Twelve weeks of endurance training increases FFA mobilization and reesterification in postmenopausal women
Journal Title (Medline/Pubmed accepted abbreviation):  J. Appl. Physiol.
Year: 2010
Volume: 109
Page numbers: 1573-1581
doi (if applicable):  10.1152/japplphysiol.00116.2010

Summary of Background and Research Design

Background:The reduction of estrogen and progesterone at menopause may affect lipid metabolism and cause the body to use a greater proportion of carbohydrates as a substrate during exercise, while using a smaller proportion of fat. It has been shown that younger people have a greater capacity to break down and burn fat compared to elderly people.
                Fatty acids are stored in the form of triglycerides (three fatty acid molecules bound to a glycerol backbone) in adipose and other tissues. In response to energy demands, fatty acids can be “mobilized”, or cleaved from the glycerol molecule, and entered into circulation. The free fatty acids (FFAs) are shuttled into the mitochondrion where they are oxidized to generate ATP. Alternatively, a FFA can be re-esterified and made into a new triglyceride molecule.

Hypothesis/Research Question:Does endurance training compensate for the menopause-related decline in fatty acid mobilization and oxidation?

Subjects:10 sedentary, post-menopausal women

Experimental design:Exercise intervention, pre-training and post-training evaluationv

Treatments and protocol:At the preliminary screening session, VO2peak (or VO2max), body composition, blood lipid levels, and relevant blood hormone levels were assessed. To determine VO2max, respiratory gases were monitored continuously while subjects cycled on a stationary bicycle. Resistance began at 50 W and increased 25 W every 3 min until volitional exhaustion. 
For fatty acid mobilization, reesterification, and oxidation studies, stable isotope methodology was utilized. Subjects were fed a standardized diet the day before the trial. On the day of the trial, the participants arrived at the laboratory after an overnight fast and were fed a standardized breakfast (560 kcal). Ninety minutes later, the subjects received a continuous infusion with isotopically labeled palmitate (a FFA, labeled with 13C) and glycerol (labeled with 2H) so that the metabolic fates of these substances could be determined. Subjects rested for 90 min and then cycled continuously for 60 min. Respiratory gas exchange, heart rate, and blood pressure data as well as blood samples were collected throughout the rest and the exercise periods. The authors looked for the rate of appearance (Ra), rate of disappearance (Rd), and other metabolic metrics of 13C-palmitate and 2H-glycerol. The pre-training trial is referred to as PRE.
                After the initial analysis, subjects completed a 12 wk endurance training program. Training increased from 30-60 min over the first 4 wks. Sessions were 3 days/wk for the first 3 wks and increased to 5 days/wk for weeks 5-12. By week 5 subjects were exercising for 60 min at 65% of their VO2peak. At weeks 10 and 12 post-training, 2 additional isotope infusion protocols were undergone, one at 65% of their initial VO2max (ABT for absolute training) and the other at 65% their new VO2max (RLT for relative training).

Summary of research findings:
  • Postmenopausal women generally have lower ability to oxidize fat during exercise compared with younger women.
  • Postmenopausal women, however, did adapt to 12 weeks of endurance training.
    • Peak power output increased by 25.3 ± 3.4% from 55.5 ± 5.98 W in PRE to 74.93 ± 4.07 W in RLT as a result of the endurance training program.
    • VO2peak also increased 16.3 ± 3.9% (p<0.05).
  • In the ABT trial, total fat oxidation was not altered vs. PRE. However, the following were observed:
    • The FFA Ra increased significantly vs. PRE, but did not in RLT.
    • FFA Rd also increased significantly vs. PRE.
    • There was an increase in the rates of oxidation of palmitate and other lipid (RoxP and RoxO, respectively) vs PRE.
    • The rate of fatty acid re-esterification (Rs) decreased, albeit nonsignificantly, vs. PRE.
  • In the RLT trial, total fat oxidation was also not changed vs. PRE. However:
    • FFA Ra or FFA Rd were increased vs. PRE.
    • Rs was higher than PRE.
    • Glycerol Ra and Rd were both elevated compared with PRE.
  • During the training program there was no caloric restriction and there were no changes in body composition, or dietary composition. Therefore, the authors attribute the changes in fat utilization solely to the 12 wk exercise program.

Interpretation of findings/Key practice applications:

A 12 wk endurance training program can improve many metabolic parameters in postmenopausal women including the utilization of fat as energy during exercise. However, total lipid metabolism still exhibited lower rates than the subjects’ younger counterparts. The findings above also indicate that, after endurance training, the adaptations observed using the same fixed workload as a percentage of original VO2peak (ABT) were not observed when the workload was the same percentage as the new VO2peak (RLT). It appears that, at RLT, fat mobilization was occurring (as evidenced by the elevated glycerol Ra and Rd), but the increase in Rs at the same time suggests that the fatty acids are not being oxidized. A likely explanation for this finding is that the subjects simply started using more carbohydrate and less lipid for fuel at this higher relative workload. Although not measured in this study, it is probable that the endurance training may have increased muscle glycogen storage and/or the ability to oxidize carbohydrate. It may be that adaptations required to better oxidize fat (e.g., increased fatty acid transport, increased mitochondrial beta-oxidation) in this situation are more difficult for the body than those required to elevate carbohydrate oxidation and may be more hormonally-dependent. Given that the subjects in the study were postmenopausal and probably had not exercised in a long time, a switchover to using more carbohydrate for fuel during the RLT could have represented an easier metabolic route of adaptation as opposed to further increasing the ability to oxidize fat.


Due to the labor intensive nature of this study, the sample size (n = 10 women) for this study was small. As such, the possibility of type II error increases. In addition, it is not clear if the results for this study would have been the same had the subjects been on the endurance training program for longer than 12 weeks. It is likely that the subjects entered the study very disadapted to physical activity and it might have taken longer to induce the types of mitochondrial adaptations for fat oxidation that are often observed in younger athletes.
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