Genes Protect Some People From Obesity

(Posted on Wednesday, July 17, 2024)

In a world where weight loss methods range from trendy diets to prescription medications, a new genetic study offers a fresh perspective. A rare genetic variation has been found to shield individuals from gaining weight, even on a high-fat diet. This enhances our understanding of the genetic factors behind obesity and suggests new, more personalized treatment options. Imagine a future where your weight loss plan is tailored to your DNA, potentially making it more effective than ever before.

The study published in Science examined the DNA of more than 640,000 people from the UK, the US, and Mexico. They focused on the parts of DNA that contain instructions for making proteins. It was found that 16 rare genetic changes linked to a person’s body mass index (BMI), a common way to measure if someone is overweight or obese. Interestingly, some of these genetic changes were found in genes that work in the brain to control how the body manages energy. This suggests that specific brain functions play a role in determining a person’s weight.

The G-Protein: Is it The “Fat” Gene?

One particularly intriguing finding involved a gene called G protein-coupled receptor 75. G proteins are molecular switches inside our cells that help transmit signals from the outside to the inside of the cell. They’re like tiny messengers that relay information about what’s happening in the body. When a signal, like a hormone, arrives at the cell surface, it activates a G protein-coupled receptor. This receptor then activates the G protein, which triggers a cascade of events inside the cell, ultimately changing how the cell behaves.

The study observed changes in G protein-coupled receptor 75 in approximately 4 out of every 10,000 individuals. Those with these variations tended to have lower BMI, weigh less, and have a 54% reduced likelihood of obesity. In experiments with mice, those lacking this gene did not gain weight even when fed a high-fat diet.

The research findings show that specific variations in the gene for G protein-coupled receptors are associated with a higher body mass index and increased vulnerability to obesity. Variations in another gene for G protein-coupled receptors are also linked to lower body fat levels. These findings demonstrate the complex role of genetic factors in weight and fat distribution, underlining the need for a comprehensive approach to understanding the genetic basis of obesity and developing effective management strategies.

This discovery is exciting because it indicates that targeting this gene could lead to new approaches for treating or preventing obesity. However, the researchers note that the study has certain limitations. For example, the results may not be universally applicable, and the complex interactions between genes and the environment still need to be fully understood.

New Doors Are Opening

The discovery of the role of the G protein-coupled receptor 75 in weight gain is exciting for several reasons. It may lead to the development of more targeted medications for obesity, allowing for more effective treatments with fewer side effects than current options. Additionally, these findings could open the door to personalized obesity treatments, where doctors may tailor treatments based on an individual’s genetic makeup. Furthermore, the research helps us better understand the complex genetic factors contributing to obesity, highlighting the importance of large-scale genetic studies to identify rare but crucial genetic differences. 

Although it may take time to translate these discoveries into actual treatments, this research provides hope for improved obesity management in the future. The GPR75 gene is particularly intriguing as its variations have been linked to lower body weight and a reduced risk of obesity, making it a promising target for developing new obesity treatments. While there are challenges in turning these findings into real-world treatments, this research marks a significant step forward in our understanding of obesity and potential future treatments.

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This story is part of a series on the current progression in Regenerative Medicine. In 1999, I defined regenerative medicine as the collection of interventions that restore tissues and organs damaged by disease, injured by trauma, or worn by time to normal function. I include a full spectrum of chemical, gene, and protein-based medicines, cell-based therapies, and biomechanical interventions that achieve that goal.

In this subseries, we focus specifically on gene therapies. We explore the current treatments and examine the advances poised to transform healthcare. Each article in this collection delves into a different aspect of gene therapy’s role within the larger narrative of Regenerative Medicine.