Jay Feldman:
How can you possibly lose fat without releasing more fat from your fat stores? I'll answer that question in today's episode of the energy balance podcast. A podcast where we explore health and nutrition from the bioenergetic view and teach you how to maximize your cellular energy to maximize your health.

In today's episode, I'll be discussing why increasing lipolysis with low carb diets, cold plunges, fasting, and excess exercise is not necessary for fat loss. I'll also go over how less lipolysis can actually lead to more fat loss. I'll discuss the role of fat release and free fatty acids in diabetes, fatty liver disease, and obesity, as well as what to focus on instead of lipolysis to support healthy fat loss.

As always, to check out the show notes where I'll link to the studies, articles, and anything else that I discussed throughout this episode, check Head over to jfeldmanwellness. com/ podcast. And with that, let's jump right in.

All right. So in this solo podcast episode, I'm going to be discussing lipolysis and the general idea that's pervade out there, which is that in order to lose fat. You need to increase the amount of fat being released from your fat stores. And then you need to burn that fat. And so with that in mind, we want to focus on things that will increase that fat release.

That's called lipolysis and then the fat burning or fat oxidation in order to lose fat. And this is things like fasting, intermittent fasting, multi day fast, cold thermogenesis, cold plunges, ice baths, all of that low carb diets exercise, especially in excessively high amounts. And various supplements as well are used to, you know, increase lipolysis, increase fat burning, and all of these are said to then increase fat loss and that these are the types of things we should be focusing on in order to lose more body fat.

Obviously, you know, makes sense. Logically, if that fat is in your fat stores, we need to get it out and then we need to burn it in order to lose body fat. And then we're also told, you know, the flip side of that, you know, the other side of that coin. Which is that we want to avoid things that decrease the release of fat from the fat stores and that decrease fat burning.

So this would be things like the consumption of carbohydrates, right? When we eat carbs that reduces the amount of fat that gets released from our fat stores and it also increases insulin, which further does that. And then we're also told that we shouldn't be eating frequently again for the same reason if we're eating multiple meals throughout the day, we're going to decrease the amount of fat released from the fat stores and the amount of fat we burn.

And so of course that's going to decrease fat loss. So our solution here is avoid carbohydrates fast, don't eat often, lower insulin as much as possible, do a lot of intense exercise and cold plunges, things that will really increase fat release and then fat burning. And as a starting place, as a bit of a disclaimer here, these sorts of interventions can increase fat loss, you can lose fat from a low carb diet, you can lose fat from fasting, you can lose fat from a lot of exercise, and cold plunges and things like that.

I'm not saying that that's not possible, but that doesn't mean that the Thank you. We're the increased release of fat and the increased amount of fat that's being burned is the driver or is responsible for that fat loss. So we're going to be discussing really that particular side that that kind of narrow part of the equation, which is really often focused on in the alternative health world.

There's quite a few issues with that. I think that that can really got us in the wrong direction. So we're going to discuss in more detail what goes on in the process of lipolysis of fat release and what that impacts in terms of body fat gain and loss, insulin sensitivity, general metabolic health, and. along those lines, how that is going to apply to what we actually want to do when it comes to, to losing body fat in a healthy way, and whether we need to be doing all these things that just increase a lot of lipolysis. So as a starting place, we're going to discuss, or let's, let's begin by discussing what tends to drive fat release from the fat stores in terms of the physiology and the kind of basic mechanisms here.

So. We're going to kind of separate this into two categories. At first we have the kind of baseline non stimulated lipolysis. This is just the natural amount of fat that's getting released from the fat stores without doing anything extra, without increasing the signals that drive fat release. And so this is typically driven by three different enzymes.

The primary one is called ATGL, adipose triglyceride lipase, which of course sounds complicated, but in terms of the name, it's actually straightforward. We have adipose, meaning adipose tissue or fat tissue. triglyceride, which is basically the, the entire kind of fat molecule with the three fatty acids and the glycerol backbone, that's the triglyceride.

And then lipase, which basically means the, that it's an enzyme that's going to break apart triglyceride break apart that fat, that lipid. That's where lipase comes from. So we have adipose triglyceride lipase, which is abbreviated to ATGL. This is the main driver of the kind of basal level of lipolysis.

Just you're, you're at rest, you're laying in your bed all day, you're not doing anything else. You're going to have some fat released from the fat stores, and that's going to start with A TGL. Break those triglycerides down into triglycerides, so it pulls off one of the fatty acids from the triglyceride, and that that's kind of the starting place.

And then there's a couple other enzymes involved. Next one is called HSL, which is hormone sensitive lipase. And this one. Is going to be more relevant when we're talking about stress induced lipolysis and and stimulated lipolysis, but it also has some amount of activity at baseline, and it helps to break those diglycerides into monoglycerides.

So it pulls off an extra one of those fatty acids. So you're just left with just one fatty acid and the glycerol backbone. And then we have an enzyme called MGL monoglyceride lipase, and that breaks down the monoglyceride into the free fatty acid and the glycerol. So we have these three steps going from the triglyceride to just free fatty acids and glycerol.

And this is happening just at baseline. Basically, we are always going to have some amount of churn in all tissues, and this includes in our, in our fat tissue. Where there's some amount of that fat being broken down and released to be used by the body. And this is a good thing. We need to use fatty acids for various things.

We use them for fuel, especially at rest when we don't need a lot of, you know, high levels of ATP produced really efficiently, we can just run on the kind of slow burning fats. You know, our muscles are a great place to where we see that happen. where they don't need a lot of energy at rest and they can just break down those fatty acids.

Fatty acids are also used for other things. They're precursors to hormones and bile and help with digestion and, and we use them for structural purposes. You know, all of our cells are, are made up of fatty structures and protein structures. And so there's a lot of reasons why we need some amount of fat just always.

Now, as you know, whether you're looking to lose fat or if you're dealing with various low energy symptoms like chronic cravings and hunger, joint pain, digestive symptoms, brain fog, poor sleep, hormonal imbalances, or various other low energy symptoms or chronic health issues, there's a ton of conflicting information out there when it comes to the best approach to optimizing your diet and lifestyle to resolve these symptoms and conditions.

And this. And so that's why I'd encourage you to head over to jfeldmanwellness. com/ energy, where you can sign up for the free energy balance mini course, where I'll walk you through how you can adjust your diet and lifestyle to resolve these low energy symptoms and lose body fat in a healthy way.

So again, head over to jfeldmanwellness. com/ energy to sign up for that free energy balance mini course. And so when we're looking at the amount of free fatty acids that are released at baseline from lipolysis, you know, the amount of fat being released from the fat stores. We generally look at the amount of glycerol appearance because glycerol is the backbone there that gets separated from the free fatty acids and that also gets released from the fat stores.

So, for basically every molecule of glycerol that gets released, we can assume that that was a part of a full triglyceride. And we can use that to estimate the amount of free fatty acids and fat in total that was released from the fat stores. And that amount of glycerol appearance at rest is generally considered to be 2 micromoles per kilogram per minute.

And they discussed this in the study titled Whole Body Lipolysis and Triglyceride Fatty Acid Cycling in Kekectic Patients with Esophageal Cancer. And they state in this quote, the basal rate of glycerol appearance in blood in the patients with cancer is which was 2. 96 micromoles per kilogram per minute was similar to that in the nutritionally matched controls which had a rate of glycerol appearance of 3. 07 micromoles per kilogram per minute but 48 percent greater than that than in normal weight volunteers which had a glycerol appearance of 2 micromoles per kilogram per minute so again to break this down We're trying to identify how much fat is released just at baseline. And in our case here, we're more focused on the normal weight volunteers.

This is just kind of an average control population where we're seeing the release of two micro moles of glycerol per kilogram per minute. We can then use that to calculate out the amount of triglyceride that's getting released per minute, and it turns out. If we were looking at an entire 24 hour day at this 2 micromoles of glycerol appearance per kilogram per minute for a 150 pound person, a pretty average sized person, this is 158 grams per day of triglyceride of fat being released from the fat stores, which is a third of a pound of body fat, essentially.

Now, a couple of things to mention here before we talk about the implications of this but just in this quote in the study. The nutritionally matched controls that they discuss along with the cancer patients, the nutritionally matched controls were cachectic patients without cancer, so it was We're talking about here patients who are basically very ill and they're losing a lot of body weight.

So in the study, they defined this as people who had lost 10 percent of or more of their body weight during the six month period during the study. But so these are people who are generally really not healthy. They're generally struggling significantly health wise. They're in a very degenerative state, whether driven by cancer or something else.

And it's worth noting here that there is a nearly 50 percent increase in lipolysis in those patients. And this Is one of many different lines of evidence showing that there is an increase in lipolysis and increase in free fatty acids during states of stress, whether we're in a severely degenerated state like this, or it's due to intense exercise or fasting or low carb diets, things that increase stress will increase lipolysis.

And we'll talk about that in a moment here, but it's certainly worth mentioning here in passing, but coming back to a real question here, which is how much fat is being released from the fat stores at baseline without doing anything. We're seeing about 158 grams or a third of a pound of fat for a 150 pound person.

Of course, if you weigh more, this would be greater. If you weigh less, it would be a little bit less, but this is a pretty significant amount of body fat, just at baseline without doing anything else. Right? So if you were to just lay in bed all day and you, we looked at the amount of fat released from your fat stores would be a third of a pound.

If you then didn't store any of that fat again, if you didn't restore any of it, you used all of it, you would be losing a third of a pound per day. Now, of course, with some activity and other things just throughout the day, just regular life, that amount increases. So this is the absolute minimum for 150 pound person that we're going to see in general.

And we're going to come back to this at the end when we talk about what this actually means in terms of fat loss and what we actually want to do here. That brings us to the next piece here, beyond just baseline lipolysis, which is the stress induced stimulated lipolysis. So anytime we incur stress, Which basically is anytime that there's an energy depletion, right?

We use more energy than we have in that moment. It increases the stress hormones to provide fuel so we can produce more energy so we can still function. Right? So if we start exercising using a lot of energy, we need to release stress hormones to break down the fuel that we have stored and start to use that.

So we can produce enough energy to survive and continue doing the activity. If we're fasting, if we're in a famine those are also times where we'd have to do the same thing. But it also happens if we're dealing with psychological stress, if we're dealing with an infection, if we're dealing with detoxification of anything irritating from our diet or from our environment, whether we're talking pesticides or some sort of bacterial toxin production like lipopolysaccharide from the intestines, all of those things can induce stress.

In order to produce enough energy to handle them and when that stress happens, we release particular hormones called stress hormones to help us deal with that stress and the main ones, the primary ones are glucagon, adrenaline and cortisol and growth hormone does fit in here as well, which we might talk about a little bit later, but the primary ones are glucagon, adrenaline and cortisol.

And these stress hormones have a number of effects. We've talked about these in the past. I'll link to some of those episodes where we look at how they interfere with mitochondrial function over time and down regulate thyroid hormone conversion and decreased testosterone production and all sorts of things.

So these are definitely hormones that we don't want to have in chronically high levels. And one thing that they do in terms of fuel use is they shift us away from glucose oxidation and toward our, our larger storage fuel of fat and fat oxidation, so we start to shift toward burning fat. And with that, we start to release more fat as well.

So these hormones stimulate the release of fat from our fat stores. And they largely do this by stimulating HSL, hormone sensitive lipase, which is how it has its name, right? It is sensitive to the hormones, these stress hormones, and it's, it's a lipase enzyme, meaning that it breaks down the fat in this case to release it as.

So that's, that's one mechanism. The other thing is they do actually increase lipase as well. So the stress hormones will increase two of the primary enzymes needed to release fat from the fat stores. And this leads to a very significant increase in lipolysis. So we were talking about our baseline levels, you know, 150 grams per day, more or less a little bit more.

And that led to, or that was at the equivalent of about a third of a pound of body fat. Well, when we include the, anything that will increase the stress hormones, we can dramatically increase multiple times, increase the amount of fat that's getting released from the fat stores, at least during moments when, what is when these hormones are being released and they're largely doing that by stimulating these two enzymes, HSL and ATGL, and we're going to focus a lot on HSL today, the hormone sensitive lipase hormones.

In order to help us answer some questions about whether we want to be increasing the activity of HSL, what that means in terms of metabolic effects and fat gain, fat loss, all of that. So that's the basics when it comes to physiology of lipolysis. And so let's talk about some of those implications. Let's talk about the relationship between lipolysis.

specifically the stress induced lipolysis from these stress hormones, activating specifically HSL, how that relates to metabolic syndrome, fatty liver disease, obesity, fat gain, and how does that relate to us if we actually want to lose fat? Do we need to be doing all of these different nutritional interventions, lifestyle interventions to maximize the stimulation of something like hormone sensitive lipase to release as much fat from our fat stores as possible?

That's the question. So when we're talking about the relationship between lipolysis And insulin resistance, fatty liver disease, cardiovascular disease in terms of some of the direct effects of the role of stress hormones and elevated levels of free fatty acids and excess levels of fat oxidation, driving insulin resistance, driving fatty liver disease, driving cardiovascular disease.

We did talk about these things in more detail on episodes one 13 and one 14 of the podcast. I'll link those in the show notes, but here we're going to focus specifically on hormone sensitive lipase and its relationship to insulin. With metabolic syndrome, fatty liver disease, and adipose tissue and body fat gain and all of that.

So let's start with this study looking at, or titled an overview of hormone sensitive lipase HSL, and they are going to describe the effects in terms of metabolic syndrome, which is that constellation of obesity and some resistance type two diabetes cardiovascular disease. And they describe here, free fatty acids are essential for maintaining energy homeostasis, but an increase in plasma free fatty acid levels is linked to obesity, insulin resistance, type 2 diabetes, and neuroinflammation.

Elevated plasma free fatty acids, due to the elevation in the lipolytic rate, which means high HSL activity, could damage lipid profiles by improving the production of very low density lipoprotein, VLDL, by the liver, pushing toward dyslipidemia. Decreasing insulin sensitivity in the tissues and causing insulin resistance development, type 2 diabetes and other metabolic abnormalities.

So, we'll kind of pause here. What they're, what they're describing is basically the implication of elevated levels of free fatty acids, largely driven by increased HSL, hormone sensitive lipase activity. In this case they're talking about it specifically increasing VLDL, but we know that it also, and we'll talk about this in a bit, it'll increase fat deposition at the liver.

It'll interfere with glucose metabolism, interfere with insulin sensitivity in the tissues, as they mentioned, and then cause these downstream negative effects like type 2 diabetes and other metabolic issues. They go on to say, additionally, many synthetic and natural HSL inhibitors have been identified.

These inhibitors provide a novel therapeutic tool that targets dyslipidemia by controlling lipid hydrolysis. and reversing insulin resistance and other obesity related metabolic problems. Inhibition of hormone sensitive lipase can improve insulin sensitivity and control of blood glucose in type 2 diabetes.

Therefore, many HSL inhibitors, both synthetic and natural, have been identified and could potentially develop into effective anti diabetic agents. So they're describing here the relationship between excess HSL activity, excess free fatty acid production, and interfering with insulin sensitivity, driving things like type two diabetes and metabolic syndrome, and that inhibiting HSL activity can improve that can reverse these states.

And again, comes back to something we've discussed prior, which is that shifting over to this fat burning state via stress is certainly not the way that we want to support our health. And we're seeing that here. And we see that play out in other disease processes as well, as I've alluded to, including fatty liver disease.

We talked about this a little bit in our fatty liver series. I'll link to those specific episodes at the show notes. But we'll take a look at this first study here titled excessive hepatic mitochondrial TCA cycle and gluconeogenesis in humans with non alcoholic fatty liver disease. May state individuals with non alcoholic fatty liver disease had 50 percent higher rates of lipolysis and 30 percent higher rates of gluconeogenesis.

Both of these, as we discussed in those episodes, are stress driven processes. And we know that in these states of metabolic syndrome, the fatty liver disease, the central issue is an issue with energy production, right? Or mitochondria not functioning well, they're getting the fuel coming in, whether it's glucose, fatty acids or other fuels, but they're not effectively able to convert that glucose into energy.

And it forces them to shift over to fatty acid oxidation, which is a very clear process going on in fatty liver disease, despite the fact that. Literally in the name, it describes how we're seeing an increase in fat deposition and deliver, right? The liver is becoming fatty. It's increasing fat yet. We see increased levels of lipolysis, right?

Fat release, free fatty acid production, and we see increased lipid oxidation in the liver. We're actually burning more fat at the same time that we're storing more. That's because that burning and fat release go hand in hand with stress, which goes hand in hand with impaired energy production, which goes hand in hand with states like fatty liver disease and the others that we're describing here.

Okay. But in any case, the central part that we're wanting to highlight here is the 50 percent higher rates of lipolysis, which is the exact same thing that we saw in cachectic patients and patients with cancer, right? These are very similar to the fatty liver disease states in that they're states of severely impaired metabolic function, severely impaired energy production, and we see higher rates of lipolysis.

So obviously what we're starting to see is that increased lipolysis and increased health don't go hand in hand. in many cases at the very least. In this next study, which is titled sources of fatty acids stored in liver and secreted via lipoproteins patients with non alcoholic fatty liver disease, they state of the triacylglycerol, which is just triglyceride or fat accounted for in the liver, 59 percent arose from non esterified fatty acids or free fatty acids, 26 percent from de novo lipogenesis, and 14.

9 percent from the diet. So what they're saying here is that they're looking at the amount of fat in the liver that's being stored in the liver and fatty liver disease. And they do a tracer study where they see what types of fuels are contributing to the fat in the liver, where they're coming from.

And so what they found was that 60 percent essentially of the fat that was being stored in the liver came from free fatty acids from the fat stores largely. So that's, you know, that 50 percent increase in my policies that we're talking about is leading to a lot of circulating fatty acids. We're obviously in a impaired metabolic state. And then those free fatty acids are getting stored partially due to the excess fatty acid oxidation that's causing the impaired metabolic state. Although there's normally a lot of other things going on here that, that are also impairing metabolism, but in any case, around 60 percent came from free fatty acids around 25, 26 percent came from de novo lipogenesis, meaning that it was produced from carbohydrate. And then 15 percent came directly from fat in the diet. So This is a quote that I think is worth sharing over and over again, because so often we're told carbohydrates are the problem and you eat the carbs and it just directly goes to the liver, especially if there's fructose in there, directly goes to the liver, directly leads to fat production.

And yet, when we look at fatty liver disease in humans, and we see where that fat's coming from 75%, is coming from fats, 15 percent from the diet, 60 percent from our own fat stores. And then around 25 percent is coming from the carbs. So obviously a very different narrative from what many of us are told, but also something that really is implicating increased lipolysis in these situations. And again, leads us to question whether that's actually going to be our solution for improving health and losing body fat, especially if we want to do it in a healthy way.

All right. So that does bring us to body fat gain, you know, fat gain, fat loss, what's going on at the adipose tissue. And The relationship with lipolysis because this is one of the central ones, right? The assumption would be and the assumption often is we're told this everywhere. If you do things to increase fat release, that's going to lead to more fat loss. Let's see if that's actually true. So first study we're going to look at here is titled decreased fatty acid esterification compensates for the reduced lipolytic activity in hormone sensitive, lipase deficient white adipose tissue.

So in this study they're looking at hormone sensitive lipase deficient mice. So these are mice that basically they've blocked their, their HSL enzyme production, and so they don't have any of that hormone sensitive lipase. So if they were in, and we'll go over this, but if they had a lot of adrenaline, they're not actually going to have increased lipolysis.

Even if they're under stress, they're not actually going to have increased lipolysis. And what they actually find in the study is that these mice have reduced body fat stores. And of course, that also tells us that the increasing lipolysis doesn't lead to less body fat, doesn't lead to less fat loss. And actually, when we have less hormone sensitive lipase, we see an increase in fat storage, an increase in fat production in the fat stores and the enzymes that are actually doing that.

So they state that here in a couple of quotes, they state it has been observed previously that hormone sensitive lipase deficient HSL knockout mice have reduced white adipose tissue stores compared to control mice. These findings contradict the expectation that the decreased lipolytic activity in white adipose tissue of the HSL knockout mice will cause the accumulation of triglycerides in that tissue.

Taken together, these results establish that in the absence of HSL, the reduced non esterified fatty acid production, the free fatty acid production is counteracted by a drastic reduction of non esterified fatty acid re esterification that provides sufficient quantities of free fatty acids for release.

into the circulation. These metabolic adaptations result in decreased fat mass and HSL knockout mice. So what they're discussing here is a really important concept to, to understand and become familiar with, which is that when we shift into the types of things that induce fat release and fat burning.

When we shift from the kind of high metabolic carbohydrate induced low stress state to a high stress state that largely involves a lot of fat release and a lot of fat oxidation, you know, a lot of fat burning. What then happens is we do have a lot more fat release from the fat tissues. But we have a lot more re esterification of fatty acids, a lot more fatty acids coming back into the fat tissues and turning back into triglycerides.

We're basically just shifting the body, you know, before it was running on a current on a kind of fuel system that came from the diet, right? Carbs coming in, some fats coming in, and our glycogen stores. And instead, we're starting to shift over to using our fat stores as our primary fuel source. Our primary fuel storage system.

And so we're releasing fuel from there and then we're storing fuel back into the fat stores. And what we find is that sure. In the short term with the stress hormones, we see a major increase in fat burning. We see a major increase in fat release, but over the long term, these hormones actually interfere with energy production and slow down the amount of fuel that gets used.

And so then we ended up restoring that fat that gets released plus whatever's coming in from the diet. And we don't actually. See just this automatic fat loss that you would assume when we see a lot more fat coming out of the, of the fat stores. And this, you know, this example of the HSL knockout mice is, is pretty clear in that regard.

And we see that here in table two, basically they show the difference here in terms of body weight in the wild type mice versus the HSL knockout mice. And when you look at the body weight, there's actually no change, but when you look at the white adipose tissue fat mass, there's a major difference. When we look at the males, there's nearly three times less white adipose tissue weight in the hormone sensitive lipase knockout mice versus the versus the wild type mice.

And you see the same, actually even more than three times decrease in the female mice. So we're seeing a major decrease in fat storage, despite having a less. hormone sensitive lipase, less lipolysis, less fat release. And along with that, in terms of that second quote, we also see less refatty acid incorporation into triglyceride and also into phospholipids.

So there's just less fat being kind of restored in both the fasted state and the fed state, which we'll we'll see here in a moment and we also see interestingly less uptake of glucose and less conversion of glucose into fat in the fat stores as well. So we see that here in figure two on the left, we're looking at the incorporation of free fatty acids into triglyceride.

And so you can see the gray bar, that's the, the knockout mice, the ones without hormone sensitive lipase, and they have way less, about half as much conversion or uptake of trig, of free fatty acids from the fat stores and converting that into triglycerides. There's again, about half as much of those free fatty acids being taken up into the fat stores and being converted into fat even after eating.

And then also when fasted. And you see the same thing in terms of phospholipids, which is a little bit less relevant to us right now in our questions here. But again, what we're seeing very clearly is that we're running less on fat stores, right? We're not using that as our storage system so much. We're not going to be storing fuel in those fat stores.

We're not going to be releasing fuel from those fat stores. And that's really the question we want to get to. We'll get to it a bit later. We'll look at that in detail, but we need to look at not just the amount of fat being released from the fat stores, but how much is being stored and the difference there and what regulates each of those.

And what we see very clearly from these mice is that just because we have significantly less release of fat from the fat stores does not mean that we're going to have a fat gain, and instead in this case, we actually see smaller amounts of body fat and much less being stored as fat as well. And that's really something that we want to emulate.

And we'll talk about how to do that, but there's some interesting things to discuss in this other study, also looking at. HSL knockout mice. This is a study titled hormone sensitive lipase deficiency in mice causes diglyceride accumulation in adipose tissue muscle and testes. And the real thing that we want to look at in this from this study is the impact of HSL deficiency on lipolysis at baseline and after stimulation by stress hormones.

And in this case, they actually use a substance called isoproteranol, which basically activates the receptors, the beta adrenergic receptors, which is, is what's activated by the stress hormones to increase fat release. And so what they state here is that figure seven demonstrates that three hours after stimulation with isoproteranol, the release of glycerol from epididymal wild type, which is the non HSL knockout mice white adipose tissue was increased 4. 3 fold. In contrast, the release of glycerol from the isoproteranol stimulated HSL knockout white adipose tissue was only marginally enhanced 1. 2 fold. The release of free fatty acids from the hormone sensitive lipase wild type and knockout white adipose tissue was enhanced by isoproteranol 4. 4 fold respectively.

Compared with HSL wild type mice, the release of free fatty acids was decreased by 35%. What's important to note here is we're not seeing zero response to stress hormones. We're just seeing a major reduction in response to stress hormones. So if we take a look at the different graphs here, we've got a few different things being shown.

Basically the two graphs on the left are the wild type mice. These are the ones that have the hormone sensitive lipase. The ones on the right are the ones that don't have the hormone sensitive lipase. And then we're looking at glycerol release and free fatty acid release, which really trend together.

They kind of diverge a little bit more in the HSL knockout mice, but that's just due to, The fact that you're, you're reducing the activity of one of the enzymes that's needed for the full breakdown from triglycerides to free fatty acids and glycerol, but in any case, the important part here. So if we look at the we'll look at in terms of the free fatty acid release, just keep things simple.

So if we look at those two graphs on the bottom here, What we see is on the left in the mice that have the their HSL intact the little white points or the, the open squares at the bottom that, that lower line, that's. at baseline. That's just the basal lipolysis without any stimulation. And then those filled in boxes, the taller line here is the one where we're seeing stimulation from the isoproteranol.

And so this is basically mimicking stress hormones. So another way to think of it, if we look at that graph on the left, is that with the stress hormones, we see a major increase in free fatty acid release. Now if we look on the right here, this is the mice without hormone sensitive lipase that we can see that the baseline level of free fatty acid release is about the same, right?

So even without the hormone sensitive lipase at baseline, those hollow not filled in circles at the bottom. Those are about the same. Both graphs, right? Those bottom lines are about the same, meaning that there's about the same amount of free fatty acid release at baseline. However, if we look at the stress hormone stimulated free fatty acid release, it's significantly less on that right on the right graph without the hormone sensitive lipase.

So again, what this tells us is that When we reduce or when these mice have reduced free fatty acid release from stress hormones, they have much lower body fat stores, even though they have about the same amount of free fatty acid release on baseline. And of course, this is something that we can apply in a, in a broad sense when we talk about.

whether we need to be stimulating lots of fat release from the fat stores in order to have less body fat stores. Of course, these mice tell us that we don't really need to. Now it's worth mentioning there is a bit of a caveat here where obviously if we take out the function of this entire HSL enzyme, we can have issues, right?

There's a number of things that can happen. Basically, Because there's a reduction in capacity for storage of fat in the adipose tissue if you have excess fat and you can't store it there, you have to store it elsewhere, it will end up over time getting deposited into the liver and other organs which can then cause insulin resistance and other metabolic issues.

So, this is why we have hormone sensitive lipase, this is why we have adipose tissue, it's because if there's excess fat, that's where we want to put it, and that makes sense, so we don't necessarily always want, or I guess another way to say it, we don't want to actually take out our hormone sets of lipase, but instead we're just using this as an example to show what happens if there's less activity in terms of hormone sets of lipase and maybe a question of whether we want to do things to put us in an environment of higher HSL activity or lower HSL activity.

Of course, the goal here is not to go and genetically knock out our capacity to produce hormone sensitive lipase, which certainly comes at a cost. And they talk a bit about that cost, but also the benefits here in this study titled Lipase. We looked at a quote from this study before. In this case, they state, human HSL mutation causes a reduction in the lipid storage capacity due to decreased p par gamma signaling.

Also, excessive circulating fatty acids leads to ectopic fat accumulation deposition in non adipose tissues such as the liver and skeletal muscle, and the development of insulin resistance. I'll just kind of pause there. What we're talking about here is inhumans, if you have less HSL activity, you have a mutation reducing activity, there is a reduction in lipid storage capacity.

So you do see less body fat, but of course if we have extra lipid and we can't store it in the body fat, over time with age, you see increased deposition in other areas like the liver and skeletal muscle and insulin resistance. So this is not something that we want. We don't want to reduce our capacity for HSL. We do want to put ourselves in an environment that doesn't require the need for increased levels of HSL, right? We don't want to necessarily be increasing the stress remote. They go on in this next quote to state, as a result of HSL deficiency, PPAR gamma signaling is lessened in adipose tissue, which causes a decrease in adipogenesis and lipid synthesis.

The capacity of adipose tissue for the storage of lipids is also, is limited. Also circulating fatty acids are relocated to the liver. lead to ectopic lipid deposition and metabolic dysfunctions such as dyslipidemia and diabetes. So again, we have reduced fat storage, which is the kind of central point we're wanting to get at here.

But there of course would be a cost if we actually had a mutation reducing our capacity for HSL production. But this tells us something else that's really important which is that if we're solely focused on what's going on at the fat tissue, what leads to the release of fat from there, what leads to the storage of fat there.

And just the internal mechanisms there, and we're not thinking about the body as a whole. We're not thinking about the other implications of storing more fat or storing less fat. We could miss a lot, right? In a case like this, we could say, Oh, there's less fat storage. That's great. And to forget the fact that that fat would have to go somewhere and would be stored elsewhere.

Now we want to be in a situation where there's not excess lipid to be stored. And we aren't activating the stress hormones at, so we don't have to worry about the, you know, fat being stored in the liver and insulin resistance or the fat being stored at the fat stores. That's why we want to focus on this as a global issue, as opposed to just zooming in into this idea of saying my policies is good or fat burning is, is good or something like that.

That's what leads to the really backward recommendations that we see. And that's what leads to. Things, you know, people saying things like you want to increase lipolysis to increase that loss. And then we'd look at these studies and obviously see that that doesn't really play it. Now we're going to go through the kind of last study here.

Last example, which was a study where we're seeing different diets in The kind of in a real world example, and we're looking at the impact on fat burning, fat released shifting from carb to fat utilization effects on stress hormones. And then we're going to see how that impacts body fat stores. And the question would be, or the assumption would be from a lot of people who say we want to increase lipolysis, they would then say, well, if you can create a diet.

Or an intervention that increases fat release and increases fat burning, you're going to have more fat loss. That would be the kind of central thesis there. Let's see if that actually plays out. So this is a study titled Energy Expenditure and Body Composition Changes After an Isocaloric Ketogenic Diet in Overweight and Obese Men.

This is a metabolic ward study where overweight and obese men We're in a, in a metabolic ward for this entire time. And they basically were put on a baseline diet, which was a high carb diet for four weeks. And it's actually kind of like a high carb, high fat diet. It was included 300 grams of carbs and a lot of sugar, actually about half of those carbs came from sugar, 147 grams.

And it was also a relatively high fat diet. At least if we're looking at research terms, their fat intake was 36 percent of their total calories, which would fall in that higher fat range. So they're at 48 percent carbs, 36 percent fat, and 16 percent protein. This would be the type of diet had most people would suggest is going to lead to lots of fat gain and lots of issues because you're having high carbs and high fat.

A lot of people will say anything with high carbs will cause fat gain. Some people will say, well, if you're eating high carbs, you have to eat low fat. We'll obviously see whether or not that's the case here. But then there, so they put on that baseline diet for four weeks and then they go on a ketogenic diet for four weeks, and this is a 6 percent carbohydrate diet, 75 77 percent fat and 17 percent protein.

And they did test and show that they were in ketosis based on ketone levels and a number of other things. So let's look at what happened on the four weeks of the baseline diet, high carb, high sugar, and relatively high fat. Diet compared to the ketogenic diet in overweight and obese men. So this is not the metabolically healthy people with tons of activity or anything like that.

But they state is that as expected, the ketogenic diet was associated with significant increases in ketones, free fatty acids, and glycerol. Fasting glucose was not significantly different between the diets, whereas glucagon significantly increased and C peptide insulin and triglycerides significantly decreased during the ketogenic diet.

Leptin was significantly decreased during the ketogenic period, thyroid stimulating hormone, TSH, and free thyroxin, free T4, concentrations were significantly increased during the ketogenic diet phase, whereas both free and total triiodothyronine, or T3, were significantly decreased. So again, just to summarize that, we saw all of the things that we would expect to see when someone goes from a high carb diet to a low carb diet, we saw increased ketones, increased lipolysis, which was evident by increased free fatty acids and glycerol, they also showed increased levels of glucagon, which is one of the main hormones driving that lipolysis, we saw a reduction in insulin, and then we also saw an increase in TSH and T4 and a decrease in In T3 suggesting impaired or reduced T4 to T3 conversion, which we have discussed many times in terms of the impact of the lack of carbohydrates on thyroid hormone conversion, and I'll link back to those episodes with these markers in mind, someone from this campus saying Increased fat burning, increased fat release is going to lead to body fat loss, right?

This is our solution for losing body fat. Of course, we would expect to see that here. And they did also see significantly increased fat oxidation. So I'll share that quote here. They state. Table 2 and figure 3c show that the 24 hour RQ respiratory quotient decreased significantly from 0. 879 during the baseline diet to 0. 775 at the start of the ketogenic period and remained approximately constant until the end of the study, indicating a rapid and persistent increase in fat oxidation. So the respiratory quotient is basically just an indicator of how much fat or carbs we're burning and the lower the value, the more. Fat we're burning, the higher the value, the more carbs we're burning.

In general, 0. 7 is about the lowest it could be. That would be 100 percent fat and 1 would be 100 percent carbs. But it gets a little complicated because there are other processes too that can affect respiratory quotient. But the important part here is that they saw very clearly increased fat burning, increased fat released, less insulin, and all the other effects you would expect to see from a ketogenic diet.

And let's see if that actually led to an increase in fat loss. So they state the subjects lost 0. 8 kilograms of body weight over the last 15 days of the baseline diet period with 0. 5 kilograms of this unintentional weight loss coming from body fat. So this was just during 15 days, about two weeks of the baseline diet.

The last two weeks they lost half a kilo of body fat, 0. 8 kilos in total. And then they state body fat loss slowed during the ketogenic diet and coincided with increased protein utilization and loss of fat free mass. Over the entire 28 day ketogenic diet period, the total weight lost was 2. 2 kg, with 0. 5 kg from loss of body fat. So a couple of things we see here. One is that the loss of body fat from 4 weeks on the ketogenic diet was the same as the loss of body fat from 15 days on the baseline diet, despite Increased fat burning and increased lipolysis along with all those other changes that we saw.

We also see that there was a 1. 7 kilogram loss of fat free mass, non body fat. A significant portion of that was water. And obviously there's some amount of muscle loss as well. And so this basically does anything but support the idea that we want to increase lipolysis and increase fat burning in order to lose weight.

Body fat. And this, of course, corroborates all the other studies we've been looking at here, which show that if you reduce the amount of fat being released during stress, and of course, if we reduce that stress, it actually helps with the loss of body fat. And that doesn't mean that that's Like our goal here is to minimize lipolysis at all costs, either.

We'll talk about what we're actually going to try to implement in order to have fat loss in a healthy way. But what it does mean is definitely that these simplified idea, this oversimplified and well, as we'll get to entirely inaccurate idea that increasing lipolysis increases fat Fat loss is certainly not the case, right?

That's very clearly shown based on the studies that we've gone through today. All right. And that brings us to the question of what do we want to do to lose fat? If just releasing fat from the fat stores is not the solution, what is the solution? How do we actually lose fat? And if, you know, if the answer is not just excessive exercise, fasting, cold plunges, low carb diets, anything that we can do to increase that release and increase fat burning, what Again, just to mention that disclaimer again, I'm not saying that those things can't lead to fat loss, but we know that the increased lipolysis and increased fat oxidation are certainly not responsible or necessary for that based on everything that we've gone to, gone through today.

So if we're not just going to try to do whatever we can to maximize fat release and maximize fat burning, what are we going to do in order to lose body fat? Well, let's take a look at this graphic that we have, which I talked about in episode 124 of the podcast. Where it's going to depict basically the overall picture of energy balance and, and help us identify exactly what we want to do.

So if we look at this graphic, this is the simplified version. We see the food coming in, which becomes fuel after it's digested and absorbed and all of that. That fuel has a few different routes. It can go, can either be further excreted, you know, it can go back out through the urine or stool to various pathways it can be used to create structure, muscle, bone, the membranes of all of our cells or the organelles, all everything requires some fuel, some structure or it can be used to produce energy or it can be converted to body fat and What we're generally told to focus on, again, from this perspective of increasing lipolysis is that we just want to release as much as we can from the fat stores as possible.

But the reality is that if we direct that fuel properly toward energy production, if a lot of that fuel is being converted toward energy, there is way less to be stored as body fat. And so if we're already having our baseline level of lipolysis, and of course, some things throughout the day that we do, just walking, movement, a little bit of stress here and there that's unavoidable, those things are going to increase fat release as well.

All that we need is to have less fuel going into the fat stores that is coming out. We don't need to drastically increase the amount of fat being released from the fat stores. Especially when we consider that just at baseline, we're going to have a third of the fat being released from the fat stores, or more, or less, I guess, as well, depending on their body size.

But again, that's not even including all of the extra fat released from the inevitable amount of stress that we will experience. Now, when it comes to maximizing that conversion of food to energy and minimizing the amount of, of food being stored as body fat, there are some other details that are worth going through.

And I discussed these in that episode 124. I'm going to discuss it briefly here, just because I do think it really adds to the picture and helps make it clearer. So we of course have that same food coming in and that food becomes substrate, which is basically just a precursor to structure, to fat, to energy, to being excreted, to hormones, you know, whatever we're using the food for.

Now, when we improve the things that convert that substrate to energy, that's mitochondrial function. That's the conversion of food to ATP. When we do that efficiently, we have a lot more that substrate going into energy, a couple of things happen. If we follow this graphic to the left, that means we have increased energy in the brain and liver, which then reduces hunger because Our hunger signals more than anything else are driven by how much energy we have, how much energy we're producing.

So if we have enough in those areas that are really our main energy sensors, hunger sensors, it helps to reduce our hunger so that we're not needing to eat more, right? Our bodies are not craving extra food because they're actually getting what they need from the food, which more than anything is, is energy.

Plus, you know, there's other, the structure and other things that we need. And so that's going to prevent kind of quote overeating, which is not really overeating. It's actually just your body calibrating how much it needs based on its energy needs. But if we're really efficient at using that food, converting it to energy, we will naturally have balanced hunger.

And then on the right part of this graphic, we see that that energy influences stress hormones. We talked about this already. When we have energy deficiencies, energy deficits, it increases the release of stress hormones. And this will do a couple of things. One is it slows down the conversion of food to energy over time.

It reduces the efficiency of mitochondrial respiration. Again, I'll link to episodes where we discuss that. And also in the short term causes increased fat release. As we talked about today, you'll have increased activity of HSL, increased lipolysis, increased fatty acids, some of which will be used for energy.

But the other thing stress hormones do is increase the storage of fuel from the blood and elsewhere into the fat stores. So, I mean, of course it has to come through the blood, but when we have that same increased fatty acids and the food that we take in that leads to fuel in the blood, We are going to increase the amount of that fuel that gets restored as fat, and we described that today in some of the examples.

And this is again very well known if we have if we use something that increases or mimics cortisol, like glucocorticoid drugs. Over time that will increase fat storage significantly. We also see this in situations like Cushing's syndrome with major overproduction of cortisol, or of course you also have a lot of fat storage.

So that's one aspect of, of the stress hormones at the impact of a lack of energy. The other thing is that those stress hormones increase hunger, causing us to eat more, and of course, storing more of that fat as food and impairing the conversion of food to energy. So with all this in mind, what is our solution?

We know that we don't just want to increase lipolysis, we don't want to just increase those stress hormones. You know, low carb diets, fasting. That's what those are going to do. So we know that those don't make sense physiologically as our primary solutions here. On the flip side, does this mean that we need to just avoid anything that could cause an increase in lipolysis? Am I saying never to exercise never to go a period without eating? You know, we need to be up all night eating to prevent any lipolysis that could go on. No, of course I'm not saying those things. It's great to get enough sleep. It's great to move and exercise and those things can all absolutely support.

Fat loss by improving our health, improving our conversion of food to energy. And they will have some stress cost to them, right? There is a stress cost to exercise, and that's okay. When we're in a place that we can handle that and recover from it. That's, that's not a big deal, right? There's some amount of stress that's going to be inevitable.

That's, that's a part of, of our existence. And that's why we have those systems. We have them to deal with the small blips throughout the day that are suboptimal. On the longer term, if we were to go through periods of excess stress, it's great that we have these stress systems in place. We certainly don't want to be trying to create a diet and lifestyle that increases stress.

That's basically activates those systems as much as possible. And so we don't need to force cold baths and cold plunges and low carb diets and fasting for fat loss. But what we do want to do is sort out what's blocking that conversion from fuel to energy, right? What's interfering with our mitochondrial function?

Is it a lack of certain nutrients? Is it our general hormonal status due to excess stress hormones or a lack of thyroid or thyroid hormone conversion or testosterone or progesterone? Is it due to stress in our environment? Is it due to other things that can interfere with mitochondrial function like endotoxin production from gut bacteria when we have an unhealthy gut microbiome? Is it due to the polyunsaturated fats which are disastrous for mitochondrial function? And on from there, there's a number of things that can affect biocontrol function. And we talk about those things all the time. So if you're looking for help with sorting out what's interfering with your energy production, I'd recommend that you listen through the podcasts that we've done on these subjects.

We've talked about gut health. We've talked about blood sugar. We've talked about hormone balance. There's. There's so many factors here. We've talked about exercise and movement. We talked about sleep. These are the central things that are going to affect our energy production. And when we optimize those and we're effectively converting the food to energy, we don't need to force you know, some sort of deficit or force major lipolysis or anything like that.

As long as we're effectively converting that food to energy and creating a good metabolic state for the body, it'll reduce the amount of food that gets stored as fat and increase the amount that gets converted to energy, and we will have fat loss in that way without increasing lipolysis, right? That doesn't mean zero lipolysis, there's always some, it's It's, we already talked about the baseline levels, which are pretty decent, plus all the extra lipolysis that comes with our day to day life.

So that's going to happen, and we just want to reduce the storage of substrate as fat by increasing the conversion to energy, increasing our overall metabolic state. That's, that's really where we want to focus. Now, beyond looking through the podcast and all of that, if you're looking for more help doing this with clear action steps and strategies, along with personalized guidance from me, head over to jfaldmanwellness.

com slash solution, where you can find all of the information for the energy balance solution program. This program includes customized health coaching, includes a video library with videos on how to restore gut health, how to regulate your blood sugar. how to boost your metabolism, how to get amazing restorative sleep, how to rebalance your hormones.

And it also has a video specifically on how to lose body fat without downregulating metabolism, without increasing stress. There's tons of other videos in there. There's also a ton of resources in there. There's a sample meal plan, there's recipes, there's a supplement guide, a calorie and macronutrient calculator.

And we also have a private community with tons of members, tons of very active members there to help support you, along with the customized health coaching for me. So, You can head over to jfeldmanwellness. com/ solution to check out all those details. If you did enjoy today's episode, please leave a like or comment if you're watching on YouTube.

And if you're listening elsewhere, please leave a review or five star rating. All of those things really do a lot to help support the podcast and are very much appreciated. As always, to check out the show notes for today's episode, where I'll link to the studies, articles, and anything else that I referenced, head over to jfeldmanwellness. com/ podcast. And with that, I'll see you on the next episode.