Some people may have trouble losing weight, while others find it hard to gain weight. Now, a team of scientists may have found the answer to why some people remain thin despite eating without restriction.
The discovery may help in studying how genes can help tackle obesity, which is a global health problem. In 2016, the World Health Organization (WHO) reported that 1.9 billion adults, 18 years and older, were overweight. Of these, over 650 million were obese.
"We all know these people: it's around one percent of the population. They can eat whatever they want and be metabolically healthy. They eat a lot, they do not do squats all the time, but they just don't gain weight," Josef Penninger, the director of the Life Sciences Institute and professor of the department of medical genetics at the University of British Columbia, said.
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The 'skinny' gene
The ALK (anaplastic lymphoma kinase) gene is the variant that facilitates resistance to weight gain, no matter what diet a person has. It helps thin people stay slim, potentially opening a new frontier in treatments for obesity.
The gene may play a role in resisting weight gain in the metabolically healthy, thin people. It is found in the hypothalamus, the region in the brain responsible for controlling appetite and how a person controls fat.
The ALK gene makes a protein called anaplastic lymphoma kinase, which is involved in cell growth. The gene is also linked to certain cancers and identified as a driver of tumor growth.
The team analyzed the DNA of more than 47,000 people between the ages of 20 and 44 years old. They looked at the data from Estonia's biobank, a biological database collected from a large percentage of the Estonian population.
The researchers identified thin, healthy individuals in the lowest 6th percentile of weight. The control group, on the other hand, were those in the 30th and 50th percentile. People from the 95th percentile were tagged as the obese group. The team identified the variants of genes that appeared to occur more often in the thin group.
After studying the database, the team found that some variants in the ALK gene were tied to low susceptibility to weight gain in naturally thin people. The team also found that deleting the gene had led to thinner flies. Further, mice genetically modified to lack the ALK gene also showed marked resistance to obesity.
Therapeutics targeting the gene
The team says that therapeutics targeting the gene might help scientists tackle and fight obesity in the future. If there could be a way to shut down the ALK gene or reduce its function, at least, people can stay skinny. At present, ALK treatments such as inhibitors are being used in cancer.
Further research is needed to see if drug inhibitors are effective for this purpose before they are trialed in humans. The team looks forward to the second stage of the study, which aims to compare the findings with biobank records on the health, DNA, and activity levels of other populations across the globe.
The team also plans to study how neurons that express the ALK regulate the brain at a molecular level to balance metabolism and promote thinness.
The study was published in the journal Cell.
Obesity and its complications
Obesity is defined as an adult having a body mass index (BMI) of 30 or more. The healthy person's BMI should range between 18.5 to 24.9. Those who have a BMI of over 25 are considered overweight.
Obesity has been tied to several health complications, some of which are life-threatening. These include type 2 diabetes, high blood pressure, certain cancers, stroke, heart disease, high cholesterol levels, gallbladder disease, and fatty liver disease, among others.
People who are obese are also at high risk for all-causes of death or mortality, osteoarthritis, sleep apnea, and breathing problems, mental illness, and low quality of life.
- Orthofer, M., Valsesia, A., Magi, R., Hager, J., Gheldof, N., Penninger, J. et al. (2020). Identification of ALK in Thinness. Cell. https://www.cell.com/cell/pdf/S0092-8674(20)30497-9.pdf?_returnURL=https%3A%2F%2Flinkinghub.elsevier.com%2Fretrieve%2Fpii%2FS0092867420304979%3Fshowall%3Dtrue