Possible Health Effects of a Wax Ester Rich Marine Oil.

The consumption of seafood and the use of fish oil for the production of nutraceuticals and fish feed have increased over the past decades due the high content of long-chain polyunsaturated omega-3 fatty acids. This increase has put pressure on the sustainability of fisheries. One way to overcome the limited supply of fish oil is to harvest lower in the marine food web. Calanus finmarchicus, feeding on phytoplankton, is a small copepod constituting a considerable biomass in the North Atlantic and is a novel source of omega-3 fatty acids. The oil is, however, different from other commercial marine oils in terms of chemistry and, possibly, bioactivity since it contains wax esters. Wax esters are fatty acids that are esterified with alcohols. In addition to the long-chain polyunsaturated omega-3 fatty acids, eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), the oil is also rich in stearidonic acid (SDA), long-chain monounsaturated fatty acids, and the long-chain fatty alcohols eicosenol and docosenol. Recent animal studies have indicated anti-inflammatory and anti-obesogenic actions of this copepod oil beyond that provided by EPA and DHA. This review will discuss potential mechanisms behind these beneficial effects of the oil, focusing on the impact of the various components of the oil. The health effects of EPA and DHA are well recognized, whereas long-chain monounsaturated fatty acids and long-chain fatty alcohols have to a large degree been overlooked in relation to human health. Recently, however the fatty alcohols have received interest as potential targets for improved health via conversion to their corresponding fatty acids. Together, the different lipid components of the oil from C. finmarchicus may have potential as nutraceuticals for reducing obesity and obesity-related metabolic disorders.

Myosin Activator Omecamtiv Mecarbil Increases Myocardial Oxygen Consumption and Impairs Cardiac Efficiency Mediated by Resting Myosin ATPase Activity.

BACKGROUND: Omecamtiv mecarbil (OM) is a novel inotropic agent that prolongs systolic ejection time and increases ejection fraction through myosin ATPase activation. We hypothesized that a potentially favorable energetic effect of unloading the left ventricle, and thus reduction of wall stress, could be counteracted by the prolonged contraction time and ATP-consumption. METHODS AND RESULTS: Postischemic left ventricular dysfunction was created by repetitive left coronary occlusions in 7 pigs (7 healthy pigs also included). In both groups, systolic ejection time and ejection fraction increased after OM (0.75 mg/kg loading for 10 minutes, followed by 0.5 mg/kg/min continuous infusion). Cardiac efficiency was assessed by relating myocardial oxygen consumption to the cardiac work indices, stroke work, and pressure-volume area. To circumvent potential neurohumoral reflexes, cardiac efficiency was additionally assessed in ex vivo mouse hearts and isolated myocardial mitochondria. OM impaired cardiac efficiency; there was a 31% and 23% increase in unloaded myocardial oxygen consumption in healthy and postischemic pigs, respectively. Also, the oxygen cost of the contractile function was increased by 63% and 46% in healthy and postischemic pigs, respectively. The increased unloaded myocardial oxygen consumption was confirmed in OM-treated mouse hearts and explained by an increased basal metabolic rate. Adding the myosin ATPase inhibitor, 2,3-butanedione monoxide abolished all surplus myocardial oxygen consumption in the OM-treated hearts. CONCLUSIONS: Omecamtiv mecarbil, in a clinically relevant model, led to a significant myocardial oxygen wastage related to both the contractile and noncontractile function. This was mediated by that OM induces a continuous activation in resting myosin ATPase.

Inadvertent phosphorylation of survival kinases in isolated perfused hearts: a word of caution.

The isolated perfused heart is an important model in cardiovascular research. We hypothesized that the perfusion procedure per se will phosphorylate some protein kinases important in pre- and postconditioning. Isolated hearts were Langendorff-perfused for 20 min with or without an intraventricular balloon (rats and mice), or in the working heart mode (mice) and compared to non-perfused controls with respect to protein phosphorylation. Rat hearts were also perfused for 20 and 50 min in the Langendorff mode to investigate the effect of perfusion time on phosphorylation. Western blot analysis showed that perfusion per se induced a massive phosphorylation of ERK 1/2, P38-MAPK, JNK, AMPK, but decreased phosphorylation of AKT in the isolated rat and mouse heart. However, during ongoing perfusion the phosphorylation of these kinases was reduced. Langendorff-perfusion without the intraventricular balloon caused less phosphorylation of ERK 1/2, P38-MAPK and JNK, but had no effect on AMPK. In working hearts phosphorylation of kinases was similar to that of Langendorff-perfused hearts without the balloon. Our findings indicate that excising, handling and perfusion induce a time dependent phosphorylation of stress kinases. The presence of the intraventricular balloon caused the strongest phosphorylation, thus Langendorff-perfused hearts might be partly protected by the perfusion procedure if stress kinases are protective in pre- and postconditioning. This might explain conflicting results obtained with different models of both pre- and postconditioning, and the isolated heart might in some situations be suboptimal for such studies.