Decreased fatty acit Â-oxidation in riboflavin-responsive, multiple acylocoenzyme a dehydrogenase-deficient patients is associated with an increase in uncoupling protein-3

Riboflavin-responsive, multiple acylcoenzyme A dehydrogenase deficiency (RR-MAD), a lipid storage myopathy, is characterized by, among others, a decrease in fatty acid (FA) ß-oxidation capacity. Muscle uncoupling protein 3 (UCP3) is up-regulated under conditions that either increase the levels of circulating free FA and/or decrease FA ß-oxidation. Using a relatively large cohort of seven RR-MAD patients, we aimed to better characterize the metabolic disturbances of this disease and to explore the possibility that it might increase UCP3 expression. A battery of biochemical and molecular tests were performed, which demonstrated decreases in FA ß-oxidation and in the activities of respiratory chain complexes I and II. These metabolic alterations were associated with increases of 3.1- and 1.7-fold in UCP3 mRNA and protein expression, respectively. All parameters were restored to control values after riboflavin treatment. We postulate that the up-regulation of UCP3 in RR-MAD is due to the accumulation of muscle FA/acylCoA. RR-MAD is an optimal model to support the hypothesis that UCP3 is involved in the outward translocation of an excess of FA from the mitochondria and to show that, in humans, the effects of FA on UCP3 expression are direct and independent of fatty acid ß-oxidation.

Integrated phenotypic and activity-based profiling links Ces3 to obesity and diabetes

Phenotypic screening is making a comeback in drug discovery as the maturation of chemical proteomics methods has facilitated target identification for bioactive small molecules. A limitation of these approaches is that time-consuming genetic methods or other means are often required to determine the biologically relevant target (or targets) from among multiple protein-compound interactions that are typically detected. Here, we have combined phenotypic screening of a directed small-molecule library with competitive activity-based protein profiling to map and functionally characterize the targets of screening hits. Using this approach, we identify carboxylesterase 3 (Ces3, also known as Ces1d) as a primary molecular target of bioactive compounds that promote lipid storage in adipocytes. We further show that Ces3 activity is markedly elevated during adipocyte differentiation. Treatment of two mouse models of obesity-diabetes with a Ces3 inhibitor ameliorates multiple features of metabolic syndrome, illustrating the power of the described strategy to accelerate the identification and pharmacologic validation of new therapeutic targets.

GM3 ganglioside and phosphatidylethanolamine-containing lipids are adipose tissue markers of insulin resistance in obese women

AimsThe association between central obesity and insulin resistance reflects the properties of visceral adipose tissue. Our aim was to gain further insight into this association by analysing the lipid composition of subcutaneous and omental adipose tissue in obese women with and without insulin resistance.MethodsSubcutaneous and omental adipose tissue and serum were obtained from 29 obese non-diabetic women, 13 of whom were hyperinsulinemic. Histology, and lipid and gene profiling were performed.ResultsIn omental adipose tissue of obese, insulin-resistant women, adipocyte hypertrophy and macrophage infiltration were accompanied by an increase in GM3 ganglioside and its synthesis enzyme ST3GAL5; in addition, phosphatidylethanolamine (PE) lipids were increased and their degradation enzyme, PEMT, decreased. ST3GAL5 was expressed predominantly in adipose stromovascular cells and PEMT in adipocytes. Insulin resistance was also associated with an increase in PE lipids in serum.InterpretationThe relevance of these findings to insulin resistance in humans is supported by published mouse studies in which adipocyte GM3 ganglioside, increased by the inflammatory cytokine tumour necrosis factor-α, impaired insulin action, and PEMT was required for adipocyte lipid storage. Thus, in visceral adipose tissue of obese humans, an increase in GM3 ganglioside secondary to inflammation may contribute to insulin resistance and a decrease in PEMT may be a compensatory response to adipocyte hypertrophy.International Journal of Obesity accepted article preview online, 26 October 2015. doi:10.1038/ijo.2015.223.

Morfologia e anatomia da semente de Esenbeckia grandiflora Mart. (Rutaceae)

Foram descritos e ilustrados aspectos morfo-anatômicos das sementes de Esenbeckia grandiflora Mart., visando o conhecimento dos tegumentos, endosperma e embrião. As sementes são de elipsóides a piramidais, marrom-escuras, anátropas, mesotestais, sem tégmem, exariladas e exalbuminosas. O embrião é axial, reto, total, branco, com cotilédones carnosos de reserva lipo-protéica, eixo hipocótilo-radícula curto e plúmula reduzida.

Morfologia e anatomia da semente de Balfourodendron riedelianum (Engler) Engler - Rutaceae

Foram descritos e ilustrados aspectos morfoanatômicos das sementes de Balfourodendron riedelianum (Engler) Engler, visando a caracterização dos tegumentos, endosperma e embrião. As sementes são elipsóides, pretas, anátropas, endotestais com tégmem reduzido, exariladas e albuminosas. O endosperma possui reserva lipo-protéica. Embrião axial, dominante, branco, com cotilédones carnosos, eixo hipocótilo-radícula curto e plúmula reduzida.

Antropometria de atletas culturistas em relacao a referencia populacional

Body builders have as their training goals the maximum muscle hypertrophy with minimum adiposity. However, the scarcity of specific standards implies often in framing wrongly those athletes either as overweight (by their BMI) or energy malnourished (by their fat stores). The objective of this study was to compare the body composition of body builders with population standards. Thirty-six adults, 26 male (27.2 ± 7.2 years) and 10 female (30 ± 6.1 years) nationwide competitive body builders, were assessed considering weight, height, body mass index, adiposity, arm and leg circumferences and skinfolds. The data were referred either as percentile or standard deviations (Z score) of population standards. Body weight and height were among the closest values from the populational mean whereas upper arm muscle circumference (for men) and body adiposity (for women) were the farterest. By using fat parameters as indicators of their protein-energy status, the undernourishment was found in 88.5% of men and 100.0% of women. Thus, it seems that body builders deserve their own anthropometric standards to avoid nutritional status misplacements.

Relação peso-comprimento e fator de condição para Cichla cf. ocellaris e Cichla monoculus (Perciformes, Cichlidae) no reservatório de Volta Grande, Rio Grande - MG/SP

The aim of this paper was to analyze the length-weight relationship and the condition factor of two species of cichlids (Cichla cf. ocellaris and Cichla monoculus) (Perciformes, Cichlidae) that were inducted in Volta Grande Reservoir, Rio Grande. There was no difference in the length-weight relationship between the sexes for Cichla cf. ocellaris and Cichla monoculus. The allometric condition factor showed a fall in the spring and another smaller one in the winter. It happens when these fishes change their feeding activity. In the spring all the reproductive behavior are developed and, in the winter, there is a shortage of prey. The variation of the relative condition factor followed the variation of the allometric condition factor due to the low contribution of the gonads weight and the small amount of accumulated fat in the total weight. The length distribution, length-weight relationship and condition factor of these fishes vary in accordance with the time of introduction into the reservoir, the characteristics of the ecosystem as well as the interactions among the species at these sites.

Fermented soy product supplemented with isoflavones affected fat depots in juvenile rats

Objectives: This study investigated the effects of soy product fermented by Enterococcus faecium and Lactobacillus jugurti supplemented with isoflavones on adipose tissue, blood lipid, and glucose levels on juvenile rats. Methods: Rats were fed a cholesterol-enriched diet for 3 wk as a preliminary treatment to create hypercholesterolemia. They were then fed a chow diet (HC), a chow diet plus fermented soy product supplemented with isoflavones (HCFI), a chow diet plus placebo (HCP), or a chow diet plus placebo supplemented with isoflavones (HCPI), respectively, for an additional 3 wk. Results: The beneficial effects of fermented soy product supplemented with isoflavones on epididymal (EPI) and retroperitoneal (RET) fat pads was likely due to isoflavones because adipocyte circumference (micrometers) in the HC group was significantly larger (EPI: 105.66 ± 13.36; RET: 134.95 ± 25.40) than that in the HCFI group (EPI: 93.17 ± 12.80; RET: 108.62 ± 15.50) and HCPI group (EPI: 93.06 ± 15.10; RET: 112.34 ± 18.21). The probiotic micro-organism accentuated the antilipogenic effect of isoflavones on RET (HCFI: 108.62 ± 15.50 micrometers versus HCPI: 112.34 ± 18.21 micrometers). Moreover, the fermented product increased glucose concentration similar to that in the chow group but did not change blood lipids. Conclusion: This product may offer new approaches to obesity prevention. © 2005 Elsevier Inc. All rights reserved.

A Comparative Genotoxicity Study of a Supraphysiological Dose of Triiodothyronine (T3) in Obese Rats Subjected to Either Calorie-Restricted Diet or Hyperthyroidism

This study was designed to determine the genotoxicity of a supraphysiological dose of triiodothyronine (T3) in both obese and calorie-restricted obese animals. Fifty male Wistar rats were randomly assigned to one of the two following groups: control (C; n = 10) and obese (OB; n = 40). The C group received standard food, whereas the OB group was fed a hypercaloric diet for 20 weeks. After this period, half of the OB animals (n = 20) were subjected to a 25%-calorie restriction of standard diet for 8 weeks forming thus a new group (OR), whereas the remaining OB animals were kept on the initial hypercaloric diet. During the following two weeks, 10 OR animals continued on the calorie restriction diet, whereas the remaining 10 rats of this group formed a new group (ORS) given a supraphysiological dose of T3 (25 μg/100 g body weight) along with the calorie restriction diet. Similarly, the remaining OB animals were divided into two groups, one that continued on the hypercaloric diet (OB, n = 10), and one that received the supraphysiological dose of T3 (25 μg/100 g body weight) along with the hypercaloric diet (OS, n = 10) for two weeks. The OB group showed weight gain, increased adiposity, insulin resistance, increased leptin levels and genotoxicity; T3 administration in OS animals led to an increase in genotoxicity and oxidative stress when compared with the OB group. The OR group showed weight loss and normalized levels of adiposity, insulin resistance, serum leptin and genotoxicity, thus having features similar to those of the C group. On the other hand, the ORS group, compared to OR animals, showed higher genotoxicity. Our results indicate that regardless of diet, a supraphysiological dose of T3 causes genotoxicity and potentiates oxidative stress. © 2013 de Sibio et al.

Moderate physical activity from childhood contributes to metabolic health and reduces hepatic fat accumulation in adult rats

Background: Obesity, oxidative stress and inflammation, by triggering insulin resistance, may contribute to the accumulation of hepatic fat, and this accumulation by lipotoxicity can lead the organ to fail. Because obesity is growing at an alarming rate and, worryingly, in a precocious way, the present study aimed to investigate the effects of moderate physical training performed from childhood to adulthood on liver fat metabolism in rats. Methods. Twenty rats that were 28days old were divided into two groups: control (C) and trained (T). The C Group was kept in cages without exercise, and the T group was submitted to swimming exercise for 1hour/day, 5days/week from 28 to 90days of age (8weeks) at 80% of the anaerobic threshold determined by the lactate minimum test. At the end of the experiment, the body weight gain, insulin sensitivity (glucose disappearance rate during the insulin tolerance test), concentrations of free fatty acids (FFA) and triglycerides (TG) and hepatic lipogenic rate were analyzed. For the statistical analysis, the Student t-test was used with the level of significance preset at 5%. Results: The T group showed lower body weight gain, FFA concentrations, fat accumulation, hepatic lipogenic rate and insulin resistance. Conclusion: The regular practice of moderate physical exercise from childhood can contribute to the reduction of obesity and insulin resistance and help prevent the development of accumulation of hepatic fat in adulthood. © 2013de Moura et al; licensee BioMed Central Ltd.

Energy Metabolism in Cardiac Remodeling and Heart Failure

Fatty acids are the main substrates used by mitochondria to provide myocardial energy under normal conditions. During heart remodeling, however, the fuel preference switches to glucose. In the earlier stages of cardiac remodeling, changes in energy metabolism are considered crucial to protect the heart from irreversible damage. Furthermore, low fatty acid oxidation and the stimulus for glycolytic pathway lead to lipotoxicity, acidosis, and low adenosine triphosphate production. While myocardial function is directly associated with energy metabolism, the metabolic pathways could be potential targets for therapy in heart failure. © 2013 by Lippincott Williams & Wilkins.

Estocagem tecidual e utilização de lipídeos em Matrinxã, Brycon cephalus (Günther, 1869)

Lipids have important biological functions, suchas membrane constituents, hormone precursors, and are efficient energy reserves, due to thers high caloric content. In fish, but not in mammals, lipid storage patterns are quite diverse. The aim of this study was to determine lipid distribution in somatic and reproductive tissues of matrinxã, Brycon cephalus, both male and female, highlighting somatic indices related to lipid dynamics. From Oct 98 to Jan 99, a total of 174 fish (8-12 each month) were sampled. After fish anesthesia, heparinized blood was collected for plasma triacylglycerol determination. Fish were individually weighed and measured, and liver, gonads and visceral fat were collected and weighed for HSI (hepatosomatic index), GSI (gonad somatic index) and MFI (mesenteric fat index) calculation. The highest values of total lipids were found in red muscle (about 18%), liver and gonads (about 16.5%). The white muscle had a lower concentration (2.5%). Analyses of variance of HSI and MFI showed fluctuations along the experimental period with lowest concentrations in the periods of highest temperatures. Matrinxã store lipids in several body tissues, including mesenteric fat, liver, muscles and gonads.

Administration of a murine diet supplemented with conjugated linoleic acid increases the expression and activity of hepatic uncoupling proteins

Daily intake of conjugated linoleic acid (CLA) has been shown to reduce body fat accumulation and to increase body metabolism; this latter effect has been often associated with the up-regulation of uncoupling proteins (UCPs). Here we addressed the effects of a CLA-supplemented murine diet (similar to 2 % CLA mixture, cis-9, trans-10 and trans-10, cis-12 isomers; 45 % of each isomer on alternating days) on mitochondrial energetics, UCP2 expression/activity in the liver and other associated morphological and functional parameters, in C57BL/6 mice. Diet supplementation with CLA reduced both lipid accumulation in adipose tissues and triacylglycerol plasma levels, but did not augment hepatic lipid storage. Livers of mice fed a diet supplemented with CLA showed high UCP2 mRNA levels and the isolated hepatic mitochondria showed indications of UCP activity: in the presence of guanosine diphosphate, the higher stimulation of respiration promoted by linoleic acid in mitochondria from the CLA mice was almost completely reduced to the level of the stimulation from the control mice. Despite the increased generation of reactive oxygen species through oxi-reduction reactions involving NAD(+)/NADH in the Krebs cycle, no oxidative stress was observed in the liver. In addition, in the absence of free fatty acids, basal respiration rates and the phosphorylating efficiency of mitochondria were preserved. These results indicate a beneficial and secure dose of CLA for diet supplementation in mice, which induces UCP2 overexpression and UCP activity in mitochondria while preserving the lipid composition and redox state of the liver.

Niemann-Pick disease type C symptomatology: an expert-based clinical description

Niemann-Pick disease type C (NP-C) is a rare, progressive, irreversible disease leading to disabling neurological manifestations and premature death. The estimated disease incidence is 1:120,000 live births, but this likely represents an underestimate, as the disease may be under-diagnosed due to its highly heterogeneous presentation. NP-C is characterised by visceral, neurological and psychiatric manifestations that are not specific to the disease and that can be found in other conditions. The aim of this review is to provide non-specialists with an expert-based, detailed description of NP-C signs and symptoms, including how they present in patients and how they can be assessed. Early disease detection should rely on seeking a combination of signs and symptoms, rather than isolated findings. Examples of combinations which are strongly suggestive of NP-C include: splenomegaly and vertical supranuclear gaze palsy (VSGP); splenomegaly and clumsiness; splenomegaly and schizophrenia-like psychosis; psychotic symptoms and cognitive decline; and ataxia with dystonia, dysarthria/dysphagia and cognitive decline. VSGP is a hallmark of NP-C and becomes highly specific of the disease when it occurs in combination with other manifestations (e.g. splenomegaly, ataxia). In young infants (<2 years), abnormal saccades may first manifest as slowing and shortening of upward saccades, long before gaze palsy onset. While visceral manifestations tend to predominate during the perinatal and infantile period (2 months–6 years of age), neurological and psychiatric involvement is more prominent during the juvenile/adult period (>6 years of age). Psychosis in NP-C is atypical and variably responsive to treatment. Progressive cognitive decline, which always occurs in patients with NP-C, manifests as memory and executive impairment in juvenile/adult patients. Disease prognosis mainly correlates with the age at onset of the neurological signs, with early-onset forms progressing faster. Therefore, a detailed and descriptive picture of NP-C signs and symptoms may help improve disease detection and early diagnosis, so that therapy with miglustat (Zavesca®), the only available treatment approved to date, can be started as soon as neurological symptoms appear, in order to slow disease progression.