JudoJosh
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This is following my past two post which attempted to explain the physiology of lipolysis. In the first post (http://anabolicminds.com/forum/weight-loss/260687-norepinephrine-mediated-lipolysis.html) I explained how the catecholamines interacted with the adrenoceptors to free stored fat. In the second post (http://anabolicminds.com/forum/weight-loss/260799-adrenergic-regulation-lipolysis.html) I pointed out both kinds of adrenoceptors and how they both work to regulate lipolysis. For this thread, I am going to focus on how we can manipulate the adrenoceptors through the use of supplementation.
I won’t really speak much about activating the beta receptors since this concept is pretty straight forward and pretty much covered in the first post. Instead I will focus on antagonizing the alpha adrenoceptors. If you recall from the adrenergic post, beta receptors are stimulatory while alpha receptors are inhibitory. So with regards to lipolysis, beta receptor stimulation will increase lipolysis while alpha receptor stimulation inhibits lipolysis. So for the goal of maximizing the rate of lipolysis your goal is to increase beta receptor stimulation AND decrease alpha receptor stimulation. So how do we inhibit alpha adrenergic activity? Enter yohimbine & rauwolscine.
Yohimbine & rauwolscine are compounds that antagonize the a2 receptor. An antagonist is a compound that binds to a receptor but it does not activate it. Instead it prevents an agonist from binding. So in this case, yohimbine or rauwolscine will bind to the a2 receptor, not activating it but preventing NE from binding which will prevent the a2 receptor from being able to slow down NE release.
Real quick, let me make a distinction here on the alpha receptors. There are two, the alpha-1 and alpha-2 receptors. The a2 receptor, like the beta receptors, use cAMP as their secondary messenger while the a1 second messenger is calcium or phosphatidylinostiol. This receptor has less significance with regard to lipolysis so for the purpose of this post, like the previous one, we will focus on a2.
Yohimbine has pretty high affinity for a2 and a weak affinity for a1. Rauwolscine has an even higher affinity for the a2 with little to no affinity for the a1. This leads me to believe that rauwolscine may be more effective due to higher potency on the same receptor but there is not much research done with rauwolscine. In contrast, we have several clinical studies that supports Yohimbines effectiveness with regard to weight loss, so we will stick with yohimbine for this thread but it should be noted that due to similarity in their structures, we can safely assume rauwolscine will also be effective through the same mechanisms.
In an in vitro study, a non-selective agonist resulted in less lipolysis then a beta agonist. They then used the non-selective agonist again but with also a a2 antagonist and the result was the same amount of lipolysis as the beta agonist. What this suggest is that if we want to maximize lipolysis our best bet is to take an a2 antagonist such as yohimbine or rauwolscine alongside with something that potentiates catecholamine release such as, caffeine, forskolin, beta-agonists, and exercise.
An important thing to note about these compounds is that they do not affect resting energy expenditure, only exercise energy expenditure. What this means is that we can not expect significant result by simply just taking an a2 antagonist. It needs to be combined with exercise in order to increases its lipolytic potential.
One thing that is important to mention is timing of beta antagonist administration. The increased lipolysis effects are negated when taken with or near ingestion of a meal. Yohimbine, when administered during times of glucose stimulation, there will be an increase of insulin secretion. This happens because there are also a2 and beta receptors on pancreatic cells and they also will become blocked (a2) and stimulated (beta). Although, when yohimbine is administered in the absence of food (during fasting) insulin levels will not increase. This means the best time to take an a2 antagonist would be first thing in the morning upon awakening and to also postpone breakfast for a few hours.
I won’t really speak much about activating the beta receptors since this concept is pretty straight forward and pretty much covered in the first post. Instead I will focus on antagonizing the alpha adrenoceptors. If you recall from the adrenergic post, beta receptors are stimulatory while alpha receptors are inhibitory. So with regards to lipolysis, beta receptor stimulation will increase lipolysis while alpha receptor stimulation inhibits lipolysis. So for the goal of maximizing the rate of lipolysis your goal is to increase beta receptor stimulation AND decrease alpha receptor stimulation. So how do we inhibit alpha adrenergic activity? Enter yohimbine & rauwolscine.
Yohimbine & rauwolscine are compounds that antagonize the a2 receptor. An antagonist is a compound that binds to a receptor but it does not activate it. Instead it prevents an agonist from binding. So in this case, yohimbine or rauwolscine will bind to the a2 receptor, not activating it but preventing NE from binding which will prevent the a2 receptor from being able to slow down NE release.
Real quick, let me make a distinction here on the alpha receptors. There are two, the alpha-1 and alpha-2 receptors. The a2 receptor, like the beta receptors, use cAMP as their secondary messenger while the a1 second messenger is calcium or phosphatidylinostiol. This receptor has less significance with regard to lipolysis so for the purpose of this post, like the previous one, we will focus on a2.
Yohimbine has pretty high affinity for a2 and a weak affinity for a1. Rauwolscine has an even higher affinity for the a2 with little to no affinity for the a1. This leads me to believe that rauwolscine may be more effective due to higher potency on the same receptor but there is not much research done with rauwolscine. In contrast, we have several clinical studies that supports Yohimbines effectiveness with regard to weight loss, so we will stick with yohimbine for this thread but it should be noted that due to similarity in their structures, we can safely assume rauwolscine will also be effective through the same mechanisms.
In an in vitro study, a non-selective agonist resulted in less lipolysis then a beta agonist. They then used the non-selective agonist again but with also a a2 antagonist and the result was the same amount of lipolysis as the beta agonist. What this suggest is that if we want to maximize lipolysis our best bet is to take an a2 antagonist such as yohimbine or rauwolscine alongside with something that potentiates catecholamine release such as, caffeine, forskolin, beta-agonists, and exercise.
An important thing to note about these compounds is that they do not affect resting energy expenditure, only exercise energy expenditure. What this means is that we can not expect significant result by simply just taking an a2 antagonist. It needs to be combined with exercise in order to increases its lipolytic potential.
One thing that is important to mention is timing of beta antagonist administration. The increased lipolysis effects are negated when taken with or near ingestion of a meal. Yohimbine, when administered during times of glucose stimulation, there will be an increase of insulin secretion. This happens because there are also a2 and beta receptors on pancreatic cells and they also will become blocked (a2) and stimulated (beta). Although, when yohimbine is administered in the absence of food (during fasting) insulin levels will not increase. This means the best time to take an a2 antagonist would be first thing in the morning upon awakening and to also postpone breakfast for a few hours.
lucky i have been using Alphamine or Alpha T2 at like 5am then play games or web browse for like 3 hours before my first meal lipolysis of peace
