The contribution of the hypothalamus and the limbic system in the regulation of the body weight
BALOYIANNIS S.J.

The regulation of the body weight involves a substantial number of peripheral and central mechanisms which control feeding behavior and energy expenditure. Among the various peripheral components leptin, which is produced by white adipose tissue, has a potent effect on feeding behavior and regulation of energy homeostasis. A substantial body of evidence suggests that leptin resistance is associated with obesity, since leptin plays a negative feedback signal role to the brain, causing an inhibition of food intake and provoking of loss of body weight. However, when the leptin levels decrease, feeding is disinhibited, in order to promote the maintenance of a relatively stable body weight. The effect of leptin is mediated through leptin receptors, which are localized in several nuclei in the ventrobasal hypothalamus, including the arcuate nucleus., which can affect various endocrine, autonomic and behavioral responses. Leptin also activates several regions, which seems to be involved in regulation of energy balance. Various neuronal networks in the hypothalamus are involved in central regulation of food intake and energy balance including ventromedial and lateral hypothalamic areas, which integrate sensory inputs from the viscera mediated through leptin, ghrelin, serotonin, dopamine and insulin, which mostly target hypothalamic nuclei, modulating energy control. In addition, leptin, ghrelin, insulin prolactin, estrogens, glucocorticoids restin and melanocortin system seems to play a very important role in controlling long term energy balance by food intake and energy depletion and expenditure. Neurons of the arcuate nucleus influenced by adiposity signals synthesizes neuropeptdie Y (NPY) which is a potent orexigenic and anabolic compound promoting hyperphagia and weight gain and reducing at the same time energy expenditure. Neurons containing NPY express both leptin and insulin receptors. Endogeneous levels of NPY in the arcuate nucleus increase normally during the night and decrease at daylight. The neurons of the arcuate nucleus of the hypothalamus are involved also in expressing proopiomelanocortin and cocain apmhetamin regulated transcript, which exert an anorectic effect. Anorectic effect is expressed, on the other hand, by the brain derived neurotrophic factor (BDNF), which in addition to promote synaptogenesis in the neuronal circuits, enhancing neuronal plasticity, affects also both glucose and lipid metabolism, reducing the body weight and food intake. Leptins increases BDNF transcripts, whereas fasting decreases them, suggesting that BDNF may act as regulatory component of leptin signalling system. Hypothalamic neurons retain synaptic plasticity throughout life, which is an important factor for the adaptation of the changeable feeding conditions and modulating the responses to body energy fuels. It is suggested that the amygdala modulates the hypothalamus with regards to regulation of food intake. Anatomic descriptions of amygdaloid lesions resulting in hyperphagia and obesity have been rather inconsistent and often contradictory. Numerous studies have examined the effects of amygdaloid lesions on food intake and body weight in rats, resulting in a similar collection of inconsistent and contradictory results. Central nucleus lesions have similarly been reported to result in either weight gain, aphagia or weight loss, or no change in food intake. Lesions of the posterodorsal amygdala may have the same effect with the lesions of the ventromedial hypothalamus inducing to hyperphagia and increase of body weight, mainly in females. Amygdala on the other hand, due to many afferent inputs from the olfactory bulb, may direct goal-oriented feeding behavior. The mesencephalic central tegmental area, which lies medial to the substantia nigra and ventral to the red nucleus, contributes substantially to the acquisition and learning of appetitive behavior. That area receives glutaminergic inputs from the prefrontal cortex, the lateral hippocampus and the stria terminalis. The brain stem plays an important role in autonomicaly organized nutrient supply by parasympathetic processes, through the dorsal nucleus of the vagus nerve. In addition it can terminate ingestion in aversive taste impulses and in mechanical or noxious properties of food, through the nucleus of the solitary tract and its central pathways. Ghrelin receptors are detected in the neurons of the nucleus of the tract solitarius of the medulla, which play an important role in cumulative food intake. In conclusion the central regulatory mechanisms of feeding behaviour and energy balance play a very important role in the maintenance of the stability of body weight. Any case of obesity necessitates a detailed investigation of the hypothalamic and pituitary glad function as well as a thorough assessment of the frontal and temporal lobe function in association with a methodical and systematic approaching of the neuropsychological profile of the patient.

Key words: Obesity, hypothalamus, amygdala, frontal lobe, temporal lobe, leptin, limbic system.