FT -> Leucine or carbohydrate supplementation reduces AMPK and eEF2 phosphorylation and extends postprandial muscle protein synthesis in rats | Endocrinology and MetabolismLeucine or carbohydrate supplementation reduces AMPK and eEF2 phosphorylation and extends postprandial muscle protein synthesis in rats
Abstract
Muscle protein synthesis (MPS) increases after consumption of a protein-containing meal but returns to baseline values within 3 h despite continued elevations of plasma amino acids and mammalian target of rapamycin (mTORC1) signaling. This study evaluated the potential for supplemental leucine (Leu), carbohydrates (CHO), or both to prolong elevated MPS after a meal. Male Sprague-Dawley rats (∼270 g) trained to consume three meals daily were food deprived for 12 h, and then blood and gastrocnemius muscle were collected 0, 90, or 180 min after a standard 4-g test meal (20% whey protein). At 135 min postmeal, rats were orally administered 2.63 g of CHO, 270 mg of Leu, both, or water (sham control). Following test meal consumption, MPS peaked at 90 min and then returned to basal (time 0) rates at 180 min, although ribosomal protein S6 kinase and eIF4E-binding protein-1 phosphorylation remained elevated. In contrast, rats administered Leu and/or CHO supplements at 135 min postmeal maintained peak MPS through 180 min. MPS was inversely associated with the phosphorylation states of translation elongation factor 2, the “cellular energy sensor” adenosine monophosphate-activated protein kinase-α (AMPKα) and its substrate acetyl-CoA carboxylase, and increases in the ratio of AMP/ATP. We conclude that the incongruity between MPS and mTORC1 at 180 min reflects a block in translation elongation due to reduced cellular energy. Administering Leu or CHO supplements ∼2 h after a meal maintains cellular energy status and extends the postprandial duration of MPS.
What is the reason for the study?
Working from the consensus that after consuming a meal muscle protein synthesis (MPS) increases and then returns to baseline within 3 hours, researchers investigated whether consumption of carbohydrates (CHO), supplemental leucine (Leu) or both (LC) would result in prolonging the elevation of MPS post meal.
Who are the participants?
Thirty-four Male Sprague-Dawley rats
What was the study design?
Experimental placebo controlled study
What was done?
Rats were provided a baseline diet of 20/50/30 (P/C/F) for 7 days. Some rats were then euthanized following fasting for 12 hours. This is done to establish a reference food deprived value. The rest were were given a meal and then euthanized either 90 min or 180 min post meal. Based on previous research, the researchers hypothesized that MPS would peak at around 90 mins and then return to baseline at around 135 mins post meal. For this reason, some of the rats were euthanized at 90 min to establish a reference for peak MPS.
Experimental interventions
Since at around 135 mins is when the researchers expected MPS to drop back down, they gave rats either CHO, Leu, LC, or placebo (water) and then euthanized them at the 180min mark (post initial meal) to see what effect each had on MPS (if either was able to prolong it or not and if so to what magnitude)
The 135min intervention amounts are listed above.
What was found?
MPS was increased in the rats that were euthanized at the 90 min mark.
At the 180min mark
- Rats that were given placebo showed MPS levels similar to the ones euthanized at the 0min mark (the ones in a food deprived state)
- Rats given either Leu, CHO or LC all showed increased MPS and to levels similar to the rats euthanized at 90 min mark, which was the MPS peak
This is seen in the graph below
What is the proposed mechanism/reason for the findings?
Researchers believe that by supplementation with either CHO, Leu, or LC resulted in decreased AMPK activation thus prolonging MPS post meal.
Limitations of the study?
Was done in rats, not humans.
What does this mean?
Previously it had been believed that additional amino acids would not increase MPS further due to mRNA translation becoming refractory (unresponsive). However given the data gathered by the researchers here (specifically on mTORC1 and MPS) they believe that the drop in MPS post meal is not due to a refractory period but rather a result of increased AMPK activity and a decrease in translation elongation activity. (Data I did not include in the “What was found” section since I figured not many people would follow and it would have taken more time to provide background information on the relationship of all these factors in order to fully understand the role being played {which I myself don’t quite fully understand yet!} so I instead focused on just reporting the MPS findings. Just know MPS and AMPK are inversely related).
Takeaway?
The intake of a Leu or CHO 2 hours after consuming a meal may extend the duration of MPS.
Side note:
Insulin was also measured in this study. Plasma insulin was increased at 90 min postmeal and returned to food deprived values in rats given the water. In the rats that were given CHO or LC, insulin maintain elevated, whereas the insulin levels for rats who were give Leu did not differ from the ones given water.
The researchers noted that while insulin did not appear to be a critical factor in extending MPS, they think their timing for when they checked insulin might have missed the peak and concluded that, “the influence of insulin signaling on the duration of MPS remains unresolved.”