There remains a pressing need for advanced strategies and solutions to address the growing obesity epidemic. Harnessing our deep understanding of the mechanisms driving adiposity and its resulting complications or comorbidities, we are set to pioneer innovative approaches and potential solutions.
In 2022, 2.5 billion people were living with overweight and of these, 890 million had obesity.1 In the next 5 years, 50 percent of the adult population is projected to be living with obesity or overweight by 2030.2 It is one of the most critical public health challenges faced globally, that will have an increasing impact on people, society and the planet, underscoring the significant and growing need for effective, long-term solutions.
Obesity and overweight are not merely about excess fat (adipose tissue); they are complex diseases intricately linked with various cardio-renal-metabolic diseases. The root causes of obesity, known as adiposity, are complex, but the impact is far-reaching, placing a significant burden on both individuals and healthcare systems. Obesity is a significant risk factor for increased morbidity and mortality, most importantly from cardiovascular disease, type 2 diabetes, kidney disease and depression.3
This is a field where scientific knowledge and progress are accelerating, and by harnessing our deep understanding of the mechanisms driving adiposity and its resulting complications or comorbidities, we are pioneering innovative approaches and potential solutions.
Understanding the biology of adipose tissue (or fat cells)
Obesity results from a chronic imbalance between energy intake and expenditure. But beneath this simple equation lies a complex web of hormonal and neurological signals—most notably through the ‘gut-brain axis,’ where hormones produced in the gastrointestinal tract signal the brain to regulate food intake, energy expenditure and glucose homeostasis.4
In people living with obesity, this signalling is often disrupted, leading to increased hunger and fat accumulation. Not all fat is the same, however.
- Subcutaneous fat, located under the skin, can serve as an energy reserve and provide insulation.
- Visceral fat, which surrounds the organs in the abdomen, poses greater health risks.
Regardless of the type of fat, this tissue acts as more than just storage—it’s metabolically active, releasing hormones and inflammatory signals that influence insulin sensitivity, appetite and organ function. This dysregulation can lead to insulin resistance, lipid overload, inflammation, and organelle stress imbalances.5
Bridging the gut-brain axis with GLP-1
Glucagon-like peptide 1 (GLP-1) is a hormone that is part of the incretin family of hormones that are secreted in response to food intake. GLP-1 is produced in the intestinal enteroendocrine called L-cells as well as part of the brain, providing a link between food intake and metabolic function.6,7
GLP-1 slows gastric emptying, promotes glucose-dependent insulin secretion and enhances a feeling of fullness to reduce food intake.8 GLP-1 receptor agonists regulate glycemic control and body weight, and research has shown that it may play a role in liver, respiratory and neurological health.8 Ongoing research is being conducted to better understand the potential in these areas.8
Beyond these areas, there is a lot of interest in understanding the full extent of GLP-1’s impact on the body; receptors are primarily located in the pancreas but are present on other organs, including the brain, heart, kidney, immune cells and lung cells for example. These findings have led to further research to explore the therapeutic potential beyond metabolic and cardiovascular disease.9,10
GLP-1 receptor agonists have been described by researchers as one of the most impactful scientific discoveries in modern medicine, given their impact on a multitude of interrelated biological mechanisms. From their effects on the heart and blood vessels, to glucose regulation, to reducing neuroinflammation and promoting nerve growth10, the GLP-1 mechanisms underscores the intricate interconnectedness of our biological systems.
The role of amylin in the biology of obesity
Amylin is a hormone co-secreted with insulin by the pancreas in response to food intake and slows gastric emptying, which helps to balance the rate glucose enters the blood stream. This prevents spikes in blood glucose levels, thereby complementing the action of insulin to maintain metabolic balance. Amylin is known to create a feeling of fullness and reduce food intake.11
Amylin also inhibits the secretion of glucagon, a hormone that raises blood glucose levels, providing another layer of control over blood sugar. This multifaceted action makes amylin an essential component of the body's natural glucose regulation process.11,12
Amylin is emerging as an important puzzle piece in unraveling the complexity of adiposity. This hormone connects how the pancreas regulates blood sugar, how the brain signals fullness, and even how organs like the liver process nutrients. By revealing these overlapping systems, we are increasingly showing that obesity is a web of metabolic and neurological interactions.
A New Era of Innovation: Holistic Care, Informed by Science
At AstraZeneca, we are advancing our research to better understand the interplay between adipose tissue and different organ systems, with a focus on multi-targeted, holistic solutions. There remains a pressing need for next-generation therapeutic solutions that can play a role in addressing this growing epidemic and provide solutions that work for different patient needs and are based on the interconnections between obesity and overweight, across cardiovascular, renal, and metabolic systems.
At AstraZeneca, our goal is to lead innovation across cardiovascular, renal and metabolic diseases. By integrating cutting-edge science with a deep understanding of how these conditions and obesity or overweight are interconnected, we are committed to delivering transformative solutions that address the full spectrum of patient needs.
