Everyone knows that insulin has potent anabolic effects in the body.  One thing that is greatly misconstrued is its method of action in this respect.

Insulin is not essentially anabolic to muscle tissue.  However, insulin is anabolic to adipose tissue (fat).  But, with regard to protein, insulin’s anabolic action comes from its potent anti-catabolic effect.  That is, protein breakdown is greatly reduced in the presence of insulin, thus accounting for insulin’s anti-catabolic actions.

There’s little doubt to the potency and effectiveness of insulin with regard to creating an environment for muscular growth in the body.  Insulin’s drawbacks are also its strengths.  Insulin is a storage hormone, and one of the things it loves to store is fatty acids.  This is mediated by the enzymes Acetyl-CoA carboxylase 1 and Acetyl-CoA carboxylase 2.  Acetyl-CoA is a very important molecule in metabolism; it’s involved in many biochemical reactions. Its main task is shuttling the carbon atoms within the acetyl group to the citric acid cycle to be oxidized for energy production.  In Layman’s terms, Acetyl CoA is like a “shipping and receiving department” for items of useful metabolic energy.  Acetyl-CoA carboxylase (ACC) is an enzyme that catalyzes carboxylation of Acetyl-CoA to produce Malonyl-CoA, this happens when one molecule of acetyl co-A is joined with one molecule of carbon dioxide (CO2).  This process requires energy that comes from ATP.

Acetyl-CoA carboxylase 2 (ACC2) is very important from a bodybuilding standpoint as it has a direct effect on nutrient consumption and bodyfat levels.  ACC2 is a regulator of how fatty acids are transferred to the mitochondria.  That is, insulin increases the production of ACC2, causing a blunted effect in fatty acids being transferred to the mitochondria.  This results in less fat being burned for energy.  When insulin is elevated in the body, fat loss is blunted because of increased ACC2.


A recent study that sought to track the effects of a mutated (null) ACC2 enzyme in mice found some interesting results that could be quite salivating to bodybuilders who are looking to maximize insulin’s potential without the fat gains associated with a high carbohydrate, insulin-potentiating, diet.

“ACC2 null mice have a normal lifespanhigher fatty acid oxidation rates, and accumulate less bodyfat.  Mutant mice fed high-fat/high-carbohydrate diets weighed less than their WT cohorts, accumulated less fat, and maintained normal levels of insulin and glucose; whereas the WT mice became type-2 diabetic with hyperglycemic and hyperinsulinemic status.”

The statement that could be most important to this article is this: “Fatty acid oxidation rates in the soleus muscle and in hepatocytes of Acc2-/- mice were significantly higher than those of WT cohorts and were not affected by the addition of insulin.”

This means, that mice with the ACC2 mutation were able to still oxidize fatty acids for energy, even in the presence of high amounts of insulin.  Fatty acid oxidation is usually blunted in the presence of insulin but not in these ACC2 mutant mice!

If we find a way to blunt ACC2 in humans, could we turn our bodies into fat burning machines that could stay lean and hard even while gorging on carbohydrates?

Could we reap the benefits of insulin (increased glycogen storage, lowering of steroid hormone binding globulin, prevention of protein breakdown), while simultaneously oxidizing fatty acids for energy as if we were on a low carbohydrate diet, all while enjoying longer, healthier lives?

The chance that we could get scientists to genetically alter our ACC2 enzyme is pretty unlikely.  However, if someone could develop a product that significantly decreases ACC2, this would be like hitting paydirt in today’s apathetic, lazy, society.

Could an ACC inhibitor be available in the near future?

Some commercial herbicides kill plants by inhibiting the carboxyltransferase (CT) domain of their plastid ACC which, in turn, catalyzes the transer of the carboxyl group from (carboxy) biotin to actetyl-CoA, and thereby shuts down fatty acid biosynthesis.

More recently, CP-640186 has been reported by Pfizer as a potent inhibitor of both isoforms of mammalian ACCs. Other potent inhibitors of mammalian ACCs have also been reported, some with significant selectivity between the two isoforms.  This selectivity could be important, as inhibition of ACC1 has shown to be fatal in embryotic development, since ACC1 is intricate to very long chain fatty acid elongation-an essential step in mammalian development.

ACC2 is a biotin dependant enzyme, which creates a fairly interesting situation whereby an inhibitor of ACC2 could be found in biotin-based food products.  This scenario would create the ability to capitalize on the fat loss phenomenon without having to resort to pharmaceutical intervention.

It’s my belief that, should an ACC2-inhibiting product be developed, it would mark a great step forward in the quest for the ultimate fat burning agent.

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