortisone increases glycogen synthetase levels, insulin is required. Unlike hydrocortisone, insulin does not increase total glycogen synthetase; it appears to act by converting the b or phospho form of synthetase to the a or dephospho form. Insulin alone does not stimulate glycogen synthesis in explants from 16-day fetal liver, although no defect in insulin binding was demonstrable. These findings support the hypothesis that the increase in liver-glycogen synthesis during the last trimester requires glucocorticoids for the developmental induction of glycogen synthetase and insulin for activation of the enzyme.

Administration of adrenaline to an isolated rat hindlimb preparation rapidly decreased muscle phosphorylase phosphatase (EC 3.1.3.17) activity and increased heat-stable and trypsin-labile phosphatase inhibitor activity. This was associated with increased tissue cyclic AMP concentrations, phosphorylase (EC 2.4.1.1) activation and glycogen synthase (EC 2.4.1.11) inactivation.

Two heat-stable and trypsin-labile inhibitors of phosphorylase phosphatase, designated inhibitor-1 and inhibitor-2, were partially purified from extracts of rabbit skeletal muscle by heating and coloumn chromatography using DEAE-dellulose and Bio-gel P-60. Inhibitor-1 exists in an active phosphorylated form and an inactive dephosphorylated form. The interconversion of phosphorylated inhibitor-1 and dephosphorylated inhibitor-1 is mediated by protein kinase dependent on adenosine 3':5'-monophosphate (cyclic AMP) and a Mn2+-stimulated phosphoprotein phosphatase. Inhibitory activity of inhibitor-2 is not influenced by treatment with either the kinase or the Mn2+-stimulated phosphatase. The molecular weights of inhibitor-1 and inhibitor-2 estimated by sodium dodecylsulfate-polyacrylamide gel electrophoresis are 26000 and 33000 respectively. Both inhibitor-1 and inhibitor-2 inhibit phosphorylase phosphatase by a mechanism which appears to be non-competitive with respect to the substrate phosphorylase a. Inhibitor fractions at early stages of purification also inhibit cyclic-AMP-dependent histone phosphorylation, but this kinase inhibitory activity resides with a protein moiety which is separable from inhibitor-1 and inhibitor-2.

Sharp increases in the concentration of chromium in plasma were found in five subjects with normal glucose utilization after administration of glucose by mouth. This rise was not observed in two diabetics when glucose tolerance was impaired; however, it appeared when glucose tolerance was improved and when trace amounts of trivalent chromium were given as a dietary supple-ment. The source of chromium which became elevated was most likely an internal pool. Possibly there is a relation between chromium and insulin function.

Chromium(III) is extensively used as a supplement for muscle development and the treatment of diabetes mellitus. However, its mode of action, essentiality, and physiological/pharmacological effects have been a subject of scientific debate for over half a century owing to the failure in identifying the molecular targets of Cr(III). Herein, by integrating fluorescence imaging with a proteomic approach, we visualized the Cr(III) proteome being mainly localized in the mitochondria, and subsequently identified and validated eight Cr(III)-binding proteins, which are predominately associated with ATP synthesis. We show that Cr(III) binds to ATP synthase at its beta subunit via the catalytic residues of Thr213/Glu242 and the nucleotide in the active site. Such a binding suppresses ATP synthase activity, leading to the activation of AMPK, improving glucose metabolism, and rescuing mitochondria from hyperglycaemia-induced fragmentation. The mode of action of Cr(III) in cells also holds true in type II diabetic male mice. Through this study, we resolve the long-standing question of how Cr(III) ameliorates hyperglycaemia stress at the molecular level, opening a new horizon for further exploration of the pharmacological effects of Cr(III). Despite common use as a diabetes mellitus supplement, chromium(III)'s pharmacological effects remain unknown. We identified the Cr(III)-proteome in cells with a metalloproteomic approach and uncovered ATP synthase as a vital target to relieve hyperglycaemia stress. [ABSTRACT FROM AUTHOR]

Following a request from the European Commission, EFSA was asked to deliver a scientific opinion on the safety and efficacy of Availa®Cr (active compound: chromium chelate of DL-methionine) as a feed additive for dairy cows. The EFSA Panel on Additives and Products or Substances used in Animal Feed (FEEDAP) Panel was assigned to this mandate. The tolerance study did not show adverse effects with respect to body weight, milk yield, haematology and blood biochemistry up to the 10-fold overdose of chromium from Availa®Cr; however, owing to deficiencies in design and reporting of the study, it provided only supportive evidence on the safety of the additive. A safe level for dairy cows could be derived from a toxicological study with laboratory rodents. Taking all together, the FEEDAP Panel considers the maximum recommended use level (8 mg Cr from Availa®Cr/cow per day; about 0.4 mg Cr/kg complete feed) as safe. Chromium DL-Met shows a genotoxic activity in vitro that is not expressed in vivo after systemic exposure; although no data on genotoxicity at the site of contact are available, the Panel notes that chromium(III) is not carcinogenic and concludes that chromium DL-Met is unlikely to pose a carcinogenic risk at levels occurring in the diet. The use of Availa®Cr in feed of dairy cows up to the recommended supplementation level would not measurably increase consumer exposure to chromium(III), and therefore is safe for consumers. The additive poses a risk to users by inhalation, it is not an irritant to skin and eyes and should be considered a sensitiser. The use of the additive is not expected to pose a risk to the environment. Since only one study could be considered for the efficacy assessment, and three studies are required, the FEEDAP Panel cannot conclude on the efficacy of Availa®Cr for dairy cows. [ABSTRACT FROM AUTHOR]

Earlier studies have shown that estrogen possess protective function against the development of pathological cardiac hypertrophy. However, the molecular mechanisms of estrogens (E2) protective effect are poorly understood. Additionally, abnormal activation of β-adrenergic signaling have been implicated in the development of pathological cardiac remodeling. However, the role of serine/threonine protein phosphatase 1 (PP1) in pathological cardiac remodeling under the influence of β-adrenergic signaling have been sparsely investigated. In this study, we assessed the downstream effects of abnormal activation of PP1 upon isoproterenol (ISO) induced pathological cardiac changes. We found that pre-treatment of 17β-estradiol (E2), tet-on estrogen receptor-α, or both significantly inhibited ISO-induced increase in cell size, hypertrophy marker gene expression and cytosolic calcium accumulation in H9c2 cells. Additionally, treatment with estrogen receptor inhibitor (ICI) reversed those effects, implicating role of E2 in inhibiting pathological cardiac remodeling. However, specific inhibition of ERα using melatonin, reduced ISO-induced PP1c expression and enhanced the level of ser-16 phosphorylated phospholamban (PLB), responsible for regulation of sarcoplasmic reticulum Ca2+-ATPase (SERCA) activity. Furthermore, hypertrophic effect caused by overexpression of PP1cα was reduced by treatment with specific inhibitor of ERα. Collectively, we found that estrogen and estrogen receptor-α have protective effect against pathological cardiac changes by suppressing PP1 expression and its downstream signaling pathway, which further needs to be elucidated. [ABSTRACT FROM AUTHOR]

Purpose: The size of polymeric nanoparticles is considered as an effective factor in cancer therapy due to enterance into tumor tissue via the EPR effect. The purpose of this work was to investigate the effective parameters on poly(lactic-co-glycolic acid)-paclitaxel (PLGA - PTX) nanoparticles size. Methods: We prepared PLGA-PTX nanoparticles via single emulsion and precipitation methods with variable paremeters including drug concentration, aqueous to organic phase volume ratio, polymer concentration, sonication time and PVA concentration. Results: PLGA-PTX nanoparticles were characterized by dynamic light scattering (DLS) and scanning electron microscopy (SEM). The results exhibited that the diameter of nanoparticles enhanced with increasing drug, polymer and PVA concentrations whereas organic to aqueous phase volume ratio and sonication time required to the optimization for a given size. Conclusion: The precipitation method provides smaller nanoparticles compared to emulsion one. Variable parameters including drug concentration, aqueous to organic phase volume ratio, polymer concentration, sonication time and PVA concentration affect diameter of nanoparticles. [ABSTRACT FROM AUTHOR]

Background: The primary cilium is an extension of the cell membrane that encloses a microtubule-based axoneme. Primary cilia are essential for transmission of environmental cues that determine cell fate. Disruption of primary cilia function is the molecular basis of numerous developmental disorders. Despite their biological importance, the mechanisms governing their assembly and disassembly are just beginning to be understood. Cilia growth and disassembly are essential events when cells exit and reenter into the cell cycle. The kinases never in mitosiskinase 2 (Nek2) and Aurora A (AurA) act to depolymerize cilia when cells reenter the cell cycle from GO. Results: Coexpression of either kinase with its kinase dead companion [AurA with kinase dead Nek2 (Nek2 KD) or Nek2 with kinase dead AurA (AurA KD)] had different effects on cilia depending on whether cilia are growing or shortening. AurA and Nek2 are individually able to shorten cilia when cilia are growing but both are required when cilia are being absorbed. The depolymerizing activity of each kinase is increased when coexpressed with the kinase dead version of the other kinase but only when cilia are assembling. Additionally, the two kinases act additively when cilia are assembling but not disassembling. Inhibition of AurA increases cilia number while inhibition of Nek2 significantly stimulates cilia length. The complex functional relationship between the two kinases reflects their physical interaction. Further, we identify a role for a PP1 binding protein, PPP1R42, in inhibiting Nek2 and increasing ciliation of ARPE-19 cells. Conclusion: We have uncovered a novel functional interaction between Nek2 and AurA that is dependent on the growth state of cilia. This differential interdependence reflects opposing regulation when cilia are growing or shortening. In addition to interaction between the kinases to regulate ciliation, the PP1 binding protein PPP1R42 directly inhibits Nek2 independent of PP1 indicating another level of regulation of this kinase. In summary, we demonstrate a complex interplay between Nek2 and AurA kinases in regulation of ciliation in ARPE-19 cells. [ABSTRACT FROM AUTHOR]

Background: The blood fluke, Schistosoma japonicum still causes severe disease in China, the Philippines and Indonesia. Although there have been some studies the molecular epidemiology of this persistent and harmful parasite, few have explored the possibility and implications of selection in S. japonicum populations. Methods: We analyzed diversity and looked for evidence of selection at three nuclear genes (SjIpp2, SjFabp and SjT22.6) in 13 S. japonicum populations. Results: SjT22.6 was found to exhibit high nucleotide diversity and was under positive selection in the mountainous region of mainland China. As a tegumental protein, its secondary and tertiary structure differed between S. japonicum strains from the mountainous and lakes regions. In contrast, SjIpp2 and SjFabp had relatively low levels of nucleotide diversity and did not show significant departure from neutrality. Conclusions: As a tegument-associated antigen-encoding gene of S. japonicum, SjT22.6 has high nucleotide diversity and appears to be under positive selection in the mountainous region of mainland China [ABSTRACT FROM AUTHOR]

In humans perturbations of centriole number are associated with tumorigenesis and microcephaly, therefore appropriate regulation of centriole duplication is critical. The C. elegans homolog of Plk4, ZYG-1, is required for centriole duplication, but our understanding of how ZYG-1 levels are regulated remains incomplete. We have identified the two PP1 orthologs, GSP-1 and GSP-2, and their regulators I-2SZY-2 and SDS-22 as key regulators of ZYG-1 protein levels. We find that down-regulation of PP1 activity either directly, or by mutation of szy-2 or sds-22 can rescue the loss of centriole duplication associated with a zyg-1 hypomorphic allele. Suppression is achieved through an increase in ZYG-1 levels, and our data indicate that PP1 normally regulates ZYG-1 through a post-translational mechanism. While moderate inhibition of PP1 activity can restore centriole duplication to a zyg-1 mutant, strong inhibition of PP1 in a wild-type background leads to centriole amplification via the production of more than one daughter centriole. Our results thus define a new pathway that limits the number of daughter centrioles produced each cycle. [ABSTRACT FROM AUTHOR]

Background/objectives: Epidemiological studies suggest a link between chromium (Cr) status and cardiovascular disease. Increased urinary excretion of Cr was reported in subjects with diabetes compared with non-diabetic controls and those with non-diabetic insulin resistance. Epigenetic alterations have been linked to the presence of Cr, and microRNA (miRNA) expression has been implicated in the pathogenesis of metabolic diseases and cardiovascular diseases (CVDs). We investigated the association between Cr excretion and miRNA expression in leukocytes from obese subjects. We also examined the relationship between altered miRNA expression and selected clinical parameters to further investigate mechanisms linking Cr to metabolic diseases and CVDs.Subjects/methods: We analyzed urinary Cr in 90 Italian subjects using inductively coupled plasma-mass spectrometry. Peripheral blood miRNA levels were screened with TaqMan Low-Density Array Human MicroRNA A. Cr level-associated expression of miRNAs was detected with multivariate regression analyses, and the top 10 candidate miRNAs were selected for validation. We also used multivariate regression analyses to assess possible associations between validated miRNAs and glycated hemoglobin (A1c) and blood pressure (BP). The validated miRNAs were further investigated by functional analysis with Ingenuity Pathway Analysis software.Results: Urinary Cr levels (mean: 0.35 μg/l; s.d.=0.24) ranged from 0.05 to 1.27 μg/l. In the screening phase, 43 miRNAs were negatively associated with Cr. Of the top 10 miRNAs selected for validation, nine (miR-451, miR-301, miR-15b, miR-21, miR-26a, miR-362-3p, miR-182, miR-183 and miR-486-3p) were downregulated in association with Cr (P-false discovery rate (FDR)<0.10). miR-451 expression was associated with A1c (β=-0.06; P=0.0416), whereas miR-486-3p expression was associated both with diastolic (β=2.1; P=0.004) and systolic BP (β=3.3; P=0.003).Conclusions: These results indicate that miR-451 and miR-486-3p are involved in the link between Cr levels and metabolic diseases and CVDs. [ABSTRACT FROM AUTHOR]

Objective: The contribution of subsidized food commodities to total food consumption is unknown. We estimated the proportion of individual energy intake from food commodities receiving the largest subsidies from 1995 to 2010 (corn, soyabeans, wheat, rice, sorghum, dairy and livestock).Design: Integrating information from three federal databases (MyPyramid Equivalents, Food Intakes Converted to Retail Commodities, and What We Eat in America) with data from the 2001-2006 National Health and Nutrition Examination Surveys, we computed a Subsidy Score representing the percentage of total energy intake from subsidized commodities. We examined the score's distribution and the probability of having a 'high' (≥70th percentile) v. 'low' (≤30th percentile) score, across the population and subgroups, using multivariate logistic regression.Setting: Community-dwelling adults in the USA.Subjects: Participants (n 11 811) aged 18-64 years.Results: Median Subsidy Score was 56·7 % (interquartile range 47·2-65·4 %). Younger, less educated, poorer, and Mexican Americans had higher scores. After controlling for covariates, age, education and income remained independently associated with the score: compared with individuals aged 55-64 years, individuals aged 18-24 years had a 50 % higher probability of having a high score (P<0·0001). Individuals reporting less than high-school education had 21 % higher probability of having a high score than individuals reporting college completion or higher (P=0·003); individuals in the lowest tertile of income had an 11 % higher probability of having a high score compared with individuals in the highest tertile (P=0·02).Conclusions: Over 50 % of energy in US diets is derived from federally subsidized commodities. [ABSTRACT FROM AUTHOR]

Objective: The obesigenic and related health effects of caloric sweeteners are subjects of much current research. Consumers can properly adjust their diets to conform to nutritional recommendations only if the sugars composition of foods and beverages is accurately measured and reported, a matter of recent concern. We tested the hypothesis that high-fructose corn syrup (HFCS) used in commercial carbonated beverages conforms to commonly assumed fructose percentages and industry technical specifications, and fulfills beverage product label regulations and Food Chemicals Codex-stipulated standards.Design: A high-pressure liquid chromatography method was developed and verified for analysis of sugars in carbonated beverages sweetened with HFCS-55. The method was used to measure percent fructose in three carbonated beverage categories. Method verification was demonstrated by acceptable linearity (R(2)>0.99), accuracy (94-104% recovery) and precision (RSD < 2%).Result: Fructose comprised 55.58% of total sugars (95% confidence interval 55.51-55.65%), based on 160 total measurements by 2 independent laboratories of 80 randomly selected carbonated beverages sweetened with HFCS-55. The difference in fructose measurements between laboratories was significant but small (0.1%), and lacked relevance. Differences in fructose by product category or by product age were not statistically significant. Total sugars content of carbonated beverages showed close agreement within product categories (95% confidence interval = 0.01-0.54%).Conclusions: Using verified analytical methodology for HFCS-sweetened carbonated beverages, this study confirmed the hypothesis that fructose as a percentage of total sugars is in close agreement with published specifications in industry technical data sheets, published literature values and governmental standards and requirements. Furthermore, total sugars content of commercial beverages is consistent with common industry practices for canned and bottled products and met the US Federal requirements for nutritional labeling and nutrient claims. Prior concerns about composition were likely owing to use of improper and unverified methodology. [ABSTRACT FROM AUTHOR]

Following a request from the European Commission, the Panel on Dietetic Products, Nutrition and Allergies (NDA) considered the evidence for setting Dietary Reference Values for chromium. Trivalent chromium (Cr(III)) has been postulated to be necessary for the efficacy of insulin in regulating the metabolism of carbohydrates, lipids and proteins. However, the mechanism(s) for these roles and the essential function of Cr(III) in metabolism have not been substantiated. The criteria for the essentiality of a trace element were considered. It was noted that attempts to create chromium deficiency in animal models have not produced consistent results, and that there is no evidence of essentiality of Cr(III) in animal nutrition. Evaluating the possibility of Cr(III) as an essential element for humans, the evidence from reported improvements associated with chromium supplementation in patients on total parenteral nutrition was considered to be the most convincing, but overall data do not provide sufficient information on the reversibility of the possible deficiencies and the nature of any dose-response curve in order to identify a dietary requirement for humans. The Panel concludes that no Average Requirement and no Population Reference Intake for chromium can be defined. Several studies assessed the effect of chromium supplementation on glucose and/or lipid metabolism. In the only study for which information on total chromium intake was available, there was no difference in parameters of glucose metabolism of normoglycaemic subjects between the placebo and chromium-supplemented periods. The Panel considered that there is no evidence of beneficial effects associated with chromium intake in healthy subjects. The Panel concluded that the setting of an Adequate Intake for chromium is also not appropriate. [ABSTRACT FROM AUTHOR]

EFSA received a request from the Hellenic Food Authority for a scientific opinion on estimation of the risk to human health from the presence of chromium (Cr) in food, particularly in vegetables, and Cr(VI) in bottled water. The CONTAM Panel derived a TDI of 0.3 mg/kg b.w. per day for Cr(III) from the lowest NOAEL identified in an NTP chronic oral toxicity study in rats. Under the assumption that all chromium in food is Cr(III), the mean and 95th percentile dietary exposure across all age groups were well below the TDI and therefore does not raise concerns for public health. In the case of drinking water, the Panel considered all chromium in water as Cr(VI). For non-neoplastic effects the lowest BMDL10 for diffuse epithelial hyperplasia of duodenum in female mice and the lowest BMDL05 for haematotoxicity in male rats in a 2-year NTP study were selected as reference points. The MOEs indicate that for non-neoplastic effects the current exposure levels to Cr(VI) via drinking water are of no concern for public health. For neoplastic effects, the CONTAM Panel selected a lowest BMDL10 for combined adenomas and carcinomas of the mouse small intestine as the reference point. Overall, the calculated MOEs indicate low concern regarding Cr(VI) intake via drinking water (water intended for human consumption and natural mineral waters) for all age groups when considering the mean chronic exposure values with the exception of infants at the upper bound (UB) exposure estimates. MOEs below 10 000 were calculated at the UB 95th percentile exposure estimates, particularly for 'Infants', 'Toddlers' and 'Other children', which were highly influenced by the relatively high occurrence values under the UB assumption. To improve the risk assessment, there is a need for data on the content of Cr(III) and Cr(VI) in food and drinking water. [ABSTRACT FROM AUTHOR]

The complexity of heart physiology has delayed the implementation of efficient, feasible, and safe therapies to fight against heart diseases for many years. As knowledge of the precise mechanisms governing cardiac hypertrophy and heart failure development increases, the availability of new therapeutic alternatives also grows. Since the cardiomyocyte physiology deeply depends on the correct calcium handling, many efforts to describe accurately the excitation-contraction coupling process in the heart and the proteins involved have been made. Among the proteins participating in calcium handling, sarco/endoplasmic reticulum Ca2+ adenosine triphosphatase-2a (SERCA2a), whose expression and function is decreased in heart failure, stands out because of its critical role regulating Ca2+ concentration in the cardiomyocyte. The importance of SERCA2a has been reflected in numerous studies aimed to describe its expression and function. Recently, gene therapy to deliver SERCA2a has shown promising results in human clinical trials. This paper reviews the current literature knowledge exploring diverse approaches to rescue SERCA2a expression in heart failure. It also discusses some data suggesting other possible therapies that could improve SERCA2a expression and function in cardiac diseases. [ABSTRACT FROM AUTHOR]

Impaired sarcoplasmic reticulum calcium cycling and depressed contractility are key characteristics in heart failure. Defects in sarcoplasmic reticulum function are characterized by decreased SERCA2a Ca-transport that is partially attributable to dephosphorylation of its regulator phospholamban by increased protein phosphatase 1 activity. Inhibition of protein phosphatase 1 through activation of its endogenous inhibitor-1 has been shown to enhance cardiac Ca-handling and contractility as well as protect from pathological stress remodeling in young mice. In this study, we assessed the long-term effects of inducible expression of constitutively active inhibitor-1 in the adult heart and followed function and remodeling through the aging process, up to 20 months. Mice with inhibitor-1 had normal survival and similar function to WTs. There was no overt remodeling as evidenced by measures of left ventricular end-systolic and diastolic diameters and posterior wall dimensions, heart weight to tibia length ratio, and histology. Higher phosphorylation of phospholamban at both Ser16 and Thr17 was maintained in aged hearts with active inhibitor-1, potentially offsetting the effects of elevated Ser2815-phosphorylation in ryanodine receptor, as there were no increases in arrhythmias under stress conditions in 20-month old mice. Furthermore, long-term expression of active inhibitor-1 via recombinant adeno-associated virus type 9 gene transfer in rats with pressure-overload induced heart failure improved function and prevented remodeling, associated with increased phosphorylation of phospholamban at Ser16 and Thr17. Thus, chronic inhibition of protein phosphatase 1, through increases in active inhibitor-1, does not accelerate age-related cardiomyopathy and gene transfer of this molecule in vivo improves function and halts remodeling in the long term. [ABSTRACT FROM AUTHOR]

: Maira Bes-Rastrollo and colleagues examine whether financial conflicts of interest are likely to bias conclusions from systematic reviews that investigate the relationship between sugar-sweetened beverages and weight gain or obesity. Please see later in the article for the Editors' Summary [ABSTRACT FROM AUTHOR]

Background: Obesity rates in the United States have risen consistently over the last four decades, increasing from about 13% of the population in 1970 to more than 34% in 2009. Dietary fructose has been blamed as a possible contributor to the obesity increase, although the consumption pattern of fructose and other key nutrients during this 40 year period remains a topic of debate. Therefore, we analyzed the USDA Loss-Adjusted Food Availability Database in combination with the USDA Nutrient Database for Standard Reference (Release 24) to determine whether fructose consumption in the US has increased sufficiently to be a casual factor in the rise in obesity prevalence. Methods: Per capita loss-adjusted food availability data for 132 individual food items were compiled and analyzed. Nutrient profiles for each of these foods were used to determine the availability of energy as well as macronutrients and monosaccharides during the years 1970-2009. The percent change in energy from food groups and individual nutrients was determined by using the year 1970 as the baseline and area-under-the-curve analysis of food trends. Results: Our findings indicate that during this 40 year period the percent change in total energy availability increased 10.7%, but that the net change in total fructose availability was 0%. Energy available from total glucose (from all digestible food sources) increased 13.0%. Furthermore, glucose availability was more than 3-times greater than fructose. Energy available from protein, carbohydrate and fat increased 4.7%, 9.8% and 14.6%, respectively. Conclusions: These data suggest that total fructose availability in the US did not increase between 1970 and 2009 and, thus, was unlikely to have been a unique causal factor in the increased obesity prevalence. We conclude that increased total energy intake, due to increased availability of foods providing glucose (primarily as starch in grains) and fat, to be a significant contributor to increased obesity in the US. [ABSTRACT FROM AUTHOR]

Background: It is clear that the coordinated and reciprocal actions of kinases and phosphatases are fundamental in the regulation of development and growth of the malaria parasite. Protein Phosphatase type 1 is a key enzyme playing diverse and essential roles in cell survival. Its dephosphorylation activity/specificity is governed by the interaction of its catalytic subunit (PP1c) with regulatory proteins. Among these, inhibitor-2 (I2) is one of the most evolutionarily ancient PP1 regulators. In vivo studies in various organisms revealed a defect in chromosome segregation and cell cycle progression when the function of I2 is blocked. Results: In this report, we present evidence that Plasmodium falciparum, the causative agent of the most deadly form of malaria, expresses a structural homolog of mammalian I2, named PfI2. Biochemical, in vitro and in vivo studies revealed that PfI2 binds PP1 and inhibits its activity. We further showed that the motifs 12KTISW16 and 102HYNE105 are critical for PfI2 inhibitory activity. Functional studies using the Xenopus oocyte model revealed that PfI2 is able to overcome the G2/M cell cycle checkpoint by inducing germinal vesicle breakdown. Genetic manipulations in P. falciparum suggest an essential role of PfI2 as no viable mutants with a disrupted PfI2 gene were detectable. Additionally, peptides derived from PfI2 and competing with RVxF binding sites in PP1 exhibit anti-plasmodial activity against blood stage parasites in vitro. Conclusions: Taken together, our data suggest that the PfI2 protein could play a role in the regulation of the P. falciparum cell cycle through its PfPP1 phosphatase regulatory activity. Structure-activity studies of this regulator led to the identification of peptides with anti-plasmodial activity against blood stage parasites in vitro suggesting that PP1cregulator interactions could be a novel means to control malaria. [ABSTRACT FROM AUTHOR]

The incidence of obesity has increased dramatically over the past several years, and in parallel, so has the prevalence of type 2 diabetes (T2D). Numerous studies have demonstrated that both obesity and T2D are associated with lower cognitive performance, cognitive decline, and dementia. Intake of dietary fructose has also increased. In fact, high-fructose corn syrup (HFCS) accounts for as much as 40% of caloric sweeteners used in the United States. Given the increase in the incidence of Alzheimer's disease (AD), characterized by an age-related decline in memory and cognitive functioning, in this report we review the effects of obesity on cognitive performance and the impact of high fructose intake in promoting cognitive decline. The paper then considers the effects of omega-3 fatty acids (FAs), which have been linked to promising results in cognitive function including ameliorating the impact of a high-fructose diet. [ABSTRACT FROM AUTHOR]

Objective:The dietary intake of fructose-rich sugar-sweetened beverages (SSB) may have a significant role in raising serum uric acid (SUA) levels as well as the risk of contracting gout and cardiovascular risk factors. Our objective was to investigate the impact of SSB intake on SUA, body mass index (BMI) and systolic blood pressure (SBP) among adolescents in Taiwan.Methods:We evaluated data from 2727 representative adolescents who were multistage sampled from 36 Junior High schools in Taiwan. We cross-sectionally collected demographic, physical, dietary and anthropometric variables, and prospectively measured clinical outcomes. Data were analyzed using multiple regression and logistic models adjusted for covariates.Results:We found that 87.7% of adolescents were SSB drinkers, with 25.1% drinking >500 ml per day of such beverages. Increased SSB intake was associated with increased waist and hip circumferences, body fat, BMI, SBP and SUA. As compared with non-drinkers, SSB drinkers had a 3.2-4.9 elevated risk of obesity. The prevalence of hyperuricemia in heavy SSB users (40.2-49.4%) was appreciably greater than that for non-users (24.2%). Adolescents who consumed >500 ml per day of heavy high-fructose corn syrup (HFCS) containing beverages had a 0.42 mg dl−1 higher SUA level and a 2.0-2.1 increased risk of developing hyperuricemia than non-drinkers. The consumption of HFCS-rich beverages was also found to interact with obesity in determining higher levels of SUA (2.2-2.4 mg dl−1 increases).Conclusion:High SSB consumption has a notable effect on increased levels of BMI and SUA. The intake of HFCS-rich beverages and BMI were likely to interactively strengthen SUA levels among obese adolescents. [ABSTRACT FROM AUTHOR]

Objectives. We described 27-year secular trends in added-sugar intake and body mass index (BMI) among Americans aged 25 to 74 years. Methods. The Minnesota Heart Survey (1980-1982 to 2007-2009) is a surveillance study of cardiovascular risk factors among residents of the Minneapolis- St Paul area. We used generalized linear mixed regressions to describe trends in added-sugar intake and BMI by gender and age groups and intake trends by weight status. Results. BMI increased concurrently with added-sugar intake in both genders and all age and weight groups. Percentage of energy intake from added sugar increased by 54% in women between 1980 to 1982 and 2000 to 2002, but declined somewhat in 2007 to 2009; men followed the same pattern (all P < .001). Added sugar intake was lower among women than men and higher among younger than older adults. BMI in women paralleled added-sugar intake, but men's BMI increased through 2009. Percentage of energy intake from added sugar was similar among weight groups. Conclusions. Limiting added-sugar intake should be part of energy balance strategies in response to the obesity epidemic. [ABSTRACT FROM AUTHOR]

This review traces the historical origins and conceptual developments leading to the current state of knowledge of the three superfamilies of protein Ser/Thr phosphatases. 'PR enzyme' was identified as an enzyme that inactivates glycogen phosphorylase, although it took 10 years before this ugly duckling was recognized for its true identity as a protein Ser/Thr phosphatase. Ethanol denaturation for purification in the 1970s yielded a phosphatase that exhibited broad specificity, which was resolved into type-1 and type-2 phosphatases in the 1980s. More recent developments show that regulation and specificity are achieved through assembly of multisubunit holoenzymes, transient phosphorylation and the action of inhibitor proteins. Still not widely appreciated, there are hundreds of discrete protein Ser/ Thr phosphatases available to counteract protein kinases, offering potential therapeutic targets. Signalling networks and modelling schemes need to incorporate the full gamut of protein Ser/ Thr phosphatases and their interconnections. [ABSTRACT FROM AUTHOR]

Chemiluminescence (CL) emission from luminol-tetrachloroaurate ([AuCl]) system studied in presence of monosaccharide sugars such as glucose and fructose was investigated on a microfluidic chip fabricated by the soft lithography technique. CL emission from the luminol-[AuCl] system at 430 nm was intensified remarkably by the catalytic activity of glucose and fructose at room temperature. Under optimized conditions, the CL emission intensity of the system was found to be linearly related to the concentration of the sugars. Based on this observation, nonenzymatic determination of total sugar (glucose, fructose, or hydrolyzable sucrose) was performed in a rapid and sensitive analytical method. The results revealed that the linearity ranged from 9 to 1,750 μM for glucose and 80 to 1,750 μM for fructose, with a limit of detection of 0.65 and 0.69 μM, respectively. The relative standard deviations determined at 250 μM based on six repetitive injections were 1.13 and 1.15 % for glucose and fructose, respectively. The developed method was successfully applied for determination of the total sugar concentration in food and beverages. [Figure not available: see fulltext.] [ABSTRACT FROM AUTHOR]

Digestible carbohydrates are one of the main sources of dietary energy in infancy and childhood and are essential for growth and development. The aim of this narrative review is to outline the intakes of digestible carbohydrates and their role in health and disease, including the development of food preferences, as well the consequences of excess carbohydrate. Key experts in these fields provided up-to-date reviews of the literature. A search of available information on dietary intakes of children below the age of 4 years was conducted from 1985 up to 2010. Articles and reports including information about sugars and/or starch intakes were selected. A number of factors limit the ability to obtain an overall picture of carbohydrate intakes and food sources in this age group. These include small numbers of intake studies, differing approaches to analysing carbohydrate, a variety of terms used to describe sugars intakes and a dearth of information about starch intakes. Data suggest that sweet taste is preferred in infancy and later food choices. There are few established adverse consequences of high intakes of digestible carbohydrate for young children. The greatest evidence is for dental caries, although this is influenced by high intake frequency and poor oral hygiene. Evidence for detrimental effects on nutrient dilution, obesity, diabetes or cognition is limited. In infants, minimum carbohydrate (mainly lactose) intake should be 40% of total energy, gradually increasing to 55% energy by the age of 2 years. [ABSTRACT FROM AUTHOR]

Cell cycle transitions depend on protein phosphorylation and dephosphorylation. The discovery of cyclin-dependent kinases (CDKs) and their mode of activation by their cyclin partners explained many important aspects of cell cycle control. As the cell cycle is basically a series of recurrences of a defined set of events, protein phosphatases must obviously be as important as kinases. However, our knowledge about phosphatases lags well behind that of kinases. We still do not know which phosphatase(s) is/are truly responsible for dephosphorylating CDK substrates, and we know very little about whether and how protein phosphatases are regulated. Here, we summarize our present understanding of the phosphatases that are important in the control of the cell cycle and pose the questions that need to be answered as regards the regulation of protein phosphatases. [ABSTRACT FROM AUTHOR]

This systematic literature review examined the role of dietary macronutrient composition, food consumption and dietary patterns in predicting weight or waist circumference (WC) change, with and without prior weight reduction. The literature search covered year 2000 and onwards. Prospective cohort studies, case-control studies and interventions were included. The studies had adult (1870 y), mostly Caucasian participants. Out of a total of 1,517 abstracts, 119 full papers were identified as potentially relevant. After a careful scrutiny, 50 papers were quality graded as A (highest), B or C. Forty-three papers with grading A or B were included in evidence grading, which was done separately for all exposure-outcome combinations. The grade of evidence was classified as convincing, probable, suggestive or no conclusion. We found probable evidence for high intake of dietary fibre and nuts predicting less weight gain, and for high intake of meat in predicting more weight gain. Suggestive evidence was found for a protective role against increasing weight from whole grains, cereal fibre, high-fat dairy products and high scores in an index describing a prudent dietary pattern. Likewise, there was suggestive evidence for both fibre and fruit intake in protection against larger increases in WC. Also suggestive evidence was found for high intake of refined grains, and sweets and desserts in predicting more weight gain, and for refined (white) bread and high energy density in predicting larger increases in WC. The results suggested that the proportion of macronutrients in the diet was not important in predicting changes in weight or WC. In contrast, plenty of fibre-rich foods and dairy products, and less refined grains, meat and sugar-rich foods and drinks were associated with less weight gain in prospective cohort studies. The results on the role of dietary macronutrient composition in prevention of weight regain (after prior weight loss) were inconclusive. [ABSTRACT FROM AUTHOR]

Background: The use of chromium supplements is widespread for the prevention and treatment of diabetes mellitus but there are conflicting reports on efficacy, possibly reflecting discrepant effects across different populations. In the present studies, we test the hypothesis that chromium supplementation raises serum chromium levels and correspondingly improves insulin sensitivity. Methods: A double blind placebo-controlled randomized trial was conducted on 31 non-obese, normoglycemic subjects. After baseline studies, the subjects were randomized to placebo or chromium picolinate 500 µg twice a day. The primary endpoint was change in insulin sensitivity as measured by euglycemic hyperinsulinemic clamp. Pre-specified secondary endpoints included fasting lipids, blood pressure, weight, body composition measured by DXA scan. Results: After 16 weeks of chromium picolinate therapy there was no significant change in insulin sensitivity between groups (p=0.83). There was, however, a strong association between serum chromium and change in insulin resistance (β = -0.83, p=0.01), where subjects with the highest serum chromium had a worsening of insulin sensitivity. This effect could not be explained by changes in physiological parameters such as body weight, truncal fat and serum lipids with chromium therapy. Conclusions: Chromium therapy did not improve insulin sensitivity in non-obese normoglycemic individuals. Further, subjects who have high serum chromium levels paradoxically had a decline in insulin sensitivity. Caution therefore should be exercised in recommending the use of this supplement. Trial registration: The study was registered on the NIH registry (clinicaltrials.gov) and the identifier is NCT00846248 [ABSTRACT FROM AUTHOR]

Control of protein phosphorylation–dephosphorylation events occurs through regulation of protein kinases and phosphatases. Phosphatase type 1 (PP-1) provides the main activity of serine/threonine protein phosphatases in the heart. Inhibitor-1 (I-1) was the first endogenous molecule found to inhibit PP-1 specifically. Notably, I-1 is activated by cAMP-dependent protein kinase A (PKA), and the subsequent prevention of target dephosphorylation by PP-1 provides distal amplification of β-adrenoceptor (β-AR) signalling. I-1 was found to be down-regulated and hypo-phosphorylated in human and experimental heart failure but hyperactive in human atrial fibrillation, implicating I-1 in the pathogenesis of heart failure and arrhythmias. Consequently, the therapeutic potential of I-1 in heart failure and arrhythmias has recently been addressed by the generation and analysis of several I-1 genetic mouse models. This review summarizes and discusses these data, highlights partially controversial issues on whether I-1 should be therapeutically reinforced or inhibited and suggests future directions to better understand the functional role of I-1 in physiological and pathological β-AR signalling. [ABSTRACT FROM PUBLISHER]

Introduction: Dental caries is a diet-associated disease which continues to be a serious health problem in most industrialized and developing countries. Strategies to maximize caries prevention should automatically consider the use of sugar substitutes. It is important that public health authorities are made cognizant of the availability of new polyol-type sugar substitutes. Review Summary: Clinical studies have shown that xylitol, a natural, physiologic sugar alcohol of the pentitol type, can be used as a safe and effective caries-limiting sweetener. Habitual use of xylitol-containing food and oral hygiene adjuvants has been shown to reduce the growth of dental plaque, to interfere with the growth of caries-associated bacteria, to decrease the incidence of dental caries, and to be associated with remineralization of caries lesions. Numerous public regulatory bodies have endorsed the use of xylitol as a caries-limiting agent. Other sugar alcohols that have been successfully used as sugar substitutes include D-glucitol (sorbitol), which, however, owing to its hexitol nature, normally has no strong effect on the mass and adhesiveness of bacterial plaque and on the growth of mutans streptococci. A tetritol-type alditol, erythritol, has shown potential as a non-cariogenic sugar substitute. Combinations of xylitol and erythritol may reduce the incidence of caries more effectively than either alditol alone. Conclusions: Partial sugar substitution with polyols is an important dietary tool in the prevention of dental caries that should be used to enhance existing fluoride-based caries prevention programmes. The most effective method of conveying this information to the public is through a proper health claim for these alditols in food labelling. The present review summarizes clinical and biochemical aspects of the above three dietary polyols and emphasizes the role of sugar substitution as a potential health-promoting strategy. Copyright © 2011 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

As dietary exposure to fructose has increased over the past 40 years, there is growing concern that high fructose consumption in humans may be in part responsible for the rising incidence of obesity worldwide. Obesity is associated with a host of metabolic challenges, collectively termed the metabolic syndrome. Fructose is a highly lipogenic sugar that has profound metabolic effects in the liver and has been associated with many of the components of the metabolic syndrome (insulin resistance, elevated waist circumference, dyslipidemia, and hypertension). Recent evidence has also uncovered effects of fructose in other tissues, including adipose tissue, the brain, and the gastrointestinal system, that may provide new insight into the metabolic consequences of high-fructose diets. Fructose feeding has now been shown to alter gene expression patterns (such as peroxisome proliferator-activated receptor-7 coactivator- 1a/ß in the liver), alter satiety factors in the brain, increase inflammation, reactive oxygen species, and portal endotoxin concentrations via Toll-like receptors, and induce leptin resistance. This review highlights recent findings in fructose feeding studies in both human and animal models with a focus on the molecular and biochemical mechanisms that underlie the development of insulin resistance, hepatic steatosis, and the metabolic syndrome. [ABSTRACT FROM AUTHOR]

Objective:The objective of this study was to analyze whether maternal negative affectivity assessed in pregnancy is related with subsequent infant food choices.Design:The study design was a cohort study.Subjects:The subjects were mothers (N=37 919) and their infants participating in the Norwegian Mother and Child Cohort Study conducted by the Norwegian Institute of Public Health.Measurements:Maternal negative affectivity assessed prepartum (Hopkins Symptom Checklist 5 (SCL-5) at weeks 17 and 30 of pregnancy), introduction of solid foods by month 3 and feeding of sweet drinks by month 6 (by the reports of the mothers) were analyzed.Results:Mothers with higher negative affectivity were 64% more likely (95% confidence interval 1.5–1.8) to feed sweet drinks by month 6, and 79% more likely (95% confidence interval 1.6–2.0) to introduce solid foods by month 3. These odds decreased to 41 and 30%, respectively, after adjusting for mother's age, body mass index (BMI) and education.Conclusion:The maternal trait of negative affectivity is an independent predictor of infant feeding practices that may be related with childhood weight gain, overweight and obesity. [ABSTRACT FROM AUTHOR]

Background: High serum uric acid concentration (hyperuricemia) has been studied for its relationship with multiple adverse health outcomes, such as metabolic syndrome. Intervention studies have produced inconsistent outcomes for the relationship between fructose intake and serum uric acid concentration. Methods: The association of dietary fructose intake with hyperuricemia risk in adults was examined using logistic regression and U.S. NHANES 1999-2004 databases. A total of 9,384 subjects, between the ages 20 and 80 years, without diabetes, cancer, or heart disease, were included. Results: The highest added or total fructose intake (quartiles by grams or % energy) was not associated with an increase of hyperuricemia risk compared to the lowest intake with or without adjustment (odds ratios = 0.515- 0.992). The associations of alcohol and fiber intakes with the risk were also determined. Compared to the lowest intake, the highest alcohol intake was associated with increased mean serum uric acid concentration (up to 16%, P < 0.001) and hyperuricemia risk (odds ratios = 1.658-1.829, P = 0.057- < 0.001); the highest fiber intake was correlated with decreases of uric acid concentration (up to 7.5%, P < 0.002) and lower risk (odds ratios = 0.448- 0.478, P = 0.001- < 0.001). Adults who were over 50 y old, male, or obese had significantly greater risk. Conclusions: The data show that increased dietary fructose intake was not associated with increased hyperuricemia risk; while increased dietary alcohol intake was significantly associated with increased hyperuricemia risk; and increased fiber intake was significantly associated with decreased hyperuricemia risk. These data further suggest a potential effect of fructose consumption in an ordinary diet on serum uric acid differs from results found in some short-term studies using atypical exposure and/or levels of fructose administration. [ABSTRACT FROM AUTHOR]

Background: Alternate day modified fasting (ADMF) is an effective strategy for weight loss in obese adults. Objective: The objective of this study was to examine the dietary and physical activity adaptations that occur during short-term ADMF, and to determine how these modulations affect rate of weight loss. Methods: Sixteen obese subjects (12 women/4 men) completed a 10-week trial consisting of 3 phases: 1) 2-week control phase, 2) 4-week ADMF controlled feeding phase, and 3) 4-week ADMF self-selected feeding phase. Results: Body weight decreased (P < 0.001) by 5.6 ± 1.0 kg post-treatment. Energy intake on the fast day was 26 ± 3% of baseline needs (501 ± 28 kcal/d). No hyperphagic response occurred on the feed day (95 ± 6% of baseline needs consumed, 1801 ± 226 kcal/d). Daily energy restriction (37 ± 7%) was correlated to rate of weight loss (r = 0.42, P = 0.01). Dietary fat intake decreased (36% to 33% of kcal, P < 0.05) with dietary counseling, and was related to rate of weight loss (r = 0.38, P = 0.03). Hunger on the fast day decreased (P < 0.05) by week 2, and remained low. Habitual physical activity was maintained throughout the study (fast day: 6416 ± 851 steps/d; feed day: 6569 ± 910 steps/d). Conclusion: These findings indicate that obese subjects quickly adapt to ADMF, and that changes in energy/ macronutrient intake, hunger, and maintenance of physical activity play a role in influencing rate of weight loss by ADMF. [ABSTRACT FROM AUTHOR]

Cardiac-specific overexpression of the catalytic subunit of protein phosphatase type 1 (PP1) in mice results in hypertrophy, depressed contractility, propensity to heart failure, and premature death. To further address the role of PP1 in heart function, PP1 mice were crossed with mice that overexpress a functional COOH-terminally truncated form of PP1 inhibitor-2 (I-2140). Protein phosphatase activity was increased in PP1 mice but was normalized in double transgenic (DT) mice. The maximal rates of contraction (+dP/dt) and of relaxation (-dP/dt) were reduced in catheterized PP1 mice but normalized in DT mice. Similar contractile abnormalities were observed in isolated, perfused work-performing hearts and in whole animals by means of echocardiography. The increased absolute and relative heart weights observed in PP1 mice were normalized in DT mice. Histological analyses indicated that PP1 mice had significant cardiac fibrosis, which was absent in DT mice. Furthermore, PP1 mice exhibited an age-dependent increase in mortality, which was abrogated in DT mice. These results indicate that 1-2 overexpression prevents the detrimental effects of PP1 overexpression in the heart and further underscore the fundamental role of PP1 in cardiac function. Therefore, PP1 inhibitors such as 1-2 could offer new therapeutic options to ameliorate the deleterious effects of heart failure. [ABSTRACT FROM AUTHOR]