The fight against obesity and related health issues is an ongoing global concern. Recent advancements at NTU Singapore have introduced a promising gut-based compound that potentially transforms the way we approach weight loss. This innovative solution aims to reduce dietary fat absorption in the intestines, offering a new avenue in managing obesity.
Researchers at NTU Singapore have pioneered an oral gut-based compound that effectively limits the absorption of dietary fat in the intestines. Unlike many weight-loss medications that primarily function by suppressing appetite or modifying glucose regulation, this novel compound takes a different approach.
The development was spearheaded by a multidisciplinary team at NTU, including Assoc Prof Andrew Tan, a Provost’s Chair in Metabolic Disorders and Vice Dean (Innovation and Enterprise) at the Lee Kong Chian School of Medicine, along with Professor Tan Choon Hong of the School of Chemistry, Chemical Engineering and Biotechnology, who contributed to the chemistry and synthesis platforms during the research phase.
This work is being furthered in collaboration with the biomedical biotech firm Aria Bioscience Pte Ltd, aiming to transition the technology into consumer healthcare products and future therapeutic applications.
Obesity ranks as one of the most significant global health concerns, impacting over one billion individuals worldwide and exacerbating chronic health issues, including type 2 diabetes, cardiovascular diseases, and liver disorders. Despite efforts to encourage healthier lifestyles, many struggle to maintain a balanced weight amidst diets rich in fat and sugar.
Recent statistics from Singapore’s National Nutrition Survey 2022 revealed that the average daily fat intake of residents increased from 94g in 2019 to approximately 100g in 2022. This rise underscores the growing impact of dietary fats on overall calorie consumption.[1]
Link Between Obesity and Fatty Liver Disease
Obesity is intricately linked to fatty liver disease, which affects around one in three adults globally, with approximately 80 percent of those affected being obese[2]. While often asymptomatic initially, the condition can lead to severe complications like cirrhosis and liver cancer, resulting in nearly two million liver-related deaths annually.
In Singapore, projections estimate that by 2030, up to 40 percent of adults—about 1.8 million individuals—will be affected by this condition.
“Our findings indicate that strategically reducing fat absorption in the gut can minimize the fat that reaches the liver, particularly during episodes of high-fat intake or for individuals who cannot engage in physical activity,” explained Assoc Prof Andrew Tan. “While diet and exercise are foundational to metabolic health, our goal is to assist in managing dietary fats while ensuring proper nutrition.”
Pathway to Consumer Products
Timothy Chen, the Executive Director of Aria Bioscience, shared that the company is actively collaborating with NTU researchers to push this technology forward through studies focused on human safety and efficacy. The immediate objective is to introduce it to consumers as an oral supplement under their medical-grade nutraceutical brand, Arialab RX.
“Our emphasis lies in conducting additional studies and clinical trials in conjunction with NTU, leveraging our expertise in product development to progress toward commercial applications,” Chen noted. “This will be essential in determining the technology’s potential as future treatments for metabolic disorders.”
A Safe Method to Alleviate Fat Build-Up in the Liver
According to a peer-reviewed study recently published in Pharmacological Research, the NTU team validated the compounds using animal models, which showed reduced intestinal fat absorption without affecting glucose or sugar uptake.
Mice subjected to a high-fat diet and treated with the compounds exhibited less weight gain and fat accumulation in the liver, with no observed toxic side effects.
The compounds act locally within the gut via two primary mechanisms: they inhibit a receptor on intestinal cells facilitating fat entry, thereby directly decreasing fat absorption, and they promote beneficial gut bacteria that generate short-chain fatty acids, known for their positive effects on metabolic health, reduced inflammation, and strengthened gut barriers.
Remaining largely confined within the gut with minimal entry into the bloodstream allows these compounds to limit their impact on other organs while relieving stress on the liver during high dietary fat intake.
Dr. Yew Kuo Chao, a Senior Consultant in Gastroenterology and Hepatology at Tan Tock Seng Hospital, commented that obesity and fatty liver disease are chronic challenges that necessitate safe strategies which deliver metabolic benefits without negatively impacting glucose regulation or causing toxicity, especially for long-term management.
“The co-development of obesity and fatty liver disease often occurs over years. By slowing fat absorption in the gut, we can reduce the fat reaching the liver, particularly during high-fat consumption or for those less able to exercise. The NTU’s local gut mechanism is aligned with a safe-focused strategy that supports natural metabolic processes, which is vital for long-term treatment of metabolic diseases.”
Nature-Inspired Design: A Distinct Advantage
The compounds have been inspired by fatty acid esters of hydroxy fatty acids (FAHFAs), which are naturally occurring lipids found in trace amounts within the human body and various foods. While these natural FAHFAs exhibit beneficial metabolic impacts, their low concentrations and susceptibility to breakdown in the digestive system limit their practical usage.
The NTU team has tackled this issue by engineering gut-stable, nature-inspired FAHFAs that preserve their advantageous properties, making them suitable for reliable oral consumption. Unlike some current fat-blocking products that completely halt fat digestion and potentially cause side effects like oily stools or digestive discomfort, the compounds designed by NTU gently slow fat absorption at the intestinal lining while enhancing a healthier gut microbiome.
When used alongside diet control and physical activity, this gut-based approach could provide additional assistance in managing excess weight and alleviating fat-related stress on the liver, especially for high metabolic risk individuals, including those with diabetes.
This research initiative is supported by NTU’s Innovation and Entrepreneurship program, emphasizing the university’s commitment to transforming fundamental science into tangible innovations capable of addressing critical public health challenges.
Professor Louis Phee, NTU Vice President (Innovation and Entrepreneurship), remarked that the collaboration highlights NTU’s position as a leading global hub for biomedical research and innovation. “To tackle significant global health challenges, we join forces with skilled industry partners to convert NTU’s research into viable solutions that fulfill real-world needs,” he stated. “This partnership exemplifies the seamless integration of academia and industry in propelling Singapore’s biomedical research advancements for the public benefit.”
