Brain Ciliary Neurotrophic Factor (CNTF) and hypothalamic control of energy homeostasis

Obesity is a chronic, metabolic disease of complex and multiple causes leading to an imbalance between energy intake and output, and to the accumulation of large amounts of body fat. It is caused by inherited as well as acquired factors, including excessive food intake, sedentary lifestyle and unhealthy eating habits. During the past 20 years, obesity among adults has risen significantly with urbanization, economic development and market globalization. According to the World HealthOrganization (WHO) statements, more than one billion people worldwide are overweight or suffer from obesity, and the number of affected children has more than doubled since 1980 in the USA and Europe. In France, the latest data from Roche show that overweighting and obesity affect, respectively, more than 30% and 14.5% of adults (ObEpi-Roche, 2009). But far more worrying are the increasing and acceleration of this problem into developing countries and, based on current trends, it is predicted that the levels of obesity will continue to rise unless action is taken now (McLellan, 2002). The consequences of obesity for adults are well known. Obesity contributes to the development of many diseases, including diabetes, hypertension, dyslipidemia (for instance, high total cholesterol or high levels of triglycerides), stroke, cardiovascular disease, and some cancers (Abelson and Kennedy, 2004). As a result, the obesity epidemic has prompted important efforts to develop safe and potent therapies. However, currently approved drugs for obesity such as appetite suppressants have limited efficacy and act acutely, with patients rapidly regaining weight after the cessation of treatment. The neurocytokine ciliary neurotrophic factor (CNTF) seems to deviate from this paradigm since its administration to rodents or patients maintains lowered body weights several weeks after terminating treatment (Lambert et al., 2001).