Obesity
The rapid increase in the prevalence of obesity, type 2 diabetes, and associated complications is now becoming a major global health problem. In 2001 almost 65% of the adult population in the United States was overweight (defined as having a body mass index (BMI) greater than 25 kg/m2), compared to 56% seen in 1994 (National Health and Nutrition examination Survey: NHANES). Even the prevalence of obesity in children and adolescents rose from 11 to 15% during this time. If weight gain continues at the present rate, the obesity rate in 2008 will be 39% in the US. Since worldwide, more than one billion adults are overweight and over 300 million are obese, the World Health Organization (WHO) has declared overweight as one of the top five risk conditions in developed nations. Severe obesity defined as having a BMI of 40kg/m 2 is associated with a 90% risk of diabetes (in the USA, 1 in 5 adults shows a pathologically decreased insulin sensitivity) making obesity the predominant cause of type 2 diabetes. Obesity is strongly linked to chronic diseases such as cardiovascular disease or some types of cancer, and is associated with increased prevalence of psychological disorders, such as depression [1–8]. To successfully fight obesity, we must analyze why dieting is not effective. The brain interprets energy restriction as a threat to survival, especially once a chronically overweight state has been established. To maintain body composition and defend achieved energy stores, neuroendocrine networks reduce energy utilization in response to decreased caloric intake. Subjects feel cold, lethargic and depressed, and are facing a strong orexigenic drive to that it is ultimately impossible difficult to resist. To cure obesity, researchers must find a way to chronically adjust the control of body composition and metabolic homeostasis based on a ‘blue-print’ of regulatory pathways regulating energy balance that includes their individual functional relevance as well as their connectivity and interaction patterns. Some of these are active in the periphery exclusively, meaning that they have no apparent effect onto the central regulation of energy homeostasis. These include the role of several transcription factors in peripheral tissues including white fat, liver and skeletal muscle. Conversely, the observation that the brain plays a critical role in the control of energy homeostasis may be explained by the fact that balancing energy metabolism represents a physiological
process with an evolutionary essential character. Central nervous circuits sense and integrate peripheral metabolic, endocrine and neuronal signals reflecting current energy status, to then orchestrate a modulating influence on both behavioral patterns and peripheral metabolic processes according to acute and chronic requirements [9, 10].
The rapid increase in the prevalence of obesity, type 2 diabetes, and associated complications is now becoming a major global health problem. In 2001 almost 65% of the adult population in the United States was overweight (defined as having a body mass index (BMI) greater than 25 kg/m2), compared to 56% seen in 1994 (National Health and Nutrition examination Survey: NHANES). Even the prevalence of obesity in children and adolescents rose from 11 to 15% during this time. If weight gain continues at the present rate, the obesity rate in 2008 will be 39% in the US. Since worldwide, more than one billion adults are overweight and over 300 million are obese, the World Health Organization (WHO) has declared overweight as one of the top five risk conditions in developed nations. Severe obesity defined as having a BMI of 40kg/m 2 is associated with a 90% risk of diabetes (in the USA, 1 in 5 adults shows a pathologically decreased insulin sensitivity) making obesity the predominant cause of type 2 diabetes. Obesity is strongly linked to chronic diseases such as cardiovascular disease or some types of cancer, and is associated with increased prevalence of psychological disorders, such as depression [1–8]. To successfully fight obesity, we must analyze why dieting is not effective. The brain interprets energy restriction as a threat to survival, especially once a chronically overweight state has been established. To maintain body composition and defend achieved energy stores, neuroendocrine networks reduce energy utilization in response to decreased caloric intake. Subjects feel cold, lethargic and depressed, and are facing a strong orexigenic drive to that it is ultimately impossible difficult to resist. To cure obesity, researchers must find a way to chronically adjust the control of body composition and metabolic homeostasis based on a ‘blue-print’ of regulatory pathways regulating energy balance that includes their individual functional relevance as well as their connectivity and interaction patterns. Some of these are active in the periphery exclusively, meaning that they have no apparent effect onto the central regulation of energy homeostasis. These include the role of several transcription factors in peripheral tissues including white fat, liver and skeletal muscle. Conversely, the observation that the brain plays a critical role in the control of energy homeostasis may be explained by the fact that balancing energy metabolism represents a physiological
process with an evolutionary essential character. Central nervous circuits sense and integrate peripheral metabolic, endocrine and neuronal signals reflecting current energy status, to then orchestrate a modulating influence on both behavioral patterns and peripheral metabolic processes according to acute and chronic requirements [9, 10].
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