Does lipid oxidation differ in gynoid and android obese women?

This study was performed to investigate whether body fat distribution influences resting metabolic rate and lipid oxidation in obese individuals. Eighty-nine obese women were divided in two groups (android obese, n = 36, BMI = 31.1 +/- 4.5 kg/m2 (mean +/- s.d.); gynoid obese, n = 53, BMI = 29.9 +/- 4.5 kg/m2 on the basis of their waist/hip ratio (0.86 +/- 0.05 vs 0.75 +/- 0.04 respectively). Body weight, per cent body fat and fat-free mass were similar in the two groups. Moreover, resting metabolic rate and respiratory quotient were also identical in android and gynoid obese women, indicating that there was no intergroup difference in the absolute level of lipid oxidation. If, like most other android obese women, they had higher rates of lipolysis and plasma FFA concentrations, the failure of android obese individuals to exhibit a higher lipid oxidation than gynoid obese women may partly explain their increased risk to develop metabolic complications.

Positive regulation of the peroxisomal beta-oxidation pathway by fatty acids through activation of peroxisome proliferator-activated receptors (PPAR).

Peroxisome proliferators regulate the transcription of genes by activating ligand-dependent transcription factors, which, due to their structure and function, can be assigned to the superfamily of nuclear hormone receptors. Three such peroxisome proliferator-activated receptors (PPAR alpha, beta, and gamma) have been cloned in Xenopus laevis. Their mRNAs are expressed differentially; xPPAR alpha and beta but not xPPAR gamma are expressed in oocytes and embryos. In the adult, expression of xPPAR alpha and beta appears to be ubiquitous, and xPPAR gamma is mainly observed in adipose tissue and kidney. Immunocytochemical analysis revealed that PPARs are nuclear proteins, and that their cytoplasmic-nuclear translocation is independent of exogenous activators. A target gene of PPARs is the gene encoding acyl-CoA oxidase (ACO), which catalyzes the rate-limiting step in the peroxisomal beta-oxidation of fatty acids. A peroxisome proliferator response element (PPRE), to which PPARs bind, has been identified within the promoter of the ACO gene. Besides the known xenobiotic activators of PPARs, such as hypolipidemic drugs, natural activators have been identified. Polyunsaturated fatty acids at physiological concentrations are efficient activators of PPARs, and 5,8,11,14-eicosatetraynoic acid (ETYA), which is the alkyne homolog of arachidonic acid, is the most potent activator of xPPAR alpha described to date. Taken together, our data suggest that PPARs have an important role in lipid metabolism.

Engineering polyhydroxyalkanoate content and monomer composition in the oleaginous yeast Yarrowia lipolytica by modifying the ß-oxidation multifunctional protein.

Recombinant strains of the oleaginous yeast Yarrowia lipolytica expressing the PHA synthase gene (PhaC) from Pseudomonas aeruginosa in the peroxisome were found able to produce polyhydroxyalkanoates (PHA). PHA production yield, but not the monomer composition, was dependent on POX genotype (POX genes encoding acyl-CoA oxidases) (Haddouche et al. FEMS Yeast Res 10:917-927, 2010). In this study of variants of the Y. lipolytica β-oxidation multifunctional enzyme, with deletions or inactivations of the R-3-hydroxyacyl-CoA dehydrogenase domain, we were able to produce hetero-polymers (functional MFE enzyme) or homo-polymers (with no 3-hydroxyacyl-CoA dehydrogenase activity) of PHA consisting principally of 3-hydroxyacid monomers (>80%) of the same length as the external fatty acid used for growth. The redirection of fatty acid flux towards β-oxidation, by deletion of the neutral lipid synthesis pathway (mutant strain Q4 devoid of the acyltransferases encoded by the LRO1, DGA1, DGA2 and ARE1 genes), in combination with variant expressing only the enoyl-CoA hydratase 2 domain, led to a significant increase in PHA levels, to 7.3% of cell dry weight. Finally, the presence of shorter monomers (up to 20% of the monomers) in a mutant strain lacking the peroxisomal 3-hydroxyacyl-CoA dehydrogenase domain provided evidence for the occurrence of partial mitochondrial β-oxidation in Y. lipolytica.

Late Proterozoic thrust tectonics, high-pressure metamorphism and Uranium mineralization in the domes area, Lufilian arc, northwestern Zambia

The following main lithostratigraphic units have been distinguished in the Domes Area. The Kibaran basement complex composed of gneisses, migmatites with amphibolite bands and metagranites is exposed in dome structures; metamorphic features of Kibaran age have been almost completely obliterated by extensive Lufilian reactivation. The post-Kibaran cover sequence is subdivided into the Lower Roan Group consisting of well-preserved quartzites with high Mg content, talc-bearing, extremely foliated schists intercalated with pseudo-conglomerates of tectonic origin and the Upper Roan Group including dolomitic marbles with rare stromatolites, metapelites and a sequence of detrital metasediments, with local volcano-sedimentary components and interlayered banded ironstones. The sediments of the Lower Roan Group are interpreted as continental to lagoonal-evaporitic deposits partly converted into the talc-kyanite + garnet assemblage characteristic of ``white schists''. The dolomites and metapelites of the Upper Roan Group are attributed to a carbonate platform sequence progressively subsiding under terrigenous deposits, whilst the detrital metasediments and BIF may be interpreted as a basinal sequence, probably deposited on oceanic crust grading laterally into marbles. Metagabbros and metabasalts are considered as remnants of an ocean-floor-type crustal unit probably related to small basins. Alkaline stocks of Silurian age intruded the post-Kibaran cover. Significant ancestral tectonic discontinuities promoted the development of a nappe pile that underwent high-pressure metamorphism during the Lufilian orogeny and all lithostratigraphic units. Rb-Sr and K-Ar and U-Pb data indicate an age of 700 Ma for the highest grade metamorphism and 500 Ma for blocking of the K-Ar and Rb-Sr system in micas, corresponding to the time when the temperature dropped below 350-degrees-400-degrees-C and to an age of about 400 Ma for the emplacement of hypabyssal syenitic bodies. A first phase of crustal shortening by decoupling of basement and cover slices along shallow shear zones has been recognized. Fluid-rich tectonic slabs of cover sediments were thus able to transport fluids into the anhydrous metamorphic basement or mafic units. During the subsequent metamorphic re-equilibration stage of high pressure, pre-existing thrusts horizons were converted into recrystallized mylonites. Due to uplift, rocks were re-equilibrated into assemblages compatible with lower pressures and slightly lower temperatures. This stage occurs under a decompressional (nearly adiabatic) regime, with P(fluid) almost-equal-to P(lithostatic). It is accompanied by metasomatic development of minerals, activated by injection of hot fluids. New or reactivated shear zones and mylonitic belts were the preferred conduits of fluids. The most evident regional-scale effect of these processes is the intense metasomatic scapolitization of formerly plagioclase-rich lithologies. Uraninite mineralization can probably be assigned to the beginning of the decompressional stage. A third regional deformation phase characterized by open folds and local foliation is not accompanied by significant growth of new minerals. However, pitchblende mineralization can be ascribed to this phase as late-stage, short-range remobilization of previously existing deposits. Finally, shallow alkaline massifs were emplaced when the level of the Domes Area now exposed was already subjected to exchange with meteoric circuits, activated by residual geothermal gradients generally related to intrusions or rifting. Most of the superficial U-showings with U-oxidation products were probably generated during this relatively recent phase.

Fat oxidation and adiposity in prepubertal children: exogenous versus endogenous fat utilization.

Fat balance plays an important role in fat mass regulation. The mechanisms by which fat intake and fat oxidation are controlled are poorly understood. In particular, no data are available on the origin, i.e. exogenous (meal intake) or endogenous (adipose tissue lipolysis), of fat oxidized during the postprandial period in children and the proportion between these two components. In this study we tested the hypothesis that there is a relationship between adiposity and the oxidative fate of fat taken with a mixed meal in a group of 15 children with a wide range of fat mass (9-64%). The combination of stable isotope analysis ([13C] enriched fatty acids added to a mixed meal) and indirect calorimetry allowed us to differentiate between the exogenous and endogenous resting fat oxidation rate over the 9-h postprandial period. During the 9 hours of the postprandial period, the children oxidized an amount of fat comparable to that ingested with the meal [26.8 (+/-2.31) g vs. 26.4 (+/-2.3) g, respectively, P = ns]. On average, exogenous fat oxidation [2.99 (+/-3.0) g/9 h] represented 10.8% (+/-0.9) of total fat oxidation. Endogenous fat oxidation, calculated as the difference between total fat oxidation and exogenous fat oxidation, averaged 23.4 (+/-1.9) g/9 h and represented 88.2% (+/-0.9) of total fat oxidation. Endogenous fat oxidation as well as exogenous fat oxidation were highly correlated to total fat oxidation (r = 0.83, P < 0.001; r = 0.84, P < 0.001, respectively). Exogenous fat oxidation expressed as a proportion of total fat oxidation was directly related to fat mass (r = 0.56, P < 0.03), while endogenous fat oxidation expressed as a proportion of total fat oxidation was inversely related (r = -0.57, P < 0.03) to the degree of adiposity. The enhanced exogenous fat oxidation observed when adiposity increases in the dynamic phase of obesity may be viewed as a protective mechanism to prevent further increase in fat mass and hence to maintain fat oxidation at a sufficient rate when the body is exposed to a high amount of dietary fat, as typically encountered in obese children.

Effect of a novel beta-adrenoceptor agonist (Ro 40-2148) on resting energy expenditure in obese women.

The aim of this single-blind, placebo-controlled study was to investigate the effects of the new beta-adrenergic compound Ro 40-2148 on resting energy expenditure (REE) at rest and after an oral glucose load in non-diabetic obese women before and after two weeks of treatment. After one week of placebo administration and after an overnight fast and one hour rest, REE and glucose and lipid oxidation rates were measured by indirect calorimetry (hood system) before and for 6 h after a single dose of placebo solution. A 75 g oral glucose tolerance test (OGTT) was performed during this period starting 90 min after the placebo administration. During the following two weeks, using a randomization design, six patients received Ro 40-2148 at a dose of 400 mg diluted in 100 ml water twice a day (i.e. 800 mg per day), while six others continued with the placebo administration. The same tests and measurements were repeated after two weeks, except for the treatment group which received the drug instead of the placebo. The 14-day period of drug administration did not increase REE measured in post-absorptive conditions. Similarly, there was no acute effect on REE of a 400 mg dose of Ro 40-2148. In contrast, glucose-induced thermogenesis was significantly increased after two weeks in the treatment group (means +/- s.e.m.: 3.7 +/- 1.3%, P = 0.047), while no change was observed in the placebo group (-0.8 +/- 0.7%, not significant). Since there was no significant change in the respiratory quotient, the increase in energy expenditure observed in the treatment group was due to stimulation of both lipid and glucose oxidation. The drug induced no variations in heart rate, blood pressure, axillary temperature or in plasma glucose, insulin and free fatty acid levels. In conclusion, this study shows that Ro 40-2148 activates glucose-induced thermogenesis in obese non-diabetic patients.

Dispersion of natural arsenic in the Malcantone watershed, Southern Switzerland: field evidence for repeated sorption-desorption and oxidation-reduction processes

In recent years, elevated arsenic concentrations have been found in waters and soils of many, countries, often resulting in a health threat for the local population. Switzerland is not an exception and this paper deals with the release and subsequent fate of arsenic in a 200-km(2) mountainous watershed, characterized by crystalline silicate rocks (gneisses, schists, amphibolites) that contain abundant As-bearing sulfide ore deposits, some of which have been mined for iron and gold in the past. Using analytical methods common for mineralogical, ground water and soil studies (XRD, XRF, XAS-XANES and -EXAFS, electron microprobe, extraction, ICP, AAS with hydride generator, ion chromatography), seven different field situations and related dispersion processes of natural arsenic have been studied: (1) release by rock weathering, (2) transport and deposition by water and ice; (3) release of As to the ground and surface water due to increasing pH; (4) accumulation in humic soil horizons; (5) remobilization by reduction in water-saturated soils and stagnant ground waters; (6) remobilization by using P-rich fertilizers or dung and (7) oxidation, precipitation and dilution in surface waters. Comparison of the results with experimental adsorption studies and speciation diagrams from the literature allows us to reconstruct and identify the typical behavior of arsenic in a natural environment under temperate climatic conditions. The main parameters identified are: (a) once liberated from the primary minerals, sorption processes on Fe-oxy-hydroxides dominate over Al-phases, such as Al-hydroxides or clay minerals and limit the As concentrations in the spring and well waters between 20 and 300 mug/l. (b) Precipitation as secondary minerals is limited to the weathering domain, where the As concentrations are still high and not yet too diluted by rain and soils waters. (c) Although neutral and alkaline pH conditions clearly increase the mobility of As, the main factor to mobilize As is a low redox potential (Eh close or below 0 mV), which favors the dissolution of the Fe-oxy-hydroxides on which the As is sorbed. (d) X-ray absorption spectroscopy (XAS) of As in water-logged humic forest soils indicates that the reduction to As III only occurs at the solid-water interface and that the solid contains As as As V (e) A and Bh horizons of humic cambisols can effectively capture As when As-rich waters flow through them. Complex spatial and temporal variation of the various parameters in a watershed results in repeated mobilization and immobilization of As, which continuously transports As from the upper to the lower part of a watershed and ultimately to the ocean. (C) 2004 Elsevier B.V. All rights reserved.

Flowering date of taxonomic families predicts phenological sensitivity to temperature: Implications for forecasting the effects of climate change on unstudied taxa.

PREMISE OF THE STUDY: Numerous long-term studies in seasonal habitats have tracked interannual variation in first flowering date (FFD) in relation to climate, documenting the effect of warming on the FFD of many species. Despite these efforts, long-term phenological observations are still lacking for many species. If we could forecast responses based on taxonomic affinity, however, then we could leverage existing data to predict the climate-related phenological shifts of many taxa not yet studied. METHODS: We examined phenological time series of 1226 species occurrences (1031 unique species in 119 families) across seven sites in North America and England to determine whether family membership (or family mean FFD) predicts the sensitivity of FFD to standardized interannual changes in temperature and precipitation during seasonal periods before flowering and whether families differ significantly in the direction of their phenological shifts. KEY RESULTS: Patterns observed among species within and across sites are mirrored among family means across sites; early-flowering families advance their FFD in response to warming more than late-flowering families. By contrast, we found no consistent relationships among taxa between mean FFD and sensitivity to precipitation as measured here. CONCLUSIONS: Family membership can be used to identify taxa of high and low sensitivity to temperature within the seasonal, temperate zone plant communities analyzed here. The high sensitivity of early-flowering families (and the absence of early-flowering families not sensitive to temperature) may reflect plasticity in flowering time, which may be adaptive in environments where early-season conditions are highly variable among years.

Fat oxidation in nonobese and obese adolescents: effect of body composition and pubertal development.

OBJECTIVES: To measure postabsorptive fat oxidation (F(ox)) and to assess its association with body composition (lean body mass [LBM] and body fat mass [BFM]) and pubertal development. DESIGN: We studied 235 control (male/female ratio = 116/119; age [mean +/- SD]: 13.1 +/- 1.7 years; weight: 45.3 +/- 10.5 kg; LBM: 34.3 +/- 7.1 kg; BFM: 11.0 +/- 4.5 kg) and 159 obese (male/female ratio = 93/66; age: 12.9 +/- 2.1 years; weight: 76.2 +/- 19.1 kg; LBM: 47.4 +/- 10.9 kg; BFM: 28.8 +/- 9.2 kg) adolescents. Postabsorptive F(ox) was calculated from oxygen consumption, carbon dioxide production, and urinary nitrogen as measured by indirect calorimetry and Kjeldahl's method, respectively. Body composition was determined by anthropometry. RESULTS: Postabsorptive F(ox) (absolute value and percentage of resting metabolic rate) was significantly (p < 0.001) higher in the obese adolescents (76.7 +/- 26.3 gm/24 hours, 42.3% +/- 18.7%) than in the control subjects (40.0 +/- 26.3 gm/24 hours, 28.7% +/- 17.0%), even if adjusted for LBM. F(ox) corrected for BFM was similar in control and in obese children, but was significantly lower in girls compared with boys (control male subjects: 62.1 +/- 29.1 gm/24 hours, control female subjects: 51.6 +/- 28.4 gm/24 hours, obese male subjects: 57.3 +/- 29 gm/24 hour, obese female subjects: 45.0 +/- 28.4 gm/24 hours). BFM and LBM showed a significant positive correlation with F(ox). By stepwise regression analysis the most important determinant of F(ox) was BFM in obese and LBM in control children. There was a significant rise in F(ox) during puberty; however, it was mainly explained by changes in body composition. CONCLUSIONS: Obese adolescents have higher F(ox) rates than their normal-weight counterparts. Both LBM and fat mass are important determinants of F(ox).

Chemical labelling of oyster shells used for time-calibrated high-resolution Mg/Ca ratios: A tool for estimation of past seasonal temperature variations

The geochemical compositions of biogenic carbonates are increasingly used for palaeoenvironmental reconstructions. The skeletal delta O-18 temperature relationship is dependent on water salinity, so many recent studies have focused on the Mg/Ca and Sr/Ca ratios because those ratios in water do not change significantly on short time scales. Thus, those elemental ratios are considered to be good palaeotemperature proxies in many biominerals, although their use remains ambiguous in bivalve shells. Here, we present the high-resolution Mg/Ca ratios of two modern species of juvenile and adult oyster shells, Crassostrea gigas and Ostrea edulis. These specimens were grown in controlled conditions for over one year in two different locations. In situ monthly Mn-marking of the shells has been used for day calibration. The daily Mg/Ca.ratios in the shell have been measured with an electron microprobe. The high frequency Mg/Ca variation of all specimens displays good synchronism with lunar cycles, suggesting that tides strongly influence the incorporation of Mg/Ca into the shells. Highly significant correlation coefficients (0.70<R<0.83, p<0.0001) between the Mg/Ca ratios and the seawater temperature are obtained only for juvenile C. gigas samples, while metabolic control of Mg/Ca incorporation and lower shell growth rates preclude the use of the Mg/Ca ratio in adult shells as a palaeothermometer. Data from three juvenile C. gigas shells from the two study sites are selected to establish a relationship: T = 3.77Mg/Ca + 1.88, where T is in degrees C and Mg/Ca in mmol/mol. (c) 2012 Elsevier B.V. All rights reserved.

Temperature-induced sex reversal is not responsible for sex-ratio distortions in grayling Thymallus thymallus or brown trout Salmo trutta.

On the basis of the experiments carried out over various years, it was concluded that (1) grayling Thymallus thymallus and brown trout Salmo trutta are resistant to temperature-induced sex reversal at ecologically relevant temperatures, (2) environmental sex reversal is unlikely to cause the persistent sex ratio distortion observed in at least one of the study populations and (3) sex-specific tolerance of temperature-related stress may be the cause of distorted sex ratios in populations of T. thymallus or S. trutta.

Effects of lactate infusion on hepatic gluconeogenesis and glycogenolysis.

Endogenous glucose production rate (EGPR) remains constant when lactate is infused in healthy humans. A decrease of glycogenolysis or of gluconeogenesis from endogenous precursors or a stimulation of glycogen synthesis, may all be involved; This autoregulation does not depend on changes in glucoregulatory hormones. It may be speculated that alterations in basal sympathetic tone may be involved. To gain insights into the mechanisms responsible for autoregulation of EGPR, glycogenolysis and gluconeogenesis were measured, with a novel method (based on the prelabelling of endogenous glycogen with 13C glucose, and determination of hepatic 13C glycogen enrichment from breath 13CO2 and respiratory gas exchanges) in healthy humans infused with lactate or saline. These measurements were performed with or without beta-adrenergic receptor blockade (propranolol). Infusion of lactate increased energy expenditure, but did not increase EGPR; the relative contributions of gluconeogenesis and glycogenolysis to EGPR were also unaltered. This indicates that autoregulation is attained, at least in part, by inhibition of gluconeogenesis from endogenous precursors. beta-adrenergic receptor blockade alone (with propranolol) did not alter EGPR, glycogenolysis or gluconeogenesis. During infusion of lactate, propranolol decreased the thermic effect of lactate but EGPR remained constant. This indicates that alterations of beta-adrenergic activity is not required for autoregulation of EGPR.

Role of the circadian clock gene Per2 in adaptation to cold temperature.

Adaptive thermogenesis allows mammals to resist to cold. For instance, in brown adipose tissue (BAT) the facultative uncoupling of the proton gradient from ATP synthesis in mitochondria is used to generate systemic heat. However, this system necessitates an increase of the Uncoupling protein 1 (Ucp1) and its activation by free fatty acids. Here we show that mice without functional Period2 (Per2) were cold sensitive because their adaptive thermogenesis system was less efficient. Upon cold-exposure, Heat shock factor 1 (HSF1) induced Per2 in the BAT. Subsequently, PER2 as a co-activator of PPARα increased expression of Ucp1. PER2 also increased Fatty acid binding protein 3 (Fabp3), a protein important to transport free fatty acids from the plasma to mitochondria to activate UCP1. Hence, in BAT PER2 is important for the coordination of the molecular response of mice exposed to cold by synchronizing UCP1 expression and its activation.