Our Approach to Obesity Research

Our Approach to Obesity Research

At Orexigen, we are committed to providing new and innovative treatment options for the millions of people struggling with obesity and weight. Losing weight and keeping it off is difficult. Comprehensive weight loss management programs consisting of diet, exercise, behavior modification counseling, and medications have been shown to help people lose weight and keep it off, which may lead to improved overall health and wellness.

Our research at Orexigen focuses on two regions in the brain: the hypothalamus and the dopamine reward system. One important role of the hypothalamus is to regulate the body’s appetite (energy intake) and metabolism (energy expenditure). The dopamine reward system interacts with the hypothalamus to regulate and control eating behaviors and cravings.

Obesity results from an energy imbalance caused by the consumption of more calories than the body is able to burn over an extended period. The cause of this imbalance is complex and is influenced by the convergence of various environmental, behavioral and genetic factors. However, at the crux of obesity is the role of the brain and CNS in regulating body weight.

The brain is the master regulator of the body, affecting every fundamental function including decisions about what we eat, when we eat, how much we eat and how much energy we burn. Over time, the brain of an obese person becomes insensitive to the “stop” signals from the body, resulting in continued consumption of food beyond the body’s energy needs. When an overweight person starts to lose weight, the brain senses the reduction in weight and causes the body to fight back by increasing hunger and food the rewarding properties of food, while also slowing down metabolism. Together, these processes combine to increase food intake and decrease energy expenditure, thereby leading to weight regain. Thus, many interventions for weight loss may be successful in the short term, but results are typically difficult to maintain.

Two basic opposing neuronal populations in the hypothalamus work through the melanocortin 4 receptor (MC-4) to maintain the body’s weight at a constant level. Activation of the proopiomelanocortin or POMC neurons reduces appetite and increases energy output. Activation of the neuropeptide Y/Agouti-Related Peptide (NPY/AgRP) neurons increases hunger and conserves energy when energy reserves, stored as fat, are low. Additionally, food consumption triggers signals in reward areas of the brain, which may lead to overconsumption due to these reward signals.