Researchers from Garvan Institute of Medical Research discovers a safe and effective alternative to beat obesity by inhibiting Y1 receptors that elevate the production of body heat and promote fat metabolism.
Even before the advent of COVID-19, the world has been battling a deadly epidemic which affected 1.9 billion adults in 2016, and forecasted to rise to 2.7 billion by 2025 – an epidemic of overweight and obesity. In the last 4 decades, the world has seen obesity reach epidemic proportions at an astronomical rate, tripling in incidence since 1975.
Obesity is defined as having abnormal or excess amounts of body fat which can adversely impair our health, leading to complications including but not limited to diabetes, cardiovascular disease and some cancers. Overweight is a milder version of obesity. While multi-factorial, obesity and overweight fundamentally develop as a result of an imbalance between calories consumed and expended. As such, diet has been playing a major role in both cause and cure.
Up until recently, scientists have relied on treatment methods which primarily hinge on brain-targeting medications that curb appetite and restrict caloric intake. However, these medications have been found to induce alarming side effects such as psychiatric or cardiovascular complications. And while some would suggest diet control and physical exercise to prevent or reverse overweight and obesity, medications may be the only solution for others. For that reason, much research has been poured into the search for safe and effective treatments, or better yet, a cure for obesity.
One team of researchers from the Garvan Institute of Medical Research, has devised a novel approach to treat diet-induced obesity – producing more body heat. Using experimental models and fat tissue biopsies from obese individuals, the team discovered the role of a particular receptor – known as Y1 – of neuropeptide Y which controls body heat production. Y1 receptors essentially promote fat-storage, and are key to minimise energy expenditure when our bodies detect conditions of starvation. They found that inhibiting Y1 alters the default mode of fat tissues from “energy-storing” to “energy-burning”, thus effectively inducing fat metabolism and fending off weight gain.
The study subjected obese mouse models with an experimental treatment that blocks Y1 receptors, also known as treatment BIBO3304, and fed the mice with a high-fat diet for over 7 weeks. The results were astonishing as these mice gained 40% less body weight as compared to normal mice which were also fed with an equally high-fat diet over the same period of time. Comparably, Y1 receptors in human fat cells appeared to operate in a similar pathway as mice, wherein its inhibition can induce body heat production, increase fat metabolism and decrease weight gain.
Besides its obesity-preventing benefits, experimental treatment BIBO3304 boasts a more valuable attribute – its superior emphasis on safety. Unlike its anti-obesity counterparts, this new therapeutic approach relies on blocking Y1 receptors in peripheral tissues to stimulate energy expenditure. This means that the treatment does not cross the blood-brain barrier and simply acts on peripheral tissues, leaving the central nervous system – our brain – untouched. A potentially stark improvement in safety is what truly sets the treatment BIBO3304 apart from past and competing anti-obesity drugs, as proclaimed by Professor Herbert Herzog, Head of the Eating Disorders Lab at Garvan.
"Our team and other groups have revealed further potential benefits in targeting the NPY-Y1 receptor system, including the stimulation of bone cell growth, and improvement in cardiovascular function and insulin resistance," Professor Herzog added. "We hope that the publication of our findings will lead to increased interest for exploring BIBO3304 and related agents as potential treatments for obesity and other health conditions."