Peroxisome proliferator activated receptors: transcriptional regulators of adipogenesis, lipid metabolism and more....

The recent discovery of lipid-activatable transcription factors that regulate the genes controlling lipid metabolism and adipogenesis has provided insight into the way that organisms sense and respond to lipid levels. Identification of the signaling pathways in which these receptors are involved will help us to understand the control of energy balance and the molecular defects underlying its disorders.

Association of different lipid measures for atherogenic lipid fractions and risk of coronary events in patients receiving combination antiretroviral therapy: the Swiss HIV Cohort Study

Background: Evidence for a better performance of different highly atherogenic versus traditional lipid parameters for coronary heart disease (CHD) risk prediction is conflicting. We investigated the association of the ratios of sma11 dense low density lipoprotein(LDL)/apoplipoprotein A, aolipoprotein B/apolipoprotein A-I and total cholesterol! HDL-cholesterol and CHD events in patients on combination antiretroviral therapy (cART).Methods: Case control study nested into the Swiss HIV Cohort Study: for each cART-treated patient with a first coronary event between April 1, 2000 and July 31, 2008 (case) we selected four control patients (1) that were without coronary events until the date of the event of the index case, (2) had a plasma sample within ±30 days of the sample date of the respective case, (3) received cART and (4) were then matched for age, gender and smoking status. Lipoproteins were measured by ultracentrifugation. Conditional logistic regression models were used to estimate the independent effects of different lipid ratios and the occurrence of coronary events.Results: In total, 98 cases (19 fatal myocardial infarctions [MI] and 79 non-fatal coronary events [53 definite MIs, 15 possible MIs and 11 coronary angioplasties or bypassesJ) were matched with 392 controls. Cases were more often injecting drug users, less likely to be virologically suppressed and more often on abacavir-containing regimens. In separa te multivariable models of total cholesterol, triglycerides, HDL-cholesterol, systolic blood pressure, abdominal obesity, diabetes and family history of CHD, small dense-LDL and apolipoprotein B were each statistically significantly associated with CHD events (for 1 mg/dl increase: odds ratio [OR] 1.05, 95% CI 1.00-1.11 and 1.15, 95% CI 1.01-1.31, respectively), but the ratiosof small dense-LDLlapolipoprotein A-I (OR 1.26, 95% CI 0.95-1.67), apolipoprotein B/apolipoprotein A-I (OR 1.02, 95% CI 0.97-1.07) and HDL-cholesterol! total cholesterol (OR 0.99 95% CI 0.98-1.00) were not. Following adjustment for HIV related and cART variables these associations were weakened in each model: apolipoprotein B (OR 1.27, 95% CI 1.00-1.30), sd-LDL (OR 1.04, 95% CI 0.99-1.20), small dense-LDLlapolipoprotein A-I (OR 1.17, 95% CI 0.87-1.58), apolipoprotein B/apolipoprotein A-I (OR 1.02, 95% CI 0.97-1.07) and total cholesterolJHDL- cholesterol (OR 0.99, 95% CI 0.99-1.00).Conclusions: In patients receiving cART, small dense-LDL and apolipoprotein B showed the strongest associations with CHD events in models controlling for traditional CHD risk factors including total cholesterol and triglycerides. Adding small dense LDLlapoplipoprotein A-l, apolipoprotein B/apolipoprotein A-I and total cholesterol! HDL-cholesterol ratios did not further improve models of lipid parameters and associations of increased risk for CHD events.

Peroxisome proliferator-activated receptors and lipid metabolism.

PPARs are nuclear hormone receptors which, like the retinoid, thyroid hormone, vitamin D, and steroid hormone receptors, are ligand-activated transcription factors mediating the hormonal control of gene expression. Two lines of evidence indicate that PPARs have an important function in fatty acid metabolism. First, PPARs are activated by hypolipidemic drugs and physiological concentrations of fatty acids, and second, PPARs control the peroxisomal beta-oxidation pathway of fatty acids through transcriptional induction of the gene encoding the acyl-CoA oxidase (ACO), which is the rate-limiting enzyme of the pathway. Furthermore, the PPAR signaling pathway appears to converge with the 9-cis retinoic acid receptor (RXR) signaling pathway in the regulation of the ACO gene because heterodimerization between PPAR and RXR is essential for in vitro binding to the PPRE and because the strongest stimulation of this gene is observed when both receptors are exposed simultaneously to their activators. Thus, it appears that PPARs are involved in the 9-cis retinoic acid signaling pathway and that they play a pivotal role in the hormonal control of lipid metabolism.

Inflammatory markers and incident heart failure risk in older adults: the Health ABC (Health, Aging, and Body Composition) study.

OBJECTIVES: The purpose of this study was to evaluate the association between inflammation and heart failure (HF) risk in older adults. BACKGROUND: Inflammation is associated with HF risk factors and also directly affects myocardial function. METHODS: The association of baseline serum concentrations of interleukin (IL)-6, tumor necrosis factor-alpha, and C-reactive protein (CRP) with incident HF was assessed with Cox models among 2,610 older persons without prevalent HF enrolled in the Health ABC (Health, Aging, and Body Composition) study (age 73.6 +/- 2.9 years; 48.3% men; 59.6% white). RESULTS: During follow-up (median 9.4 years), HF developed in 311 (11.9%) participants. In models controlling for clinical characteristics, ankle-arm index, and incident coronary heart disease, doubling of IL-6, tumor necrosis factor-alpha, and CRP concentrations was associated with 29% (95% confidence interval: 13% to 47%; p < 0.001), 46% (95% confidence interval: 17% to 84%; p = 0.001), and 9% (95% confidence interval: -1% to 24%; p = 0.087) increase in HF risk, respectively. In models including all 3 markers, IL-6, and tumor necrosis factor-alpha, but not CRP, remained significant. These associations were similar across sex and race and persisted in models accounting for death as a competing event. Post-HF ejection fraction was available in 239 (76.8%) cases; inflammatory markers had stronger association with HF with preserved ejection fraction. Repeat IL-6 and CRP determinations at 1-year follow-up did not provide incremental information. Addition of IL-6 to the clinical Health ABC HF model improved model discrimination (C index from 0.717 to 0.734; p = 0.001) and fit (decreased Bayes information criterion by 17.8; p < 0.001). CONCLUSIONS: Inflammatory markers are associated with HF risk among older adults and may improve HF risk stratification.

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.

Composition of electricity generation portfolios, pivotal dynamics and market prices

We use a simulation model to study how the diversification of electricity generation portfoliosinfluences wholesale prices. We find that technological diversification generally leads to lower market prices but that the relationship is mediated by the supply to demand ratio. In each demand case there is a threshold where pivotal dynamics change. Pivotal dynamics pre- and post-threshold are the cause of non-linearities in the influence of diversification on market prices. The findings are robust to our choice of behavioural parameters and match close-form solutions where those are available.

The impact of gender composition on team performance and decision-making: Evidence from the field

We investigate whether the gender composition of teams affect theireconomic performance. We study a large business game, played in groups ofthree, where each group takes the role of a general manager. There are twoparallel competitions, one involving undergraduates and the other involvingMBAs. Our analysis shows that teams formed by three women aresignificantly outperformed by any other gender combination, both at theundergraduate and MBA levels. Looking across the performancedistribution, we find that for undergraduates, three women teams areoutperformed throughout, but by as much as 10pp at the bottom and by only1pp at the top. For MBAs, at the top, the best performing group is two menand one woman. The differences in performance are explained bydifferences in decision-making. We observe that three women teams are lessaggressive in their pricing strategies, invest less in R&D, and invest more insocial sustainability initiatives, than any other gender combination teams.Finally, we find support for the hypothesis that it is poor work dynamicsamong the three women teams that drives the results.

Abnormal Lung Function and Risk for Heart Failure in the Elderly: The Health, Aging, and Body Composition Study

Background: Chronic obstructive pulmonary disease (COPD) has been associated with increased risk for heart failure (HF). The impact of subclinical abnormal spirometric findings on HF risk among older adults without history of COPD is not well elucidated. Methods: We evaluated 2125 participants (age 73.6±2.9 years; 50.5% men; 62.3% white; 45.6/9.4% past/current smokers; body mass index [BMI] 27.2±4.6 kg/m2) without prevalent COPD or HF who underwent baseline spirometry in the Health ABC Study. Abnormal lung function was defined either as forced vital capacity (FVC) below lower limit of normal (LLN) or forced expiratory volume in 1st sec (FEV1) to FVC ratio below LLN. Results: On follow-up (median, 9.4 years), 68 of 350 (19.4%) participants with abnormal lung function developed HF, as compared to 172 of 1775 (9.7%) participants with normal lung function (hazard ratio [HR], 2.31; 95% confidence interval [CI], 1.74 -3.06; P<.001). This increased risk persisted after adjusting for all other independent predictors of HF in the Health ABC Study, BMI, incident coronary events, and several inflammatory markers (HR, 1.82; 95% CI, 1.30 -2.54; P<.001), and remained constant over time. Baseline FVC and FEV1 had a linear association with HF risk (Figure). In adjusted models, HF risk increased by 21% (95% CI, 10 -36%) per 10% decrease in FVC and 18% (95% CI, 10 -28%) per 10% decrease in FEV1 (both P<.001); this association persisted among participants with normal lung function at baseline. Findings were consistent across sex, race, and smoking status. Conclusions: Subclinical abnormal spirometric findings are prevalent among older adults and are independently associated with risk for incident HF.

Estimating parliamentary composition through electoral polls

Any electoral system has an electoral formula that converts voteproportions into parliamentary seats. Pre-electoral polls usually focuson estimating vote proportions and then applying the electoral formulato give a forecast of the parliament's composition. We here describe theproblems arising from this approach: there is always a bias in theforecast. We study the origin of the bias and some methods to evaluateand to reduce it. We propose some rules to compute the sample sizerequired for a given forecast accuracy. We show by Monte Carlo simulationthe performance of the proposed methods using data from Spanish electionsin last years. We also propose graphical methods to visualize how electoralformulae and parliamentary forecasts work (or fail).

European research funding and regional technological capabilities: Network composition analysis

We use network and correspondence analysis to describe the compositionof the research networks in the European BRITE--EURAM program. Our mainfinding is that 27\% of the participants in this program fall into one oftwo sets of highly ``interconnected'' institutions --one centered aroundlarge firms (with smaller firms and research centers providing specializedservices), and the other around universities--. Moreover, these ``hubs''are composed largely of institutions coming from the technologically mostadvanced regions of Europe. This is suggestive of the difficulties of attainingEuropean ``cohesion'', as technically advanced institutions naturally linkwith partners of similar technological capabilities.

Resistance to diet-induced obesity and associated metabolic perturbations in haploinsufficient monocarboxylate transporter 1 mice

The monocarboxylate transporter 1 (MCT1 or SLC16A1) is a carrier of short-chain fatty acids, ketone bodies, and lactate in several tissues. Genetically modified C57BL/6J mice were produced by targeted disruption of the mct1 gene in order to understand the role of this transporter in energy homeostasis. Null mutation was embryonically lethal, but MCT1 (+/-) mice developed normally. However, when fed high fat diet (HFD), MCT1 (+/-) mice displayed resistance to development of diet-induced obesity (24.8% lower body weight after 16 weeks of HFD), as well as less insulin resistance and no hepatic steatosis as compared to littermate MCT1 (+/+) mice used as controls. Body composition analysis revealed that reduced weight gain in MCT1 (+/-) mice was due to decreased fat accumulation (50.0% less after 9 months of HFD) notably in liver and white adipose tissue. This phenotype was associated with reduced food intake under HFD (12.3% less over 10 weeks) and decreased intestinal energy absorption (9.6% higher stool energy content). Indirect calorimetry measurements showed ∼ 15% increase in O2 consumption and CO2 production during the resting phase, without any changes in physical activity. Determination of plasma concentrations for various metabolites and hormones did not reveal significant changes in lactate and ketone bodies levels between the two genotypes, but both insulin and leptin levels, which were elevated in MCT1 (+/+) mice when fed HFD, were reduced in MCT1 (+/-) mice under HFD. Interestingly, the enhancement in expression of several genes involved in lipid metabolism in the liver of MCT1 (+/+) mice under high fat diet was prevented in the liver of MCT1 (+/-) mice under the same diet, thus likely contributing to the observed phenotype. These findings uncover the critical role of MCT1 in the regulation of energy balance when animals are exposed to an obesogenic diet.

Hesperiidae (Lepidoptera, Hesperioidea) from Ponta Grossa, Paraná, Brazil: 70 years of records with special reference to faunal composition of Vila Velha State Park

Hesperiidae (Lepidoptera, Hesperioidea) de Ponta Grossa, Paraná, Brazil: 70 anos de registros com especial referência à composição faunística do Parque Estadual de Vila Velha. O município de Ponta Grossa se destaca por apresentar originalmente uma paisagem peculiar onde capões isolados de Floresta Ombrófila Mista são interligados por grandes extensões de fitofisionomias estépicas, também denominadas campos. No entanto, ambos os ecossistemas atualmente se encontram altamente ameaçados pela ocupação humana, restando na região o Parque Estadual de Vila Velha, cuja composição florística tem sido recentemente relacionada com o bioma Cerrado. Poucos trabalhos são dedicados à caracterização da fauna dos campos e sua relação com outras fitofisionomias estépicas brasileiras, motivo que suscitou a realização deste estudo. Após reunir informações de coletas realizadas por mais de 70 anos, são listadas 225 espécies de Hesperiidae (Lepidoptera, Hesperioidea) presentes no município, entre elas 162 indicadoras de ambientes florestais e 53 de áreas abertas. O Parque Estadual de Vila Velha contribui para a conservação de 65% delas enquanto sua composição se mostra intimamente relacionada tanto aos Pampas como ao Cerrado, em detrimento de hábitats florestais. Tal relação é dada provavelmente pela localização geográfica de Vila Velha, visto que a similaridade da fauna de Hesperiidae se encontrou influenciada pelas distâncias geográficas das amostras no presente estudo. A flora de Vila Velha também deve afetar diretamente a composição observada de Hesperiidae, uma vez que uma grande parte de suas espécies são também encontradas em áreas de Cerrado. No entanto, estudos em ambientes campestres brasileiros ainda se fazem necessários, especialmente em enclaves de Cerrado no Paraná e em São Paulo, para que se adquira um melhor entendimento da dinâmica de suas comunidades.

Lipid and energy contents in the bodies of queens of Atta sexdens rubropilosa Forel (Hymenoptera, Formicidae): pre-and post-nuptial flight

The nuptial flight allows males and females to meet and copulate and both need energy to perform this activity. Before leaving the nest, males and females are well nourished and ready to mate. However, little is known about the lipid and energy contents in females before the nuptial flight (virgins) and after it (mated females). In this work we measured lipid concentrations in relation to body weight in these individuals. Our results showed that 16.82% of the bodies of young virgin females one month before mating flight are composed of lipids, contrasting with the 32.62% lipid content in mated females who had not excavated their nest yet, and 32.88% in those who had. The energy content measured for virgin females was 2942.63 J, contrasting with 6110.01 J for queens before excavating the nest and 5677.51 J after excavation. Based on our results, we conclude that the body mass, and therefore the lipid and energy contents in the bodies of Atta sexdens rubropilosa queens double during the last month before the nuptial flight. This energy resource is fundamental to the activities required during the nuptial flight, digging the nest and the founding of the colony.