With that being said, let's take a look at what the scientists did to "investigate the role of MC4R in the modulation of muscle work efficiency, and test the hypothesis that energy restriction alters economy of activity through decreasing the response to central activation of MC4R" (Almudarij 2017).
For their study, the scientists used male Sprague-Dawley rats (total N = 48) which were selected to measure adaptive thermogenesis in a baseline population - not because Martin et al. (2010) have mad ethe argument that these animals are potentially metabolically morbid, anyway, but rather because they are metabolically morbid. Just as metabolically morbid as human beings for whom the ever-increasing obesity rates indicate that we are similarly susceptible to diet-induced obesity and the associated detrimental health effects.
These rats were subjected to 3 weeks of 50% calorie restriction (CR). Over the course of this - in rodent years - intermediate time period, the scientists assessed their lab animals resting and nonresting energy expenditure (EE) and calculated the total, as well as the activity-associated EE, muscle thermogenesis, and sympathetic outflow.
|Figure 1: Three weeks of 50% calorie restriction (CR) significantly suppressed both resting and nonresting EE, including physical activity-related EE, i.e. the energy you spend while working out (Almundarij 2017).|
Dieting is when you leave only 360kcal not 600kcal in the gym, despite doing the same workout
What is particularly interesting, yet often forgotten when we talk about dieting (especially within the fitness community), is the fact that the energy that you will burn during exercise will also decrease significantly (see Figure 1G). One of the implications of the study at hand we cannot ignore is that the reduced physical activity energy expenditure stems from "the dampening of both the amount and energetic cost of activity" (Almundarij 2017) - and the latter, i.e. the reduced energy expenditure in response to a standardized exercise regimen amounts to a 30-40% decrease in EE that would degrade the 600kcal you believe to be burning on the treadmill to a meager 360-420 kcal/session!
|Figure 2: Fat & lean mass and the rel. (%) difference in body comp. w/ ad-libitum vs. restricted diet (Almundarij 2017).|
|Illustration of the allegedly over-simplified example calculation to show the significance of the fasting-induced reduction in AIEE for meal timing and fat loss as observed in Garaulet 2013.|
Let's illustrate that with a simple example (see Figure to the left). Let's assume the reduction in AIEE is indeed 40%. Let's further assume that you'd "burn" ~1000kcal from working out and walking in your waking phase before the PM meal and only 150kcal after the PM meal when eating an energetically balanced. According to Cooker, that would put your effective AIEE while dieting to 600kcal + 150kcal when you eat in the PM, but 1000kcal + 90kcal if you eat the meal in the AM. Obviously, this oversimplified example assumes that the metabolism would not slow down over the day (which will be the case). Eventually, the difference will thus certainly be smaller (maybe 15% instead of the 31% in my example). That does not mean, though, that it could not still be statistically and practically significant (note: it is unlikely that a relevant reduction would be observed for intermittent fasting in the absence of a significant caloric deficit).
is the first report of reduced muscle NETO [norepinephrine turnover], indicating lower SNS drive to skeletal muscle after 3 weeks of food restriction (Fig. 2), an effect not seen during short-term energy restriction (Dulloo et al. 1988)" (Almundarij 2017).With the importance of skeletal muscle to both resting and activity EE, (Zurlo et al. 1990; Gallagher et al. 1998), "this low SNS drive" could, as the authors further point out significantly "contribute to both the resting and nonresting aspects of adaptive thermogenesis" (Almundarij 2017).
|Figure 3: The MC4R induced increase in energy expenditure in the study at hand is probably not coincidentally of a similar magnitude as the effects of nicotine (Almundarij 2017).|
"[...] provide potential avenues to counter adaptive thermogenesis and [thus to] promote continued weight loss and weight maintenance through targeting physical activity EE and skeletal muscle thermogenesis (Almundarij 2017).Now the bad news is that the melanocortin 4 receptor agonists Almundarij et al. used in their study are not (yet?) ready to be used in human beings. Other tools to increase the decreased norepinephrine turnover in skeletal muscle, however, are available and you'll all be familiar with their names: caffeine or ephedrine (and to a lesser extent green tea extract).
|Figure 5: There is a link for nicotine and there may even be a link of caffeine to the melanocortin 4 receptor - one that's mediated by the POMC neurons.|
In a different context this relationship has already been established (Bhorkar 2014), whether and to which extent caffeine stimulates the melanocortin 4 receptors (MC4R), however, is - at least as far as I know - not known. Anyway... when all is said and done, there's still no doubt that caffeine, even when it's used alone, will still have a significant enough effect on the sympathetic nervous system (SNS) to promote weight loss and weight maintenance in multiple diet studies (Dulloo 1989; Westerterp‐Plantenga 2005) - and let's be honest: many people won't even care if that involves an increase in MC4R activity or not ;-)
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