| Summary: | Obesity leads to alterations in myocardial metabolism, expressed as an increased utilization of fat for energy purposes at the expense of carbohydrate. This shift in energy metabolism is associated with impairment of ventricular function which can lead to heart failure. This thesis raises the question of whether dietary supplementation with Calanus oil, a novel marine oil derived from the marine copepod, Calanus finmarchicus (Norwegian, raudåte), can attenuate obesity-related changes in metabolism and associated co-morbidities. The major finding in this thesis project was that dietary Calanus oil was able to prevent obesity-related shifts in myocardial metabolism and restore the capacity of the heart to utilize carbohydrate as energy source. In addition, we demonstrated that Calanus oil had a cardioprotective action, in the sense that recovery ventricular function following an ischemic insult of hearts from mice receiving high-fat diet with Calanus oil was superior to that of control hearts. To examine the mechanism involved, we exposed H9c2 cardiomyoblast to lipotoxic stress (palmitic acid) with and without micromolar concentrations of hydrolysed wax ester from Calanus oil (WEH). Live cell imaging revealed major cell death in response to palmitiate-exposure, while co-incubation with WEH almost completely rescued the cells. Further analyses suggested that WEH protects H9c2 cardiomyocytes from lipotoxicity by attenuating the associated ER stress, as well as alleviating palmitate-induced impairment of autophagic flux. This thesis also showed that Calanus oil, at least to some extent, were able to antagonize obesity-induced changes in the gut microbiota composition. In conclusion, the present results show that dietary supplementation with Calanus oil has the potential to attenuate obesity-induced alterations in myocardial metabolism and, in addition, protect the heart towards ischemic stress, and may therefore be an alternative to anti-obesity/anti-diabetic drugs.
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