About My Health Careers Internship MedBlogs Contact us

Genetic Cause Behind Obesity Among Some People Identified

by Mohamed Fathima S on March 7, 2019 at 1:39 PM
Font : A-A+

Genetic Cause Behind Obesity Among Some People Identified

A genetic mechanism that plays a vital role in at least 10 percent of all cases of obesity has been found out by the researchers, that would help identify individuals with treatable forms of the condition. Also, the findings shed importance on the biology of the hormone leptin, which is synthesized in fat cells and its primary function is controlling hunger. According to the results, the amount of leptin present in the bloodstream and how the brain responds to it determines how much weight a person will gain.

Obesity is a major public-health problem in the United States and around the world, with an estimated 650 million people suffering from the condition. One of the biggest challenges of this ever-worsening condition is figuring out why people become obese in the first place, and why some people are more vulnerable to obesity than others.


The scientists report this week in Nature Medicine that, in mice, alterations in the cellular machinery that regulates leptin production can lead to a form of obesity treatable with leptin therapy. Evidence from human genetics studies further suggests that a similar mechanism may contribute to obesity in a subset of patients.

How leptin is finetuned

Discovered 25 years ago by Rockefeller scientist Jeffrey M. Friedman, the Marilyn M. Simpson Professor, leptin has been the subject of many thousands of studies exploring its structure and function. "We've learned a lot about leptin," says Olof Dallner, research associate and lead author of the new report, "but we didn't actually understand the basic biology of what regulates the leptin gene."

The gene coding for the leptin hormone is regulated by adjacent DNA sequences and regulatory factors that turn the gene on in fat cells, and that also controls the amount of leptin being made. As they explored this process, Dallner and his colleagues zeroed in on one of these regulatory factors, called a long non-coding RNA, or lncRNA, which they identified together with colleagues at the University of Pennsylvania.

When the researchers engineered mice without this specific lncRNA and fed them a high-fat diet, the mice became obese, but their fat cells produced significantly lower amounts of leptin. This unusual finding suggested to the scientists that the leptin gene could not express normal levels of the hormone without the lncRNA to help it along. In comparison, a group of unaltered control mice fed the same diet gained weight and produced the expected amount of leptin.

Moreover, when these low-leptin mice were treated with injections of leptin, they lost weight--in other words, the hormone essentially cured them. And that, the researchers say, raises the exciting possibility that some humans whose obesity is caused by a similar genetic anomaly could also lose weight with leptin therapy. (A pharmaceutical form of leptin was approved by the U.S. Food and Drug Administration in 2014.)

The fact that there may be obese people with such potentially leptin-curbing mutations was suggested by analyzing data from a large study, known as a genome-wide association study (GWAS), that included the complete genetic profiles of more than 46,000 people. Together with collaborators at the Mount Sinai School of Medicine, the Rockefeller team found that people with alterations in the human version of the lncRNA had lower leptin levels.

A potentially-treatable subtype of obesity

The number of obese people whose disease may be the result of the dysregulation of the leptin gene is not known, Dallner says, but there is reason to believe it could contribute to as many as 10 percent of all obesity cases.

For Dallner, who spent the better part of nine years working on the project, the heterogeneity of the obese population--the fact that different people are obese for different reasons--is the most interesting takeaway from the research. "The important part for me is that we set out to study the leptin gene in mice, and we ended up concluding that different mechanisms can cause obesity in humans," he says.

Most obese people, he explains, become resistant to leptin (which would normally curb their appetites) because they have a lot of fat. Fat cells produce high amounts of leptin and, as the hormone accumulates, the brain appears to stop responding to it.

"But there is a large subset of humans who are obese and still are relatively low in leptin," Dallner says. "We now think that many of them may have these or similar gene variants that affect the expression of the leptin gene. This gives them less leptin from an early age, making them a little bit hungrier than everyone else."

These people remain sensitive to the hormone, however, and early clinical studies have shown that obese people with low leptin levels do in fact lose a significant amount of weight when treated with leptin. But the possible mechanisms underlying such cases were not understood, until now.

Dallner says that while the exact interplay between lncRNA and the leptin gene remains unclear, there is no doubt that the two are connected. "When we studied the lncRNA, we realized it was completely co-regulated with leptin. It's expressed where leptin is expressed. When leptin is down the lncRNA is down, and vice versa. That was really the key moment, when I saw that and thought, 'Something is really going on here.'"

Source: Eurekalert

News A-Z
News Category
What's New on Medindia
Ways to Manage Stress during COVID-19 Pandemic
Can Adjusting Fatty Acid Intake Improve Mood in Bipolar Disorder Patients?
Insulin Resistance Doubles the Risk of Major Depressive Disorder
View all

Medindia Newsletters Subscribe to our Free Newsletters!
Terms & Conditions and Privacy Policy.

More News on:
Bariatric Surgery Obesity Bulimia Nervosa Genetics and Stem Cells Body Mass Index Liposuction Battle of the Bulge Diabesity Hunger Fullness and Weight Control Diet and Nutrition for Healthy Weight Loss 

Recommended Reading
Malnutrition to Obesity - The Big Leap
Obesity is the root cause of problems like diabetes, heart disease, stroke, arthritis and gall ......
Obesity is a condition where there is excess accumulation of body fat which poses a risk to the ......
Obesity during Pregnancy: Know the Risks
Women with a body mass index >30 are obese and are at a higher risk for gestational diabetes during ...
Anti-Quick Fix Weight Loss
Trying to lose weight? Weight loss is not a race or a competition against time but a lifestyle ......
Battle of the Bulge
The ‘battle of bulge’ is the toughest of all battles. Once you put on weight it is so difficult to g...
Body Mass Index
Body mass index (BMI) is a simple tool that is generally used to estimate the total amount of body f...
Bulimia Nervosa
The term ''Bulimia'' refers to episodes of uncontrolled excessive eating, known as "binges," followe...
With more than one billion people affected, diabesity is the largest epidemic in the world today. Fo...
Diet and Nutrition for Healthy Weight Loss
Correct diet and a planned exercise regime is the mantra of healthy and sustainable weight loss....
Hunger Fullness and Weight Control
An erratic way of eating or any metabolic disturbance in the hunger fullness signals is one of the m...
Liposuction is a cosmetic procedure, which is used to suck out the excess or abnormal fat deposition...

Disclaimer - All information and content on this site are for information and educational purposes only. The information should not be used for either diagnosis or treatment or both for any health related problem or disease. Always seek the advice of a qualified physician for medical diagnosis and treatment. Full Disclaimer

© All Rights Reserved 1997 - 2021

This site uses cookies to deliver our services. By using our site, you acknowledge that you have read and understand our Cookie Policy, Privacy Policy, and our Terms of Use