Modeling Fatty Acid Transfer from Artery to Cardiomyocyte

Abstract

Despite the importance of oxidation of blood-borne long-chain fatty acids (Fa) in the cardiomyocytes for contractile energy of the heart, the mechanisms underlying the transfer of Fa from the coronary plasma to the cardiomyocyte is still incompletely understood. To obtain detailed insight into this transfer process, we designed a novel model of Fa transfer dynamics from coronary plasma through the endothelial cells and interstitium to the cardiomyocyte, applying standard physicochemical principles on diffusion and on the chemical equilibrium of Fa binding to carrier proteins Cp, like albumin in plasma and interstitium and Fatty Acid-Binding Proteins within endothelium and cardiomyocytes. Applying these principles, the present model strongly suggests that in the heart, binding and release of Fa to and from Cp in the aqueous border zones on both sides of the cell membranes form the major hindrance to Fa transfer. Although often considered, the membrane itself appears not to be a significant hindrance to diffusion of Fa. Proteins, residing in the cellular membrane, may facilitate transfer of Fa between Cp and membrane. The model is suited to simulate multiple tracer dilution experiments performed on isolated rabbit hearts administrating albumin and Fa as tracer substances into the coronary arterial perfusion line. Using parameter values on myocardial ultrastructure and physicochemical properties of Fa and Cp as reported in literature, simulated washout curves appear to be similar to the experimentally determined ones. We conclude therefore that the model is realistic and, hence, can be considered as a useful tool to better understand Fa transfer by evaluation of experimentally determined tracer washout curves.

The influence of placental metabolism on fatty acid transfer to the fetus

“…The model did not distinguish between membrane transport kinetics and the kinetics of disassociation of insoluble fatty acids from binding proteins in the plasma or cytosol. Depending on the physiological or experimental system, the effects of albumin association and dissociation on fatty acid transfer may need to be taken into account explicitly (9,12,34,35). Furthermore, other transport processes may exist, including active and selective transport systems (e.g., the recently discovered DHA transporter [36]) and endocytotic uptake of lipoproteins (37).…”

Maximum Aerobic Function: Clinical Relevance, Physiological Underpinnings, and Practical Application

“…The emphasis on MFO is important for increasing long-term energy, reducing cardiometabolic risks, and slowing aging (Finch and Stanford, 2004). As the primary site for ATP production, mitochondrial fat oxidation is a significant energy source for skeletal and cardiac muscles, especially during fasting, resting, and low-to moderate-intensity physical activities, and for liver, kidney, adipose, and many other tissues, with ketone bodies, metabolized from fats, being an additional energy source, along with glucose, for the brain (El Bacha et al, 2010;Arts et al, 2015). Increased fat oxidation can also help reduce reactive oxygen species (ROS) production (El Bacha et al, 2010).…”

Intra-cardiac transfer of fatty acids from capillary to cardiomyocyte

“…Theoretically, in all fluid compartments two zones can be identified: a bulk zone far away from cell membranes, and a boundary zone, being the fluid layer in close vicinity to the cell membrane. A notable drop in the concentration of non-protein bound Fa characterizes this boundary zone [5]. Fa are delivered to cell membranes either by direct translocation of Fa from the Fa-binding protein (albumin or FABP), i.e., the so-called contact pathway, or preceded by release from the Fa-binding protein as free Fa in the aqueous solution, followed by free Fa diffusion towards and dissolution in the cell membrane, i.e., the so-called detach pathway [5].…”

“…A notable drop in the concentration of non-protein bound Fa characterizes this boundary zone [5]. Fa are delivered to cell membranes either by direct translocation of Fa from the Fa-binding protein (albumin or FABP), i.e., the so-called contact pathway, or preceded by release from the Fa-binding protein as free Fa in the aqueous solution, followed by free Fa diffusion towards and dissolution in the cell membrane, i.e., the so-called detach pathway [5]. Albumin serves as Fa-carrier protein in the extracellular boundary zones.…”

“…To gain better insight into the myocardial transfer of Fa previously we developed a mathematical model based upon standard physical and physicochemical principles, including diffusion-facilitating Fa carriers in the extra-and intracellular compartments [5]. The model allowed for experimental testing.…”