The human hypothalamus in metabolic and episodic disorders
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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Hypothalamus and neuroendocrine diseases: The use of human-induced pluripotent stem cells for disease modeling
2021, Handbook of Clinical NeurologyCitation Excerpt :The hypothalamus is the central key regulator of food intake and energy expenditure and receives neuronal and circulatory input from the entire body including the CNS and periphery, and the main regions of the hypothalamus involved in the control of food intake and energy balance are the anterior and tuberal regions. Among several causes, dysfunctions of the hypothalamic neurogenesis can lead to several endocrine diseases such as obesity (hypothalamic obesity disorder) (Swaab, 2006; Maggi et al., 2014; see Chapter 8 in Volume 179). The mutation of the MC4R gene is the most common known monogenic form of obesity in humans (Thaler et al., 2013); however, more than 200 genetic variants have been identified linked to obesity, and a holistic understanding remains elusive where multiple genetic variants are common and play small effects to contribute to obesity susceptibility (Rajamani et al., 2018).
Central nervous system tumours among adolescents and young adults (15–39 years) in Southern and Eastern Europe: Registration improvements reveal higher incidence rates compared to the US
2017, European Journal of CancerCitation Excerpt :Expanding an already established collaboration on childhood malignancies [14–16] and following approval of a pre-defined common protocol, 14 cancer registries operating in 12 SEE countries (Belarus, Croatia, Cyprus, Malta, Montenegro, Greater Poland, Portugal Central, Portugal North, Romania-Cluj, Romania-Iasi, Serbia Central, Slovenia, Turkey-Izmir and Ukraine) provided data on incident primary CNS tumours diagnosed among AYAs (15–39 years) with variable registration periods extending from 1990 to 2014. The definition of the AYAs age spectrum has been based on the guidelines by the National Cancer Institute [11]. For comparability reasons, data on AYAs CNS tumour cases were additionally extracted from the SEER database covering 18 registries in the US [13,17].
MRI atlas of the human hypothalamus
2012, NeuroImageCitation Excerpt :The wide range of tasks controlled by a very small part of the brain makes the hypothalamic region particularly prone to involvement in several disorders. Significantly, the human hypothalamus has been implicated in homeostatic and developmental disorders, including sudden infant death syndrome, Prader–Willi syndrome, disturbance of biological rhythms, infertility, and diabetes and obesity (Gordon, 2010; Kalsbeek et al., 2010; Swaab, 2006), as well as in episodic brain disorders such as migraine, depression, narcolepsy and cluster headaches (Overeem et al., 2002; Swaab, 2006). Besides these, the hypothalamus is subject to many different types of lesions, including developmental abnormalities (Rathke's cleft cysts, hamartoma), primary tumors of the central nervous system (hypothalamic glioma), systemic tumors affecting the brain, inflammatory and granulomatous diseases (sarcoidosis) and lesions arising from the surrounding structures (Loes et al., 1991; Saleem et al., 2007).
Hypothalamic volume and asymmetry in the pediatric population: a retrospective MRI study
2022, Brain Structure and FunctionGeneration of neuropeptidergic hypothalamic neurons from human pluripotent stem cells
2015, Development (Cambridge)