High fatty acid availability after exercise alters the regulation of muscle lipid metabolism

Journal Title (Medline/Pubmed accepted abbreviation): Metab. Clin. Exp.
Year: 2011
Volume: 60
doi (if applicable): 10.1016/j.metab.2010.08.004

Summary of background and research design

Background: Exercise causes an increase in fatty acid mobilization from adipose tissue in order to supply energy to the working muscles. Also, the increase in fatty acids in the blood causes an increase in intramyocellular triacylglycerol (IMTG), which is a storage molecule for fatty acids inside muscle cells (i.e. a long-term energy reserve).

Hypothesis: Exercise will increase 1) the activity of glycerol-3-phosphate acyltransferase (GPAT) and diacylglycerol acyltransferase (DGAT), two enzymes in the IMTG synthesis pathway, 2) the number of fatty acid transporters on the muscle cell membrane, 3) the amount of perilipins, the proteins that are associated with intracellular fat droplets.

Subjects: 7 untrained, healthy females, age 27 ± 4

Experimental design: randomized, cross-over

Treatments: Overnight (16 hrs) infusion of 1) saline or 2) lipid in the form of a 20% lipid emulsion at 0.11 g fat/kg body weight/hr and heparin. This amount of lipid puts the participants at a high physiological fatty acid concentration.

Protocol: Before the study, the participants were evaluated for body composition and then VO2max  was determined on a stationary bicycle.  The night before the trials, the subjects consumed a standardized dinner.  They then reported to the laboratory the next morning after an overnight fast.  They completed 45 min of treadmill exercise followed by 45 min of cycling at 65% their VO2max.  They had 3 low fat, standard meals during the rest of the day.  Between 3:00 pm on the exercise day and 7:00 am the next day, the participants were infused with saline or the lipid solution.  Blood samples were also acquired at defined time points.  At 6:30 am the next morning, resting O2 consumption and CO2 expiration were measured in order to estimate rates of substrate oxidation (fat vs. carbohydrates).  At 9:00 am the next morning, a muscle biopsy from the vastus lateralis (quadriceps) was acquired to be analyzed for enzyme amounts and activity.

Summary of research findings
  • The lipid infusion caused the blood lipid levels to reach 0.84 ± 0.14 mM, compared to 0.22 ± 0.04 mM with the saline infusion.
  • The activity of GPAT increased slightly but to a statistically significant degree.  DGAT activity and concentrations of diacylglyceride and ceramide (lipid intermediates) also increased, but the difference was not statistically significant.
  • The fatty acid transporter FAT/CD36 showed a higher level of association with the muscle membrane (p = .005), but muscle cell concentration was not increased (p = 0.59).  This means that although expression of the FAT/CD36 protein was not altered by the lipid infusion, there was greater translocation of this transporter protein to the cell membrane to facilitate entry of fatty acids into the cell.
  • The resting exchange ratio (RER, a report of the ratio of fat:carbohydrate that is burned for energy) nor the rate of lipid oxidation was different between the saline vs. the lipid infusion.
  • Perilipin content was not different between treatments.

Interpretation of findings/Key practice applications

High concentrations of lipids after exercise causes muscles to increase the amount of fat stored in the muscle. This is presented as a benefit, in that insulin resistance as a result of high fatty acid concentrations was prevented (shown in a previous study). However, the authors did not discuss the benefits and detriments of fat stored in muscle.


It is not clear if the effects achieved with intravenous administration of a lipid emulsion could be achieved via oral administration of lipid. In addition, the subjects were untrained in this study. It would be interesting to see if more highly trained subjects would have had a more robust response (e.g., higher enzyme activities, greater transporter activity) than observed for untrained subjects.

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