Ketosis IV: Cellular Regulation

As we have seen already the control of ketosis is controlled through a variety of mechanisms in our bodies. And, most importantly, many of these mechanisms are intricately tied to our bodies’ own energy sensing pathways. We have seen ketosis regulation at a variety of levels throughout our bodies.  It can be controlled through conscious action, by eating a high-fat diet or fasting.  It can be controlled throughout our internal environment by hormones and other signaling molecules like insulin and glucagon.  And now we will go down a bit farther even, and look at how ketosis is controlled at the cellular level.  Again this one will be a technical article, so as always if you have questions post them to comments!

Ketosis Part III: Hormonal and Enzymatic Regulation

Alright, and we’re back!  So our story so far has covered what ketone bodies are and how they are formed, and some of the ways we can turn our bodies into ketone body creating machines.   This article will look further at some ways the creation of ketone bodies is regulated.  As I did with the last article I will put out the “lots of science” disclaimer on this article.  This one will be more technical than the last one was, it is just the nature of the beast when you are talking about some of these complex biochemical pathways.

I know that all the weird letters and numbers that represent proteins in our body don’t really mean much to most people, but remember they are really just designations for various receptors our body uses to recognize each specific chemical in our body.  It is important to remember that things in our body usually can’t just go in and out cells and tissues as they please.  Few things in our body just happen.  They are all controlled by various receptors and proteins that help to move them.  So, while I will be presenting the actual biochemistry here, I hope I can bring each section home at the end and give everyone a take home message that will be meaningful.

Ketosis Part II: Regulation

Now that we have a good idea of what ketone bodies are, and how they start to get formed and where I think it is time to loot at the regulation of the process.  I think what has been really interesting to me in researching this topic is that I expected to find some sort of “master switch” for ketosis.  What I mean by that is I figured that something would happen that would turn on ketosis, and as such you are either in ketosis or out of ketosis.  However, as we saw in the last article everyone produces small amounts of ketones at rest, and ketosis is physiologic process that just happens when the substrates are available and are not being used for other processes. 

There are two main types of regulators for ketogenesis, and while they may seem very different to some people, I think they are rather similar.  It all depends on what energy our body is using, and in what amounts.  Ketogenesis can be controlled either through physiologic processes or through enzymatic processes.  We will start with the physiologic ways that ketosis is controlled, and then go to the enzymatic/hormonal ways, since those are probably a bit more complicated.

When we talk about physiologic processes that induce ketosis we are talking about what is going on in our body to make it start naturally producing ketone bodies.  There are three main ways this happens, and a fourth little trick people use to jump start the process (any guesses now what that is?).  The three ways are: starvation/fasting, prolonged exercise, and a low carb/high fat diet.  Let’s take a look at each of these in turn.

Ketosis Part I

Everyone has heard of it, some of you may love it, some of you may hate it.  While most people know the general facts about ketosis, I have been hearing a lot about it lately, and it seems like every time you talk to someone different about it they have a different opinion on it.  Some people think it is the ideal state for our bodies to be in, while some think of it like the plague, and something to be avoided at all costs. Well, I am going to try and clear up some of the confusion on the matter.  This won’t be an easy, or small task, so bear with me as I try and go through all the facts to make sure I get everything right.   As a general game plan I think a good place to start will be what are ketone bodies, how are they made, how are they transported and what tissues can use them.  Then we can move into their metabolism, uses, and long term ketosis.  Other topics will come up along the way, but that is what the information I hope to synthesize here for you.  In order to transmit all of this information we will have to get fairly technical, and I will have some pretty complicated figures presented, but hopefully I can pull out the main points of them for everyone.  Well, let’s get started.

Cornerstone #3: Eating to satiety

The first two cornerstones have focused on what to eat and when to eat.  Now we focus on the obvious next question: How much to eat?  As I previously talked about our body has an incredible ability to regulate its energy intake all by itself.  Without conscience effort of what, and when to eat, humans should be able to regulate their energy balance on a completely unconscious level.  This process is regulated in many ways throughout the body, but I think one of the key ways to maintain this balance is to always eat to satiety, or fullness.

Benefits of Intermittent Fasting

We are going to take a quick break from our regularly scheduled programming because I just stumbled upon this new study from FASEB. The study is titled "Timed high-fat diet resets circadian metabolism and prevents obesity".  The wording "Timed high-fat diets"  is kind of confusing, but if you read the paper what they did was an intermittent fasting protocol.  Rats were separated into one of 4 different groups: an ad libitum low-fat diet (AL-LF), an ad libitum high-fat diet (AL-HF), a restricted feeding low-fat diet (RF-LF), or finally a restricted feeding high-fat diet (RF-HF).  The restricted feeding group was only allowed to eat for 4 hours/day, while the ad lib groups could eat whenever they want.

The results were pretty striking.  The RF-HF mice consumed the same amount of calories as the AL-LF mice, but had a 12% reduction in body weight compared to them.  Also, the RF-HF mice also had lower cholesterol levels, higher insulin sensitivity, and lower inflammatory markers than all the other study groups.  The RF-HF mice also showed signs of improved lipid oxidation, showing that the fat they consumed ended up being burned for energy, and not stored.  Not to mention that the HF diet was based on soybean oil and these are mice that are predisposed to become obese on a high-fat diet.  Finally you might think that these researchers were starving these mice on the RF protocols, but the RF-HF mice had lower ghrelin, indicating a higher degree of satiety.

A lot of people think that the benefits of intermittent fasting come from reducing calorie intake due to the small eating window.  However, this study shows that even if you eat the same amount of food, and pretty crappy food at that, eating in an IF way can help you improve your health.  I have found that I naturally tend to eat in a restricted feeding type way, with most of my eating happening a 6 to 8 hour window just naturally.  I just thought this was a pretty interesting study and showed some of the very powerful benefits of IF protocols for health.

Cornerstone #2: Eating when Hungry

Our bodies are an incredible thing.  They are able to control so many different processes and chemical levels all inside a contained system with no external support.  This type of internal regulation is known as homeostasis, and allows us to do things like always keep a constant temperature, ensure our blood pressure doesn’t get too high, and even keep a proper pH balance within the body.  The body even has its own homeostatic controls for energy balance, and uses these to help control how much energy goes in and out.  Now, I assume most of you are asking yourself that if the body can internally control things like blood pressure and energy balance, why are there so many people with hypertension and obesity?  Well, these homeostatic controls can break down, especially in the perfect storm of the Standard American Diet (SAD). 

This internal control of energy is nice and all, but how can that help us?  Well, I think it leads us to my 2^nd cornerstone for health: Eating only when hungry.  Do you think our hunter-gatherer ancestors stopped at noon to eat lunch just because it was lunch time?  No way!  They ate when they needed to.  Obviously this eating strategy is starting to look like it’s on to something from an evolutionary perspective, but lets take a look at what the current science says about this.