The Ultimate Guide To Leptin and Weight Loss

Hi, this is Galit Goldfarb, nutritionist and medical scientist, and welcome to my blog where you will find great articles to help you transform your health easily through practical lifestyle changes based on science. My articles will guide you, step-by-step, to lasting weight loss and better health for you and your family no matter your current situation. 

Today I will talk about why people stop losing weight while dieting and give you five tips to help you change this immediately:

If you’re finding it hard to lose weight or have reached a weight loss plateau or feel you have uncontrolled food cravings, you may have a hormonal issue.

One of the primary regulators of body weight is our hormones, in particular, the satiety hormone leptin. 

It is now known that leptin is a key regulator of energy balance. The leptin system evolved to keep us from starving and from excess eating, both which lower our chances of survival.

Leptin is produced and released from our fat cells in response to two things:

    1. The amount of fat tissue we have
    2. The previous amount of food we ate

The hormone leptin produced from our fat cells is then carried in the bloodstream to the brain.

Leptin reaches the hypothalamus area of our brain which in turn regulates our food intake and energy expenditure. (9)

Leptin from fat cells then enters the brain cells through a receptor on the membrane which activates certain pathways (STATS, PI3K) that enter the nucleus of the cell and control gene expression for proteins associated with appetite, reproduction, growth and metabolism.

  • When high levels of leptin reach our brain cells, they “tell” our brain that the body has enough energy stored and it can reduce appetite while inducing reproduction and growth. 
  • When there are low levels of leptin reaching our brain cells, this informs the brain that there are not enough stores of fat and that the brain should increase appetite, reduce reproduction and growth.

When we begin a new weight management program, or in other words a “diet”, we start losing weight and hopefully some fat tissue, but after some time, if we just reduce the number of calories we are eating and don’t change the foods we consume, then we will stop losing weight. When weight and fat tissue is lost, the brain gets less signaling from leptin telling the brain that there aren’t enough energy stores in the form of fat – in other words, that energy stores are dwindling. Then the brain induces hunger in order to increase fat cells that will raise leptin levels to what they were before we began dieting. So when we lose fat, the brain tells us that we don’t have enough energy reserves and that we need to eat. (18, 19)

The body is resisting weight loss, and that’s why it’s so difficult to lose weight.

This situation can be changed if we change the foods we eat while we are losing weight. More on this in a minute. But first I want to look into the reason why most people find it so hard to lose weight.

Since leptin is produced by fat cells in proportion to their numbers and size, obese and overweight people should in fact have very high levels of leptin. We know that once leptin reaches the brain, it sends the message to reduce appetite. So why doesn’t this happen in most overweight individuals?

Leptin doesn’t reduce appetite in obese people because the leptin isn’t entering the brain cells.

Overweight or obese individuals may find it extremely hard to lose weight because their cell receptors for leptin become desensitized. Or, in other words, their cells become leptin resistant. The body feels that it is starving even though it has more than enough energy stores in the form of fat. Leptin doesn’t enter the brain cells, and the brain assumes that the body is starving and in turn increases appetite, hunger and food cravings. (20)

But how does leptin resistance happen?

There are five major factors that make a person’s cells resistant to leptin. These factors, in turn, increase appetite and pile on the pounds leaving us feeling totally out of control over our appetite.

So lets look at the five major factors that make cells resistant to leptin:

  1. The more fat tissue we have in our body, the less sensitive our brain cells become to leptin. The brain cells need more leptin for the same effects to occur. Leptin, being produced by fat cells is produced according to the amounts of fat tissue we have. However, leptin is similar to alcohol in that the more our brain gets used to alcohol,  the less sensitive we become to its effects and the more alcohol we need to produce the same effects. So, with leptin, the more weight you gain and the more fat cells you have, the less control leptin will have over your appetite and the hungrier you will feel. The concept behind this mechanism is that as body size grows, more energy is needed to fuel it. The tissues don’t take up the leptin and leptin is left to circulate in the body. Since leptin has a structural and functional resemblance to pro-inflammatory cytokines such as interleukin-6 and has been shown to influence C-reactive protein (2, 3) levels (which is an indicator of heart disease), high levels of circulating leptin leads to inflammation. Inflammation, in turn, also leads to more insulin resistance and damage to our tissues, making the situation worse with time. High circulating leptin levels have also been shown to be involved in high blood pressure, decreased fertility, heart disease, stroke, and diabetes. (13)
  2. Another cause for leptin resistance is inflammation from other sources. Ingestion of high amounts of animal products leads to inflammation for a number of reasons: Animals have their community of microbes, just as we humans have. When meat is cooked before it’s eaten, the bacteria is killed off, but the microbes have lipopolysaccharides (or endotoxins on their cell membranes which are toxic to our cells and are not removed during the cooking process. These endotoxins attach onto toll-like receptors on the cell surface and trigger an immune response which cause higher intestinal permeability causing more inflammation as well as accumulation of visceral fat. This inflammation blocks the pathway by which leptin enters the cells and the path where leptin influences gene expression to curb hunger, reproduce and grow. More on endotoxins in my article titled The Effects of ENDOTOXINS on your HEALTH
  3. Lipid metabolite accumulation – lipid metabolites from the breakdown of fats enter the cells, and when there is an accumulation of these lipid metabolites, they activate a protein which dampens insulin and leptin sensitivity.  Excess lipid metabolite accumulation in cells happens when we eat too much food, too much fat or too much fructose.
  4. When we have Insulin resistance – Insulin regulates blood sugar levels and works hand in hand with leptin. Insulin also regulates leptin secretion (through a post-transcriptional mechanism, and through glucose metabolism). (7) The presence of insulin in the bloodstream increases neural pathways in the brain that indicates to your body to reduce food intake. Insulin and leptin together act in the brain to reduce appetite and food consumption.
  5. Gene mutations. There are eight gene mutations that are known to cause leptin deficiency and leptin resistance. These mutations are rare, and all cause extreme obesity in infancy, excessive hunger, and appetite.

To put it shortly, it is mostly inflammation from any source that blocks weight loss. 

Now that we understand the mechanism by which leptin resistance influences weight gain, how can we improve leptin sensitivity:

Here are seven steps to improve leptin sensitivity:

  1. Change the composition of your diet: 

If you are overweight and find it hard to curb your appetite, or you are in the process of losing weight on a calorie restriction diet, but you have reached a weight loss plateau, the only way to trigger the body back to weight loss is by changing the composition of your diet. You can’t prevent your internal control system from wanting to increase fat storage after fat stores are lost while continuing on the same diet. Here are the necessary dietary changes to help you lose weight:

    1. Increase fiber rich foods (11) such as whole grains, fruits, vegetables, beans, and lentils. These foods adjust the gut microbiome to induce weight loss and modify leptin and other hormones that regulate satiety and energy intake.
    2. Reduce refined and processed foods. These foods increase inflammatory markers leading to chronic inflammation and insulin and leptin resistance.
    3. Reduce animal products from your diet to no more than twice weekly as they have high levels of naturally occurring endotoxins and trans fat which induces inflammation. These foods may also influence the microbiome negatively.
    4. Choose organic animal products as they have no antibiotics which will not reduce the range of bacteria in your gut and lead you down the path to many health disorders.
    5. Eat foods rich in antioxidants since these foods reduce oxidative stress which in turn reduces inflammation. Berries, in particular, are rich in flavonoids which boost leptin sensitivity. 
  1. Reduce sugar consumption: 

The consumption of a high-fructose diet is associated with a reduction in leptin levels and reduced expression of leptin receptor in rats. Fructose consumption increases levels of triglycerides and triggers inflammation leading to leptin and insulin resistance. Consume fruits separate from other foods to enjoy all of their benefits. See my article on food combining titled The Best Food Combining Principles And Why to understand how to do this best.

  1. Ensure a good night’s rest: 

Sleep increases leptin levels. See my extensive article on this subject titled Importance of a Good Night’s Sleep for Health and Weight Loss

  1. Take food supplements that increase leptin sensitivity.
    1. Spirulina blue-green algae are linked with reduced cholesterol levels, potent anti-viral activity, reduction of allergies and even weight loss. Research shows that dried spirulina is a great source of the amino acid leucine, which has been shown to increase insulin and leptin sensitivity. (4)
    2. Turmeric has a broad range of therapeutic properties including enhancing leptin sensitivity as well as insulin sensitivity (5, 6)
    3. Green tea contains EGCG, a chemical substance which has been shown to decrease leptin resistance in mice. (12)
    4. Get enough Vitamin D. For more on this crucial vitamin, check my article titled Vitamin D and the Connection to Health and Weight – All Your Questions Answered 
  1. Exercise regularly but not too intensively: 

Physical activity when not extreme has anti-inflammatory properties — in response to stress from physical activity the body produces IL-6 which goes to the brain and produces an anti-inflammatory effect. As a result, leptin sensitivity increases and so does insulin sensitivity. The body recognizes that we did some physical activity and therefore inflammation is reduced.

  1. Support hormonal balance by reducing stress, and exposure to environmental pollutants: 

An example of a widespread pollutant you want to reduce exposure of is Bisphenol A (BPA), the highest volume synthetic chemical produced worldwide. BPA has been in commercial use since 1957. Today BPA is used to make plastic because it is clear and robust. BPA is used in water bottles, to line water pipes, inside many food and beverage cans, and in thermal paper used in sales receipts. BPA has replaced lead in most of these. The problem with BPA is that it exhibits estrogen-like properties and exposure to it has been shown to increase the amount of fat mass and elevate serum leptin levels and leptin resistance. (14) BPA may also interfere with hormonal control of hunger and satiety. (15) Another study examining middle-aged and elderly Chinese adults found that BPA was positively associated with generalized obesity, abdominal obesity (belly fat), and insulin resistance, which we know is related to leptin resistance. The global rise in exposure to BPA coincides with the increase in obesity rates. (16) Since BPA has been found to leach into foods held in containers lined or made with BPA, I recommend choosing glass Tupperware for food storage, choosing foods sold in glass containers and reusing them for food storage. Using glass drinking bottles and staying away from canned foods including canned fish is also crucial. 

Another chemical that has been linked to leptin and insulin resistance is perfluorooctanoic acid (PFOA). This chemical is found in teflon and other non stick pans. I recommend stainless steel cookware. Perfluorochemicals are also found in pesticide residues and even in some clothes we wear. These pollutants become more concentrated the higher up the food chain we go. Therefore the best way to reduce exposure is to reduce consumption of animal products, especially fish which get all the contamination from run off into water bodies. See my article on this subject titled Cookware: Which Should You Use For Health And Why

  1. For people with leptin gene mutations, leptin administration was approved in the US in 2014.

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