Maternal adipose tissue response to nicotine administration in the pregnant rat: effects on fetal body fat and cellularity

1. Nicotine has been implicated as a causative factor in the intrauterine growth retardation associated with smoking in pregnancy. A study was set up to ascertain the effect of nicotine on fetal growth and whether this could be related to the actions of this drug on maternal adipose tissue metabolism. 2. Sprague-Dawley rats were mated and assigned to control and nicotine groups, the latter receiving nicotine in the drinking-water throughout pregnancy. Animals were weighed at regular intervals and killed on day 20 of pregnancy. Rates of maternal adipose tissue lipolysis and lipogenesis were measured. Fetal and placental weights were recorded and analysis of fetal body water, fat, protein and DNA carried out. 3. Weight gains of mothers in the nicotine group were less in the 1st and 2nd weeks of pregnancy, but similar to controls in the 3rd week. Fetal body-weights, DNA, protein and percentage water contents were similar in both groups. Mean fetal body fat (g/kg) was significantly higher in the nicotine group (96.2 (SE 5.1)) compared with controls (72.0 (SE 2.9)). Rates of maternal lipolysis were also higher in the nicotine group. 4. The cause of these differences and their effects on maternal and fetal well-being is discussed.

Variation in the FFAR1 gene modifies BMI, body composition and plasma lipids but not plasma insulin or Beta-cell function in overweight subjects

Background FFAR1 receptor is a long chain fatty acid G-protein coupled receptor which is expressed widely, but found in high density in the pancreas and central nervous system. It has been suggested that FFAR1 may play a role in insulin sensitivity, lipotoxicity and is associated with type 2 diabetes. Here we investigate the effect of three common SNPs of FFAR1 (rs2301151; rs16970264; rs1573611) on pancreatic function, BMI, body composition and plasma lipids. Methodology/Principal Findings For this enquiry we used the baseline RISCK data, which provides a cohort of overweight subjects at increased cardiometabolic risk with detailed phenotyping. The key findings were SNPs of the FFAR1 gene region were associated with differences in body composition and lipids, and the effects of the 3 SNPs combined were cumulative on BMI, body composition and total cholesterol. The effects on BMI and body fat were predominantly mediated by rs1573611 (1.06 kg/m2 higher (P = 0.009) BMI and 1.53% higher (P = 0.002) body fat per C allele). Differences in plasma lipids were also associated with the BMI-increasing allele of rs2301151 including higher total cholesterol (0.2 mmol/L per G allele, P = 0.01) and with the variant A allele of rs16970264 associated with lower total (0.3 mmol/L, P = 0.02) and LDL (0.2 mmol/L, P<0.05) cholesterol, but also with lower HDL-cholesterol (0.09 mmol/L, P<0.05) although the difference was not apparent when controlling for multiple testing. There were no statistically significant effects of the three SNPs on insulin sensitivity or beta cell function. However accumulated risk allele showed a lower beta cell function on increasing plasma fatty acids with a carbon chain greater than six. Conclusions/Significance Differences in body composition and lipids associated with common SNPs in the FFAR1 gene were apparently not mediated by changes in insulin sensitivity or beta-cell function.

Obesity and body fat classification in the metabolic syndrome: impact on cardiometabolic risk metabotype

Obesity is a key factor in the development of the metabolic syndrome (MetS), which is associated with increased cardiometabolic risk. We investigated whether obesity classification by body mass index (BMI) and body fat percentage (BF%) influences cardiometabolic profile and dietary responsiveness in 486 MetS subjects (LIPGENE dietary intervention study). Anthropometric measures, markers of inflammation and glucose metabolism, lipid profiles, adhesion molecules and haemostatic factors were determined at baseline and after 12 weeks of 4 dietary interventions (high saturated fat (SFA), high monounsaturated fat (MUFA) and 2 low fat high complex carbohydrate (LFHCC) diets, 1 supplemented with long chain n-3 polyunsaturated fatty acids (LC n-3 PUFAs)). 39% and 87% of subjects classified as normal and overweight by BMI were obese according to their BF%. Individuals classified as obese by BMI (± 30 kg/m2) and BF% (± 25% (men) and ± 35% (women)) (OO, n = 284) had larger waist and hip measurements, higher BMI and were heavier (P < 0.001) than those classified as non-obese by BMI but obese by BF% (NOO, n = 92). OO individuals displayed a more pro-inflammatory (higher C reactive protein (CRP) and leptin), pro-thrombotic (higher plasminogen activator inhibitor-1 (PAI-1)), pro-atherogenic (higher leptin/adiponectin ratio) and more insulin resistant (higher HOMA-IR) metabolic profile relative to the NOO group (P < 0.001). Interestingly, tumour necrosis factor alpha (TNF-α) concentrations were lower post-intervention in NOO individuals compared to OO subjects (P < 0.001). In conclusion, assessing BF% and BMI as part of a metabotype may help identify individuals at greater cardiometabolic risk than BMI alone.

Vision of the body and the differentiation of perceived body side in touch

Although tactile representations of the two body sides are initially segregated into opposite hemispheres of the brain, behavioural interactions between body sides exist and can be revealed under conditions of tactile double simultaneous stimulation (DSS) at the hands. Here we examined to what extent vision can affect body side segregation in touch. To this aim, we changed hand-related visual input while participants performed a go/no-go task to detect a tactile stimulus delivered to one target finger (e.g., right index), stimulated alone or with a concurrent non-target finger either on the same hand (e.g., right middle finger) or on the other hand (e.g., left index finger = homologous; left middle finger = non-homologous). Across experiments, the two hands were visible or occluded from view (Experiment 1), images of the two hands were either merged using a morphing technique (Experiment 2), or were shown in a compatible vs incompatible position with respect to the actual posture (Experiment 3). Overall, the results showed reliable interference effects of DSS, as compared to target-only stimulation. This interference varied as a function of which non-target finger was stimulated, and emerged both within and between hands. These results imply that the competition between tactile events is not clearly segregated across body sides. Crucially, non-informative vision of the hand affected overall tactile performance only when a visual/proprioceptive conflict was present, while neither congruent nor morphed hand vision affected tactile DSS interference. This suggests that DSS operates at a tactile processing stage in which interactions between body sides can occur regardless of the available visual input from the body.

Water quality trends in the Windrush catchment: Nitrogen speciation and sediment interactions

For the predominantly agricultural River Windrush catchment, spatial variations in concentrations of nitrogen species and suspended sediment were strongly related to geology and land use. Temporal patterns of NO3- and NO2- concentrations during the three year study were highly correlated with seasonal variations in baseflow. Suspended sediment concentrations were mainly controlled by storm discharge. Variations in total ammonium concentrations reflected both flow controls. Suspended sediment effects total ammonium and organic nitrogen transport to the aquatic system, and in-stream cycling processes. Organic nitrogen did not display consistent seasonal variations, but concentrations occasionally exceeding those of NO3-. Overall, NO3- and organic nitrogen were the most important at 60% and -40%, of total nitrogen load, respectively. Future assessments of agriculture impact on river water quality should consider the total nitrogen load, and not solely that of NO3-.

Physical activity attenuates the body mass index-increasing influence of genetic variation in the FTO gene 1-3.

BACKGROUND: Intronic variation in the FTO (fat mass and obesity-associated) gene has been unequivocally associated with increased body mass index (BMI; in kg/m(2)) and the risk of obesity in populations of different ethnicity. OBJECTIVE: We examined whether this robust genetic predisposition to obesity can be attenuated by being more physically active. DESIGN: The FTO variant rs1121980 was genotyped in 20,374 participants (39-79 y of age) from the European Prospective Investigation into Cancer and Nutrition-Norfolk Study, an ethnically homogeneous population-based cohort. Physical activity (PA) was assessed with a validated self-reported questionnaire. The interaction between rs1121980 and PA on BMI and waist circumference (WC) was examined by including the interaction term in mixed-effect models. RESULTS: We confirmed that the risk (T) allele of rs1121980 was significantly associated with BMI (0.31-unit increase per allele; P < 0.001) and WC (0.77-cm increase per allele; P < 0.001). The PA level attenuated the effect of rs1121980 on BMI and WC; ie, whereas in active individuals the risk allele increased BMI by 0.25 per allele, the increase in BMI was significantly (P for interaction = 0.004) more pronounced (76%) in inactive individuals (0.44 per risk allele). We observed similar effects for WC (P for interaction = 0.02): the risk allele increased WC by 1.04 cm per allele in inactive individuals but by only 0.64 cm in active individuals. CONCLUSIONS: Our results showed that PA attenuates the effect of the FTO rs1121980 genotype on BMI and WC. This observation has important public health implications because we showed that a genetic susceptibility to obesity induced by FTO variation can be overcome, at least in part, by adopting a physically active lifestyle.

Effect of polymorphisms in the PPARGC1A gene on body fat in Asian Indians

OBJECTIVE: To evaluate whether polymorphisms in the peroxisome proliferator-activated receptor-gamma coactivator-1 alpha (PPARGC1A) gene were related to body fat in Asian Indians. METHODS: Three polymorphisms of PPARGC1A gene, the Thr394Thr, Gly482Ser and +A2962G, were genotyped on 82 type 2 diabetic and 82 normal glucose tolerant (NGT) subjects randomly chosen from the Chennai Urban Rural Epidemiology Study using PCR-RFLP, and the nature of the variants were confirmed using direct sequencing. Linkage disequilibrium (LD) was estimated from the estimates of haplotypic frequencies using an expectation-maximization algorithm. Visceral, subcutaneous and total abdominal fat were measured using computed tomography, whereas dual X-ray absorptiometry was used to measure central abdominal and total body fat. RESULTS: None of the three polymorphisms studied were in LD. The genotype (0.59 vs 0.32, P=0.001) and allele (0.30 vs 0.17, P=0.007) frequencies of Thr394Thr polymorphism were significantly higher in type 2 diabetic subjects compared to those in NGT subjects. The odds ratio for diabetes (adjusted for age, sex and body mass index) for the susceptible genotype, XA (GA+AA) of Thr394Thr polymorphism, was 2.53 (95% confidence intervals: 1.30-5.04, P=0.009). Visceral and subcutaneous fat were significantly higher in NGT subjects with XA genotype of the Thr394Thr polymorphism compared to those with GG genotype (visceral fat: XA 148.2+/-46.9 vs GG 106.5+/-51.9 cm(2), P=0.001; subcutaneous fat: XA 271.8+/-167.1 vs GG 181.5+/-78.5 cm(2), P=0.001). Abdominal (XA 4521.9+/-1749.6 vs GG 3445.2+/-1443.4 g, P=0.004), central abdominal (XA 1689.0+/-524.0 vs GG 1228.5+/-438.7 g, P<0.0001) and non-abdominal fat (XA 18763.8+/-8789.4 vs GG 13160.4+/-4255.3 g, P<0.0001) were also significantly higher in the NGT subjects with XA genotype compared to those with GG genotype. The Gly482Ser and +A2962G polymorphisms were not associated with any of the body fat measures. CONCLUSION: Among Asian Indians, the Thr394Thr (G --> A) polymorphism is associated with increased total, visceral and subcutaneous body fat.

Chirikov diffusion in the asteroidal three-body resonance (5,-2,-2)

The theory of diffusion in many-dimensional Hamiltonian system is applied to asteroidal dynamics. The general formulation developed by Chirikov is applied to the NesvornA1/2-Morbidelli analytic model of three-body (three-orbit) mean-motion resonances (Jupiter-Saturn-asteroid). In particular, we investigate the diffusion along and across the separatrices of the (5, -2, -2) resonance of the (490) Veritas asteroidal family and their relationship to diffusion in semi-major axis and eccentricity. The estimations of diffusion were obtained using the Melnikov integral, a Hadjidemetriou-type sympletic map and numerical integrations for times up to 10(8) years.

Rapid and slow modulation of nitrate reductase activity in the red macroalga Gracilaria chilensis (Gracilariales, Rhodophyta): influence of different nitrogen sources

Nitrate is one of the most important stimuli in nitrate reductase (NR) induction, while ammonium is usually an inhibitor. We evaluated the influence of nitrate, ammonium or urea as nitrogen sources on NR activity of the agarophyte Gracilaria chilensis. The addition of nitrate rapidly (2 min) induced NR activity, suggesting a fast post-translational regulation. In contrast, nitrate addition to starved algae stimulated rapid nitrate uptake without a concomitant induction of NR activity. These results show that in the absence of nitrate, NR activity is negatively affected, while the nitrate uptake system is active and ready to operate as soon as nitrate is available in the external medium, indicating that nitrate uptake and assimilation are differentially regulated. The addition of ammonium or urea as nitrogen sources stimulated NR activity after 24 h, different from that observed for other algae. However, a decrease in NR activity was observed after the third day under ammonium or urea. During the dark phase, G. chilensis NR activity was low when compared to the light phase. A light pulse of 15 min during the dark phase induced NR activity 1.5-fold suggesting also fast post-translational regulation. Nitrate reductase regulation by phosphorylation and dephosphorylation, and by protein synthesis and degradation, were evaluated using inhibitors. The results obtained for G. chilensis show a post-translational regulation as a rapid response mechanism by phosphorylation and dephosphorylation, and a slower mechanism by regulation of RNA synthesis coupled to de novo NR protein synthesis.

Dynamics of Dissolved Forms of Carbon and Inorganic Nitrogen in Small Watersheds of the Coastal Atlantic Forest in Southeast Brazil

Based on the fact that streamwater quality reflects landscape conditions, the objectives of this study were: to investigate nitrogen (N), carbon (C), and major ion concentrations in six streams crossing minimally disturbed Atlantic Forest areas, with similar geomorphological characteristics; to determine N and C fluxes in one of these pristine streams (Indaia); and assess the impact of human activity on the biogeochemistry of two other streams in the same region, crossing urbanized areas. The distribution pattern of carbon and inorganic nitrogen dissolved forms, as well as the major ion and biogenic gas concentrations in the streamwater, was similar in pristine streams, indicating that the C and N dynamics were determined by influence of some factors, such as climate, atmospheric deposition, geology, soil type, and land covering, which were analogous in the forested watersheds. The urban streams were significantly different from the pristine streams, showing low dissolved oxygen concentrations, high respiration rates, and high concentrations of carbon dioxide, dissolved inorganic nitrogen, dissolved inorganic carbon, and major ion. These differences were attributed to anthropogenic impact on water quality, especially domestic sewage discharge. Additionally, in the Indaia stream, it was possible to observe the importance of rainfall over temporal dynamics of dissolved carbon forms, and also, the obtained specific flux of dissolved inorganic nitrogen was relatively elevated (approximately 11 kg ha(-1) year(-1)). These results reveal the influence of human activity over the biogeochemistry of coastal streams and also indicate the importance N export of Atlantic Forest to the ocean.

Reactive oxygen and nitrogen species balance in the determination of thyroid hormones-induced cardiac hypertrophy mediated by renin-angiotensin system

Role of reactive oxygen species (ROS)/nitric oxide (NO) balance and renin-angiotensin system in mediating cardiac hypertrophy in hyperthyroidism was evaluated in an in vivo and in vitro experimental model. Male Wistar rats were divided into four groups: control, thyroid hormone, vitamin E (or Trolox, its hydrosoluble analogue), thyroid hormone + vitamin E. Angiotensin II receptor (AT1/AT2) gene expression, immunocontent of AT1/AT2 receptors, angiotensinogen, NADPH oxidase (Nox2), and nitric oxide synthase isoforms, as well as ROS concentration (hydrogen peroxide and superoxide anion) were quantified in myocardium. Thyroid hormone increased ROS and NO metabolites, iNOS, nNOS and eNOS isoforms and it was accompanied by cardiac hypertrophy. AT1/AT2 expression and the immunocontent of angiotensinogen and Nox2 were enhanced by thyroid hormone. Antioxidants reduced ROS levels, Nox2, AT1/AT2, NOS isoforms and cardiac hypertrophy. In conclusion, ROS/NO balance may play a role in the control of thyroid hormone-induced cardiac hypertrophy mediated by renin-angiotensin system. (C) 2011 Elsevier Ireland Ltd. All rights reserved.

In situ impedance spectroscopy study of the electrochemical corrosion of Ti and Ti-6Al-4V in simulated body fluid at 25 degrees C and 37 degrees C

The corrosion resistance of Ti and Ti-6Al-4V was investigated through electrochemical impedance spectroscopy, EIS, potentiodynamic polarisation curves and UV-Vis spectrophotometry. The tests were done in Hank solution at 25 degrees C and 37 degrees C. The EIS measurements were done at the open circuit potential at specific immersion times. An increase of the resistance as a function of the immersion time was observed, for Ti (at 25 degrees C and 37 degrees C), and for Ti-6Al-4V (at 25 degrees C), which was interpreted as the formation and growth of a passive film on the metallic surfaces. (C) 2009 Elsevier Ltd. All rights reserved.

The GATA-type transcriptional activator Gat1 regulates nitrogen uptake and metabolism in the human pathogen Cryptococcus neoformans

Nitrogen uptake and metabolism are essential to microbial growth. Gat1 belongs to a conserved family of zinc finger containing transcriptional regulators known as GATA-factors. These factors activate the transcription of Nitrogen Catabolite Repression (NCR) sensitive genes when preferred nitrogen sources are absent or limiting. Cryptococcus neoformans GAT1 is an ortholog to the Aspergillus nidulans AreA and Candida albicans GAD genes. In an attempt to define the function of this transcriptional regulator in C. neoformans, we generated null mutants (gat1 Delta) of this gene. The gat 1 mutant exhibited impaired growth on all amino acids tested as sole nitrogen sources, with the exception of arginine and proline. Furthermore, the gat1 mutant did not display resistance to rapamycin, an immunosuppressant drug that transiently mimics a low-quality nitrogen source. Gal is not required for C. neoformans survival during macrophage infection or for virulence in a mouse model of cryptococcosis. Microarray analysis allowed the identification of target genes that are regulated by Gat1 in the presence of proline, a poor and non-repressing nitrogen source. Genes involved in ergosterol biosynthesis, iron uptake, cell wall organization and capsule biosynthesis, in addition to NCR-sensitive genes, are Gat1-regulated in C. neoformans. (C) 2010 Elsevier Inc. All rights reserved.