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There are conflicting data on the associations between copper and glycemia, plasma lipids, and atherosclerotic diseases. Copper has both pro-oxidant and antioxidant effects. We performed a cross-sectional analysis to investigate the associations between dietary copper intake and metabolic variables and serum high-sensitivity C-reactive protein (hs-CRP) in asymptomatic subjects from a population-based cohort (n = 1197) and between serum copper concentration and markers of oxidative stress, including plasma nitrotyrosine (NT) and total antioxidant status (TAS), hs-CRP, and metabolic variables in a subgroup of men from this cohort (n = 231). In all subjects, diastolic blood pressure and circulating glucose, uric acid, and total and LDL-cholesterol concentrations significantly decreased, whereas the hs-CRP concentration increased, from the lowest to the highest tertile of copper intake. In the male subgroup, glucose and total and LDL-cholesterol and TAS decreased, whereas hs-CRP and NT concentrations increased from the lowest to the highest tertile of serum copper concentration. In multiple regression models, dietary copper intake was inversely associated with diastolic blood pressure (P = 0.002), fasting glucose (P < 0.001), total cholesterol (P < 0.001), LDL-cholesterol (P < 0.001), and uric acid (P < 0.001) and was directly associated with the hs-CRP concentration (P < 0.001). Serum copper concentrations were inversely associated with glucose (P < 0.001), total cholesterol (P < 0.001), LDL-cholesterol (P < 0.001), and TAS (P < 0.001) and were directly associated with hs-CRP (P < 0.001) and NT concentrations (P < 0.001). Marginal copper deficiency is associated with an unfavorable metabolic pattern, but copper supplementation might not be recommended in view of its association with inflammation and markers of oxidative stress.

Population densities of birds and mammals have been shown to decrease with body mass at approximately the same rate as metabolic rates increase, indicating that energetic needs constrain endotherm population densities. In ectotherms, the exponential increase of metabolic rate with body temperature suggests that environmental temperature may additionally constrain population densities. Here we test simple bioenergetic models for an ecologically important group of ectothermic vertebrates by examining 483 lizard populations. We find that lizard population densities decrease as a power law of body mass with a slope approximately inverse to the slope of the relationship between metabolic rates and body mass. Energy availability should limit population densities. As predicted, environmental productivity has a positive effect on lizard density, strengthening the relationship between lizard density and body mass. In contrast, the effect of environmental temperature is at most weak due to behavioral thermoregulation, thermal evolution, or the temperature dependence of ectotherm performance. Our results provide initial insights into how energy needs and availability differentially constrain ectotherm and endotherm density across broad spatial scales. Key words: ectotherms; energetic constraints; energetic equivalence rule; environmental temperature; lizards; metabolic theory; population density.

Background: Humans are commonly exposed to multiple environmental chemicals, including tetrabromobisphenol A (TBBPA; a flame retardant), triclosan (an antimicrobial agent), and bisphenol A (BPA; polycarbonate plastics). These chemicals are readily absorbed and may interact with each other. Objectives: We sought to determine whether TBBPA, given alone or in combination with triclosan, can modulate the concentrations of BPA and 17[beta]-estradiol (E2). Methods: Female and male CF-1 mice were each given a subcutaneous injection of 0-27 mg TBBPA, with or without concurrent 0.33 mg triclosan, followed by dietary administration of 50 [micro]g/kg body weight [sup.14]C-BPA. Radioactivity was measured in blood serum and tissues through liquid scintillation counting. In subsequent experiments, female and male CF-1 mice were each given a subcutaneous injection of 0 or 1 mg TBBPA and E2 was measured in urine 2-12 h after injection. Results: Doses as low as 1 mg TBBPA significantly elevated [sup.14]C-BPA concentrations in the uterus and ovaries of females; in the testes, epididymides, vesicular-coagulating glands, and preputial glands of males; and in blood serum, heart, lungs, and kidneys of both sexes; urinary E2 concentrations were also elevated. Lower doses of TBBPA or triclosan that had no effects on their own elevated [sup.14]C-BPA concentrations when the two substances were given concurrently. Conclusion: These data indicate that TBBPA, triclosan, and BPA interact in vivo, consistent with evidence that TBBPA and triclosan inhibit enzymes that are critical for BPA and E2 metabolism. https://doi.org/10.1289/EHP1329, Introduction Tetrabromobisphenol A (TBBPA; CAS 79-94-7) is the most-produced flame retardant, with global use over 170,000 metric tons/y (Environment Canada and Health Canada 2013). Approximately 80% of TBBPA is used [...]

Author(s): Maria J. Rodrguez-Colman [1]; Matthias Schewe [2]; Maaike Meerlo [1]; Edwin Stigter [1]; Johan Gerrits [3]; Mia Pras-Raves [3]; Andrea Sacchetti [2]; Marten Hornsveld [1]; Koen C. Oost [1]; [...]

Background&sol;Objectives: Certain populations with a large proportion of indigenous American (IA) genetic ancestry may be evolutionarily adapted to traditional diets high in legumes and complex carbohydrates, and may have a detrimental metabolic response to US diets high in refined carbohydrates and added sugars. We tested whether IA ancestry modified the metabolic response to a US versus traditional Mexican diet in a controlled dietary intervention. Subjects&sol;Methods: First and second generation Mexican immigrant women (n=53) completed a randomized crossover feeding trial testing the effects of a US versus traditional Mexican diet. The metabolic response to the diets was measured by fasting serum concentrations of glucose, insulin, insulin-like growth factor-1 (IGF-1), IGF-binding protein-3 (IGFBP-3), adiponectin, C-reactive protein, interleukin-6 and computed homeostasis model assessment for insulin resistance (HOMA[sub.IR]). Blood collected at baseline was used for genotyping, and estimation of African, European and IA ancestries with the use of 214 ancestry informative markers. Results: The genetic ancestral background was 56% IA, 38% European and 6% African. Women in the highest IA ancestry tertile ( [greater than] 62%) were shorter in height, less educated and less acculturated to the US lifestyle, and tended to have higher waist-to-hip ratio compared with women in the middle and lowest IA ancestry tertiles, respectively. Compared with the US diet, the traditional Mexican diet tended to reduce glucose, insulin, IGF-1, IGFBP-3 and HOMA[sub.IR] among women in the middle IA ancestry group (IA ancestry [precedes/equal to]45-62%), whereas having no effect on biomarkers related to inflammation. Conclusions: We observed modest interactions between IA ancestry and the metabolic response to a US versus traditional Mexican diet among Mexican immigrant women. European Journal of Clinical Nutrition (2017) 71, 395-401; doi: 10.1038/ejcn.2016.211; published online 14 December 2016, Author(s): M Santiago-Torres [1]; J De Dieu Tapsoba [1]; M Kratz [1]; J W Lampe [1]; K L Breymeyer [1]; L Levy [1]; X Song [1]; A Villaseñor [2]; C-Y [...]

Background&sol;Objectives: Normal-weight women frequently restrict their caloric intake and exercise, but little is known about the effects on body weight, body composition and metabolic adaptations in this population. Subjects&sol;Methods: We conducted a secondary analysis of data from a randomized controlled trial in sedentary normal-weight women. Women were assigned to a severe energy deficit (SEV: -1062[+ or -]80 kcal per day; n=9), a moderate energy deficit (MOD: -633[+ or -]71 kcal per day; n=7) or energy balance (BAL; n=9) while exercising five times per week for 3 months. Outcome variables included changes in body weight, body composition, resting metabolic rate (RMR) and metabolic hormones associated with energy conservation. Results: Weight loss occurred in SEV (-3.7[+ or -]0.9 kg, P [less than] 0.001) and MOD (-2.7[+ or -]0.8 kg; P=0.003), but weight loss was significantly less than predicted (SEV: -11.1[+ or -]1.0 kg; MOD: -6.5[+ or -]1.1 kg; both P [less than] 0.001 vs actual). Fat mass declined in SEV (P [less than] 0.001) and MOD (P=0.006), whereas fat-free mass remained unchanged in all groups (P [greater than] 0.33). RMR decreased by -6[+ or -]2% in MOD (P=0.020). In SEV, RMR did not change on a group level (P=0.66), but participants whose RMR declined lost more weight (P=0.020) and had a higher baseline RMR (P=0.026) than those whose RMR did not decrease. Characteristic changes in leptin (P=0.003), tri-iodothyronine (P=0.013), insulin-like growth factor-1 (P=0.016) and ghrelin (P=0.049) occurred only in SEV. The energy deficit and adaptive changes in RMR explained 54% of the observed weight loss. Conclusions: In normal-weight women, caloric restriction and exercise resulted in less-than-predicted weight loss. In contrast to previous literature, weight loss consisted almost exclusively of fat mass, whereas fat-free mass was preserved. European Journal of Clinical Nutrition (2017) 71, 365-371; doi: 10.1038/ejcn.2016.203; published online 26 October 2016, Author(s): K Koehler [1, 2]; M J De Souza [1]; N I Williams [1] Introduction Caloric restriction, exercise or a combination thereof is essential for successful weight loss.[sup.[1, 2, 3]] [...]

The androgen-secreting Leydig cells produce cGMP, but the pathways responsible for generation and actions of this intracellular messenger have been incompletely characterized in these cells. Here, we show the presence of mRNA transcripts for the membrane-bound and soluble guanylyl cyclases (sGC), the cGMP-specific phosphodiesterase 5, and the cGMP-dependent protein kinase I (PKG I) and PKG II in purified rat Leydig cells from adult animals. Stimulation of both guanylyl cyclases and inhibition of phosphodiesterase 5 in vitro were accompanied by elevations in cGMP and androgen production, whereas inhibition of sGC and PKG led to a decrease in steroidogenesis. The stimulatory action of cGMP on steroidogenesis was preserved in cells with inhibited cAMP-dependent protein kinases. Experiments with exogenously added substrates revealed the dependence of cGMP-induced progesterone and androgen synthesis on cholesterol but not on 22-OH cholesterol, pregnenolone, progesterone, and [[DELTA].sup.4]-androstenedione. Treatment with nitric oxide donor increased phosphorylation of the steroidogenic acute regulatory protein (STAR). In contrast, inhibition of sGC and PKG, but not protein kinase A, significantly reduced StAR phosphorylation. These results suggest that cGMP contributes to the control of basal steroidogenesis in Leydig cells through the PKG-dependent modification of the StAR protein. cGMP; steroidogenic acute regulatory protein

Chlorogenic acids (CGA) are abundant phenolic compounds in coffee, with caffeoylquinic (CQA), feruloylquinic (FQA), and dicaffeoylquinic (diCQA) acids being the major subclasses. Despite the potential biopharmacological properties attributed to these compounds, little is known about their bioavailability in humans. In this study, we evaluated the distribution profile of the major CGA isomers and metabolites in plasma and urine of 6 healthy adults for 4 h after brewed coffee consumption. Three CQA isomers and 3 diCQA isomers were identified in the plasma of all subjects after coffee consumption, whereas 2 FQA were identified in only 1 subject. Two plasma concentration peaks were observed, the first at 0.5-1.0 h and the second at 1.5-4.0 h after coffee consumption. The molar ratio CQA:diCQA was 12.2 in the brewed coffee, whereas in plasma it ranged from 0.6-2.9. The molar ratios 5-CQA:3-CQA and 5-CQA:4-CQA were consistently higher in plasma than in the brew. The main CGA metabolites identified in urine after coffee consumption were: dihydrocaffeic, gallic, isoferulic, ferulic, vanillic, caffeic, 5-CQA, sinapic, [rho]-hydroxybenzoic, and [rho]-coumaric acids (gallic and dihydrocaffeic acids being the major ones). This study indicates that the major CGA compounds present in coffee are differentially absorbed and/or metabolized in humans, with a large inter-individual variation. Moreover, urine does not appear to be a major excretion pathway of intact CGA compounds in humans.

Specific estrogen metabolites may initiate and promote hormone-related cancers. In epidemiological studies, significantly lower excretion of urinary estradiol (E2) and lower ratio of urinary 2-hydroxy estrogens to 16[alpha]-hydroxyestrone (2:16 OH-E1) have been reported in prostate cancer cases compared to controls. Although soy supplementation has been shown to increase the ratio 2:16 OH-E1 in women, no studies to our knowledge have investigated the effects of soy supplementation on estrogen metabolism in men. The objective of this randomized controlled trial was to determine the effects of soy protein isolate consumption on estrogen metabolism in men at high risk for developing advanced prostate cancer. Fifty-eight men supplemented their habitual diets with 1 of 3 protein isolates: 1) isoflavone-rich soy protein isolate (SPI +) (107 mg isoflavones/d); 2) alcohol-washed soy protein isolate (SPI-) (

The degradation of taurine, isethionate and sulfoacetate in Cupriavidus necator (Ralstonia eutropha) H16 was shown by enzyme assays to be inducible, and each pathway involved sulfoacetaldehyde, which was subject to phosphatolysis by a common sulfoacetaldehyde acetyltransferase (Xsc, H16_B1870) to yield acetyl phosphate and sulfite. The neighbouring genes encoded phosphate acetyltransferase (Pta, H16_B1871) and a hypothetical protein [domain of unknown function (DUF)81, H16_B1872], with eight derived transmembrane helices. RT-PCR showed inducible transcription of these three genes, and led to the hypothesis that H16_B1872 and orthologous proteins represent a sulfite exporter, which was named TauE.

Ramadan is the holiest month in the Islamic calendar and Muslims fast during this month. We designed this study to evaluate the effect of Ramadan fasting on plasma lipids profile and serum glucose among healthy Jordanian students. Ramadan fasting entails major changes in sleep pattern, physical activity and eating habits, which may cause changes in metabolism both in health and disease. This cohort study was performed during Ramadan in October 2006 (Islamic year 1427). The subjects were 70 healthy Jordanian students (male and female) from three Jordanian universities who fasted during Ramadan. Their mean age was 21 [+ or -]1.6 years. We evaluated some anthropometric parameters as body weight (Kg), pulse rate (per minute) and systolic and diastolic blood pressure (mmHg). All parameters at 4 week of Ramadan were significantly lower than pre-Ramadan values, 2 weeks after Ramadan fasting, body weight and other parameters had a trend to recoup to pre-Ramadan status; however, they were still lower than the pre-Ramadan values. We evaluated blood glucose, triglycerides (TG), cholesterol, low-density lipoprotein LDL), high-density lipoprotein (HDL), and Triglycerides at 1 day before, at week 1, 2, 4 of the Ramadan month and after tow weeks after the end of Ramadan. It was found that high-density lipoprotein (HDL) cholesterol increased significantly during Ramadan, which indicated positive association with pulse rate and fat intake and negative association with systolic blood pressure and weight. . The LDLc was significantly reduced at the end of fasting. A reduction in the average TC value was observed at the end of fasting but the difference was not statistically and there no significant rise in the TG and blood sugar values at the end of fasting. This study indicated that Ramadan fasting led to a decrease weight, LDLc significantly, and significant not statistically reduction in the average TC value, and significantly increasing in HDLc was noted during Ramadan. There was a non-significant rise in the TG, and blood sugar value at the end of fasting. It seems that the effect of Ramadan fasting on serum lipid levels may be closely related to the nutritional diet or biochemical response to starvation. Key words: Ramadan fasting, cholesterol, high-density lipoprotein (HDL), low density lipoprotein (LDL), triglycerides (TG), INTRODUCTION Ramadan fasting is one of the 5 pillars of Islam and one of the most significant ibadat (worships) of Islam (1) Throughout the world, millions of Muslims fast during [...]

During migration, many songbirds eat primarily fruit while depositing fat. Given that some fruits contain mostly carbohydrate and others contain mostly lipid, the ability of birds to fatten may depend on the macronutrient composition of the fruit. Stable isotopes of carbon may be useful in determining the source of nutrients used for synthesizing fat, because the enzyme that regulates the transfer of carbon skeletons from carbohydrate into fat synthesis has a higher affinity for [sup.12]C than for [sup.13]C, whereas dietary lipids can be directly incorporated into animal fat. Thus, fat stores of animals that are synthesized directly from dietary lipid should have isotopic signatures similar to dietary lipid, whereas biosynthesis of fats from dietary carbohydrates should produce changes in isotopic signatures. We tested these predictions by manipulating the concentrations and isotopic signatures of macronutrients in diets fed to Yellow-rumped Warblers (Dendroica coronata). The [[delta].sup.13]C of depot fat in birds fed high-lipid diets was similar to that of dietary lipid, whereas [[delta].sup.13]C of depot fat in birds fed low-lipid diets indicated that a combination of dietary lipid and carbohydrate were used to synthesize depot fat. Models that incorporated 8 [per thousand] discrimination between dietary carbohydrate and depot fat consistently estimated the proportion of dietary lipid and carbohydrate routed into depot fat. Stable-isotope analysis of macronutrients in the diet of wild birds combined with estimates of the effects of diet composition on the isotopic signature of depot fat in birds offer a method to identify the relative importance of nutritional resources used by songbirds to deposit fat. Received 18 May 2005, accepted 6 August 2006. Key words: depot fat, migration, songbirds, stable isotopes, stopover. Durante la migracion, muchas aves canoras se alimentan primariamente de frutas mientras acumulan grasas. Dado que algunas frutas contienen mayormente carbohidratos y que otras contienen principalmente lipidos, la habilidad de las aves para engordar podria depender de la composicion de macronutrientes de las frutas. Los isotopos estables de carbono podrian ser utiles a la hora de determinar la fuente de los nutrientes usada para sintetizar las grasas, debido a que la enzima que regula la transferencia de esqueletos de carbono desde carbohidratos a sintesis de grasa tiene una afinidad mayor por el [sup.12]C que por el [sup.13]C, mientras que los lipidos de la dieta pueden ser incorporados directamente a la grasa animal. De este modo, las reservas de grasa de los animales que son sintetizadas directamente a partir de los lipidos dietarios deberian presentar caracteristicas isotopicas similares a la de los lipidos dietarios, mientras que la biosintesis de grasas a partir de carbohidratos dietarios deberia producir cambios en las caracteristicas isotopicas. Evaluamos estas predicciones manipulando las concentraciones y las caracteristicas isotopicas de los macronutrientes en las dietas provistas a Dendroica coronata. El [[delta].sup.13]C en los depositos de grasa de las aves alimentadas con dietas de alto contenido lipidico fue similar al de los lipidos dietarios, mientras que el [[delta].sup.13]C en los depositos de grasa de las aves alimentadas con dietas de bajo contenido lipidico indico el uso de una combinacion de lipidos y carbohidratos dietarios para sintetizar los depositos de grasa. Los modelos que incorporaron una discriminacion del 8 [por millar] entre los carbohidratos dietarios y los depositos de grasa estimaron de forma consistente la proporcion de lipidos dietarios y de carbohidratos destinados a los depositos de grasa. Los analisis de isotopos estables de los macronutrientes en la dieta de aves silvestres, combinados con los estimados de los efectos de la composicion de la dieta sobre la caracteristica isotopica de los depositos de grasa en las aves, ofrecen un metodo para identificar la importancia relativa de los recursos nutricionales usados por las aves canoras para almacenar grasa.

Torpor, a state characterized by a well-orchestrated reduction of metabolic rate and body temperature ([T.sub.b]), is employed for energetic savings by organisms throughout the animal kingdom. The nucleotide AMP has recently been purported to be a primary regulator of torpor in mice, as circulating AMP is elevated in the fasted state, and administration of AMP causes severe hypothermia. However, we have found that the characteristics and parameters of the hypothermia induced by AMP were dissimilar to those of fasting-induced torpor bouts in mice. Although administration of AMP induced hypothermia (minimum [T.sub.b] = 25.2 [+ or -] 0.6[degrees]C) similar to the depth of fasting-induced torpor (24.9 [+ or -] 1.5[degrees]C), ADP and ATP were equally effective in lowering Tb (minimum [T.sub.b]: 24.8 [+ or -] 0.9[degrees]C and 24.0 [+ or -] 0.5[degrees]C, respectively). The maximum rate of [T.sub.b] fall into hypothermia was significantly faster with injection of adenine nucleotides (AMP: -0.24 [+ or -] 0.03; ADP: -0.24 [+ or -] 0.02; ATP: -0.25 [+ or -] 0.03[degrees]C/min) than during fasting-induced torpor (-0.13 [+ or -] 0.02[degrees]C/min). Heart rate decreased from 755 [+ or -] 15 to 268 - 17 beats per minute (bpm) within 1 min of AMP administration, unlike that observed during torpor (from 646 [+ or -] 21 to 294 [+ or -] 19 bpm over 35 min). Finally, the hypothermic effect of AMP was blunted with preadministration of an adenosine receptor blocker, suggesting that AMP action on Tb is mediated via the adenosine receptor. These data suggest that injection of adenine nucleotides into mice induces a reversible hypothermic state that is unrelated to fasting-induced torpor. core body temperature; adenosine; hibernation; heart rate doi: 10.1152/ajpregu.00888.2006

The reduced metabolism derived from daily torpor enables numerous small mammals, including Siberian hamsters, to survive periods of energetic challenge. Little is known of the neural mechanisms underlying the initiation and expression of torpor. Hypothalamic neuropeptide Y (NPY) contributes to surviving energetic challenges by both increasing food ingestion and reducing metabolic expenditure. Intracerebroventricular injections of NPY in cold-acclimated Siberian hamsters induce torpor-like hypothermia comparable to natural torpor. Multiple NPY receptor subtypes have been identified, and the Y1 receptor and Y5 receptor both contribute to the orexigenic effect of NPY. The purpose of this research was to compare and contrast the effects of Y1 receptor activation by a specific Y1 agonist ([D-[Arg.sup.25]]-NPY) or Y5 receptor activation by a specific Y5 agonist ([D-[Trp.sup.34]]-NPY) on body temperature and subsequent food intake in cold-acclimated Siberian hamsters. Intracerebroventricular injections of Y1 agonist produced torporlike hypothermia closely resembling that induced by intracerebroventricular NPY. The intracerebroventricular Y5 agonist infrequently produced hypothermia reaching criterion for torpor and that failed to resemble either NPY-induced or natural torpor. Combined injections of Y1 and Y5 agonists resulted in hypothermia comparable to Y5 agonist treatments alone, negating the mimicry of NPY treatment seen with Y1 agonist alone. Prior treatment with Y1 agonist or Y5 agonist surprisingly had lingering effects on NPY-induced torpor expression, Y1 agonist enhanced and Y5 agonist inhibited the effect of NPY. The ability of NPY to induce torporlike hypothermia, especially its initiation, most likely involves activation of the NPY Y1 receptor subtype. thermoregulation; body temperature; metabolism; neuropeptides; ingestive behavior doi:10.1152/ajpregu.00790.2006

Epistatic interactions among quantitative trait loci (QTL) contribute substantially to the variation in complex traits. The main objectives of this study were to (i) compare three- vs. four-step genome scans to identify three-way epistatic interactions among QTL belonging to a metabolic pathway, (ii) investigate by computer simulations the power and proportion of false positives (PFP) for detecting three-way interactions among QTL in recombinant inbred line (RIL) populations derived from a nested mating design, and (iii) compare these estimates to those obtained for detecting three-way interactions among QTL in RIL populations derived from diallel and different partial diallel mating designs. The single-nucleotide polymorphism haplotype data of B73 and 25 diverse maize inbreds were used to simulate the production of various RIL populations. Compared to the three-step genome scan, the power to detect three-way interactions was higher with the four-step genome scan. Higher power to detect three-way interactions was observed for RILs derived from optimally allocated distance-based designs than from nested designs or diallel designs. The power and PFP to detect three-way interactions using a nested design with 5000 RILs were for both the 4-QTL and the 12-QTL scenario of a magnitude that seems promising for their identification.

We measured metabolic heat production ([H.sub.m]) of perching and foraging Black-capped Chickadees (Poecile atricapillus) to determine if the heat produced during foraging activity, or exercise thermogenesis, could replac.e thermoregulatory heat production requirements. [H.sub.m] and activity of chickadees in winter were measured at ambient temperatures ([T.sub.a]) ranging from -11.5[degrees] to 15.5[degrees]C. Mean activity amplitude recorded with an activity detector was significantly higher in foraging birds than perching birds. [H.sub.m] did not vary significantly between perching and foraging birds, indicating that heat produced during foraging does substitute for heat produced by shivering for thermoregulation. Evaporative water loss and dry thermal conductance did not vary significantly between perching and foraging chickadees. These results suggest that heat produced from locomotor muscles during foraging activity substitutes for thermoregulatory requirements in glean-and-hang foraging species, such as chickadees, as well as in ground-foraging birds. Key words: activity metabolism, Black-capped Chickadee, foraging, heat production, oxygen consumption, Poecile atricapillus. Medimos la produccion de calor metabolico ([H.sub.m]) de individuos de la especie Poecile atricapillus que se encontraban perchados y forrajeando para determinar si el calor producido durante la actividad de forrajeo (termogenesis mediante ejercicio) podria reemplazar los requerimientos de produccion de calor necesarios para la regulacion de la temperatura. La [H.sub.m] y la actividad de las aves en el invierno fueron medidos a temperatura ambiente ([T.sub.a]), entre--11.5[degrees] y 15.5[degrees]C. La amplitud media de la actividad registrada con un detector de actividad fue significativamente mayor en las aves que se encontraban forrajeando que en las que se encontraban perchadas. La [H.sub.m] no vario significativamente entre aves que estaban forrajeando y aves que estaban perchadas, lo que indica que el calor producido durante el forrajeo sustituye al calor producido tiritando para regular la temperatura. La perdida de agua por evaporacion y la conductancia termica seca no variaron significativamente entre aves que estaban forrajeando y aves que estaban perchadas. Estos resultados sugieren que el calor producido por los musculos locomotores durante la actividad de forrajeo sustituye los requerimientos de regulacion de la temperatura en aves que forrajean colgandose y tomado presas del sustrato como lo hace P. atricapillus, asi como en aves que forrajean en el suelo.

The 5,10-methylenetetrahydrofolate reductase (MTHER) 677-->T polymorphin and B vitamins are studied as modulators of one-carbon metabolism in 10,601 adults from the Norwegian Colorectal Cancer Prevention cohort using plasma total homocysteine as the main outcome measure. The study provides comprehensive data on the MTHER-B vitamin network, which has major effects on the transfer of one-carbon units.

In humans, inactivating mutations in the gene of the thyroid hormone transporter monocarboxylate transporter 8 (MCT8; SLC16A2) lead to severe forms of psychomotor retardation combined with imbalanced thyroid hormone serum [...]

Abstract: Acylation-stimulating protein (ASP) and interaction with its receptor C5L2 influences adipocyte metabolism. We examined insulin resistance and differentiation-mediated regulation of C5L2 and the mechanistic impact on both C5L2 cell-surface [...]

The role of vitamin C on diabetes mellitus is unknown. The purpose of this study was to examine the effect of oral administration of vitamin C on some of the metabolic parameters of diabetic rats. Diabetes was induced by intraperitoneal injection of STZ (60 mg [kg.sup.-1] body weight at 12 weeks of age). Vitamin C (10, 50, 100 mg [kg.sup.-1] body weight) was administered orally for a period of four weeks to normal and diabetic male Wistar rats. In some experiments vitamin C was given either before or after the induction of diabetes mellitus. Glucose tolerance test (GTT) was performed on fasted normal, diabetic and vitamin C-treated rats at the end of the experimental period. Blood sugar level and weight were also recorded on a weekly basis for each rat in different groups. Vitamin C significantly (p Key words: ROS, vitamin C, antioxidants, diabetes, glucose, INTRODUCTION Diabetes mellitus (DM) is currently taking its place as one of the main threats to human health in the 21st century. In the past two decades the number of [...]

Bacterial acetyl-coenzyme A (acetyl-CoA) synthetase (AceCS), an evolutionarily conserved enzyme that converts acetate to acetyl-CoA, is activated by sirtuin-mediated deacetylation. Two recent studies show that this mechanism of regulation is also crucial for mammalian AceCS activity, indicating that control of metabolism at the step of converting acetate to acetyl-CoA is conserved. These findings highlight a metabolic regulatory network controlled by sirtuins that has implications for the mechanisms of calorie restriction and modulation of mammalian lifespan.

Continuous recording of ruminal pH in cannulated cattle has been practiced to study rumen metabolism. However, most systems reported did not permit animal mobility during pH recording. Therefore, the objective of this study was to develop a continuous rumen pH data acquisition system that permitted animal mobility during data acquisition. A further objective was to compare the pH readings obtained using the continuous recording system to readings obtained at the same time using spot sampling. The continuous recording system was composed of a heavy-duty electrode and a data logger. The electrode was attached to a 0.5-kg weight to help maintain the electrode in the ventral sac of the rumen. The electrode was connected via a 0.5-m cable to a lightweight data logger that was mounted on the animal's back using a belt wrapped around the girth. The data logger was battery powered and could hold over 13,000 pH data values. A personal digital assistant was used to configure and download data from the data logger during the experiment. Ruminal pH was continuously recorded (every 10 s) using a dry Holstein cow fed alfalfa hay ad libitum in a 3-d experiment to compare the performance of the continuous system to spot samples taken from the ventral sac of the rumen, the same location as the continuous electrode. The spot samples were collected 3 times per d for 3 d. At every sampling time, 3 replicate samples were collected, pH was determined immediately using a handheld pH meter, and readings were averaged (n = 3) and compared with the average of the 3 pH readings recorded using the continuous system at the same time. The pH recorded by spot sampling (6.63 [+ or -] 0.04) was greater (P = 0.009) than that of the continuous system (6.56 [+ or -] 0.03), with a correlation of r = 0.88 (P = 0.002). The continuous recording system has the potential to facilitate measurement of ruminal pH in free-roaming cattle. Key words: ruminal pH, continuous recording, cattle

Fifty-five observations were used to determine the ME content of 8 foods containing different protein sources. The major protein sources tested included low-oligosaccharide whole soybeans; 2 low-oligosaccharide, low-phytate whole soybeans; 2 conventional soybean meals; low-ash poultry meal; low-oligosaccharide, low-phytate soybean meal; and conventional whole soybeans. The ME content of all foods ranged from 3,463 to 4,233 kcal/kg of DM. The first objective was to utilize the observed ME data and test the accuracy of the modified Atwater equation. In this study, the modified Atwater equation generally underpredicted ME compared with the observed ME (residual mean = 247 kcal/kg). The second objective was to use individual data to develop an equation, based on the chemical composition of the food, to predict the ME content of the foods. A multivariate regression analysis was used to predict ME content based on chemical composition. Five models were fitted to the data. Model 1 included CP, ether extract (EE), and crude fiber (CF). Because the foods varied in protein sources, and the ratio of total AA (TAA) to non-AA (NAA) CP ranged from 3.5:1 to 14.4:1, it was hypothesized that accounting for the proportion of TAA and NAA in CP would improve the fit of the model. Therefore, model 2 included TAA, NAA, EE, and CF. Defining CP in terms of TAA and NAA improved the [r.sup.2] of the model from 0.46 to 0.79. Subsequently, models 3, 4, and 5 replaced the CF term with ADF, NDF, and hemicellulose (HEM). Model 3 included TAA, NAA, EE, and NDF. Model 4 included TAA, NAA, EE, ADF, and HEM. Model 5 included TAA, NAA, EE, and HEM. Defining dietary fiber in terms of HEM improved the [r.sup.2] of model 2 from 0.79 to 0.81. Residual analysis suggested that replacing the CF term with HEM (model 5) improved the prediction of ME content. In contrast, defining fiber in terms of NDF (model 3) did not result in an improvement over model 2, whereas the ADF term (model 4) did not (P > 0.34) contribute to the overall model. Fractionating CP into TAA and NAA components further defined the chemical composition of the food. These data suggest that defining protein composition improves the accuracy of predicting the ME content of dog foods. Key words: amino acid, crude protein, dog, fiber, metabolizable energy

This study on primiparous sows was designed to 1) determine the impact of nursing a large litter on LH secretion and follicular development, and 2) investigate the metabolic adaptations by which milk yield increases with litter size. At farrowing, crossbred, primiparous sows were assigned to 1 of 3 experimental groups differing in litter size and feed allowance. Sows with 13 or 14 piglets (13AL, n = 7) were fed ad libitum. Sows with 7 piglets were fed ad libitum (7AL, n = 6) or were feed-restricted (7R, n = 8). The restriction was based on the estimated energy deficiency for the 13AL sows. On d 9 [+ or -] 1 of lactation, a jugular catheter was surgically implanted. Serial blood samplings and glucose tolerance tests were performed in mid- and late lactation. Sows were slaughtered 3 d after weaning, and ovarian characteristics were recorded. During lactation, the 7AL sows lost no or little body reserves, and their estimated energy balance was near zero. The 13AL and 7R sows exhibited similar negative energy balances and similar losses of backfat and estimated lipid content. Litter growth rate was greater (P < 0.05) in the 13AL than in the 7AL and 7R groups. After weaning, the volume of the largest 14 follicles was smaller (P < 0.05) in sows nursing 13 or 14 piglets than in sows with 7 piglets. Plasma concentrations of LH and LH pulse frequency did not differ between groups (P > 0.1). The longer glucose half-life on d 16 than on d 27 of lactation (22.5 vs. 18.8 min; P < 0.05) indicated a lower glucose tolerance in mid- than in late lactation. The area under the insulin curve was greater in the 7AL than in the 13AL sows (P = 0.08) and intermediate in the 7R group, with no differences in glucose profiles. This led to the suggestion that the 7AL sows were more resistant to insulin than the 13AL sows. In all groups of sows, follicular development after weaning was correlated with LH secretion in midlactation. Active follicular development was associated with prolonged secretion of insulin in response to glucose challenge. Our results show that besides litter size, a sow's metabolic status in lactation influences follicular maturation after weaning and also indicate that the metabolic adaptations by which primiparous sows nursing large litters increase litter growth rate and body reserve mobilization do not involve an accentuated peripheral insulin resistance. Key words: insulin, lactation, litter size, metabolism, reproduction, sow

A diabetic state induces the activity and abundance of glycine N-methyltransferase (GNMT), a key protein in the regulation of folate, methyl group, and homocysteine metabolism. Because the folate-dependent one-carbon pool is a source of methyl groups and 5-methyltetrahydrofolate allosterically inhibits GNMT, the aim of this study was to determine whether folate status has an impact on the interaction between diabetes and methyl group metabolism. Rats were fed a diet containing deficient (0 ppm), adequate (2 ppm), or supplemental (8 ppm) folate for 30 days, after which diabetes was initiated in one-half of the rats by streptozotocin treatment. The activities of GNMT, phosphatidylethanolamine N-methyltransferase (PEMT), and betaine-homocysteine S-methyltransferase (BHMT) were increased about twofold in diabetic rat liver; folate deficiency resulted in the greatest elevation in GNMT activity. The abundance of GNMT protein and mRNA, as well as BHMT mRNA, was also elevated in diabetic rats. The marked hyperhomocysteinemia in folate-deficient rats was attenuated by streptozotocin, likely due in part to increased BHMT expression. These results indicate that a diabetic state profoundly modulates methyl group, choline, and homocysteine metabolism, and folate status may play a role in the extent of these alterations. Moreover, the upregulation of BHMT and PEMT may indicate an increased choline requirement in the diabetic rat. choline; phosphatidylethanolamine; betaine-homocysteine S-methyltransferase

Abstract: Bicarbonate is a simple single carbon molecule that plays surprisingly important roles in diverse biological processes. Among these are photosynthesis, the Krebs cycle, whole-body and cellular pH regulation, and [...]

TGF-[beta]-activated kinase-1 (TAK1), also known as MAPKK kinase-7 (MAP3K7), is a candidate effector of multiple circuits in cardiac biology and disease. Here, we show that inhibition of TAK1 in mice by a cardiac-specific dominant-negative mutation evokes electrophysiological and biochemical properties reminiscent of human Wolff-Parkinson-White syndrome, arising from mutations in AMP-activated protein kinase (AMPK), most notably, accelerated atrioventricular conduction and impaired AMPK activation. To test conclusively the biochemical connection from TAK1 to AMPK suggested by this phenotype, we disrupted TAK1 in mouse embryos and embryonic fibroblasts by Cre-mediated recombination. In TAK1-null embryos, the activating phosphorylation of AMPK at T172 was blocked, accompanied by defective AMPK activity. However, loss of endogenous TAK1 causes midgestation lethality, with defective yolk sac and intraembryonic vasculature. To preclude confounding lethal defects, we acutely ablated floxed TAK1 in culture by viral delivery of Cre. In culture, endogenous TAK1 was activated by oligomycin, the antidiabetic drug metformin, 5-aminoimidazole-4-carboxamide riboside (AICAR), and ischemia, well established triggers of AMPK activity. Loss of TAK1 in culture blocked T172 phosphorylation induced by all three agents, interfered with AMPK activation, impaired phosphorylation of the endogenous AMPK substrate acetyl CoA carboxylase, and also interfered with activation of the AMPK kinase LKB1. Thus, by disrupting the endogenous TAK1 locus, we prove a pivotal role for TAK1 in the LKB1/AMPK signaling axis, an essential governor of cell metabolism. cardiac | MAPK | metabolism | cre/lox

Our results in a previous study indicated that the portal absorption of intragastrically fed [alpha]-ketoglutarate (AKG) was limited in young pigs. Our aim was to quantify the net portal absorption, first-pass metabolism, and whole-body flux of enterally infused AKG. In study 1, we quantified the net portal nutrient absorption in young pigs (n = 9) given an intraduodenal infusion of milk replacer [10 mL/(kg * h)] and either saline (control) or 930 [micro]mol/(kg. h) AKG for 4 h. In study 2, we quantified the luminal disappearance of a duodenal AKG bolus in young pigs (n = 7). In study 3, we quantified the whole-body kinetics of [sup.13]C-AKG metabolism when infused either enterally (n = 9) or intravenously (n = 9) in young pigs. In study 1, when compared with the control group, enteral AKG infusion increased (P< 0.01) the arterial (13.8 [+ or -] 1.7 vs. 27.4 [+ or -] 3.6 [micro]mol/L) and portal (22.0 [+ or -] 1.4 vs. 64.6 [+ or -] 5.9 [micro]mol/L) AKG concentrations and the net portal absorption of AKG [19.7 [+ or -] 2.8 vs. 95.2 [+ or -] 12.0 [micro]mol/(kg * h)]. The mean fractional portal appearance of enterally infused AKG was 10.23 [+ or -] 1.3%. In study 2, the luminal disappearance of AKG was 663 [micro]mol/(kg * h), representing 63% of the intraduodenal dose. In study 3, the wholebody [sup.13]C-AKG flux [4685 [+ or -] 666 vs. 801 [+ or -] 67 [micro]mol/(kg * h)] was higher (P < 0.05) when given enterally than intravenously, but [sup.13]C[O.sub.2] recovery was not different (37.3 [+ or -] 1.0 vs. 36.2 [+ or -] 0.7%dose). The first-pass splanchnic [sup.13]C-AKG utilization was ~80%, of which 30% was oxidized to [sup.13]C[O.sub.2]. We conclude that the intestinal absorption of AKG is limited in young pigs largely due to substantial first-pass gastrointestinal metabolism.

Cytochrome P450 (CYP) 3A4 is the most promiscuous of the human CYP enzymes and contributes to the metabolism of [approximately equal to] 50% of marketed drugs. It is also the isoform most often involved in unwanted drug--drug interactions. A better understanding of the molecular mechanisms governing CYP3A4--ligand interaction therefore would be of great importance to any drug discovery effort. Here, we present crystal structures of human CYP3A4 in complex with two well characterized drugs: ketoconazole and erythromycin. In contrast to previous reports, the protein undergoes dramatic conformational changes upon ligand binding with an increase in the active site volume by >80%. The structures represent two distinct open conformations of CYP3A4 because ketoconazole and erythromycin induce different types of coordinate shifts. The binding of two molecules of ketoconazole to the CYP3A4 active site and the clear indication of multiple binding modes for erythromycin has implications for the interpretation of the atypical kinetic data often displayed by CYP3A4. The extreme flexibility revealed by the present structures also challenges any attempt to apply computational design tools without the support of relevant experimental data. drug metabolism | structural flexibility | x-ray crystallography | inhibitor | substrate

The endogenous substance pyruvate is of major importance to maintain energy homeostasis in the cells and provides a window to several important metabolic processes essential to cell survival. Cell viability is therefore reflected in the metabolism of pyruvate. NMR spectroscopy has until now been the only noninvasive method to gain insight into the fate of pyruvate in the body, but the low NMR sensitivity even at high field strength has only allowed information about steady-state conditions. The medically relevant information about the distribution, localization, and metabolic rate of the substance during the first minute after the injection has not been obtainable. Use of a hyperpolarization technique has enabled 10-15% polarization of [sup.13][C.sub.1] in up to a 0.3 M pyruvate solution, i.v. injection of the solution into rats and pigs allows imaging of the distribution of pyruvate and mapping of its major metabolites lactate and alanine within a time frame of [approximately equal to]10 s. Real-time molecular imaging with MRI has become a reality. [sup.13]C | dynamic nuclear polarization | hyperpolarized | MRI | spectroscopy

Silent Information Regulator 2 (Sir2) enzymes (or sirtuins) are NAD+-dependent deacetylases that modulate gene silencing, aging and energy metabolism. Previous work has implicated several transcription factors as sirtuin targets. Here, we investigated whether mammalian sirtuins could directly control the activity of metabolic enzymes. We demonstrate that mammalian Acetyl-CoA synthetases (AceCSs) are regulated by reversible acetylation and that sirtuins activate AceCSs by deacetylation. Site-specific acetylation of mouse AceCS1 on Lys-661 was identified by using mass spectrometry and a specific anti-acetyl-AceCS antibody. SIRT1 was the only member of seven human Sir2 homologues capable of deacetylating AceCS1 in cellular coexpression experiments. SIRT1 expression also led to a pronounced increase in AceCS1-dependent fatty-acid synthesis from acetate. Using purified enzymes, only SlRT1 and SIRT3 exhibited high catalytic efficiency against acetylated AceCS1. In mammals, two AceCSs have been identified: cytoplasmic AceCS1 and mitochondrial AceCS2. Because SIRT3 is localized to the mitochondria, we investigated whether AceCS2 also might be regulated by acetylation, and specifically deacetylated by mitochondrial SIRT3. AceCS2 was completely inactivated upon acetylation and was rapidly reactivated by SlRT3 deacetylation. Lys-635 of mouse AceCS2 was identified as the targeted residue. Using reversible acetylation to modulate enzyme activity, we propose a model for the control of AceCS1 by SIRT1 and of AceCS2 by SIRT3. acetate | deacetylation | Sir2 | acetyltransferase | metabolism

Vascular ATP-sensitive potassium ([K.sub.ATP]) channels have an important role in hypoxic vasodilation. Because [K.sub.ATP] channel activity depends on intracellular nucleotide concentration, one hypothesis is that hypoxia activates channels by reducing cellular ATP production. However, this has not been rigorously tested. In this study we measured [K.sub.ATP] current in response to hypoxia and modulators of cellular metabolism in single smooth muscle cells from the rat femoral artery by using the whole cell patch-clamp technique. [K.sub.ATP] current was not activated by exposure of cells to hypoxic solutions (P[O.sub.2] ~35 mmHg). In contrast, voltage-dependent calcium current and the depolarization-induced rise in intracellular calcium concentration ([[[Ca.sup.2+].sub.i]]) was inhibited by hypoxia. Blocking mitochondrial ATP production by using the ATP synthase inhibitor oligomycin B (3 [micro]M) did not activate current. Blocking glycolytic ATP production by using 2-deoxy-D-glucose (5 mM) also did not activate current. The protonophore carbonyl cyanide m-chlorophenylhydrazone (1 [micro]M) depolarized the mitochondrial membrane potential and activated [K.sub.ATP] current. This activation was reversed by oligomycin B, suggesting it occurred as a consequence of mitochondrial ATP consumption by ATP synthase working in reverse mode. Finally, anoxia induced by dithionite (0.5 mM) also depolarized the mitochondrial membrane potential and activated [K.sub.ATP] current. Our data show that: 1) anoxia but not hypoxia activates [K.sub.ATP] current in femoral artery myocytes; and 2) inhibition of cellular energy production is insufficient to activate [K.sub.ATP] current and that energy consumption is required for current activation. These results suggest that vascular [K.sub.ATP] channels are not activated during hypoxia via changes in cell metabolism. Furthermore, part of the relaxant effect of hypoxia on rat femoral artery may be mediated by changes in [[[Ca.sup.2+].sub.i]] through modulation of calcium channel activity. smooth muscle; ion channels; potassium channels

Minimal model analysis of intravenous glucose tolerance test (IVGTT) glucose and insulin concentrations offers a validated approach to measuring insulin sensitivity, but model identification is not always successful. Improvements may be achieved by using alternative settings in the modeling process, although results may differ according to setting, and care must be exercised in combining results. IVGTT data (12 samples, regular test) from 533 men without diabetes was modeled by the traditional nonlinear regression (NLR) approach, using five different permutations of settings. Results were evaluated with reference to the more robust Bayesian hierarchical (BH) approach to model identification and to the proportion of variance they explained in known correlates of insulin sensitivity (age, BMI, blood pressure, fasting glucose and insulin, serum triglyceride, HDL cholesterol, and uric acid concentration). BH analysis was successful in all cases. With NLR analysis, between 17 and 35 IVGTTs were associated with parameter coefficients of variation (PCVs) for minimal model parameters [S.sub.I] (insulin sensitivity) and [S.sub.G] (glucose effectiveness) of >100%. Systematic use of each different approach in combination reduced this number to five. Mean (interquartile range) [S.sup.NLR.sub.I] was then 3.14 (2.29-4.63) [min.sup.-1] * [mU.sup.-1] * - 1 x [10.sup.-4] and 2.56 (1.74-3.83) [min.sup.-1] * [mU.sup.-1] * 1 x [10.sup.-4] for [S.sup.BH.sub.I] (correlation 0.86, P < 0.0001). [S.sup.NLR.sub.I] explained, on average, 10.6% of the variance in known correlates of insulin sensitivity, whereas [S.sup.BH.sub.I] explained 8.5%. In a large body of data, which BH analysis demonstrated could be fully identified, use of alternative modeling settings in NLR analysis could substantially reduce the number of analyses with PCVs > 100%. [S.sup.NLR.sub.I] compared favorably with [S.sup.BH.sub.I] in the proportion of variance explained in known correlates of insulin sensitivity. parameter estimation; population modeling; metabolic syndrome

Thiazolidinediones (TZDs) are insulin-sensitizing agents used in the treatment of type 2 diabetes. A widely held view is that their action is secondary to transcriptional events that occur when TZDs bind to the nuclear receptor PPAR[gamma] in the adipocyte and stimulate adipogenesis. It has been proposed that this increases insulin sensitivity, at least in part, by increasing the expression and release of adiponectin, an adipokine that activates the fuel-sensing enzyme AMP-activated protein kinase (AMPK). In this study, we report that TZDs also acutely activate AMPK in skeletal muscle and other tissues by a mechanism that is likely independent of PPAR[gamma]-regulated gene transcription. Thus incubation of isolated rat EDL muscles in medium containing 5 [micro]M troglitazone for 15 min (too brief to be attributable to transcription) significantly increased pAMPK and pACC. At a concentration of 100 [micro]M, troglitazone maximally increased these parameters and caused twofold increases in 2-deoxy-D-glucose uptake and the oxidation of exogenous [[sup.14]C]palmitate. Time course studies revealed that troglitazone-induced increases in pAMPK and pACC abundance at 15 min were paralleled by an increase in the AMP-to-ATP ratio and that by 60 min all of these parameters had returned to baseline values. Increases in pAMPK and pACC were also observed in skeletal muscle, liver, and adipose tissue in intact rats 15 min after the administration of a single dose of troglitazone (10 mg/kg, ip). Likewise, troglitazone and another TZD, pioglitazone, caused rapid increases in pAMPK and pACC of equal magnitude in Swiss 3T3 fibroblasts with and without sufficient PPAR[gamma] to mediate the expression of target genes. The results indicate that TZDs can act within minutes to activate AMPK in mammalian tissues. They suggest that this effect is associated with a change in cellular energy state and that it is not dependent on PPAR[gamma]-mediated gene transcription. acetyl-coenzyme A carboxylase; adiponectin; diabetes; insulin sensitivity; metabolism

Sepsis promotes insulin resistance and reduces protein synthesis in skeletal muscle of adults. The effect of sepsis on insulin-stimulated muscle protein synthesis has not been determined in neonates, a highly anabolic population that is uniquely sensitive to insulin. Overnight fasted neonatal pigs were infused for 8 h with endotoxin [lipopoly-saccharide (LPS), 0 and 10 [micro]g * [kg.sup.-1] * [h.sup.-1]]. Glucose and amino acids were maintained at fasting levels, insulin was clamped at either fasting or fed (2 or 10 [micro]U/ml) levels, and fractional protein synthesis rates were determined at the end of the infusion. LPS infusion induced a septic-like state, as indicated by a sustained elevation in body temperature, heart rate, and cortisol. At fasting insulin levels, LPS reduced fractional protein synthesis rates in gastrocnemius muscle (-26%) but had no effect on the masseter and heart. By contrast, LPS stimulated liver protein synthesis (+28%). Increasing insulin to fed levels accelerated protein synthesis rates in gastrocnemius (controls by +38%, LPS by +60%), masseter (controls by +50%, LPS by +43%), heart (controls by +34%, LPS by +40%), and diaphragm (controls by +54%, LPS by +29%), and the response to insulin was similar in LPS and controls. Insulin did not alter protein synthesis in liver, kidney, or jejunum in either group. These findings suggest that acute endotoxemia lowers basal fasting muscle protein synthesis in neonates but does not alter the response of protein synthesis to insulin. growth; amino acids; protein metabolism; insulin resistance; sepsis

The choroid plexus epithelium secretes electrolytes and fluid in the brain ventricular lumen at high rates. Several channels and ion carriers have been identified as likely mediators of this transport in rodent choroid plexus. This study aimed to map several of these proteins to the human choroid plexus. Immunoperoxidase-histochemistry was employed to determine the cellular and subcellular localization of the proteins. The water channel, aquaporin (AQP) 1, was predominantly situated in the apical plasma membrane domain, although distinct basolateral and endothelial immunoreactivity was also observed. The [Na.sup.+]-[K.sup.+]-ATPase [[alpha].sub.1]-subunit was exclusively localized apically in the human choroid plexus epithelial cells. Immunoreactivity for the [Na.sup.+]-[K.sup.+]-2[Cl.sup.-] cotransporter, NKCC1, was likewise confined to the apical plasma membrane domain of the epithelium. The [Cl.sup.-]/HC[O.sup.-.sub.3] exchanger, AE2, was localized basolaterally, as was the [Na.sup.+]-dependent [Cl.sup.-]/HC[O.sup.-.sub.3] exchanger, NCBE, and the electroneutral [Na.sup.+]-HC[O.sup.-.sub.3] cotransporter, NBCn1. No immunoreactivity was found toward the [Na.sup.+]-dependent acid/base transporters NHE1 or NBCe2. Hence, the human choroid plexus epithelium displays an almost identical distribution pattern of water channels and [Na.sup.+] transporters as the rat and mouse choroid plexus. This general cross species pattern suggests central roles for these transporters in choroid plexus functions such as cerebrospinal fluid production. immunohistochemistry; metabolism; cerebrospinal fluid secretion

AMP-activated protein kinase (AMPK) is an energy sensor that regulates cellular metabolism. When activated by a deficit in nutrient status, AMPK stimulates glucose uptake and lipid oxidation to produce energy, [...]

The combination of high-throughput methods of molecular biology with advanced mathematical and computational techniques has propelled the emergent field of systems biology into a position of prominence. Unthinkable a decade ago, it has become possible to screen and analyze the expression of entire genomes, simultaneously assess large numbers of proteins and their prevalence, and characterize in detail the metabolic state of a cell population. Although very important, the focus on comprehensive networks of biological components is only one side of systems biology. Complementing large-scale assessments, and sometimes at the risk of being forgotten, are more subtle analyses that rationalize the design and functioning of biological modules in exquisite detail. This intricate side of systems biology aims at identifying the specific roles of processes and signals in smaller, fully regulated systems by computing what would happen if these signals were lacking or organized in a different fashion, We exemplify this type of approach with a detailed analysis of the regulation of glucose utilization in Lactococcus lactis. This organism is exposed to alternating periods of glucose availability and starvation. During starvation, it accumulates an intermediate of glycolysis, which allows it to take up glucose immediately upon availability. This notable accumulation poses a nontrivial control task that is solved with an unusual, yet ingeniously designed and timed feedforward activation system. The elucidation of this control system required high-precision, dynamic in vivo metabolite data, combined with methods of nonlinear systems analysis, and may serve as a paradigm for multidisciplinary approaches to fine-scaled systems biology. biochemical systems theory | control system | feedforward activation | lactococcus lactis | metabolic pathway

Bacteroides thetaiotaomicron is a prominent member of our normal adult intestinal microbial community and a useful model for studying the foundations of human-bacterial mutualism in our densely populated distal gut microbiota. A central question is how members of this microbiota sense nutrients and implement an appropriate metabolic response. B. thetaiotaornicron contains a large number of glycoside hydrolases not represented in our own proteome, plus a markedly expanded collection of hybrid two-component system (HTCS) proteins that incorporate all domains found in classical two-component environmental sensors into one polypeptide. To understand the role of HTCS in nutrient sensing, we used B. thetaiotaomicron GeneChips to characterize their expression in gnotobiotic mice consuming polysaccharide-rich or-deficient diets. One HTCS, BT3172, was selected for further analysis because it is induced in vivo by polysaccharides, and its absence reduces B. thetaiotaomicron fitness in polysaccharide-rich diet-fed mice. Functional genomic and biochemical analyses of WT and BT3172-defident strains in vivo and in vitro disclosed that [alpha]-mannosides induce BT3172 expression, which in turn induces expression of secreted [alpha]-mannosidases. Yeast two-hybrid screens revealed that the cytoplasmic portion of BT3172's sensor domain serves as a scaffold for recruiting glucose-6-phosphate isomerase and dehydrogenase. These interactions are a unique feature of BT3172 and specific for the cytoplasmic face of its sensor domain. Loss of BT3172 reduces glycolytic pathway activity in vitro and in vivo. Thus, this HTCS functions as a metabolic reaction center, coupling nutrient sensing to dynamic regulation of monosaccharide metabolism. An expanded repertoire of HTCS proteins with diversified sensor domains may be one reason for B. thetaiotaomicron's success in our intestinal ecosystem. Bacteroides thetaiotaomicron | glycoside hydrolases | gut microbial ecology | metabolic regulation | signal transduction

Although it has been proposed that high fiber consumption can prevent proliferative diseases of the colon, the clinical data to support this hypothesis have been inconsistent. To provide a more robust measure of the effects of fiber on colonic mucosal growth than previous studies, we evaluated both cell proliferation and colonic mucosal protein synthesis in nine healthy volunteers after they consumed a typical Western diet ( metabolism; cancer; short-chain fatty acids