Understanding Leptin, Its Regulation, Resistance And Associated Disease

Leptin, also known as an appetite suppressant or satiety chemical, is a hormone released by the adipose cells or fat cells which help in maintaining healthy body weight by balancing the amount of food intake. It doesn’t affect our hunger and food intake directly in our everyday meals but rather acts to alter your food portions and control energy expenditure over a longer period of time to help maintain an apt body weight.

This Story also Contains

1. Leptin-Resistance
2. Hyperphagia And Severe Obesity
3. Leptin Sensitivity Vs Insulin
4. Associated Diseases
5. Regulation Of Leptin

Leptin basically targets a part of the brain called the hypothalamus. When a person eats enough food, leptin is released into the bloodstream, where it travels to the brain, signalling that they are full and that they can burn calories at a normal rate. Leptin makes you feel less hungry and gives the feeling of being full and satisfied. It tells the brain that it has enough fat stored. The levels of Leptin tend to peak between midnight and dawn, thus making one less hungry at night. So, we can conclude that sleep plays a major role in regulating leptin levels, and lack of sleep disrupts all hormones including leptin. Our brain perceives a lack of sleep as a lack of energy that needs to be replaced by food. Thus, leptin acts as a feel-full hormone and its autoregulation maintains appetite and energy reserve.

Leptin-Resistance

People with Leptin resistance have a decrease in the ability to suppress hunger. So, one of the major symptoms of leptin resistance is constantly feeling hungry and increasing food intake contributing to obesity and a decrease in metabolism. It also resists the burning of calories during intense workouts. Leptin resistance is believed to be the driving cause of fat gain in humans.

What Causes Leptin-Resistance?

There are many identified causes of Leptin resistance. All major causes are directly or indirectly amplified by obesity. Discussed below are a few major causes.

• High Levels of Leptin: Recent studies suggest that higher levels of leptin may lead to leptin resistance in some individuals.
• Gene Mutation: As a result of gene mutation structural changes in the leptin molecule occurs along with the deterioration of leptin-receptor function accompanied by inflammation of the hypothalamus and endoplasmic reticulum (ER) stress.
• Inflammation: Inflammation contributes to leptin resistance by directly affecting the brain, particularly at the hypothalamus.
• Transport across BBB: Change in the transport of Leptin molecules across the Blood-Brain Barrier (BBB) may also cause Leptin resistance.
• Free Fatty Acids: The presence of elevated levels of free fatty acids in the bloodstream of certain individuals increases the levels of fat metabolites and thus interferes with the signaling of leptin.

Remember that the level of Leptin in an individual is directly proportional to its fat mass. As the fat mass increases the level of leptin in the body also increases and vice versa.

Leptin testing is not available in many labs due to a lack of awareness. In India, it’s usually done for individuals with severe or type 3 obesity. A blood test is usually conducted to check the level of leptin.

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Hyperphagia And Severe Obesity

Leptin receptor deficiency (LRD) causes a condition called severe obesity in the early stages of life. LRD is inherited in an autosomal recessive pattern. The affected individuals look normal weight initially but as they grow lack of leptin receptors triggers hunger. Extreme hunger leads to hyperphagia or excessive eating causing severe obesity. Leptin resistance is now believed to be the leading driver of fat gain in humans. It may be one major cause of why most diets do not work efficiently.

The affected individuals might also have a condition known as hypogonadotropic hypogonadism, caused by reduced production of hormones such as luteinizing hormone (LH) which affects menstruation and fertility in women, follicle-stimulating hormone (FSH), and gonadotropin-releasing hormone (GnRH). Reduced levels of the mentioned hormones may also cause delayed puberty and infertility.

LRD can be reversed to a large extent by avoiding the consumption of processed food, increasing fibre and protein intake, exercising regularly, and improving the sleep cycle.

Leptin Sensitivity Vs Insulin

The synthesis and secretion of leptin are directly stimulated by insulin through the PI3K-PKBmTOR pathway. Leptin increases insulin sensitivity by decreasing adiposity and lipotoxicity. In Leptin resistant or deficient individuals, leptin therapy has been seen to show significant results in reversing type 2 diabetes.

Associated Diseases

Disruption of Leptin signals may also increase the risk of many associated diseases such as Obesity, Type 2 diabetes, Alzheimer’s disease, etc. Also, since high leptin levels are directly associated with body fat, severe obesity causes a condition called hyperleptinemia, where the level of leptin shoots up leading to other associated diseases such as depression, fatty liver disease, Mendenhall syndrome, and addiction to food.

Regulation Of Leptin

Recent studies suggest that increasing physical activity, cutting down on sugar, and getting proper sleep can regulate leptin levels in the human body. Food items such as whole grains, legumes, green leafy vegetables, and fruits such as berries are found to increase leptin sensitivity. The regulation of leptin is thus crucial for perpetuating body homeostasis, immune function, bone, and overall body metabolism.

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