Many molecules are involved in the regulation of feeding behavior, and they and their receptors are located in the brain hypothalamus and adipocytes. On the basis of evidence suggesting an association between the brain and adipose tissue, we propose the concept of the brain-adipose axis. This model consists of (l) the expression of endogenous molecules and/or their receptors in the hypothalamus and peripheral adipose tissue, (2) the function of these molecules as appetite regulators in the brain, (3) their existence in the general circulation as secreted proteins and (4) the physiological affects of these molecules on fat cell size and number. These molecules can be divided into two anorexigenic and orexigenic classes. In adipose tissue, all orexigenic molecules possess adipogenic activity, and almost all anorexigenic molecules suppress fat cell proliferation. Although the manner, in which they present in the circulating blood connect the brain and peripheral adipocytes, remains to be well-organized, these observations suggest the positive feedback axis affecting molecules in the hypothalamus and adipose tissue. Analysis of the disturbance and dysregulation of this axis might promote the development of new anti-obesity drugs useful in treating the metabolic syndrome.