In rats so..

Exercise Effects on Muscle Insulin Signaling and Action
Selected Contribution: Acute cellular and molecular responses to resistance exercise
Fadia Haddad and Gregory R. Adams

Training protocols apply sequential bouts of resistance exercise (RE) to induce the cellular and molecular responses necessary to produce compensatory hypertrophy. This study was designed to 1) define the time course of selected cellular and molecular responses to a single bout of RE and 2) examine the effects of interbout rest intervals on the summation of these responses. Rat muscles were exposed to RE via stimulation of the sciatic nerve in vivo. Stimulated and control muscles were obtained at various time points post-RE and analyzed via Western blot and RT-PCR. A single bout of RE increased intracellular signaling (i.e., phosphorylations) and expression of mRNAs for insulin-like growth factor-I system components and myogenic markers (e.g., cyclin D1, myogenin). A rest interval of 48 h between RE bouts resulted in much greater summation of myogenic responses than 24- or 8-h rest intervals. This experimental approach should be useful for studying the regulatory mechanisms that control the hypertrophy response. These methods could also be used to compare and contrast different exercise parameters (e.g., concentric vs. eccentric, etc.).

The MGF and IGf-1 mRNA was much higher for the 48 hr group showing a summation effect. The 24 hr group showed increase but lower than the 48 hr group. The 8 hr rest group was clearly inferior. I know this a rat study, but it shows there might be a summation effect.

I think one way to lower fatigue is top keep the reps higher. Now we know that heavy weight do not necessarily mean higher protein synthesis. Maybe hit hard for 3-4 weeks, dealod, then repeat.

but after 48 hours, won’t the acute molecular response to exercise be over? If they stimulate again after it’s over, then it’s not really summation. is it?
If you look at figure 2c, at 40 hours, there wasn’t much left of the response. There was a lot left in the IGF-1 response, though.

Anyway, let’s call it summation. Why summation at 48 hours and not 24? And would this change with being trained? I really wish someone would study this in trained humans.. as It would have great implications for training frequency.

but after 48 hours, won’t the acute molecular response to exercise be over? If they stimulate again after it’s over, then it’s not really summation. is it?
If you look at figure 2c, at 40 hours, there wasn’t much left of the response. There was a lot left in the IGF-1 response, though.

I am talking more about the MGF and IGF-1 graphs ( 4 B & 4D). The IGf and MGF clearly show a summation effect. Will the MRNA results translate to increased protein? I don’t know. That is one problem looking at mRNA levels and not protein.

When I used to work in a lab, my post doc used to talk about how the genomics people think its all about mRNA while the proteonomics people think it is all about the protein.

I haven’t really looked at the phosphorylation of all those molecular factors. Those things are kind of weird and we don’t have a good grasp of it.

Anyway, let’s call it summation. Why summation at 48 hours and not 24? And would this change with being trained? I really wish someone would study this in trained humans.. as I’d would have great implications for training frequency.

Good questions. i don’t know. According to the authors, “It is not immediately clear why a second bout of exercise
imposed 8 h after the first would be so markedly
inferior in producing an enhanced response compared
with 24 or 48 h of rest (i.e., MGF, IGF-I, myogenin,
cyclin D1 mRNA). One explanation might be that some
signaling mechanisms enter a refractory period after
an exercise bout, thereby blunting the response to a
second exercise stimulus.”

And this is something that the study you quoted showed too I believe.

There might be some mechanism inherent in the muscle which dampens the sensitivity of the muscle to tension and stretch. We know how integrins sense mechanical load and activate signaling pathways. Maybe those signals get down regulated.

Funny, but fastest CSA grow in Werbom study was then frequency was 12 times a week.
It was an occlusion study

Yeah.. the occlusion thing is pretty interesting. We can get hypertrophy through low intensity occlusion and high intensity regular resistance training. Maybe they increase MPS in different ways, and maybe the occlusion one is less susceptible to a refractory period after a work out. Pure speculation, of course.