Raina Kranz & Kimberley Andrews
Thyroid Nation

Leptin and its multi-layer functions and malfunctions

What is Leptin? Leptin is a peptide hormone secreted mainly by adipocytes (also known as fat cells), with a variety of physiological roles.

What does Leptin do when the levels are normal?

  • It regulates food intake
  • Controls energy storage
  • Suppresses appetite
  • Create satiety
  • Maintains healthy weight

What Happens when Leptin levels are abnormal?

  • Obesity (leptin resistance)
  • Increase inflammation
  • Increase risk of metabolic syndrome
  • Increase risk of type 2 diabetes
  • Increase risk cardiovascular disease
  • Emerging evidence of involvement with autoimmune disease

Decreased and elevated levels of leptin are not normal and either can contribute to disease. The factors that can alter our leptin levels are as follows;

What decreases leptin levels?

  • Sleep deprivation
  • Increased testosterone
  • Short term Fasting
  • Long term caloric restriction which in-turn increases leptin levels

What increases leptin levels?

  • Perceived emotional stress
  • Increased estrogen
  • Dexamethasone
  • Increased Insulin
  • Long term caloric restriction and yo-yo dieting
  • Obesity
  • Restrictive diets and low calorie meals
  • High, intake of sugar/processed foods

What stabilizes leptin levels?

  • Exercise (varied intensity levels of exercise that include both cardiovascular and resistance training)
  • Balanced eating (not over or under eating)
  • Not skipping meals
  • Balanced macronutrients (Good Carbohydrates, Good Fats and Proteins)
  • Proper amounts of sleep
  • Balanced levels of emotional stress
  • Decreased inflammation
  • Reduce processed sugar and processed food intake

Role-Of-Leptin-Yo-Yo-Dieting-In-Immune-System-Weight-LossWhat are leptin receptors? 

Leptin is a hormone that sends signals and informs the brain whether the body is nourished or starving. These signals are transmitted by a molecular switch on specific brain cells that receive the signal. These switches are proteins known as receptors. There are a number of such leptin receptors that respond to the molecule. Other tissues besides the brain can respond to this compound and there are a variety of forms of such receptors in the human body. Variations in the leptin receptor signaling is associated with obesity.

What is Leptin receptor deficiency?

Leptin receptor deficiency is a condition that causes severe obesity beginning in the first few months of life. Affected individuals are of normal weight at birth, but they are constantly hungry and quickly gain weight. The extreme hunger leads to chronic excessive eating (hyperphagia) and obesity. Beginning in early childhood, affected individuals develop abnormal eating behaviors such as fighting with other children over food, hoarding food, and eating in secret. People with leptin receptor deficiency also have hypogonadotropic hypogonadism, which a condition is caused by reduced production of hormones that direct sexual development. Affected individuals experience delayed puberty or do not go through puberty, and may be unable to conceive children (infertile).

How common is leptin receptor deficiency?

The prevalence of leptin receptor deficiency is unknown. It has been estimated to account for up to 3 percent of individuals with severe obesity and hyperphagia that begins in early childhood. Leptin receptor deficiency is caused by mutations in the LEPR gene. This gene provides instructions for making a protein called the leptin receptor, which is involved in the regulation of body weight. The leptin receptor protein is found on the surface of cells in many organs and tissues of the body including a gland in the brain called the hypothalamus. The hypothalamus controls hunger and thirst as well as other functions such as sleep, moods, and body temperature. It also regulates the release of many hormones that have functions throughout the body. Leptin receptor deficiency is a rare cause of obesity. Researchers are studying the factors involved in more common forms of obesity.

What’s affected with leptin if it is not genetic?

In discussing the more common forms of how leptin and leptin receptors affect our health and our weight. This is a variation of leptin levels and issues with signaling to the receptor that lifestyle may be causing rather than a genetic defect at birth. You can say, we may doing this to ourselves. Weakened leptin signaling = leptin resistance. When leptin levels and leptin receptors are working as they should this results in a decreased appetite and healthy body weight. When the signaling to the receptors are less -this leads to a deficiency of leptin to be received by the brain even with high levels of leptin available. This is leptin resistance. Leptin is also very important for optimal function of the immune system. Leptin is a cytokine like hormone with pro-inflammatory properties that as of late has been linked to autoimmune diseases. There is increasing evidence that leptin is involved with enhancing immune reactions that are commonly associated with inflammation and both high and low levels of leptin may contribute to autoimmune diseases. Although, most of the studies have been done with Rheumatoid arthritis and Multiple Sclerosis, more investigation is being done on a variety of autoimmune diseases.

There are 3 areas of which leptin affects our body.

  • Peripheral (also known as non-hypothalamic) here leptin is found in a wide range of cells. It modulates energy expenditure, fetal & maternal metabolism, puberty, activates immune cells and interacts with other hormones & energy regulators, such as; insulin , glucagon, insulin growth factor, growth hormone, glucocorticoids, cytokines and metabolites.
  • Circulatory System (also known as hypothalamic) modulates T-Cell activity in the immune system – affects the HPA axis suggesting a role in a stress response.
  • The Brain here, altered brain protein & neuronal functions can change cognitive abilities and are associated with anorexia, depression, Alzheimer’s and HIV.

Role-Of-Leptin-Yo-Yo-Dieting-In-Immune-System-Weight-Loss Leptin acts on receptors on the lateral hypothalamus to inhibit hunger and the medial hypothalamus to stimulate satiety.

  1. A lesion in the lateral hypothalamus causes anorexia ( due to lack of hunger signals)
  2. A lesion in the medial hypothalamus causes excessive hunger ( due to a lack of satiety signals)
  3. The absence of leptin or its receptors will lead to uncontrolled hunger resulting in obesity.
  4. Fasting and dieting, very low caloric intake will lower leptin levels and possibly decrease the size of your fat cells to an abnormal level causing the secretion of leptin levels to increase appetite – the result is weight gain.
  5. Leptin levels are altered more with lower calories than with higher calories

Similar to chronic inflammation – chronically elevated leptin levels are associated with obesity, over eating and inflammation related diseases;

  • Hyper-tension
  • Metabolic Syndrome
  • Cardio-vascular disease

In simple enough terms, just like calming the immune system in autoimmune diseases, you can say calming the leptin levels or stabilizing them is key to maintaining good health, a healthy weight and hormonal state. Since elevated leptin is pro inflammatory, you can make the obvious connection that it will affect those with autoimmune disease. You can also see that it may play a factor in acquiring autoimmune disease, in addition to the link to metabolic syndrome and heart disease. Lower levels of (leptin = L), will eventually increase levels of it. Restrictive diets and diets too low in caloric intake will lower the L levels and weight loss will be a result. If this is an extreme for your natural set point, then the body will go into survival mode and increase L levels to bring the body back up to the set point for you.

Yo-Yo Dieting

This is what occurs in yo-yo dieting, the loss of weight and the return of the weight that was lost. The issue most do not take into account is… when you lose weight about 50% is from fat and 50% is from muscle tissue. Once you have lost muscle there is only one way to get it back, resistance training. That means your weight gain will be of 100% fat – you have gained back more fat than you have lost initially. This is why exercise is an important component of reversing leptin variations or resistance. Exercise (combined resistance and cardiovascular) does not affect leptin levels one way or the other, it is neutral. Increasing muscle mass (lean body mass) naturally increases your metabolism. The increase in appetite is gradual and is not induced by increased L levels, so there will not have this chronic elevation in leptin levels, which increases the leptin resistance and weight gain. When slowly increasing your caloric intake back to appropriate levels for energy expenditure you are actually assisting the body back to normal, rather than the body insisting on it – by increasing L levels. By increasing your good carbohydrate intake slowly to accommodate your exercise you are assisting the body to achieve normal leptin levels. The issue comes when the body is making that decision for you and you are fighting it by continuing to restrict calories and carbohydrates below what you need for your body to function. When considering weight loss, moderation is key. Gradually, decreasing daily caloric intake by 15-20% of total calories needed to function (BMR) and low intensity cardiovascular activity 3x per week. By keeping exercise to a minimum and caloric restriction to a minimum when just starting your weight loss process, you will be allowing your body to adjust slowly to altering leptin levels. As you become fit and gradually lose weight, an increase in exercise intensity and frequency will be needed to lose more weight or maintain fitness. The actual need to decrease caloric intake as you become fit will not be needed as you will find you will need to actually increase caloric intake to put on and maintain lean body mass.

How to calculate your BMR

The BMR formula uses the variables of height, weight, age and gender to calculate the Basal Metabolic Rate (BMR). This is more accurate than calculating calorie needs based on body weight alone. The only factor it omits is lean body mass and thus the ratio of muscle-to-fat a body has. Remember, leaner bodies need more calories than less leaner ones. Therefore, this equation will be very accurate in all but the very muscular (will underestimate calorie needs) and the very fat (will over-estimate calorie needs).

English BMR Formula

Women: BMR = 655 + (4.35 x weight in pounds) + (4.7 x height in inches) – (4.7 x age in years) Men: BMR = 66 + (6.23 x weight in pounds) + (12.7 x height in inches) – (6.8 x age in year)

Metric BMR Formula

Women: BMR = 655 + (9.6 x weight in kilos) + (1.8 x height in cm) – (4.7 x age in years) Men: BMR = 66 + (13.7 x weight in kilos) + (5 x height in cm) – (6.8 x age in years) Once you know your BMR, you can calculate your Daily Calorie Needs based on your activity level using the Harris Benedict Equation. The Harris Benedict Equation is a formula that uses your BMR and then applies an activity factor to determine your total daily energy expenditure (calories). The only factor omitted by the Harris Benedict Equation is lean body mass. Remember, leaner bodies need more calories than less leaner ones. Therefore, this equation will be very accurate in all but the very muscular (will under-estimate calorie needs) and the very fat (will over-estimate calorie needs).

Role-Of-Leptin-Yo-Yo-Dieting-In-Immune-System-Weight-LossHarris Benedict Formula

To determine your total daily calorie needs, multiply your BMR by the appropriate activity factor, as follows:

  • If you are sedentary (little or no exercise): Calorie-Calculation = BMR x 1.2
  • If you are lightly active (light exercise/sports 1-3 days/week): Calorie-Calculation = BMR x 1.375
  • If you are moderately active (moderate exercise/sports 3-5 days/week): Calorie-Calculation = BMR x 1.55
  • If you are very active (hard exercise/sports 6-7 days a week): Calorie-Calculation = BMR x 1.725
  • If you are extra active (very hard exercise/sports & physical job or 2x training): Calorie-Calculation = BMR x 1.9

Total Calorie Needs Example

If you are sedentary, multiply your BMR (1745) by 1.2 = 2094. This is the total number of calories you need in order to maintain your current weight. Once you know the number of calories needed to maintain your weight, you can easily calculate the number of calories you need to eat in order to gain or lose weight:

Calories needed to lose weight

There are approximately 3500 calories in a pound of stored body fat. So, if you create a 3500-calorie deficit through diet, exercise or a combination of both, you will lose one pound of body weight. The calorie deficit can be achieved either by calorie-restriction alone, or by a combination of fewer calories in (diet) and more calories out (exercise). This combination of diet and exercise is best for lasting weight loss. Indeed, sustained weight loss is difficult or impossible without increased regular exercise. If you want to lose fat, a useful guideline for lowering your calorie intake is to reduce your calories by at least 500, but not more than 1000 below your maintenance level. For people with only a small amount of weight to lose, 1000 calories will be too much of a deficit. As a guide to minimum calorie intake, the American College of Sports Medicine (ACSM) recommends that calorie levels never drop below 1200 calories per day for women or 1800 calories per day for men. Even these calorie levels are quite low. An alternative way of calculating a safe minimum calorie-intake level is by reference to your body weight or current body weight. Reducing calories by 15-20% below your daily calorie maintenance needs is a useful start. You may increase this depending on your weight loss goals.

About the Authors

Raina Kranz is a Certified Physical Trainer and team member of Thyroid Nation Radio. Find her at Kimberley Andrews is a Certified Health Coach and Certified Thyroid Health Coach. You can listen to them both on Thyroid Nation Radio. Also, please check out their Facebook group, Thyroid Healing Journey, Raina’s website

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