The Role of the Central Nervous System (CNS) in Obesity
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 people eat, when we eat, how much we eat and how much energy we burn. When an overweight person starts to lose weight, the brain causes the body to fight back by increasing hunger and slowing down metabolism, making it more difficult to burn calories and thereby counteracting weight loss. 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. 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 work through the melanocortin 4 receptor (MC-4) in concert to maintain the body’s weight at a constant level. Proopiomelanocortin or POMC neurons function to reduce appetite and increase energy output. Neuropeptide Y/Agouti-Related Peptide (NPY/AgRP) neurons increase hunger and conserve energy when energy reserves, stored as fat, are low.
The Orexigen Approach
Our lead product candidates, Contrave® (naltrexone SR/bupropion SR) and Empatic™ (zonisamide SR/bupropion SR), reflect our understanding of how the brain appears to regulate appetite and metabolism, as well as the mechanisms that come into play to limit weight loss over time.