In the last articles, I have explained how we get hungry and the role of Leptin, Ghrelin and other gut hormones. Today, I would like to address Leptin and Insulin resistance.
If you are dieting but fail to lose weight, or you have reached a plateau, balancing your Leptin levels might be beneficial to you.
Both leptin deficiency and leptin excess are associated with severe metabolic, endocrine, and immunological consequences.
Some people are Leptin resistant because of genetic mutations of Leptin receptors. Others become Leptin resistant due to their lifestyle and nutritional habits.
Congenital Leptin deficiency
All hormones in our body need receptors to be effective. In some human beings, the receptor specifically made for leptin is alternated, moreover there is a mutation in the genes.
This disturbes the balance of food intake and energy expenditure, leading to obesity and disregulation of neuroendocrine and immune function, as well as glucose and fat metabolism.
It was shown in recent studies with humans with leptin deficiency that some neuroendocrine, metabolic, or immune disturbances of these patients could be restored by leptin replacement therapy.
The percentage of people born with this mutation is fairly low, thankfully. So, let’s address the part of the population dealing most with Leptin resistance: Those who are obese and those who are dieting.
Leptin and obesity
It may be surprising at first that Leptin levels in obese patients are actually very high.
As I explained in the last article, Leptin levels are often associated with body fat percentage.
Thus, you would think that in obese people, Leptin should be low.
Their body fat percentage is high enough, so the brain should recognize that more food is not needed. Hunger should be depressed, so that these people could lose weight.
Unfortunately, the body adapts to every circumstance. If your Leptin levels have been very high for a prolonged time of period, along with a diet high in sugar, especially fructose (sugar in fruits), your body will not react to Leptin as it did before.
The real reason for high Leptin levels in obese patients is oftentimes Leptin resistance. Just as for people born with a mutation in the Leptin receptor, there is a lot of Leptin in your blood but it cannot bind to its receptor. If you know about the pathological mechanism of Diabetes (Type 2), this is exactly the same.
The brain fails to notice that body fat percentage is high enough and thus cannot decrease hunger. As Leptin influences the release of many other hormones, this leads to a disturbance for the metabolism in general, as well as the immune system and other endocrine organs.
What leads to Leptin resistance?
There are many factors that could make your body Leptin resistant. In fact, there are many studies on this topic and the mechanisms of Leptin resistance in obese people are not found out yet. However, it has been proven that your nutrition plays a major role in the development of Leptin resistance.
In a recent study, researchers fed mice fructose for 6 months and found that they became resistant to the feeding-inhibitory effects of Leptin. Moreover, they decided to change the diet to high fructose and high fat, which led to even more weight gain. Once they removed fructose from the diet, the mice lost weight and their body responded to Leptin as it did before.
After that, they wanted to know how sucrose (simple sugar) would influence Leptin levels. This is a topic that still needs more investigation. However, the researchers found that the sucrose solution increased a protein involved in the so-called HBP (hexosamine biosynthetic pathway).
It was found that the end product of this metabolic pathway contributes to Insulin resistance, as it can alter the Insulin receptor. Some of these proteins are required for Leptin signaling. Therefore, researchers assume that a diet high in sucrose effects Leptin resistance as well.
Lastly, the researchers fed the mice saturated fats and examined the effects on Leptin levels. It was found that a diet high in saturated fats blocked Leptin transport among the brains blood barrier, which means that Leptin cannot bind to its receptor. This was not the case when the mice were fed polyunsaturated fats (healthy fats as in olive oil, nuts etc.). In fact, those seemed to reduce Leptin resistance and improve signaling processes.
The picture above looks highly complicated but it basically explains what the researchers found out in their studies:
In the top right corner you can see the Leptin receptors, failing to bind Leptin that is released from the fat cells (left bottom corner). There are also Insulin receptors, which are not working properly as well. More on that in the next Part. As the Hormones are not activating certain signal pathways, the brain does not recognize we have enough body fat. It reacts in a way that is called “Adiposity signals”. This means that it sends signals to increase hunger and leads to hypertrophy of our heart.
The finding of the researchers point out the importance of nutrition in the development of Leptin resistance. A diet high in fructose and sucrose, thus in simple carbohydrates, as well as saturated fats, is a major contributor to the development of Leptin resistance and thus obesity. We can now use this knowledge to reverse the effect and “reset” Leptin levels.
In the next Part I address Insulin resistance more thoroughly and then finally in Part 3 there will be tips on how to reset your Leptin and Insulin levels naturally, as well as a FREE Meal Plan to kickstart fat loss.
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