“The combination of decreased energy expenditure and dysregulation of systems controlling energy intake during reduced weight maintenance tend to bias physiological responses toward weight regain.” (1)
“Turns out, weight gain and loss isn’t so much about energy as it is about information… food is far more than fuel; it’s a language that programs every function of your cells. If you’ve been gaining weight, it’s because you are eating foods and doing activities that, in essence, tell your body to pack on the pounds.” – Dr. Cate Shanahan, Deep Nutrition
In a previous article I wrote on the subject, I hoped to shed light on this idea that consciously controlling energy (calories) may be failing the population. The reason, I believe, has something to do with the core belief upon which the approaches are based. The problem is that this core belief is an oversimplified view of the human body – a belief that overlooks the network of signals that control the body’s energy. This belief involves the idea that an individual seeking to address the excess energy problem can consciously control the energy he/she takes in, and match it up with the energy expended.
If you look around you, you’ll see that this method is not working for us.
Today I continue with this discussion of the forces controlling energy balance with the hope of helping us all understand the actions we can take to cause real, lasting change for the betterment of our overall health. More specifically, we will keep working on developing an answer to the following question:
How do we effectively address the excess accumulation of fat, while also ensuring that we target the overall health of the body at the same time?
To answer this question we need some more background, including an explanation of what does control our energy balance, internally. This article serves to show you the numerous factors that interact to regulate your body’s energy. It is an attempt to dive into this metabolic complexity, to get you to see what really is in power.
In doing so we’ll have to go through some of the many biological processes involved, focusing on the key signaling molecules, along with their interaction with the brain. We’ll examine some of the main hormones the body uses to control energy, and look at the damage that occurs when these hormones are disrupted.
As we go through this, keep in mind that the goal is not to understand all of this information. You do not need to understand the incredible complexity that is your metabolism for you to achieve the overarching goal of healthy, sustainable weight loss. Rather, it will be to your benefit if you can understand these three things:
- The body is supported by a complex, dynamic network of signaling molecules that constantly interact with cells throughout the body to maintain a state of metabolic homeostasis.
- This network is in constant communication with the external world via our diet, lifestyle choices, and other environmental factors
- Excess weight gain arises when this system fails
As we continue on, keep your focus on understanding the network to the extent that your behavior leads to helping, not harming, the network as a whole. I encourage you to consider how your actions may impact the hormones discussed below so that you can begin formulating ideas as to what actions may be taken to achieve our ultimate goal of sustained, healthy weight loss. Because there is no need to understand all the details, feel free to gloss over anything you don’t want to waste precious energy on taking in.
Achieving Homeostasis: A Balance Between Endocrine and Neural Systems:
At the foundation of the human body are trillions of individual cells, all performing their own specific function, while also communicating with other cells to perform functions as a network. Cells do this through several different mechanisms, the most important of which to understand for today is hormonal communication (the endocrine system).
The endocrine system is the main system controlling metabolism. This system syncs up with the brain and other neural circuitry, creating a vastly complex system that works to keep the entire body in a state of energetic equilibrium. It does this by continuously monitoring the state of internal energy, both from food intake and long-term energy stores. Based on the energetic state that is sensed, the body responds with the release of hormones to prompt specific changes.
These responses to hormonal signals include a variety of changes in metabolic processes. This includes behavior modification, such as a signal to begin eating when low blood sugar is sensed, or a motivative signal to get up and go for a walk when high blood sugar is sensed. This also includes internal changes, such as variations in basal metabolic rate, with the body burning more energy at rest when energy levels are high (or alternatively, burning less energy at rest when low energy is sensed.
It may be beneficial to dive into some of these processes. We’ll start at an interesting place – by going back to my neuroscience textbook. Don’t worry, I won’t get into how arcuate neurons secrete neuropeptide Y and agouti-related peptides, in response to leptin and insulin, which have opposite effects, and… no, we need not get into that. Rather, I will show you a macroscopic view of how the brain controls behaviors, and how most of it is completely subconscious.
My textbook’s framework for describing the overall process is insightful – here’s the summary:
“The ability of cells, organs, and organisms to survive and function in the face of changing conditions, such as alterations in temperature or nutrient availability depends on the mechanisms that maintain a relatively constant internal mileu. Complex brain circuits orchestrate the physiological processes that redistribute and transform internal resources… to correct and anticipate deviations from homeostasis. Tightly integrated with these circuits are neural systems medicating behaviors… Motivational states adjust the vigor and incidence of these behaviors according to biological needs… The strength of a motivational state depends not only on internal conditions, but also on external incentive stimuli such as food or estrus odors.”
Okay, so what did all that mean? Basically, it comes down to a series of hormones that analyze the situation in the body, and give that info to the neural processes controlling behavior, so that the body can achieve homeostasis. Here of course, we’re talking specifically about the example of regulating food intake and energy expenditure.
This then communicates with “motivational states,” which drive whether or not you are willing to perform certain actions, such as taking the stairs or starting to prepare lunch. This motivation comes from inputs such as circadium clocks and goal-directed behavior, and calculates trade-offs with other states of the body (e.g. am I too tired to prepare this meal – yes, I’ll just order pizza instead).
All in all, it could look something like this: Hormones examine the state of the body and determine that there is too much energy circulating, and it needs to get burned. This information gets sent to the brain, where it checks in with other systems to determine what could be done to burn this energy. It decides that metabolism needs to speed up to burn that energy, which it can do through unconscious behaviors (e.g. increased thermogenesis), along with some conscious behavior (e.g. get up from the desk and take a walk).
The bottom line is this: metabolism is tightly regulated by a number of hormones and other signaling systems. Based on signals these hormones receive about the state of the body (fat stores, food intake, metabolism, etc.), they send signals to the brain to produce either autonomic behaviors (i.e. things you can’t control), as well as conscious behaviors (e.g. eating and movement).
If you want to make real changes to your body, you have to understand how it has been designed so that you can make decisions that are in-line with this design. If you want to be healthy (e.g. lose fat mass and keep it off), then the avoidance of choices that fight this biological network may best be avoided.
The Effect of Calorie Restriction on Metabolism
If you want to lose weight in a healthy, sustainable fashion, then taking actions that support strong metabolic health is a must.
And yet, as we saw in the previous discussion of calorie balance, the common weight loss method using calorie restriction often does the opposite – calorie restriction often sends a signal to the body that programs it to hold onto, not release and utilize, that excess stored fat.
The problem with conscious calorie balance is that it overlooks the complex network that is metabolism, overthrowing the complex inner network with an unsupported claim that we can choose to each less and exercise more, and in doing so, force the body to release and burn fat.
Again, it is worth bringing up how, in reading through all the chapters in a neuroscience textbook, there was never any mention of the frontal cortex (your conscious decision-making center) in regards to how it can overrule the body’s metabolic processes. The frontal lobe cannot just step in and say, “excuse me leptin, I’m not actually starving, we can stop our chronic overeating now.” While you may think you have conscious control over what you eat, because you can win the occasional battle over whether or not to eat that muffin, in the long term your body will win the war (as is demonstrated by the 70% overweight statistic).
The truth is, you don’t get to decide that – your body does. And it does it through a complex series of hormones which are tightly integrated with neural circuitry. Yes, the frontal lobe, including its decision-making capabilities, is part of the neural circuitry, and as part of that circuitry, it has input into this system that can cause change. But if we are going to make any progress towards a healthy form of weight loss, we must understand the limitations of that cortical input and understand its integration with the many other factors that are also at play.
You don’t get to make the decision as to whether your body releases stored fat, but you do have the ability to understand how your actions lead to changes in your metabolism, and in turn, you do have the ability to make choices that may help your metabolism do its job right – to help your metabolism understand that it has an extra, unhealthy load of fat that it can release and burn.
By stepping outside of the calorie balance paradigm that often works directly against the body’s natural circuitry, we get away from the idea that the body can be overpowered by what the frontal lobe thinks it needs. By stepping outside of the calorie balance paradigm, we open up a world of options for choices we can make that are aligned with the body’s natural biology.
Now that you understand this, we can get to work picking apart this metabolic network so that we may gain some insight into how we can use our conscious minds to make decisions that bias the entire system towards weight loss. I’ll continue with this below.
Alternatively, if you think you’ve had enough of the complexity of metabolism and want to move onto what is most important, at this point, feel free to skip ahead to the final installment of this series where I discuss the key signal driving excess fat accumulation.
An Introduction to Signaling Molecules involved in Metabolism
Let’s get back into that biology, focusing on more detail about these key hormones. Again, it is not particularly important that you know all about all of these, but it is important to get an understanding of some of the key players here.
That being said, I do have a major note of caution with complexity. I don’t want you to get bogged down in the complexity, but I also don’t want you to forget that these systems are extremely complex. I will simplify these systems for you, but you must remember that these are simplified versions. Therefore, after reading this, don’t think you have all the information you need about any of these hormones. Very few, if any, have that sort of understanding of how all these hormones work, let alone how the whole network of hormones interact.
I’ve said it before, but it’s important, so I’ll say it again. The point of the following information is to get a general understanding of how hormones work, particularly these main hormones, within this complex system that controls weight. When we understand that there is a complex system regulating energy, independent of conscious control, then we can make choices that are in line with these biological systems, rather than the status quo choice (calorie balance) that tends to fight against biology.
I am going to start with a summary in all its complexity, and then break it down for you. The purpose of this is, again, for you to see that your entire metabolism is beyond comprehensible, but we can do some work to understand pieces of it, which we can use to our advantage. Here is a summary from this article.
“The signaling network underlying hunger, satiety and metabolic status includes the hormonal signals leptin and insulin from energy stores, and cholecystokinin, glucagon-like peptide-1, ghrelin and peptide YY3-36 from the gastrointestinal tract, as well as neuronal influences via the vagus nerve from the digestive tract. This information is routed to specific nuclei of the hypothalamus and brain stem, such as the arcuate nucleus and the solitary tract nucleus respectively, which in turn activate distinct neuronal networks. Of the numerous neuropeptides in the brain, neuropeptide Y, agouti gene-related peptide and orexin stimulate appetite, while melanocortins and alpha-melanocortin-stimulating hormone are involved in satiety. Of the many gastrointestinal peptides, ghrelin is the only appetite-stimulating hormone, whereas cholecystokinin, glucagon-like peptide-1 and peptide YY3-36 promote satiety.”
I know that most of that sounds like a foreign language – but again, it’s not important that you understand it all. Rather, just appreciate the complexity, and take a little bit of time to understand some of the main players (none of which mentioned involve the frontal lobe, by the way). I’ll simplify these “players” the best I can.
I’ll start with leptin, because there is a large quantity of strong evidence demonstrating how it can greatly impact people’s weight. Simplifying greatly, leptin tells the body when to eat, based on fat storage levels. We know this because cases in which the body cannot respond to leptin lead to uncontrollable eating, which of course leads to severe weight gain.
We can examine studies from the lab that involve ob/ob mice – mice that lack the Ob gene, which codes for leptin. Just remember: no Ob gene, no leptin, no signal to suppress hunger. But, if you give mice lacking this gene some leptin, their appetite gets suppressed, and their weight and glucose levels normalize. This occurs because the binding of leptin signals appetite suppression. High levels of leptin tell the body that there is plenty of energy stored, and eating behavior should be decreased. Additionally, db/db mice lack the receptor for leptin, and the result is the same – no signal received, no appetite suppression, even if there is leptin floating around.
You can think of leptin as a regulator of long-term signaling. It is the main messenger between fat stores and the brain, telling the body when there is enough energy saved up, and therefore when to eat less (or on the flip side, when too much fat is lost, and therefore need to eat more, also known as the bane of any weight loss journey). Stay tuned for more on leptin shorty.
Another commonly known hormone is ghrelin. To learn this one, I remembered that “ghrelin makes my stomach growlin.” Basically, when the stomach is empty, or when mealtime comes around, ghrelin rises, signaling that we should have more food. You can think of this one as a short-term hormone. When the stomach empties, it sends out a signal, but levels drops back down after a few minutes. So when the hunger signal from ghrelin turns on, we feel hungry. But, we can easily ride this signal out if we know we don’t really need to eat, because ghrelin levels will soon drop back down. Additionally, ghrelin usually rises and falls with your circadium rhythm, the body’s natural clock. When you wake up in the morning and your body needs energy, ghrelin is released, making you hungry. Again, since this is a short-term signal that continuously fluctuates, this signal is generally easy to push through.
Another important hormone I’ll discuss is cholocystokenin (CCK). CCK is secreted from the gut in response to sensing nutrients. Following a meal, it is released into the blood from cells in the gut, leading to inhibition of food intake (3).
CCK is an important messenger from the gut. When you consume healthy meals, with good fats and healthy protein, CCK signals to the brain, causing feelings of satiety and inhibition of food intake (it would also rise in response to a crappy meal with crappy fats and proteins, but you wouldn’t want to do that, would you).
All these hormones are hard at work to keep weight in balance. When they function properly, homeostasis is maintained, and your weight remains at a nice, healthy level. Let’s see how that works with a very simplified example:
You wake up in the morning, hang out for a while until ghrelin kicks in, making you feel hungry, as well as connecting with the hypothalamus to create motivation to eat. So you eat, the stomach senses specific nutrients (i.e. fat and protein), and CCK says “we’re all good! No more food please.” Over time, if you happen to start gaining too much, leptin kicks in, telling the brain “we’ve got enough fat stored up. Let’s reduce this eating behavior!” Overall, your appetite gets suppressed, and you don’t eat as much during the day.
Remember, these hormones all link up with neural structures to produce behavior. They all feed back to the hypothalamus, the master controller of homeostatic control. For example (again greatly simplified), high ghrelin levels around lunch time, combined with low levels of leptin, communicate with the hypothalamus to initiate a deeply ingrained behavior – eating. Nope, it wasn’t your conscious decision making that got that muffin in your mouth. It was the job of all these key players working behind the scenes.
Hormone Disruption
Problems occur when these mechanisms get disrupted, and in the case we’re speaking about, the body can no longer maintain a healthy weight. For example, like the mice previously discussed, there have been human cases of those with genetic mutations who either don’t produce leptin (ob/ob), or otherwise don’t have the leptin receptor (db/db). These people suffer from a chronic, unwavering urge to eat. Since the long-term signal for “there is enough energy, stop eating” doesn’t exist, the body always thinks it is starving. Although these problems are serious when they occur, these cases are rare – and obviously, excess weight is not a rare problem.
Because genetic cases like these are rare, they clearly are not the reason for this obesity epidemic. However, these cases do shed light on what happens when these hormones aren’t able to do their job. Most of the population isn’t overweight because they lack leptin or its receptor – but, many people are overweight because leptin isn’t doing its job. Or rather, leptin is just trying to do its job, but can’t keep up with the industrial food paradigm that continuously overwhelms it. Leptin is just trying its hardest to do what it knows what to do, given the signals it receives. I’ll dive into this further, because it’s crucial to understanding weight (mis)management.
Leptin Dysregulation and Weight Mismanagement
1. Leptin Resistance
Leptin resistance is a primary factor causing the extreme difficulties losing weight. Hormone resistance is such a major problem today, you’re probably familiar with the term. The typical metaphor used for understanding resistance is thinking about the signal like an annoying sound that just gets louder and louder. Just because the sound gets louder doesn’t make you listen to it more; rather, you are more apt to work to stop listening to it, by covering your ears. Resistance works in the same way. If a signal is being overproduced, then cells stop listening to it by downregulating receptors. The body responds by sending out more signal, to which cells respond by listening even less. The end result is a body with constantly high levels of that hormone, of which the cells completely ignore.
This happens with leptin in obesity – fat stores secrete leptin to tell the body to eat less. But when the body doesn’t eat less, the fat stores grow, sending out an even larger leptin signal. Meanwhile, the body is continuously downregulating receptors for leptin, so that it doesn’t have to listen to the signal. The end result is someone with large stores of fat, loads of circulating leptin, and a body that doesn’t respond to the signal that it needs to stop eating.
This is a primary reason why those that are overweight continue to put on so much weight. While this person is obviously aware of his/her weight problem, the body is not. And it is what the body knows that is important, not the conscious mind.
So now what happens when this person tries to lose weight by cutting back on the calories?
2. Calorie Balance sends the wrong signal to leptin and other hormones
It is well-documented that, following weight loss, appetite is increased and metabolism is reduced (1,2). Leptin is one of the main reasons for this, because following weight reduction due to caloric restriction, leptin levels fall, creating a reduction is hunger suppression (1,2).
By decreasing calorie consumption to lose weight, leptin levels fall, and the body gets the signal that it is starving and needs to amp up the food intake. That’s why it always feels like you are starving after losing several pounds – because the body literally thinks it is. (Note, the magic number for these starvation signals in the literature is at 10% loss of body fat (1,2)).
Other hormones get the wrong signal as a result of caloric restriction as well. Dr. Joseph Proietto from Melbourne conducted a 2009 study, in which 50 obese patients lost 10 percent of their body fat. Once again these researchers found that leptin levels were down, along with about a 20% increase in ghrelin (hunger), along with a disruption in CCK (3).
And it gets worse because it is not only measurable at the hormone level, but at the neural level as well. Researchers can actually look at the individual’s brains after losing weight, and see the hunger effect there as well. Going back to Rosenbaum’s research – his team found that, “during maintenance of a 10% or greater reduced body weight, there are increases in neural activity of brain areas that are associated with reward valuation and processing of food-related stimuli and decreases in neural activity of brain areas related to restraint in response to food” (1).
This team of researchers were able to see increased activity in visual areas that respond to food, along with increased activity in the areas that deal with rewards. This means that these reduced-weight patients were more sensitive to seeing food, and the reward of getting that food felt stronger. Additionally, the areas that restrained response to food had decreased activity, likely making inhibitive behavior less likely.
This explains the typical weight loss story: eat less, lose weight, mess up appetite hormones, be super hungry, gain the weight back. At every level of the body, from signaling molecules, all the way up through to neural patterns, caloric restriction leads to the same thing: hunger. This is why calorie restriction fails.
So no, it’s not a character flaw – the increased hunger, decreased willingness to work out, along with the obsession with food, and the inability to turn down that cake – it’s not because you lack willpower or are weak. It’s not because you’re a bad person. It’s because the hormones in your body are creating signals in the brain that say that you are starving, and you need food. It’s that simple.
Sustained weight loss involves reprogramming the body’s hormones
So what are you left to do with it? Well of course, there is good news, because there is another way. You can lose weight without focusing solely on conscious caloric restriction. Instead of fighting against these metabolic pathways, you can shift your lifestyle patterns to optimize the functioning of these metabolic pathways, and program them in such a way that the body wants to lose weight. You can reprogram these pathways so that your body sees the real picture – that it has plenty of fat stores that it needs to get rid of. And the way to do this begins with going back to consuming the foods that were traditionally eaten. Ditch the industrial not-so-foods, start eating real food, and the body becomes capable of getting rid of the fat.
Why do I know this? Because every successful weight loss program involves a switch back to real food. Here are some examples. Note that I’ve picked these studies because they do a good job of tying in the weight loss success with hormone levels.
You may have heard of the ketogenic diet. It is currently sweeping the nation due to its almost magical ability to help people lose weight and fight off disease. A couple studies from the last few years show why.
Again, it is well established that weight loss leads to a decrease in CCK and leptin, and an increase in ghrelin. Two studies examined what happens when these weight-reduced subjects go into ketosis. What they found was that, when these weight reduced subjects went into ketosis, the hormone levels didn’t shift: “when subjects were ketotic… CCK secretion was sustained at concentrations before weight loss” (3). A second study had similar findings with ghrelin: “When participants were ketotic, the weight loss induced increase in ghrelin was suppressed” (4).
One of the main reasons people love the ketogenic diet is because it is great for shedding pounds, while also being great and suppressing appetite. These studies show us why. Weight loss is generally accompanied by increased ghrelin, and decreased CCK and leptin. But a high fat diet counteracts this. And it makes sense why – CCK is released in response to protein and fat. In low calorie diets used for weight loss, fat is the first thing to go because it is the highest in calories. But taking out the fat stops the signal that you’re full.
But you don’t have to go full on keto to get the same effects. Similar results have been shown on high fat diets themselves. Remember how one of the major problems with weight loss due to calorie restriction is a reduction in resting energy expenditure? Well, a 2012 controlled feeding study found that the type of diet used following 10% weight loss mattered for how the body fought back against this weight loss. They found that the decline in resting energy expenditure was greatest for those on the low fat diet, while the very low carb diet had the smallest decline in resting energy expenditure. That means that those consuming more fat and protein burned more energy at rest, while those that consumed more carbohydrate, particularly higher glycemic carbs, had the largest reduction in energy burned at rest.
Once again we see that the shift from high glycemic carbohydrates to a diet higher in fat, mitigates the body’s fight to hold on to excess fat.
If you remember anything, remember this: the body’s ability to regulate food intake is not based on calories. There is no mechanism that involves the sensing of the energy stored in the chemical bonds. Rather, the body senses nutrients, which is why the Standard American Diet is the perfect way to trick the body into eating more and more. To get the body to know it has consumed enough food, it has to be given nutritious foods, with plenty of fat, sufficient protein, and ample amounts of micronutrients.
In this article I focused on a small number of hormones and used examples of how these hormones detect protein and fat, which is one reason why high-fat diets work well for weight loss. However, there is no one magical diet. The high-fat diet works wonders for many people, but the other end of the macronutrient spectrum can work too. Diets that focus on high micronutrient density (i.e. plant-based diets) can also be successful at curbing hunger while providing the body with the nutrients it needs to properly function (e.g. a large supply of antioxidants to help the mitochondria burn the large load of fat the body needs to lose).
The bottom line is that when the body receives the signals and resources that it has been designed to understand and utilize, it does a good job of maintaining a healthy weight. When the body gets the correct resources and signals, the body takes care of itself (maintains homeostasis), via these complex systems (for more, continue here). We gain weight due to specific environmental causes, all based on these systems failing to respond to novel signals, resulting in dysregulation and dysfunction of this metabolic system.
I’m getting a little ahead of myself here, because before we get into a serious discussion on our dietary choices, we need one more piece of information.
I seem to have left something out…
All of the hormones discussed today play important roles in the functioning of the body’s metabolism. Moreover, problems that arise out of these signaling pathways can be disastrous, leading to problems such as the inability to curb hunger. With an understanding of these hormones we have some insight into how we may take actions that align with the network, biasing it towards weight loss while maintaining an overall state of good health.
Yet, we still have some room for greater insight as to practical actions we can take to address the problem – how can our actions lead to results when what we’re tring to address is so interwoven?
While these hormones cause problems when they are disrupted, I do not believe them to be the root cause of this energy dysregulation epidemic – no, that fault lies on another hormone, one that needs special attention. And, if we understand this one specific hormone that seems to be responsible for driving most of the dysregulation and dysfunction, then maybe we could focus on approaches that best address this one hormone?
We’ll look into these questions up next.
References:
- Hinkle, W., Cordell, M., Leibel, R., Rosenbaum, M., & Hirsch, J. (2013). Effects of Reduced Weight Maintenance and Leptin Repletion on Functional Connectivity of the Hypothalamus in Obese Humans, 8(3). http://doi.org/10.1371/journal.pone.0059114
- Rosenbaum, M., Kissileff, H. R., Mayer, L. E. S., Hirsch, J., & Rudolph, L. (2011). Energy Intake in Weight-Reduced Humans, 95–102. http://doi.org/10.1016/j.brainres.2010.05.062.Energy
- Chearskul, S., Delbridge, E., Shulkes, A., Proietto, J., & Kriketos, A. (2008). Effect of weight loss and ketosis on postprandial cholecystokinin and free fatty acid concentrations 1 – 3, 1238–1246.
- P Sumithran, L A Prendergast, E Delbridge, K Purcell, A Shulkes, A Kriketos & J Proietto. “Ketosis and appetite-mediating nutrients and hormones after weight loss.” European Journal of Clinical Nutrition (2013) 67, 759–764 (2013). doi:10.1038/ejcn.2013.90
- Ebbeling, C. B., Swain, J. F., Feldman, H. a, Wong, W. W., Hachey, D. L., Garcia-lago, E., & Ludwig, D. S. (2012). Effects of Dietary Composition During Weight Loss Maintenance: A Controlled Feeding Study. The Journal of the American Medical Association, 307(24), 2627–2634. http://doi.org/10.1001/jama.2012.6607.
- Kandel, Eric R., James H. 1932- Schwartz, Jessel, Thomas M., Siegelbaum, Steven A., and A. J. Hudspeth. Principles of Neural Science. 5th ed. New York: McGraw-Hill, Health Professions Division, 2012.