Approximately 2.1 billion people worldwide (about one-third of the population) are overweight or obese. Without interventions, it is estimated that almost half of the world's adults will be overweight or obese by 2030.
This is not just an unhealthy trend; deadly and expensive. Each year, approximately 2.8 million people die from causes attributable to a high body mass index. Economically, weight-related medical expenses cost approximately $2 trillion a year. Diabetes, which is closely linked to obesity, is also on the rise (killing approximately 1.5 million adults annually).
The causes of these complex metabolic disorders are not fully understood. Management is challenging and treatments challenging. UW Medicine researchers are looking beyond the digestive system and traditional knowledge of glucose metabolism to deepen our understanding. From the gut to critical neuronal centers in the brain. And eventually, discoveries are being made that could change how diabetes is treated and weight control.
Normal animals, including humans, "maintain" a certain body weight. Research conducted decades ago revealed that animals deprived of food may eat more than usual to achieve a process called hyperphagia. When body weight returns to normal, food intake normalizes.
Approximately one-third of people in the world are overweight or obese.
Schwartz and his team study how brain mechanisms manage food intake, energy balance, and glucose metabolism. They are pioneers in investigating how disorders in the system can lead to obesity and diabetes. Twenty years of research to arrange puzzle pieces is now evolving into findings that could lead to the development of paradigm-shifting treatments.
In the 1990s, Schwartz and his team asked a new question about the process of food intake: when an animal is starving, the body goes into hyperphagia. or how does the “catch” signal the brain to begin the act of eating? They thought this could be the signal for a drop in insulin that encourages hunger and eating to increase nutritional levels. Research elsewhere has shown that hunger stimulates a series of neuropeptide Y (NPY) neurons in the hypothalamus. He found that infusing the brains of fasting rats with insulin blocked the activation of NPY neurons. As a result, hungry mice significantly reduced their eating habits. "It was the first link in the chain between the action of an environmental hormone and a change in neural circuitry associated with feeding behavior," says Schwartz.
In the years when insulin was first used to treat diabetes, thousands of papers on its role in glucose metabolism were published. All tissues need glucose, and when blood sugar rises, insulin-sensitive tissues assume that the body clears some of this sugar and other tissues passively consume it. "It has been known for decades that insulin accounts for only about 50 percent of glucose metabolism. The other 50 percent is below the radar screen."
Another piece of the diabetes puzzle fell into place with the discovery of leptin in the 1990s. Leptin is a hormone produced by fat cells, and insulin – in addition to regulating sugar – regulates fat storage. In uncontrolled diabetes, the body loses its ability to produce insulin. As a result, insulin stops controlling fat storage, fat begins to break down, and leptin levels drop. In this case, no matter how much is eaten, insulin and leptin levels do not increase.
Researchers have found that administering leptin directly to the brain of diabetic animals returns blood sugar to normal.
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