The human hypothalamus in metabolic and episodic disorders

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Publisher Summary

This chapter focuses on the role of human hypothalamus in metabolic and epidemic disorders. Various clinical observations illustrate the importance of hypothalamic mechanisms for governing satiety and hunger. In Diencephalic syndrome or hypothalamo-optic-pathway glioma, emaciation of the entire body is found in infancy and childhood. Lesions in the ventromedial hypothalamic area cause increased appetite and obesity, whereas tumors in the lateral hypothalamic area (LHA) may cause anorexia. Additionally, hypercortisolism in Cushing's syndrome or due to corticosteroid therapy may cause obesity accompanied by depression, hypertension, and circadian disturbances. Uncommon, intractable hypothalamic obesity syndrome occurs after cranial insults, which is often coupled with other hypothalamo–pituitary disturbances that may exacerbate obesity, such as growth hormone deficiency or hypothyroidism. In disorders of eating and metabolism, there is frequent hypothalamic comorbidity in terms of mood, sleep and rhythm disorders due to the intense hypothalamic interconnectivity and integrative mechanisms. These symptoms often occur in an episodic way and generally have a different prevalence for the sexes. Circadian and seasonal fluctuations and sleep disorders may also point to the involvement of the suprachiasmatic nucleus (SCN) in symptom expression.

Section snippets

The hypothalamus in disorders of eating and metabolism

Obesity is one of the most pressing health problems in the Western world. It is, among other things, responsible for 65–75% of essential hypertension, diabetes mellitus and cardiovascular problems (Hall et al., 2001). This epidemic is in need of therapeutics, but only limited progress has been made as far as the pharmacotherapy of this condition is concerned (Van der Ploeg, 2000; Clapham et al., 2001). The etiologies of eating disorders, such as anorexia nervosa, bulimia nervosa and obesity,

Bulimia nervosa

Bulimia nervosa is characterized by recurrent episodes of binge eating, at least twice a week for a period of 3 months. Large amounts of food are eaten in a discrete period and patients have the feeling that they cannot stop. There is recurrent inappropriate compensatory behavior to prevent weight gain such as vomiting or excessive exercise (DSM IV). Although all the signs and symptoms of this disorder point to a hypothalamic process, no postmortem studies have been performed so far due to a

Development of the fetal hypothalamus, birth and programing of metabolism

The coupling of the various hypothalamic systems may not only have its physiological basis in adult adaptive mechanisms (e.g. in the coupling of starvation and anovulation and the fall/winter increase in eating behavior and body weight to accumulate a backup for the winter), but may also already be involved in fetal hypothalamic adaptive mechanisms (e.g. programing of body weight) and in the fetal involvement in the process of birth. The human fetal hypothalamus seems to be quite mature at the

Summary and conclusions

The crucial role of the human hypothalamus in eating and metabolic disorders has already been known for a long time from studies on patients with hypothalamic tumors or other lesions causing a spectrum of disorders that run from the ventromedial hypothalamic syndrome with hyperphagia and obesity to anorexia. Such lesions, however, give only information on the level of large brain structures. Recently, functional scanning and molecular genetic studies of mutations and polymorphisms affecting the

Acknowledgment

The author would like to thank Ms. W.T.P. Verweij and Ms. T. Eikelboom for their secretarial support, and Dr. J. Kruisbrink for providing the references.

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