UP scientists home in on gene that could play pivotal role in diet-induced obesity

Researchers at the University of Pretoria (UP) may have identified the gene that is responsible for diet-related obesity. By exploring the role of the novel gene Slc7a8, they have made a potential breakthrough in current knowledge about the cellular mechanisms that drive fat accumulation. This understanding is crucial in developing effective treatments.

“Obesity doesn’t affect everyone in the same way,” says Professor Melvin Ambele of UP’s Institute for Cellular and Molecular Medicine. “Its impact on organs can be seen early on in the weight gain process, which can later lead to some of the conditions linked to obesity.”

The study investigated the impact of Slc7a8 on obesity by feeding knockout mice (those in which the gene was inactivated) and wild type mice (for which the gene was left unaltered) a high-fat diet or a control diet over 14 weeks, with illuminating results.

For the mice on a control diet, the scientists found that deleting Slc7a8 had no significant impact on food intake or weight gain, indicating the gene’s critical role under high-fat dietary conditions. Wild type mice on a high-fat diet exhibited significant weight gain and increased caloric intake compared with those on a control diet. Conversely, knockout mice on the same high-fat diet gained less weight and had lower tissue mass in various fat depots and liver, suggesting that Slc7a8 deletion offers protection against diet-induced obesity.

Moreover, the study found that Slc7a8 deletion improved glucose metabolism and reduced fat accumulation in critical organs such as the liver, lungs, muscles, heart and kidneys. These findings suggest that Slc7a8 may play a role in protecting against obesity-related conditions, such as non-alcoholic fatty liver disease (now known as metabolic dysfunction-associated steatotic liver disease) and other metabolic syndromes. Additionally, Slc7a8 deletion improved inflammation profiles in adipose tissue, further indicating its potential as a therapeutic target for obesity and its associated comorbidities.

This groundbreaking research identified a key factor involved in fat cell formation and lipid storage, providing a promising target for developing new obesity treatments.

“Unlike current pharmaceutical options, which often have short-term outcomes and undesirable side-effects, targeting Slc7a8 could offer a more sustainable solution by addressing the root cause of excess fat storage,” Prof Ambele says.

The study also highlights the importance of including both males and females in obesity research. Historically, preclinical studies in animals have focused on males due to their faster and more straightforward development of obesity. However, this research demonstrates that obesity develops differently in males and females, as it is influenced by hormonal and physiological differences. By including females in the study, researchers gain a more comprehensive understanding of obesity, enabling the development of tailored interventions and treatment strategies for both sexes.

The prevalence of obesity is a significant concern, with recent global statistics showing that one in eight people worldwide are living with obesity. In Africa, the situation is more dire, with one in five adults affected; in South Africa, the figure is even higher, with one in four adults living with obesity. A recent survey by the Human Sciences Research Council revealed that 50% of adults in South Africa are overweight or obese, painting a troubling picture of the country’s health.

“Obesity not only poses serious health risks, including an increased likelihood of developing cardio metabolic diseases, but it also has an impact on the labour force and economy,” Prof Ambele explains. “Despite these challenges, there is hope. Obesity is preventable, and with the right strategies, individuals, communities and governments can all contribute to combating this epidemic.”

The research offers a beacon of hope in the fight against obesity, underscoring the potential for new treatments and interventions.

In the meantime, the researchers suggest adopting the following measures to work towards creating a healthier future where obesity is no longer a widespread threat but a manageable condition.

Nutritional interventions:

• Limit energy intake from fats and sugars.
• Increase consumption of fruit, vegetables, legumes, wholegrains and other nutrient-rich foods.
• Engage in regular physical activity to balance energy intake and expenditure.

Government interventions:

• Introduce strong policies involving key sectors like health, agriculture and urban planning.
• Ensure the availability and affordability of healthy foods for all consumers.
• Restrict the marketing of high-fat and high-sugar foods and those with a high salt content, particularly marketing that targets children and teenagers.
• Implement sugar taxes and salt reduction mandates to discourage the consumption of unhealthy foods.
• Promote the development of recreational areas to encourage physical activity.

Click on the infographic in the sidebar to learn more about the rates of obesity in Africa. 

Researchers

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  Professor Melvin Ambele

  Professor Melvin Ambele is a senior research officer in the Department of Oral and Maxillofacial Pathology, seconded to the Institute for Cellular and Molecular Medicine at the University of Pretoria (UP). He completed his undergraduate studies at the University of Buea in Cameroon and his PhD studies in Biological Chemistry at the University of Cape Town in 2014. From 2014 to 2016, Prof Ambele was a postdoctoral research fellow in UP’s Faculty of Health Sciences.

  He says he prefers doing research at UP because it is a prestigious research-intensive university with excellent infrastructure to support teaching and research across various disciplines

  His research focuses on identifying molecular targets that regulate lipid accumulation and the formation of adipocytes. Obesity is increasing worldwide at an alarming rate, and a recent survey by the Human Sciences Research Council shows that 50% of South African adults are overweight or obese.

  “The identification and characterisation of such targets would serve as a candidate for anti-obesity drug development to combat obesity and associated metabolic disorders,” Prof Ambele explains. “This will be greatly significant in addressing the United Nations’ Sustainable Development Goal (SDG) 3 to ensure good health and well-being for all, and in that way, contribute to the betterment of the world.”

  Prof Ambele leads a team of researchers that includes postgraduate students. He works across faculties with Dr Pontsho Moela and Dr Ntlotlang Mokgautsi of the Department of Biochemistry, Genetics and Microbiology in the Faculty of Natural and Agricultural Sciences.

  Prof Ambele says the research team may have identified a key gene that is responsible for lipid accumulation in adipocytes and the development of obesity. In preclinical studies, deleting this gene in mice not only significantly improved glucose metabolism and reduced lipid accumulation in various adipose tissues, but also led to a substantial decrease in lipid accumulation in critical organs such as the liver, lungs, muscles, heart and kidneys. These groundbreaking findings suggest that the gene, Slc7a8, could be a promising target for developing new anti-obesity treatments that may also protect against obesity-related conditions, including metabolic dysfunction-associated steatotic liver disease and other metabolic syndromes.

  This new, ongoing research aims to unravel the detailed molecular mechanisms through which Slc7a8 mediates lipid accumulation in adipose tissues and other critical organs, to serve as a viable therapeutic target for obesity.

  “The alarming global rise in obesity, which is a complex multi-systemic disease with no readily available treatment, has been my primary motivation for conducting research in this field to identify potentially viable targets for drug development,” Prof Ambele says. “I hope to effectively identify and characterise a key molecular factor that could be successfully targeted for the treatment of obesity and its associated comorbidities.”

  His research matters because obesity is also a risk factor with regard to various non-communicable diseases like diabetes, cardiovascular diseases, certain cancers, neurological disorders, chronic respiratory diseases and digestive disorders.

  “These conditions have a significant impact on the quality of life globally,” Prof Ambele says. “Identifying an effective molecular target could offer a promising opportunity for the successful development of a drug to treat obesity and these related comorbidities.”

  This would enable countries around the world to achieve SDG 3 targets for good health and well-being

  His advice to school learners or undergraduates interested in his field is to pursue their passion and to focus on finding solutions to issues of global significance like obesity.

  “Research in obesity offers great opportunities for both learning and career development.”

  Prof Ambele’s interests include football, wildlife safari and singing.

  More from this Researcher

Related Infographic

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  Weighing in on obesity rates