Leptin and Ghrelin

April 18, 2016

Put your science caps on...


Leptin and Ghrelin are two very important hormones - at least in my opinion, when it comes to satiety and level of hunger. I think this is one of the toughest things individuals have to deal with regardless if they are trying to lose weight or gain weight.


Both hormones interact with the same receptors in the brain, and are essentially opposites of one another. Leptin is produced (primarily) by your fat cells to signal satiety, or a feeling of being "full." Ghrelin, on the other hand, is produced in the intestines and signals the brain that you are hungry. Generally, you can think of these opposing hormones in a way that when one is high, the other is low, and vice versa.


Here is a list of common situations that cause a change in levels of leptin (from Wikipedia):

  • Leptin level is decreased after short-term fasting (24–72 hours), even when changes in fat mass are not observed.

  • Leptin plays a critical role in the adaptive response to starvation.

  • In obese patients with obstructive sleep apnea, leptin level is increased, but decreased after the administration of continuous positive airway pressure. In non-obese individuals, however, restful sleep (i.e., 8–12 hours of unbroken sleep) can increase leptin to normal levels.

  • Serum level of leptin is reduced by sleep deprivation.

  • Leptin level is increased by perceived emotional stress.

  • Leptin level is decreased by increases in testosterone levels and increased by increases in estrogen levels.

  • Leptin level is chronically reduced by physical exercise training.

  • Leptin level is increased by dexamethasone.

  • Leptin level is increased by insulin.

  • Leptin levels are paradoxically increased in obesity.

​So, for the most part, everything on that list makes sense. Remember, when your leptin levels drop and more receptors are opened up, that causes ghrelin to be produced and cause your brain to send those hunger signals. Fasting makes you hungry, starving yourself makes you hungry, lack of sleep makes you hungry, stress makes you hungry, etc.


However, the most surprising point on that list is the last one (in bold). Levels of leptin increase with obesity? One would hypothesize that since leptin reduces appetite, you would think that someone gaining weight must have low levels of leptin and high levels of ghrelin, causing them to be hungry all the time and eat more.


Although leptin reduces appetite as a circulating signal, obese individuals generally exhibit a higher circulating concentration of leptin than normal weight individuals due to their higher percentage body fat. These people show resistance to leptin, similar to resistance of insulin in type 2 diabetes, with the elevated levels failing to control hunger and modulate their weight.


What we now know is that we can actually develop a resistance to leptin. That isn't all that surprising when you think about it. Both leptin and ghrelin are hormones that interact with the pleasure and reward part of the brain known as the Nucleus accumbens. This is the part of the brain that makes you feel good about certain things such as food or sex, and rewards you for achieving these things. It is also susceptible to addiction. Unfortunately for those of you reading this that are obese or overweight, your adipose tissues are producing more and more leptin as you gain more and more weight, making you resistant to the higher levels of leptin. So, the more resistant you are to leptin, the more you are going to feel hungry.


Time and time again I hear about individuals who have had some success losing weight, they are eating healthier, watching their calories, exercising regularly, but then all of sudden the scale stops moving. Sound familiar?


There is a theory referred to as the "Set Point Theory" which states that everyone has a theoretical "basement" and "ceiling" weight. Your body gets comfortable at the weight that you are currently at because you have probably been there for a consistent period of time. Your body doesn't want that to change. In fact, as soon as you start losing weight, survival mechanisms kick into gear trying to reverse the effects of your weight loss. Despite your best efforts to try and lose weight and make yourself healthier, your body is being told that something is wrong and you're losing too much weight. Regardless of how heavy or overweight you are, if you are losing weight, your body does its best to keep you alive as it seems to believe you are going to die.


Think of our early ancestors who may not have eaten for a few days. Maybe times were tough, hunting wasn't going so well, so food is scarce. Rather than continuing to lose weight and risk dying, your body puts on the brakes and does whatever it can to slow down the weight loss, despite your best efforts to eat less and less and exercise more and more.


Dieters who lose weight, particularly those with an overabundance of fat cells, experience a drop in levels of circulating leptin. This drop causes reversible decreases in thyroid activity, sympathetic tone, and energy expenditure in skeletal muscle, and increases in muscle efficiency and parasympathetic tone. The result is that a person who has lost weight below their natural body fat set-point has a lower basal metabolic rate than an individual at the same weight who is of that natural weight; these changes are leptin-mediated, homeostatic responses meant to reduce energy expenditure and promote weight regain as a result of fat cells being shrunken below normal size. Many of these changes are reversed by peripheral administration of recombinant leptin to restore pre-diet levels. A decline in levels of circulating leptin also changes brain activity in areas involved in the regulatory, emotional, and cognitive control of appetite that are reversed by administration of leptin.


Keep in mind that individuals with eating disorders pass over the hump of eating just enough to maintain weight and enter a very unhealthy zone of body decay. This is not where you want to be. Simply eating less and less will eventually cause you to lose weight, but also at the expense of losing muscle mass, bone density, hormonal control, etc. You will essentially starve your body, your energy levels will disappear, and you will not feel like yourself.


So how can this be changed? Leptin control. Here's what we know:

  • Eating healthy and exercising causes leptin levels to drop. This causes increased ghrelin levels making you hungry.

  • Eating beyond your needs causes leptin levels to rise making you not hungry any more.

  • However, chronically eating beyond your needs causes an increase in body fat and therefore a resistance to leptin, increasing hunger.

So how can we use this to our advantage?


Well, there is not a single answer for everyone, or in other words, a "one size fits all" option. We all lead different lives, have different life schedules, and make food choices based on personal preference, convenience, time, family needs, etc. I oftentimes give my clients different ideas and tools to ry and experiment with to see what fits their lifestyle the best. If you are reading this and would like to learn more about the hormones Leptin and Ghrelin and how you can take control of your hormones and go beyond what standard diet advice can offer you, come speak to me, I would love to help!


Tyler Robbins B.Sc. CSCS
Director of Fitness
Head of CrossFit


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