Graduated from Faculty of Medicine, Kyushu University, 1962 and Doctoral Course, 1967, the author was Professor of Internal Medicine, School of Medicine, Oita Medical University 1992-2002 and given Emeritus Professor from the University at the retirement. Invited as a professor to Faculty of Nutritional Sciences, Nakamura Gakuen University 2002. Mechanisms of energy intake and expenditure regulated by the brain have been the main theme challenged by the author. The following particular research projects have been investigated: 1) Animal models with distorted circadian rhythms in ingestive behavior and general activity including advanced or delayed shift and/or disappearance of the rhythm were produced and analyzed pathophysiologically. 2) Extraction and identification of tissue- and blood-born substances which regulate appetite and energy expenditure. Novel short-chain polyhydroxymonocarboxylates and glucose analogues were precipitated from the brain, cerebrospinal fluid and blood. Their structural characteristics were clarified in relation to the pathophysiological functions. 3) Brain histamine neurons were found to involve in homeostatic regulation of energy metabolism, i.e., (a) ingestive behavior through H1- and H3-receptors in the ventromedial and the paraventricular nuclei in the hypothalamus, (b) peripheral glucose and lipid metabolism, (c) masticatory function, (d) thermoregulation, (e) circadian rhythms of ingestive and ambulatory behavior, and (f) metabolic balance under energy deficiency. Our recent topics in this project are that most of adipokines have close relation with regulatory metabolic functions driven by histamine neuron systems. Concentration of histamine in the cerebrospinal fluid increased predominantly in anorexia nervosa, but decreased contrary in obese patients. The author and his group have indicated that hypothalamic histamine neurons play an essential key role not only in homeostatic control of energy metabolism, but in development of the energy-imbalance at pathological states.