Apolipoprotein O is mitochondrial and promotes lipotoxicity in heart

Diabetic cardiomyopathy is a secondary complication of diabetes with an unclear etiology. Based on a functional genomic evaluation of obesity-associated cardiac gene expression, we previously identified and cloned the gene encoding apolipoprotein O (APOO), which is overexpressed in hearts from diabetic patients. Here, we generated APOO-Tg mice, transgenic mouse lines that expresses physiological levels of human APOO in heart tissue. APOO-Tg mice fed a high-fat diet exhibited depressed ventricular function with reduced fractional shortening and ejection fraction, and myocardial sections from APOO-Tg mice revealed mitochondrial degenerative changes. In vivo fluorescent labeling and subcellular fractionation revealed that APOO localizes with mitochondria. Furthermore, APOO enhanced mitochondrial uncoupling and respiration, both of which were reduced by deletion of the N-terminus and by targeted knockdown of APOO. Consequently, fatty acid metabolism and ROS production were enhanced, leading to increased AMPK phosphorylation and Ppara and Pgc1a expression. Finally, we demonstrated that the APOO-induced cascade of events generates a mitochondrial metabolic sink whereby accumulation of lipotoxic byproducts leads to lipoapoptosis, loss of cardiac cells, and cardiomyopathy, mimicking the diabetic heart-associated metabolic phenotypes. Our data suggest that APOO represents a link between impaired mitochondrial function and cardiomyopathy onset, and targeting APOO-dependent metabolic remodeling has potential as a strategy to adjust heart metabolism and protect the myocardium from impaired contractility

Effects of High-Intensity Interval Training versus Continuous Training on Physical Fitness, Cardiovascular Function and Quality of Life in Heart Failure Patients

Introduction Physical fitness is an important prognostic factor in heart failure (HF). To improve fitness, different types of exercise have been explored, with recent focus on high-intensity interval training (HIT). We comprehensively compared effects of HIT versus continuous training (CT) in HF patients NYHA II-III on physical fitness, cardiovascular function and structure, and quality of life, and hypothesize that HIT leads to superior improvements compared to CT. Methods Twenty HF patients (male:female 19:1, 64±8 yrs, ejection fraction 38±6%) were allocated to 12-weeks of HIT (10*1-minute at 90% maximal workload—alternated by 2.5 minutes at 30% maximal workload) or CT (30 minutes at 60–75% of maximal workload). Before and after intervention, we examined physical fitness (incremental cycling test), cardiac function and structure (echocardiography), vascular function and structure (ultrasound) and quality of life (SF-36, Minnesota living with HF questionnaire (MLHFQ)). Results Training improved maximal workload, peak oxygen uptake (VO2peak) related to the predicted VO2peak, oxygen uptake at the anaerobic threshold, and maximal oxygen pulse (all P<0.05), whilst no differences were present between HIT and CT (N.S.). We found no major changes in resting cardiovascular function and structure. SF-36 physical function score improved after training (P<0.05), whilst SF-36 total score and MLHFQ did not change after training (N.S.). Conclusion Training induced significant improvements in parameters of physical fitness, although no evidence for superiority of HIT over CT was demonstrated. No major effect of training was found on cardiovascular structure and function or quality of life in HF patients NYHA II-III

Etude ethnopharmacologique des medicaments a base de plantes utilises par les tradipraticiens pour le traitement du diabete et de l’hypertension dans quelques communes du Benin

La médecine traditionnelle constitue une part importante et souvent sous-estimée dans la prévention et la guérison de nombreuses maladies. Elle est beaucoup plus utilisée dans les pays en voie de développement pour soulager les patients atteints de maladies chroniques. Ainsi, le but de cette étude est de contribuer à la valorisation des médicaments à base de plantes utilisés par les tradipraticiens pour le traitement du diabète et de l’hypertension dans les Communes de Adjohoun, Dangbo, Bonou, Porto-Novo, Akpro-Missereté, d’Abomey-Calavi et de Dassa-Zoumé. La méthodologie est basée sur des enquêtes ethnopharmacologiques réalisées à l’aide de questionnaires auprès des tradipraticiens des Communes. Au total, 109 médicaments à base de plantes ont été recensés dont 52 pour le diabète et 57 pour l’hypertension. Les feuilles (47,4%) sont les organes les plus utilisés. La décoction (61,5%) est le mode de préparation le plus sollicité et l’administration se fait majoritairement par voie orale. Toutes les informations recueillies permettront de sélectionner les cinq médicaments à base de plantes les plus proposés par les tradipraticiens pour chaque maladie afin d’évaluer l’efficacité thérapeutique et l’innocuité de ces médicaments à base de plantes. English title: Ethnopharmacological study of phytomedicines used by traditional healers for the treatment of diabetes and hypertension in some municipalities of Benin Abstract Traditional medicine is an important and often underestimated part in the prevention and cure of many diseases. It is used much more in developing countries to treat patients with chronic diseases. Thus, the aim of this study is to contribute to the enhancement of herbal medicines used by traditional healers for the treatment of diabetes and hypertension in the municipalities of Adjohoun, Dangbo, Bonou, Porto-Novo, Akpro-Missereté , Abomey-Calavi and Dassa-Zoumé. The methodology is based on ethnopharmacological surveys carried out using questionnaire from traditional healers in the Municipalities. A total of 109 herbal medicines have been identified, including 52 for diabetes and 57 for hypertension. The leaves (47.4%) are the most used organs. A decoction (61.5%) is the most popular method of preparation and administration is mainly by oral route. All the information gathered will help to select the five herbal medicines most used by traditional healers for each disease in order to assess the therapeutic efficacy and safety of these herbal medicines. Keywords: Therapeutic, Decoction, Prevention, Efficacy, Safet

Investigation of the role of sigma1-receptors in inositol 1,4,5-trisphosphate dependent calcium signaling in hepatocytes.

In hepatocytes, as in other cell types, Ca(2+) signaling is subject to complex regulations, which result largely from the intrinsic characteristics of the different inositol 1,4,5-trisphosphate receptor (InsP(3)R) isoforms and from their interactions with other proteins. Although sigma1 receptors (Sig-1Rs) are widely expressed in the liver, their involvement in hepatic Ca(2+) signaling remains unknown. We here report that in this cell type Sig-1R interact with type 1 isoforms of the InsP(3) receptors (InsP(3)R-1). These results obtained by immunoprecipitation experiments are confirmed by the observation that Sig-1R proteins and InsP(3)R-1 colocalize in hepatocytes. However, Sig-1R ligands have no effect on InsP(3)-induced Ca(2+) release in hepatocytes. This can be explained by the rather low expression level expression of InsP(3)R-1. In contrast, we find that Sig-1R ligands can inhibit agonist-induced Ca(2+) signaling via an inhibitory effect on InsP(3) synthesis. We show that this inhibition is due to the stimulation of PKC activity by Sig-1R, resulting in the well-known down-regulation of the signaling pathway responsible for the transduction of the extracellular stimulus into InsP(3) synthesis. The PKC sensitive to Sig-1R activity belongs to the family of conventional PKC, but the precise molecular mechanism of this regulation remains to be elucidated.Journal ArticleResearch Support, Non-U.S. Gov'tSCOPUS: ar.jinfo:eu-repo/semantics/publishe