Hungry Forever, Fullness Never

When Popping a Pill is the Only Solution for Weight Loss

A mismatch between calories consumed and calories expelled is the basis of weight gain. But obesity is also affected by genetic, environmental and lifestyle factors. While we don’t have a hold over genetic and environmental factors changing our lifestyle and improving our health is in our hands. Many individuals put on weight during puberty years and as young adults as they adopt the so-called modernized eating habits that includes mostly junk or processed foods. These guys also love to spend time on their favorite couch watching television or fidgeting with their smartphone. When overweight/obesity strikes these individuals, it is purely because of their lifestyle and they are to be blamed entirely. For those suffering from haphazard lifestyle changes getting in touch with reputed dietitian nutritionists at www.firsteatright.com can help you lose weight and stay active. But there are exceptional cases where the person is affected by obesity in the first few months after birth. What’s the case with these people?

All in the Gene
There are almost 118 genes associated with obesity and some of them encode leptin (LEP), leptin receptor (LEPR) and others. Leptin is a hormone that regulates satiety and energy expenditure and its level is directly dependent on the presence of fat in the cells. Leptin receptor deficiency is a condition that causes severe obesity since the first few months of life. This condition is inherited from parents, but the parents might never show symptoms of it in their lifetime as it is inherited in an autosomal recessive pattern. Individuals with this condition are born with a normal birth weight but feel hungry constantly after few months of life and put on excess weight in sometime. Like the name suggests, affected people don’t have the ability to realize satiety due to deficiency of a receptor indicating fullness and they stay hungry for most part of the day. Such hunger results in hyperphagia (chronic excessive eating) and in turn, obesity. These individuals might also suffer from underdeveloped sexual organs and might be unable to bear offspring.

People with leptin receptor deficiency develop strange behavior too as their hunger triggers them to fight with other children for food, hoard food or even secretly eat them inside restrooms to satisfy their hunger. This deficiency is caused due to mutations in the LEPR gene. This gene gives out instructions for making a protein called the leptin receptor (regulating body weight). This protein is found in cells of different organs and tissues and also in the hypothalamus, part of the brain that controls hunger, thirst and sleep. The leptin hormone switches on the leptin receptor. Fat cells in the body release leptin. More the number of fat cells in the body greater is the release of leptin. As the fat stores increase, in the hypothalamus of the brain the binding of leptin to the receptor sends chemical signals that affect hunger and start producing a feeling of fullness. In leptin receptor deficiency, the gene mutation prevents the receptor from responding to leptin and hence, resulting in excess weight gain and hunger.

Lifestyle Intervention is not the Solution
In a strange condition such as leptin receptor deficiency increasing your physical activity by indulging in vigorous-intensity exercises or reducing calorie intake by following a strict diet is not going to solve the problem. Even obesity surgeries (bariatric surgeries) fail to produce the desired effect and the only option left out now is to choose a drug-based treatment approach. A few years back a group of researchers found that treating the patient with a peptide (a compound that activates the melanocortin 4 receptor (MC4R)) could regulate body weight. Leptin binds to LEPR and produces the melanocyte-stimulating hormone (MSH). MSH binds to its receptor and sends the satiety signal to the body. But when the LEPR gene is mutated the entire process shuts off. The patient suffers from incessant hunger which raises the risk of obesity. In the study, the researchers used a peptide that binds to the MC4R in the brain which helps the patient realize satiety levels. The researchers also observed significant weight loss in these patients. But why the peptide causes such an improvement in satiety signaling is yet to be discovered. We can hope for a drug that helps people with LEPR gene mutation to avoid obesity by using it and by also exercising and eating healthy food.