Obesity is characterized by an excess storage of body fat and promotes the risk for complex disease traits such as diabetes mellitus and cardiovascular diseases. The obesity prevalence in Europe is rising and meanwhile ranges from 10 to 20% in men and 15-25% in women. Body fat accumulation occurs in states of positive energy balance and is favored by interactions among environmental, psychosocial and genetic factors. Energy balance is regulated by a complex neuronal network of anorexigenic and orexigenic neurons which integrates peripheral and central hormonal and neuronal signals relaying information on the metabolic status of organs and tissues in the body. A key component of this network is the central melanocortin pathway in the hypothalamus that elicits metabolic and behavioral adaptations for the maintenance of energy homeostasis. Genetic defects in this system cause obesity in mice and humans. In this review we emphasize mouse models with spontaneous natural mutations as well as targeted mutations that contributed to our understanding of the central melanocortin system function in the control of energy balance.Keywords Energy balance Ă Melanocortin Ă Mouse models Ă Obesity
ObesityObesity is characterized by an excess of body fat and promotes the risk for the development of complex disease traits like diabetes mellitus, cardiovascular dysfunctions, certain forms of cancer and sleep-breathing disorders. World Health Organization defines obesity by a body mass index (BMI) larger than 30 kg/m 2 , whereas overweight is defined by a BMI between 25 and 29.9 kg/m 2 . The obesity prevalence in Europe ranges from 10 to 20% in men and 15-25% in woman. Body fat mass is influenced by interactions among environmental, psychosocial and genetic factors. Promotion of positive energy balance causes obesity in humans as well as in mice (for review see [4,20,33]).The mouse has proven itself as an excellent model for investigations on human diseases as development and genetics are similar in mouse and man. Furthermore, genetic engineering techniques in the mouse became wellestablished and reliable tools in the last two decades. In this mini review we highlight different mouse models which have been instrumental to study body weight regulation and the development of obesity.The melanocortin system and its role in the regulation of energy homeostasisThe lipostatic hypothesis for the control of food intake postulates that adipose tissue produces a hormone in proportion to the amount of fat and acts on the central nervous system to reduce feeding and increase energy expenditure for maintaining energy balance [32].