A groundbreaking study has revealed what regulates a gene pivotal to appetite control—offering new insights into the causes of obesity and paving the way for potential new treatments. This international breakthrough, involving a University of Auckland scientist, arrives as the global medical community rethinks how obesity is diagnosed and managed.

The Role of Genetics in Obesity

Obesity currently affects more than one in three New Zealand adults, making it a pressing public health concern. Scientists have long known that even small changes in the MC4 receptor—a gene that plays a crucial role in regulating food intake—can lead to obesity. However, what controlled this gene’s function remained a mystery.

Associate Professor Kathy Mountjoy, a co-author of the study from the University of Auckland, explains that despite years of pharmaceutical research, drugs designed to activate the MC4 receptor have largely failed due to unwanted side effects.

The Key Discovery: OTP Gene

Now, thanks to research led by Dr. Chen Liu at the University of Texas, the missing piece of the puzzle has been found—a newly discovered gene called orthopedia (OTP). This gene regulates how MC4 is expressed in the brain’s hypothalamus, the area responsible for appetite and energy storage.

Initial genetic data from the UK Biobank identified OTP as a candidate linked to obesity, but its function remained unclear. However, experiments on mice with mutations in OTP confirmed that its disruption led to obesity.

"The key point is that the OTP gene regulates the expression of the MC4 gene in the brain’s hypothalamus—and its disruption causes obesity in mice and humans," says Mountjoy, who also contributed New Zealand-sourced DNA to the study.

Implications for Treatment

While there are currently no drugs targeting OTP, this discovery could prompt the development of new treatments aimed at regulating this gene and addressing obesity at its root cause. Mountjoy acknowledges that while developing such drugs will be a challenge, the findings offer a promising direction for future obesity treatments.

Rethinking Obesity Diagnosis

This study coincides with a major global review that challenges how obesity is diagnosed. Traditionally, obesity has been defined based on Body Mass Index (BMI), a measurement of height and weight. However, experts argue that BMI fails to account for a person’s overall body composition, including fat, muscle, and bone mass.

The review proposes a new classification system that considers whether obesity is contributing to chronic disease or poses minimal health risk. According to University of Auckland’s Professor Sir Collin Tukuitonga, these revised guidelines could reduce stigma and lead to better medical care for individuals affected by obesity.

Weight Loss Surgery and Local Impact

As obesity research advances, experts in weight management, including Dr. Daniel Mafi of Bay Surgery in Tauranga, continue to offer surgical solutions such as Gastric Bypass and Gastric Sleeve procedures. These surgeries provide effective options for individuals struggling with obesity, particularly when traditional methods like diet and exercise prove ineffective.

With discoveries like the role of OTP in obesity, the future of weight management could see a shift towards more targeted, gene-based therapies, providing new hope for those affected by the condition.

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