The balance within phospholipids (PL) between Saturated Fatty Acids (SFA) and mono-or poly-Unsaturated Fatty Acids (UFA), is known to regulate the biophysical properties of cellular membranes. As a consequence, perturbating this balance alters crucial cellular processes in many cell types, such as vesicular budding and the trafficking/function of membrane-anchored proteins. The worldwide spreading of the Western-diet, which is specifically enriched in saturated fats, has been clearly correlated with the emergence of a complex syndrome, known as the Metabolic Syndrome (MetS), which is defined as a cluster of risk factors for cardiovascular diseases, type 2 diabetes and hepatic steatosis. However, no clear correlations between diet-induced fatty acid redistribution within cellular PL, the severity/chronology of the symptoms associated to MetS and the function of the targeted organs have been established. In an attempt to fill this gap, we analyzed in the present study PL remodeling in rats exposed during 15 weeks to a High Fat/High Fructose diet (HFHF) in several organs, including known MetS targets. We show that fatty acids from the diet can distribute within PL in a very selective way, with PhosphatidylCholine being the preferred sink for this distribution. Moreover, in the HFHF rat model, most organs are protected from this redistribution, at least during the early onset of MetS, at the exception of the liver and skeletal muscles. Interestingly, such a redistribution correlates with clear-cut alterations in the function of these organs.

Exercise training offers possible nonpharmacological therapy for cardiovascular diseases including hypertension. High-intensity intermittent exercise (HIIE) training has been shown to have as much or even more beneficial cardiovascular effect in patients with cardiovascular diseases than moderate-intensity continuous exercise (CMIE) training. The aim of this study was to investigate the effects of the two types of training on cardiac remodeling of spontaneously hypertensive rats (SHR) induced by hypertension. Eight-week-old male SHR and normotensive Wistar-Kyoto rats (WKY) were divided into four groups: normotensive and hypertensive control (WKY and SHR-C) and hypertensive trained with CMIE (SHR-T CMIE) or HIIE (SHR-T HIIE). After 8 wk of training or inactivity, maximal running speed (MRS), arterial pressure, and heart weight were all assessed. CMIE or HIIE protocols not only increased final MRS and left ventricular weight/body weight ratio but also reduced mean arterial pressure compared with sedentary group. Then, left ventricular tissue was enzymatically dissociated, and isolated cardiomyocytes were used to highlight the changes induced by physical activity at morphological, mechanical, and molecular levels. Both types of training induced restoration of transverse tubule regularity, decrease in spark site density, and reduction in half-relaxation time of calcium transients. HIIE training, in particular, decreased spark amplitude and width, and increased cardiomyocyte contractility and the expression of sarco(endo)plasmic reticulum Ca2+-ATPase and phospholamban phosphorylated on serine 16. NEW & NOTEWORTHY High-intensity intermittent exercise training induces beneficial remodeling of the left ventricular cardiomyocytes of spontaneously hypertensive rats at the morphological, mechanical, and molecular levels. Results also confirm, at the cellular level, that this type of training, as it appears not to be deleterious, could be applied in rehabilitation of hypertensive patients.

In Duchenne muscular dystrophy (DMD), deficiency of the cytoskeletal protein dystrophin leads to well-described defects in skeletal muscle but also to dilated cardiomyopathy (DCM). In cardiac cells, the subsarcolemmal localization of dystrophin is thought to protect the membrane from mechanical stress. The dystrophin deficiency leads to membrane instability and a high stress-induced Ca2+ influx due to dysregulation of sarcolemmal channels such as stretch-activated channels (SACs). In this work divalent cation entry has been explored in isolated ventricular Wild Type (WT) and mdx cardiomyocytes in two different conditions: at rest and during the application of an axial stretch. At rest, our results suggest that activation of TRPV2 channels participates to a constitutive basal cation entry in mdx cardiomyocytes.Using microcarbon fibres technique, an axial stretchwas applied to mimic effects of physiological conditions of ventricular filling and study on cation influx bythe Mn2+-quenching techniquedemonstrated a high stretch-dependentcationic influx in dystrophic cells, partially due to SACs. Involvement of TRPs channels in this excessive Ca2+ influx has been investigated using specific modulators and demonstratedboth sarcolemmal localization and an abnormal activity of TRPV2 channels. In conclusion, TRPV2 channels are demonstrated here to play a key role in cation influx and dysregulation in dystrophin deficient cardiomyocytes, enhanced in stretching conditions.