Leptin is not associated independently with hypertension in Japanese-Brazilian women

We evaluated the relationship of leptin with hypertension adjusted for body mass index (BMI) and/or waist circumference in a population of Japanese-Brazilian women aged > or = 30 years with centrally distributed adiposity. After excluding diabetic subjects, the study subjects - who participated in a population-based study on the prevalence of metabolic syndrome - showed prevalence rates of obesity (BMI > or = 25 kg/m²) and central adiposity (waist > or = 80 cm) of 32.0 and 37.8%, respectively. The hypertensive group (N = 162) was older, had higher BMI (24.9 ± 4.2 vs 23.3 ± 3.4 kg/m², P < 0.001), waist circumference (81.1 ± 10.1 vs 76.3 ± 8.2 cm, P < 0.001) and insulin levels (8.0 ± 6.2 vs 7.1 ± 4.9 µU/mL, P < 0.05) than the normotensive group (N = 322) and showed an unfavorable metabolic profile (higher 2-h plasma glucose, C-reactive protein and non-HDL cholesterol levels). Leptin did not differ between groups (8.2 ± 6.8 vs 7.2 ± 6.6 ng/mL, P = 0.09, for hypertensive vs normotensive, respectively) and its levels correlated significantly with anthropometric variables but not with blood pressure. Logistic regression analysis indicated that age and waist were independently associated with hypertension but not with homeostasis model assessment of insulin resistance or leptin levels. The lack of an independent association of hypertension with metabolic parameters (2-h glucose, C-reactive protein and non-HDL cholesterol) after adjustment for central adiposity suggested that visceral fat deposition may be the common mediator of the disturbances of the metabolic syndrome. Our data indicate that age and waist are major determinants of hypertension in this population of centrally obese (waist > or = 80 cm) Japanese-Brazilian women, but do not support a role for leptin in the elevation of blood pressure.

Health in early adulthood: the contribution of the 1978/79 Ribeirão Preto birth cohort

The increase in non-communicable chronic diseases of adults is due to demographic changes and changes in the risk factors related to physical activity, smoking habits and nutrition. We describe the methodology for the evaluation of persons at 23/25 years of age of a cohort of individuals born in Ribeirão Preto in 1978/79. We present their socioeconomic characteristics and the profile of some risk factors for chronic diseases. A total of 2063 participants were evaluated by means of blood collection, standardized questionnaires, anthropometric and blood pressure measurements, and methacholine bronchoprovocation tests. The sexes were compared by the chi-square test, with alpha = 0.05. Obesity was similar among men and women (12.8 and 11.1%); overweight was almost double in men (30.3 vs 17.7%). Weight deficit was higher among women than among men (8.6 and 2.6%). Women were more sedentary and consumed less alcohol and tobacco. Dietary fat consumption was similar between sexes, with 63% consuming large amounts (30 to 39.9 g/day). Metabolic syndrome was twice more frequent among men than women (10.7 vs 4.8%), hypertension was six times more frequent (40.9 vs 6.4%); altered triglyceride (16.1 vs 9.8%) and LDL proportions (5.4 vs 2.7%) were also higher in men, while women had a higher percentage of low HDL (44.7 vs 39.5%). Asthma and bronchial hyper-responsiveness were 1.7 and 1.5 times more frequent, respectively, among women. The high prevalence of some risk factors for chronic diseases among young adults supports the need for investments in their prevention.

The reciprocal interaction between sleep and type 2 diabetes mellitus: facts and perspectives

Type 2 diabetes mellitus is a systemic disease characterized by intolerance to glucose and peripheral resistance to insulin. This endocrine disease affects fundamental mechanisms of the central nervous system and jeopardizes the balance of vital functions such as the cardiovascular and circadian rhythm. The increased prevalence of metabolic disorders in our society is aggravated by endemic voluntary postponement of bedtime and by the current sedentary lifestyle, leading to epidemic proportions of obese people. Diabetes and chronic loss of sleep share the fact that both affect millions and one is detrimental to the other. Indeed, sleep deficits have marked modulatory effects on glucose metabolism and insulin sensitivity and foster metabolic syndrome that culminates in sleep disorders like restless syndrome and sleep apnea, which in turn lead to poor sleep quality. We examine the hypothesis that these two worldwide emerging disorders are due to two interlinked cycles. In our paradigm, we establish an intimate relationship between diabetes and sleep disturbances and postulate possible mechanisms that provide support for this conjecture. In addition, we propose some perspectives about the development of the reciprocal interaction between predictor components of metabolic syndrome and sleep disturbances that lead to poor sleep quality. The ability to predict the development and identify or associate a given mode of sleep disturbance to diabetes would be a valuable asset in the assessment of both. Furthermore, major advances in care coupled with healthy lifestyles can ensure a higher quality of life for people with diabetes.

The effect of thyroid hormones on the white adipose tissue gene expression of PAI-1 and its serum concentration

Metabolic syndrome is associated with an increased risk of developing cardiovascular diseases and Plasminogen activator inhibitor 1 (PAI-1) overexpression may play a significant role in this process. A positive correlation between adipose tissue gene expression of PAI-1 and its serum concentration has been reported. Furthermore, high serum levels of thyroid hormones (T3 and T4) and PAI-1 have been observed in obese children. The present study evaluates the impact of thyroid hormone treatment on white adipose tissue PAI-1 gene expression and its serum concentration. Male Wistar rats (60 days old) were treated for three weeks with T4 (50 µg/day, Hyper) or with saline (control). Additionally, 3T3-L1 adipocytes were treated for 24 h with T4 (100 nM) or T3 (100 nM). PAI-1 gene expression was determined by real-time PCR, while the serum concentration of PAI-1 was measured by ELISA using a commercial kit (Innovative Research, USA). Both the serum concentration of PAI-1 and mRNA levels were similar between groups in retroperitoneal and epididymal white adipose tissue. Using 3T3-L1 adipocytes, in vitro treatment with T4 and T3 increased the gene expression of PAI-1, suggesting non-genomic and genomic effects, respectively. These results demonstrate that thyroid hormones have different effects in vitro and in vivo on PAI-1 gene expression in adipocytes.

Beneficial effects of exercise training (treadmill) on insulin resistance and nonalcoholic fatty liver disease in high-fat fed C57BL/6 mice

C57BL/6 mice develop signs and symptoms comparable, in part, to the human metabolic syndrome. The objective of the present study was to evaluate the effects of exercise training on carbohydrate metabolism, lipid profile, visceral adiposity, pancreatic islet alterations, and nonalcoholic fatty liver disease in C57BL/6 mice. Animals were fed one of two diets during an 8-week period: standard (SC, N = 12) or very high-fat (HF, N = 24) chow. An exercise training protocol (treadmill) was then established and mice were divided into SC and HF sedentary (SC-Sed, HF-Sed), exercised groups (SC-Ex, HF-Ex), or switched from HF to SC (HF/SC-Sed and HF/SC-Ex). HF/HF-Sed mice had the greatest body mass (65% more than SC/SC-Sed; P < 0.0001), and exercise reduced it by 23% (P < 0.0001). Hepatic enzymes ALP (+80%), ALT (+100%) and AST (+70%) were higher in HF/HF mice than in matched SC/SC. Plasma insulin was higher in both the HF/HF-Sed and HF/SC-Sed groups than in the matched exercised groups (+85%; P < 0.001). Pancreatic islets, adipocytes and liver structure were greatly affected by HF, ultimately resulting in islet β-cell hypertrophy and severe liver steatosis. The HF group had larger islets than the SC/SC group (+220%; P < 0.0001), and exercise significantly reduced liver steatosis and islet size in HF. Exercise attenuated all the changes due to HF, and the effects were more pronounced in exercised mice switched from an HF to an SC diet. Exercise improved the lipid profile by reducing body weight gain, visceral adiposity, insulin resistance, islet alterations, and fatty liver, contributing to obesity and steatohepatitis control.

Is arterial stiffness in HIV-infected individuals associated with HIV-related factors?

We investigated the association between pulse wave velocity (PWV) and HIV infection, antiretroviral treatment-related characteristics, viral load, immune status, and metabolic changes in a cross-sectional study nested in a cohort of HIV/AIDS patients who have been followed for metabolic and cardiovascular changes since 2007. The study included patients recruited from the cohort (N = 261) and a comparison group (N = 82) of uninfected individuals, all enrolled from April to November 2009. Aortic stiffness was estimated using the carotid-femoral PWV (Complior-Artech, Paris, France). The groups were similar with respect to age, metabolic syndrome, diabetes mellitus, Framingham score, and use of antihypertensive and hypolipidemic medications. Hypertension was more frequent among the controls. Individuals with HIV had higher triglyceride, glucose and HDL cholesterol levels. Among individuals with HIV/AIDS, those with a nadir CD4+ T-cell count <200 cells/mm³ had a higher PWV (P = 0.01). There was no statistically significant difference when subjects were stratified by gender. Heart rate, age, male gender, and blood pressure were independently correlated with PWV. Nadir CD4+ T-cell count did not remain in the final model. There was no significance difference in PWV between HIV-infected individuals and uninfected controls. PWV was correlated with age, gender, and blood pressure across the entire population and among those infected with HIV. We recommend cohort studies to further explore the association between inflammation related to HIV infection and/or immune reconstitution and antiretroviral use and PWV.

Argyrophil cell density in the oxyntic mucosa is higher in female than in male morbidly obese patients

Obesity is a multifactorial disorder often associated with many important diseases such as diabetes, hypertension and other metabolic syndrome conditions. Argyrophil cells represent almost the total population of endocrine cells of the human gastric mucosa and some reports have described changes of specific types of these cells in patients with obesity and metabolic syndrome. The present study was designed to evaluate the global population of argyrophil cells of the gastric mucosa of morbidly obese and dyspeptic non-obese patients. Gastric biopsies of antropyloric and oxyntic mucosa were obtained from 50 morbidly obese patients (BMI >40) and 50 non-obese patients (17 dyspeptic overweight and 33 lean individuals) and processed for histology and Grimelius staining for argyrophil cell demonstration. Argyrophil cell density in the oxyntic mucosa of morbidly obese patients was higher in female (238.68 ± 83.71 cells/mm2) than in male patients (179.31 ± 85.96 cells/mm2) and also higher in female (214.20 ± 50.38 cells/mm2) than in male (141.90 ± 61.22 cells/mm2) morbidly obese patients with metabolic syndrome (P = 0.01 and P = 0.02, respectively). In antropyloric mucosa, the main difference in argyrophil cell density was observed between female morbidly obese patients with (167.00 ± 69.30 cells/mm2) and without (234.00 ± 69.54 cells/mm2) metabolic syndrome (P = 0.001). In conclusion, the present results show that the number of gastric argyrophil cells could be under gender influence in patients with morbid obesity. In addition, gastric argyrophil cells seem to behave differently among female morbidly obese patients with and without metabolic syndrome.

From Escherichia coli heat-stable enterotoxin to mammalian endogenous guanylin hormones

The isolation of heat-stable enterotoxin (STa) from Escherichia coli and cholera toxin from Vibrio cholerae has increased our knowledge of specific mechanisms of action that could be used as pharmacological tools to understand the guanylyl cyclase-C and the adenylyl cyclase enzymatic systems. These discoveries have also been instrumental in increasing our understanding of the basic mechanisms that control the electrolyte and water balance in the gut, kidney, and urinary tracts under normal conditions and in disease. Herein, we review the evolution of genes of the guanylin family and STa genes from bacteria to fish and mammals. We also describe new developments and perspectives regarding these novel bacterial compounds and peptide hormones that act in electrolyte and water balance. The available data point toward new therapeutic perspectives for pathological features such as functional gastrointestinal disorders associated with constipation, colorectal cancer, cystic fibrosis, asthma, hypertension, gastrointestinal barrier function damage associated with enteropathy, enteric infection, malnutrition, satiety, food preferences, obesity, metabolic syndrome, and effects on behavior and brain disorders such as attention deficit, hyperactivity disorder, and schizophrenia.

Serum uric acid and disorders of glucose metabolism: the role of glycosuria

Hyperuricemia has been associated with hypertension, diabetes mellitus, and metabolic syndrome. We studied the association between hyperuricemia and glycemic status in a nonrandomized sample of primary care patients. This was a cross-sectional study of adults ≥20 years old who were members of a community-based health care program. Hyperuricemia was defined as a value >7.0 mg/dL for men and >6.0 mg/dL for women. The sample comprised 720 participants including controls (n=257) and patients who were hypertensive and euglycemic (n=118), prediabetic (n=222), or diabetic (n=123). The mean age was 42.4±12.5 years, 45% were male, and 30% were white. The prevalence of hyperuricemia increased from controls (3.9%) to euglycemic hypertension (7.6%) and prediabetic state (14.0%), with values in prediabetic patients being statistically different from controls. Overall, diabetic patients had an 11.4% prevalence of hyperuricemia, which was also statistically different from controls. Of note, diabetic subjects with glycosuria, who represented 24% of the diabetic participants, had a null prevalence of hyperuricemia, and statistically higher values for fractional excretion of uric acid, Na excretion index, and prevalence of microalbuminuria than those without glycosuria. Participants who were prediabetic or diabetic but without glycosuria had a similarly elevated prevalence of hyperuricemia. In contrast, diabetic patients with glycosuria had a null prevalence of hyperuricemia and excreted more uric acid and Na than diabetic subjects without glycosuria. The findings can be explained by enhanced proximal tubule reabsorption early in the course of dysglycemia that decreases with the ensuing glycosuria at the late stage of the disorder.

Investigation of the effects of peppermint (Mentha piperita) on the biochemical and anthropometric profile of university students

The hypolipidemic effects of several medicinal plants have already been demonstrated, but many plants commonly used to treat diseases still need to be studied. Peppermint (Mentha piperita) is widely consumed by the population for different purposes, but not for the treatment of dyslipidemias. The objective of this study was to examine the effects of this plant on human biochemical and anthropometric profiles and blood pressure, based on the administration of peppermint juice twice daily for 30 days. Blood samples were collected before and after the treatment in order to determine the glycemic and lipid profiles, and the Body Mass Index (BMI) analysis was performed. Results indicated that 41.5% of the subjects showed a reduction in glycemia, 66.9% in total cholesterol levels, 58.5% in triacylglycerides, 52.3% in LDL-c (low-density lipoproteins) indices, 70% in GOT (glutamic-oxaloacetic transaminase) levels, 74.5% in GPT (glutamic-pyruvic transaminase) levels, and that 52% presented an increase in HDL-c (high-density lipoprotein cholesterol) indices. Also, 52.5% showed a decrease in blood pressure and 48.7% in BMI. The use of peppermint by humans can be considered beneficial in the prevention and treatment of risk factors of chronic degenerative diseases.

L’impact d’une diète néonatale déficiente en nutriments essentiels à la défense antioxydante sur le métabolisme énergétique à long terme

Les prématurés subissent un stress oxydant qui résulte d’une défense antioxydante faible et/ou d’une charge oxydante. Des données suggèrent qu’un stress oxydant peut affecter le métabolisme énergétique et mener au syndrome métabolique. Hypothèse: Une faible défense antioxydante tôt dans la vie est suffisante pour affecter le métabolisme énergétique à long terme. Méthodes: Quatre groupes de cobayes (n=21) ont reçu entre leurs 3e et 7e jours de vie une diète standard (C-1sem, C-14sem) ou une diète déficiente (DC-1sem, DC-14sem). À 7 jours, les groupes C-1sem et DC-1sem ont été sacrifiés, le plasma et le foie collectés. Les groupes C-14sem et DC-14sem ont reçu la diète standard jusqu’à 14sem de vie. La glycémie et les triglycérides plasmatiques ont été mesurés à 1, 3, 11, et 13-14sem. La tolérance au glucose a été évaluée à 13sem. Les antioxydants hépatiques et les protéines régulant le métabolisme énergétique ont été analysés à 1 et 14sem. Résultats: Un statut redox oxydé du glutathion était associé avec la diète déficiente et était maintenu oxydé au moins jusqu’à 14sem (p<0.01). Les faibles niveaux de triglycérides plasmatiques et de glycémies, ainsi qu’une meilleure tolérance au glucose à 14sem (p<0.05) étaient associés avec un statut redox plus oxydé. Conclusion: Le faible taux de glutathion observé chez les prématurés a été reproduit dans notre modèle. Puisque nos données suggèrent un rôle protecteur d’un redox plus oxydé et que l’environnement redox est un important régulateur métabolique influençant le développement, il faudrait faire attention avant d’initier des traitements antioxydants agressifs chez les prématurés.

Interventions thérapeutiques prometteuses dans un modèle in vivo de stéatohépatite non alcoolique

La stéatohépatite non alcoolique (NASH) est une pathologie du foie dont l’amplitude et les répercussions sont de plus en plus préoccupantes dans le monde médical ou biomédical. Elle est associée à l’obésité, au syndrome métabolique et au diabète sucré de type II. La recherche de la thérapie optimale pour le NASH est un domaine en plein essor puisqu’aucun traitement n’est suffisamment efficace à ce jour. La présente étude fait le point sur de nouvelles possibilités de traitements qui se sont avérés efficaces pour contrer les différentes lésions métaboliques et cellulaires rencontrées dans un modèle in vivo chez le rat où le NASH est induit par l’ingestion d’une diète riche en gras. Cette étude démontre, tout d’abord, que les traitements durant six semaines avec l’acide ursodéoxycholique (UDCA) et son dérivé le NCX 1000, possédant des propriétés donatrices de monoxyde d’azote, à doses équimolaires, protègent de manière équivalente le foie contre le stress oxydatif, l’hyperinsulinémie, l’inflammation et la fibrose causés par la stéatohépatite. De plus, la combinaison d’une plus faible dose de NCX 1000 avec un antioxydant lipophile tel que la vitamine E offre une protection similaire, particulièrement au niveau des paramètres du stress oxydatif. Par ailleurs, l’étude illustre aussi que la silibinine, composé polyphénolique actif du chardon marie (Silybum marianum) et utilisé en traitement pendant 5 semaines, possède un pouvoir hépatoprotecteur, des propriétés antioxydantes et un effet hypoinsulinémique dans ce modèle de stéatohépatite d’origine nutritionnelle. Le potentiel thérapeutique de ces composés en fait des candidats de choix pour le traitement du NASH qui méritent de faire l’objet d’études cliniques poussées.

Étude des interactions entre les cellules progénitrices endothéliales et l’adiponectine

L’adiponectine, une adipokine aux niveaux plasmatiques inversement associés aux composantes du syndrome métabolique, protège contre l’athérosclérose et réduit les risques d’infarctus du myocarde. Les cellules progénitrices endothéliales (EPCs) jouent un rôle dans la réparation vasculaire et leur nombre est réduit chez les patients atteints de maladies cardiovasculaires. Nous croyons que les effets de l’adiponectine peuvent s’expliquer entre autres via ses interactions avec les EPCs. Trois sous-population d’EPCs, isolées du sang de donneurs sains, ont été caractérisées par immunophénotypage par cytométrie en flux. L’expression des récepteurs de l’adiponectine, AdipoR1, AdipoR2 et H-cadherin par les EPCs et les cellules endothéliales a été évaluée par qPCR. Les effets de l’adiponectine sur la migration et l’apoptose des EPCs et sur l’apoptose des HUVECs ont été étudiés. L’expression de l’élastase des neutrophiles par les EPCs et son activité ont été testées. Les résultats de qPCR montrent que l’AdipoR1 est plus fortement exprimé que l’AdipoR2 alors qu’H-cadhérine n’est pas détectable dans les EPCs. Les EPCs précoces expriment aussi l’élastase. L’expression d’AdipoR1 a été confirmée par immunobuvardage. L’adiponectine augmente de façon significative la survie de deux sous-populations d’EPCs, mais pas celle des HUVECs, en condition de privation de sérum. L’activité de l’élastase a été confirmée dans le milieu conditionné par les EPCs. Les EPCs expriment les récepteurs de l’adiponectine et l’élastase. L’adiponectine protège les EPCs contre l’apoptose et pourrait augmenter leur capacité de réparation vasculaire. L’activité élastase des EPCs pourrait moduler localement l’activité de l’adiponectine par la génération de sa forme globulaire.

Transition nutritionnelle et facteurs de risque de maladies cardiovasculaires au Bénin : étude dans la ville secondaire de Ouidah et sa périphérie rurale

Ce travail a été réalisé avec l'appui du Centre Collaborateur de l'OMS sur la Transition Nutritionnelle et le Développement (TRANSNUT) de l'Université de Montréal, en collaboration avec deux parténaires du Bénin: l'Institut de Sciences Biomédicales Appliquées (ISBA) de Cotonou et l'Institut Régional de Santé Publique de Ouidah.

Rôle de la protéine phosphatase PPM1A dans l'homéostasie hépatique du glucose et des lipides

L’insuline est une hormone essentielle qui induit des réponses complexes dans l’organisme pour maintenir l’homéostasie du glucose et des lipides. La résistance à son action est un phénomène pathologique observé dans un large éventail de situations, allant de l’obésité et du syndrome métabolique à la stéatose hépatique et au diabète de type 2, qui aboutissent au développement de l’athérosclérose et de la mortalité. Des avancées remarquables ont été réalisées dans notre compréhension des mécanismes moléculaires responsables du développement de la résistance à l’action de l’insuline. En particulier, l’induction d’un stress cellulaire par des taux élevés d’acides gras libres (AGL) et des cytokines, via l’activation des protéines Ser/Thr kinases, qui augmente la phosphorylation sur des résidus sérine, des molécules critiques impliquées dans la signalisation insulinique (p. ex. IR, IRS et p85) et conduit à la diminution de la réponse cellulaire à l’insuline. Cependant, la plupart des chercheurs ont limité leur travail dans l’investigation du rôle des protéines kinases susceptibles de modifier la réponse cellulaire à l’insuline. Donc, peu de données sont disponibles sur le rôle des Protéines Ser/Thr phosphatases (PS/TPs), même si il est bien établi que la phosphorylation de ces protéines est étroitement régulée par un équilibre entre les activités antagonistes des Ser/Thr kinases et des PS/TPs. Parmi les PS/TPS, PPM1A (également connu sous le nom PP2Cα) est une phosphatase particulièrement intéressante puisqu’il a été suggéré qu’elle pourrait jouer un rôle dans la régulation du métabolisme lipidique et du stress cellulaire. Ainsi, en se basant sur des résultats préliminaires de notre laboratoire et des données de la littérature, nous avons émis l’hypothèse selon laquelle PPM1A pourrait améliorer la sensibilité à l’insuline en diminuant l’activité des protéines kinases qui seraient activées par le stress cellulaire induit par l’augmentation des AGL. Ces effets pourraient finalement améliorer le métabolisme glucidique et lipidique dans l’hépatocyte. Ainsi, pour révéler le rôle physiologique de PPM1A à l’échelle d’un animal entier, nous avons généré un modèle animal qui la surexprime spécifiquement dans le foie. Nous décrivons ici notre travail afin de générer ce modèle animal ainsi que les premières analyses pour caractériser le phénotype de celui-ci. Tout d’abord, nous avons remarqué que la surexpression de PPM1A chez les souris C57BL/6J n’a pas d’effets sur le gain de poids sur une longue période. Deuxièmement, nous avons observé que PPM1A a peu d’effets sur l’homéostasie du glucose. Par contre, nous avons montré que sa surexpression a des effets significatifs sur l’homéostasie du glycogène et des triglycérides. En effet, nous avons observé que le foie des souris transgéniques contient moins de glycogène et de triglycérides que le foie de celles de type sauvage. De plus, nos résultats suggèrent que les effets de la surexpression de PPM1A pourraient refléter son impact sur la synthèse et la sécrétion des lipides hépatiques puisque nous avons observé que sa surexpression conduit à l’augmentation la triglycéridémie chez les souris transgéniques. En conclusion, nos résultats prouvent l’importance de PPM1A comme modulateur de l’homéostasie hépatique du glucose et des lipides. Des analyses supplémentaires restent cependant nécessaires pour confirmer ceux-ci et éclaircir l’impact moléculaire de PPM1A et surtout pour identifier ses substrats.