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The capillary transport system for free fatty acids in the heart
C A Goresky1, W Stremmel, C P Rose
1University Medical Clinic, Montreal General Hospital, Quebec, Canada.
Insights
Free fatty acids are crucial for heart energy. A specific protein in heart capillaries facilitates their uptake by heart muscle cells, ensuring efficient energy supply.
Area of Science:
- Cardiovascular Physiology
- Cellular Metabolism
- Biochemistry
Background:
- Free fatty acids (FFAs) are vital energy substrates for cardiac muscle.
- The mechanism of FFA transport across cardiac capillary endothelium is not fully understood.
- Membrane fatty acid-binding proteins (mFABPs) are implicated in FFA uptake by various cells.
Purpose of the Study:
- To clarify the mechanism of free fatty acid uptake by cardiac muscle.
- To investigate the role of membrane fatty acid-binding protein in cardiac FFA transport.
Main Methods:
- Utilized multiple-indicator dilution experiments in isolated rat hearts.
- Employed labeled albumin, sucrose, and palmitate in perfusates.
- Tested the effects of a specific monoclonal antibody against rat liver mFABP and control supernatants.
Main Results:
- Specific antibody against mFABP significantly inhibited palmitate uptake by cardiac capillaries.
- Control supernatants showed only minor inhibition of palmitate uptake, attributed to increased albumin concentration.
- Data suggest mFABP mediates FFA transfer across cardiac endothelial cells.
Conclusions:
- Membrane fatty acid-binding protein plays a crucial role in mediating free fatty acid transfer across cardiac capillary endothelium.
- This protein facilitates FFA delivery to cardiac muscle cells for energy production.
- Passive diffusion cannot account for the observed FFA uptake kinetics.
Abstract:
The nature of the process by which free fatty acids, which are tightly bound to albumin, traverse the endothelium of cardiac capillaries to reach the cardiac muscle cells, so that they are extracted to a net extent of approximately 40%, needs clarification. Previous studies have indicated that a membrane fatty acid-binding protein provides for carrier-mediated uptake of free fatty acids by isolated hepatocytes, cardiomyocytes, and jejunal mucosal cells. A monoclonal monospecific antibody was prepared against purified membrane fatty acid-binding protein from rat liver. Multiple-indicator dilution experiments were carried out in the isolated rat heart with labeled albumin, sucrose, and palmitate in the presence of control perfusate or perfusate containing either specific antibody or comparable nonspecific myeloma cell supernatant (each of the latter containing additional albumin, in identical concentrations). Analysis of the labeled-sucrose curves provided a permeability-surface area product for sucrose to which that for palmitate could be compared. In comparison with control supernatants, myeloma supernatant produced a minor inhibition of palmitate uptake, as a result of the increase in albumin concentration. The specific antibody, which contained identical albumin concentrations, produced a major inhibition of palmitate uptake, significantly greater than with the myeloma supernatant. The data indicate that the membrane fatty acid-binding protein mediates the transfer of free fatty acid across the endothelial cells of cardiac capillaries for presentation to heart muscle. Passive intramembrane lateral diffusion of palmitate could not provide an explanation for the findings.