Different transcriptional control of metabolism and extracellular matrix in visceral and subcutaneous fat of obese and rimonabant treated mice.

BACKGROUND: The visceral (VAT) and subcutaneous (SCAT) adipose tissues play different roles in physiology and obesity. The molecular mechanisms underlying their expansion in obesity and following body weight reduction are poorly defined. METHODOLOGY: C57Bl/6 mice fed a high fat diet (HFD) for 6 months developed low, medium, or high body weight as compared to normal chow fed mice. Mice from each groups were then treated with the cannabinoid receptor 1 antagonist rimonabant or vehicle for 24 days to normalize their body weight. Transcriptomic data for visceral and subcutaneous adipose tissues from each group of mice were obtained and analyzed to identify: i) genes regulated by HFD irrespective of body weight, ii) genes whose expression correlated with body weight, iii) the biological processes activated in each tissue using gene set enrichment analysis (GSEA), iv) the transcriptional programs affected by rimonabant. PRINCIPAL FINDINGS: In VAT, "metabolic" genes encoding enzymes for lipid and steroid biosynthesis and glucose catabolism were down-regulated irrespective of body weight whereas "structure" genes controlling cell architecture and tissue remodeling had expression levels correlated with body weight. In SCAT, the identified "metabolic" and "structure" genes were mostly different from those identified in VAT and were regulated irrespective of body weight. GSEA indicated active adipogenesis in both tissues but a more prominent involvement of tissue stroma in VAT than in SCAT. Rimonabant treatment normalized most gene expression but further reduced oxidative phosphorylation gene expression in SCAT but not in VAT. CONCLUSION: VAT and SCAT show strikingly different gene expression programs in response to high fat diet and rimonabant treatment. Our results may lead to identification of therapeutic targets acting on specific fat depots to control obesity.

Beneficial effects of combinatorial micronutrition on body fat and atherosclerosis in mice.

AIMS: More than two billion people worldwide are deficient in key micronutrients. Single micronutrients have been used at high doses to prevent and treat dietary insufficiencies. Yet the impact of combinations of micronutrients in small doses aiming to improve lipid disorders and the corresponding metabolic pathways remains incompletely understood. Thus, we investigated whether a combination of micronutrients would reduce fat accumulation and atherosclerosis in mice. METHODS AND RESULTS: Lipoprotein receptor-null mice fed with an original combination of micronutrients incorporated into the daily chow showed reduced weight gain, body fat, plasma triglycerides, and increased oxygen consumption. These effects were achieved through enhanced lipid utilization and reduced lipid accumulation in metabolic organs and were mediated, in part, by the nuclear receptor PPARα. Moreover, the micronutrients partially prevented atherogenesis when administered early in life to apolipoprotein E-null mice. When the micronutrient treatment was started before conception, the anti-atherosclerotic effect was stronger in the progeny. This finding correlated with decreased post-prandial triglyceridaemia and vascular inflammation, two major atherogenic factors. CONCLUSION: Our data indicate beneficial effects of a combination of micronutritients on body weight gain, hypertriglyceridaemia, liver steatosis, and atherosclerosis in mice, and thus our findings suggest a novel cost-effective combinatorial micronutrient-based strategy worthy of being tested in humans.

Comparison of randomized branch sampling with and without replacement at the first stage

Abstract

Role of fat oxidation in the long-term stabilization of body weight in obese women.

Two studies were performed to investigate the association between body fat mass and fat oxidation. The first, a cross-sectional study of 106 obese women maintaining stable body weight, showed that these two variables were significantly correlated (r = 0.56, P less than 0.001) and the regression coefficient indicated that a 10-kg change in fat mass corresponded to a change in fat oxidation of approximately 20 g/d. The second, a prospective study, validated this estimate and quantifies the long-term adaptations in fat oxidation resulting from body fat loss. Twenty-four moderately obese women were studied under controlled dietary conditions at stable weight before and after mean weight and fat losses of 12.7 and 9.8 kg, respectively. The reduction in fat oxidation was identical to that predicted by the above regression. We conclude that changes in fat mass significantly affect fat oxidation and that this process may contribute to the long-term regulation of fat and energy balance in obese individuals.

Prevention and management of potential adverse events during transapical aortic valve replacement.

BACKGROUND AND AIM OF THE STUDY: Transapical transcatheter aortic valve replacement (TAVR) is a new minimally invasive technique with a known risk of unexpected intra-procedural complications. Nevertheless, the clinical results are good and the limited amount of procedural adverse events confirms the usefulness of a synergistic surgical/anesthesiological management in case of unexpected emergencies. METHODS: A review was made of the authors' four-year database and other available literature to identify major and minor intra-procedural complications occurring during transapical TAVR procedures. All implants were performed under general anesthesia with a balloon-expandable Edwards Sapien stent-valve, and followed international guidelines on indications and techniques. RESULTS: Procedural success rates ranged between 94% and 100%. Life-threatening apical bleeding occurred very rarely (0-5%), and its incidence decreased after the first series of implants. Stent-valve embolization was also rare, with a global incidence ranging from 0-2%, with evidence of improvement after the learning curve. Rates of valve malpositioning ranged from 0% to < 3%, whereas the risk of coronary obstruction ranged from 0% to 3.5%. Aortic root rupture and dissection were dramatic events reported in 0-2% of transapical cases. Stent-valve malfunction was rarely reported (1-2%), whereas the valve-in-valve bailout procedure for malpositioning, malfunctioning or severe paravalvular leak was reported in about 1.0-3.5% of cases. Sudden hemodynamic management and bailout procedures such as valve-in-valve rescue or cannulation for cardiopulmonary bypass were more effective when planned during the preoperative phase. CONCLUSION: Despite attempts to avoid pitfalls, complications during transapical aortic valve procedures still occur. Preoperative strategic planning, including hemodynamic status management, alternative cannulation sites and bailout procedures, are highly recommended, particularly during the learning curve of this technique.

Fructose and metabolic diseases: new findings, new questions.

There has been much concern regarding the role of dietary fructose in the development of metabolic diseases. This concern arises from the continuous increase in fructose (and total added caloric sweeteners consumption) in recent decades, and from the increased use of high-fructose corn syrup (HFCS) as a sweetener. A large body of evidence shows that a high-fructose diet leads to the development of obesity, diabetes, and dyslipidemia in rodents. In humans, fructose has long been known to increase plasma triglyceride concentrations. In addition, when ingested in large amounts as part of a hypercaloric diet, it can cause hepatic insulin resistance, increased total and visceral fat mass, and accumulation of ectopic fat in the liver and skeletal muscle. These early effects may be instrumental in causing, in the long run, the development of the metabolic syndrome. There is however only limited evidence that fructose per se, when consumed in moderate amounts, has deleterious effects. Several effects of a high-fructose diet in humans can be observed with high-fat or high-glucose diets as well, suggesting that an excess caloric intake may be the main factor involved in the development of the metabolic syndrome. The major source of fructose in our diet is with sweetened beverages (and with other products in which caloric sweeteners have been added). The progressive replacement of sucrose by HFCS is however unlikely to be directly involved in the epidemy of metabolic disease, because HFCS appears to have basically the same metabolic effects as sucrose. Consumption of sweetened beverages is however clearly associated with excess calorie intake, and an increased risk of diabetes and cardiovascular diseases through an increase in body weight. This has led to the recommendation to limit the daily intake of sugar calories.

Clinical relevance of L-carnitine-supplemented total parenteral nutrition in postoperative trauma. Metabolic effects of continuous or acute carnitine administration with special reference to fat oxidation and nitrogen utilization.

Carnitine-free total parenteral nutrition (TPN) is claimed to result in a carnitine deficiency with subsequent impairment of fat oxidation. The present study was designed to evaluate the possible benefit of carnitine supplementation on postoperative fat and nitrogen utilization. Sixteen patients undergoing total esophagectomy were evenly randomized and received TPN without or with L-carnitine supplementation (74 mumol.kg-1.d-1) during 11 postoperative days. On day 11, a 4-h infusion of L-carnitine (125 mumol/kg) was performed in both groups. The effect of supplementation was evaluated by indirect calorimetry, N balance, and repeated measurements of plasma lipids and ketone bodies. Irrespective of continuous or acute supplementation, respiratory quotient and fat oxidation were similarly maintained throughout the study in both groups whereas N balance appeared to be more favorable without carnitine. We conclude that carnitine-supplemented TPN does not improve fat oxidation or promote N utilization in the postoperative phase.

Size and fat content of gynes in relation to the mode of colony founding in ants (Hymenoptera; Formicidae)

In ants, there are two main processes of colony founding, the independent and the dependent modes. In the first case young queens start colony founding without the help of workers, whereas in the second case they are accompanied by workers. To determine the relation between the mode of colony founding and the physiology of queens, we collected mature gynes of 24 ant species. Mature gynes of species utilizing independent colony founding had a far higher relative fat content than gynes of species employing dependent colony founding. These fat reserves are stored during the period of maturation, i.e. between the time of emergence and mating, and serve as fuel during the time of colony founding to nurture the queen and the brood. Gynes of species founding independently but non claustrally were found to have a relative fat content intermediate between the values found for gynes founding independently and those founding dependently. This suggests that such gynes rely partially on their fat reserves and partially on the energy provided by prey they collect to nurture themselves and the first brood during the time of colony founding. Study of the fat content of mature gynes of all species has shown that it gives a good indication of the mode of colony founding.

Cross-sectional analysis of testosterone therapies in hypopituitary men on stable pituitary hormone replacement.

OBJECTIVE: The last decade has seen a proliferation in options for testosterone replacement. However, little is known as to the benefits of different treatment modalities. Our objective was to determine the testosterone prescription pattern and to examine the impact on various outcome measures. SUBJECTS AND METHODS: A total of 816 adult-onset hypopituitary males on stable pituitary replacement for at least 1 year were identified from the KIMS database. Patients were classified as either eugonadal (n = 106), or hypogonadal (n = 710) on intramuscular (IM, n = 558), oral (n = 74), transdermal (n = 61), and depot (n = 17) testosterone. RESULTS: After 1 year of stable pituitary replacement therapy, body composition, cardiovascular parameters, GH replacement and quality of life were not significantly different in androgen-replaced hypogonadal patients compared to eugonadal patients. There were no differences in outcome variables within the hypogonadal group according to the testosterone replacement regimen used and no difference in response to GH therapy. CONCLUSIONS: The majority of hypopituitary patients in the last decade have received IM testosterone. Body composition, cardiovascular parameters, GH replacement and quality of life were not different between eugonadal and hypogonadal patients and were not differentially affected by the mode of testosterone replacement. These findings are reassuring that there is no major difference in response to different testosterone replacement regimens.

Community replacement of neritic carbonate organisms during the late Valanginian platform demise: A new record from the Provence Platform

The Valanginian is marked by a major platform demise inducing a hiatus in the northern Tethyan neritic carbonate record from the top of the lower Valanginian to the lower Hauterivian. New biostratigraphic and chemostratigraphic data from the Ollioules section (Provence Platform, southern France) are presented here, demonstrating that a large part of the upper Valanginian is preserved in an inner platform environment. The thick, upper Valanginian, aggrading carbonate succession is observed in an aborted rift domain, implying relatively low subsidence. In this context, a relatively long-term sea-level rise was required to sustain a keep-up style of carbonate production. Like the Apulian Platform, the remarkable preservation of the Provence Platform may have been favored by its remoteness from terrigenous source areas, as suggested by the low clastic inputs and low P-accumulation rates. Two main biotic community replacements are observed in Ollioules. The first saw the development of abundant microbialites and algae at the onset of the late Valanginian. A Tubiphytes concentration occurred during the coolest climatic conditions and the transition towards arid conditions, whereas the subsequent Lithocodium-Bacinella and orbitolinids assemblages developed under low nutrient conditions during a warmer interval. Both assemblages may have been triggered by increased alkalinity. The second community replacement saw the installation of coral- and rudist-dominated communities during the latest Valanginian to early Hauterivian. They indicate a change to oligotrophic, open marine conditions. Six medium-scale sequences have been defined in Ollioules, indicating short-term transgressive-regressive trends superimposed on a long-term transgression. Low nutrient inputs and relatively low subsidence in an aggradational context may explain the survival of the isolated Provence Carbonate Platform during a time of widespread drowning episodes and platform demise in the northern Tethyan domain. (c) 2012 Elsevier B.V. All rights reserved.

Low-fat dairy products and blood pressure: follow-up of 2290 older persons at high cardiovascular risk participating in the PREDIMED study

High blood pressure (BP) has been ranked as the most important risk factor worldwide regarding attributable deaths. Dietary habits are major determinants of BP. Among them, frequent intake of low-fat dairy products may protect against hypertension. Our aim was to assess the relationship between low-fat dairy product intake and BP levels and their changes after 12 month follow-up in a cohort of asymptomatic older persons at high cardiovascular risk recruited into a large-scale trial assessing the effects of Mediterranean diets on cardiovascular outcomes. Data from 2290 participants, including 1845 with hypertension, were available for analyses. Dairy products were not a specific part of the intervention; thus, data were analysed as an observational cohort. Dietary information was collected with validated semi-quantitative FFQ and trained personnel measured BP. To assess BP changes, we undertook cross-sectional analyses at baseline and at the end of follow-up and longitudinal analyses. A statistically significant inverse association between low-fat dairy product intake and systolic BP was observed for the 12-month longitudinal analysis. In the longitudinal analysis, the adjusted systolic and diastolic BP were significantly lower in the highest quintile of low-fat dairy product intake ( 2 4·2 (95% CI 2 6·9, 2 1·4) and 2 1·8 (95% CI 2 3·2, 2 0·4) mmHg respectively), whereas the point estimates for the difference in diastolic BP indicated a modest non-significant inverse association. Intake of low-fat dairy products was inversely associated with BP in an older population at high cardiovascular risk, suggesting a possible protective effect against hypertension.

Low-fat dairy products and blood pressure: follow-up of 2290 older persons at high cardiovascular risk participating in the PREDIMED study

High blood pressure (BP) has been ranked as the most important risk factor worldwide regarding attributable deaths. Dietary habits are major determinants of BP. Among them, frequent intake of low-fat dairy products may protect against hypertension. Our aim was to assess the relationship between low-fat dairy product intake and BP levels and their changes after 12 month follow-up in a cohort of asymptomatic older persons at high cardiovascular risk recruited into a large-scale trial assessing the effects of Mediterranean diets on cardiovascular outcomes. Data from 2290 participants, including 1845 with hypertension, were available for analyses. Dairy products were not a specific part of the intervention; thus, data were analysed as an observational cohort. Dietary information was collected with validated semi-quantitative FFQ and trained personnel measured BP. To assess BP changes, we undertook cross-sectional analyses at baseline and at the end of follow-up and longitudinal analyses. A statistically significant inverse association between low-fat dairy product intake and systolic BP was observed for the 12-month longitudinal analysis. In the longitudinal analysis, the adjusted systolic and diastolic BP were significantly lower in the highest quintile of low-fat dairy product intake ( 2 4·2 (95% CI 2 6·9, 2 1·4) and 2 1·8 (95% CI 2 3·2, 2 0·4) mmHg respectively), whereas the point estimates for the difference in diastolic BP indicated a modest non-significant inverse association. Intake of low-fat dairy products was inversely associated with BP in an older population at high cardiovascular risk, suggesting a possible protective effect against hypertension.

Low-fat dairy products and blood pressure: follow-up of 2290 older persons at high cardiovascular risk participating in the PREDIMED study

High blood pressure (BP) has been ranked as the most important risk factor worldwide regarding attributable deaths. Dietary habits are major determinants of BP. Among them, frequent intake of low-fat dairy products may protect against hypertension. Our aim was to assess the relationship between low-fat dairy product intake and BP levels and their changes after 12 month follow-up in a cohort of asymptomatic older persons at high cardiovascular risk recruited into a large-scale trial assessing the effects of Mediterranean diets on cardiovascular outcomes. Data from 2290 participants, including 1845 with hypertension, were available for analyses. Dairy products were not a specific part of the intervention; thus, data were analysed as an observational cohort. Dietary information was collected with validated semi-quantitative FFQ and trained personnel measured BP. To assess BP changes, we undertook cross-sectional analyses at baseline and at the end of follow-up and longitudinal analyses. A statistically significant inverse association between low-fat dairy product intake and systolic BP was observed for the 12-month longitudinal analysis. In the longitudinal analysis, the adjusted systolic and diastolic BP were significantly lower in the highest quintile of low-fat dairy product intake ( 2 4·2 (95% CI 2 6·9, 2 1·4) and 2 1·8 (95% CI 2 3·2, 2 0·4) mmHg respectively), whereas the point estimates for the difference in diastolic BP indicated a modest non-significant inverse association. Intake of low-fat dairy products was inversely associated with BP in an older population at high cardiovascular risk, suggesting a possible protective effect against hypertension.