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. 2011 Oct 14:2:49.
doi: 10.3389/fendo.2011.00049. eCollection 2011.

Hypothalamic obesity in patients with craniopharyngioma: profound changes of several weight regulatory circuits

Christian L Roth  1
Affiliations

Hypothalamic obesity in patients with craniopharyngioma: profound changes of several weight regulatory circuits

Christian L Roth. Front Endocrinol (Lausanne). .

Abstract

One of the most striking examples of dysfunctional hypothalamic signaling of energy homeostasis is observed in patients with hypothalamic lesions leading to hypothalamic obesity (HO). This drastic condition is frequently seen in patients with craniopharyngioma (CP), an embryological tumor located in the hypothalamic and/or pituitary region, frequently causing not only hypopituitarism, but also leading to damage of medial hypothalamic nuclei due to the tumor and its treatment. HO syndrome in CP patients is characterized by fatigue, decreased physical activity, uncontrolled appetite, and morbid obesity, and is associated with insulin and leptin resistance. Mechanisms leading to the profoundly disturbed energy homeostasis are complex. This review summarizes different aspects of important clinical studies as well as data obtained in rodent studies. In addition a model is provided describing how medial hypothalamic lesion can interact simultaneously with several weight-regulating circuitries.

Keywords: autonomous nervous system; gut hormones; hyperphagia; hypothalamic lesion; morbid obesity; neuropeptides.

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Figures

Figure 1
Figure 1
Representative coronal (A), midsagittal brain MRI (B), and schematic overview (C,D) of a patient with hypothalamic obesity and hyperphagia following surgery for CP. Lesion affects the ARC, VMN, DMN, and the posterior part of the AHA, but not the LHA. DMN, dorsomedial nucleus; LHA, lateral hypothalamus; VMN, ventromedial nucleus; PVN, paraventricular nucleus; ARC, arcuate nucleus; AHA, anterior hypothalamic area.
Figure 2
Figure 2
Key regulators of energy homeostasis in the brain. Model of weight regulatory circuits and hypothalamic nuclei potentially affected by craniopharyngioma and surgery (gray area). The lesion of medial hypothalamic nuclei (ARC, VMN, DMN) typically does not involve the lateral hypothalamus (LHA) potentially leading to unbalanced expression and secretion of orexigens (MCH, orexigens A and B) by the LHA. Additionally the communication to (1) higher cortical brain areas and limbic system involved in food reward and eating behavior, (2) pituitary, and (3) hindbrain nuclei (AP, area postrema, NTS: solitary tract nucleus) affecting the autonomous nervous control of effectors in pancreas, liver, adipose tissue, GI tract, muscle, CV system might be affected as well. CRF, corticotrophin relasing factor; TRH, thyrotropin-releasing hormone; NPY, neuropeptide-Y; GABA, gamma aminobutyric acid; BDNF, brain-derived neurotrophic factor; POMC, proopiomelanocortin; AgRP, agouti-related peptide; CART, cocaine amphetamine regulated transcript; α-MSH, alpha-melanocyte stimulating hormone.
Figure 3
Figure 3
Hypothetical model of disturbed energy homeostasis in hypothalamic obesity.
Figure 4
Figure 4
Summary of metabolic and clinical findings involved in dysregulated energy balance in hypothalamic obesity.
See this image and copyright information in PMC

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