The “fasted” state or the “post absorptive” state is basically the phase that occurs once all the glucose and fats have been stored away (as discussed in the “fed” state). Now, in the “fasted” state the body naturally tries to maintain blood glucose levels within a range of 4-6 mmol/L, thus keeping this in mind, we can delve into the processes at play that allow for this to occur.
It is important to note that the body really strives to maintain these fasted blood glucose levels, as tissues and organs such as the brain rely heavily on glucose and its subsequent conversion to ATP as its main source of energy. Having said this, the body has an amazing adaptive potential that we will delve into and explore below.
So, Important tissues and organs we will focus on in describing the physiological adaptions that occur once the body enters the “fasted” state include, the liver, skeletal muscle, adipose tissue, the brain & heart.
To begin we find that in the “fasted” state the pancreatic alpha cells of the islets of langerhans produce and secrete the hormone glucagon in response to a detected drop in blood glucose levels. Glucagon is subsequently released into the blood stream and essentially has the function of raising blood glucose levels. Thus, glucose can continue to supply tissues and organs, especially the brain.
Now, let’s look at the cascade of events that glucagon initiates which result in the increase of blood glucose levels in the “fasted’ state. If we first observe what occurs in the liver we find that glycogen is being broken down (glycogenolysis) into glucose and the resulting glucose is being released into the blood stream. Thus, as stated above glucose can continue to supply said tissues and organs.
Gluconeogenesis is also occurring in the liver and this occurs by the liver breaking down proteins into their amino acid substrates. These amino acids are then converted to ketoacids which enter the gluconeogenesis process and subsequently create “new” glucose. It is important to note that a by-product of this process is the formation of ammonia which the liver converts to urea and eventually will be excreted via the kidneys as urine.
So we can already get the feel that the liver is really working hard to keep the blood glucose levels within the desired range for homeostasis. Luckily, the adipose (fat) tissue comes in and gives the liver a hand by breaking down its stored triglycerides (lipolysis) into the form of free fatty acids and glycerol. The glycerol ‘backbone’ makes its way into the blood stream, reaches the liver and it too will enter the process of gluconeogenesis resulting in the production of more glucose. As I mentioned in the previous blog post on the “fed” state, the heart relies on fatty acids as its main form of fuel, thus some of the said free fatty acids released into the blood stream will find their way to the heart and supply it with its preferred form of energy.
It is important to note that skeletal muscle has its own supply of glycogen that it can break down into glucose and ultimately ATP to supply its energy needs. However these glycogen stores are also a limited resource that will be depleted. So, the skeletal muscle will also utilise the circulating free fatty acids provided by the adipose tissue and utilise these as an energy source.
If we quickly observe what the above paragraphs are describing in relation to blood glucose levels we find that the plasma glucose levels drop slightly with fasting. However the free fatty acid levels increase with fasting, yet they will not increase to the point of surpassing the plasma glucose levels. Keep this little note in mind, as it relates to the following paragraphs.
So, these free fatty acids that the adipose (fat) tissue so graciously has provided us with, will also find their way to the liver. It is in the liver that the fatty acids undergo a process known as beta-oxidation, which produces acetyl-coA. Now, it is during the prolonged “fasted” state that acetyl-coA cannot follow its ‘normal’ path into the Krebs cycle as there is far too much being synthesised in the liver. Thus the liver needs to do something with all this acetyl-coA it has yielded from the free fatty acids. The liver adapts beautifully and starts to convert the abundant acetyl-coA into ketone bodies.
Ketone bodies is a term I’m sure the majority of us have heard about as there is even diets that essentially claim to put the body into a state of ketone utilisation. It is important to mention that these ketone bodies produced in the liver consist of acetone, acetoacetate & and the most abundant being beta hydroxybutyrate. Basically these ketone bodies provide a source of energy to the tissues and organs, and thus the utilisation of ketone bodies is an adaptive shift occurring in the body when its preferred source of energy (glucose) is limited.
An example of how these ketone bodies are used by our organism during prolonged fasting can be highlighted by what occurs in the brain. The brain needs glucose yet it adapts and utilises ketone bodies in prolonged fasted states. It does this by converting the ketone body back to acetyl-coA, which then enters the Krebs cycle to produce ATP which the brain ultimately utilises as energy. If we look at plasma levels we find that around the two day mark of fasting 70% of the brains energy requirements will be supplied via glucose and 30% via ketone bodies. The heart will also use ketone bodies and the subsequent conversion to acetyl-coA for the production of ATP (energy).
Now, here comes the little side note in regards to plasma levels we mentioned earlier. We previously stated that in the “fasted” state glucose levels drop slightly and fatty acid levels increase, yet they do not surpass the blood glucose level. Now, ketone bodies are being produced and these ketone levels in the plasma do surpass the blood glucose levels. So what we find is that after a week or so of fasting the energy supply to the brain shifts to 70% coming from ketone bodies and 30% via glucose. A MASSIVE ADAPTIVE SHIFT!
It is important to note that after weeks of fasting the protein comprising skeletal muscle further breaks down. Thus these proteins will also be broken down into amino acids and find their way to the liver where they will participate in gluconeogenesis. I’d like to mention that these processes are not as clear cut as this blog post may lead one to believe. These processes are occurring in different levels of intensity at various times, however generally speaking the skeletal muscle will be the last to breakdown as the body needs muscular tissue to move and breath. Thus, glycogen stores and adipose tissue will be drawn on more so in the initial period of fasting with essential muscular tissue being the last to be broken down.
Thus above I have highlighted a brief depiction of what occurs in the fasted state under the influence of the hormone glucagon. To recap on the effects glucagon initiates, it stimulates glycogen breakdown, it promotes gluconeogenesis, promotes the release of glucose into the blood stream from the liver & it promotes lipolysis or the breakdown of triglycerides.
To recap the “fasted” state, it is basically the opposite of the “fed” state (highlight in my previous blog post), encompassing glycogenolysis (breakdown of glycogen), gluconeogenesis, lipolysis, ketogenesis & the degradation of proteins.
I hope this blog post has highlighted how the body operates in the “fasted” state and how it utilises the macronutrients for various physiological processes.
Please feel free to contact me with any questions you may have.
Giancarlo Nerini – Licensed Acupuncturist