Molecular mechanism of lipid-induced cardiac insulin resistance and contractile dysfunction

Publication date: Available online 13 June 2016Source: Prostaglandins, Leukotrienes and Essential Fatty AcidsAuthor(s): Yilin Liu, Dietbert Neumann, Jan F.C. Glatz, Joost J.F.P. LuikenAbstractLong-chain fatty acids are the main cardiac substrates from which ATP is generated continually to serve the high energy demand and sustain the normal function of the heart. Under healthy conditions, fatty acid β-oxidation produces 50–70% of the energy demands with the remainder largely accounted for by glucose. Chronically increased dietary lipid supply often leads to excess lipid accumulation in the heart, which is linked to a variety of maladaptive phenomena, such as insulin resistance, cardiac hypertrophy and contractile dysfunction. CD36, the predominant cardiac fatty acid transporter, has a key role in setting the heart on a road to contractile dysfunction upon the onset of chronic lipid oversupply by translocating to the cell surface and opening the cellular ‘doors’ for fatty acids. The sequence of events after the CD36-mediated myocellular lipid accumulation is less understood, but in general it has been accepted that the excessively imported lipids cause insulin resistance, which in turn leads to contractile dysfunction. There are several gaps of knowledge in this proposed order of events which this review aims to discuss. First, the molecular mechanisms underlying lipid-induced insulin resistance are not yet completely disclosed. Specifically, several mediators have been ...
Source: Prostaglandins, Leukotrienes and Essential Fatty Acids (PLEFA) - Category: Lipidology Source Type: research