Hypothalamic regulation of food intake and clinical therapeutic applications

Simpson, Katherine Anne; Martin, Niamh; Bloom, Stephen R.

doi:10.1590/s0004-27302009000200002

Cited by 115 publications

(88 citation statements)

References 76 publications

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“…Like its near neighbor, the infundibular nucleus (also termed the arcuate nucleus of the hypothalamus), damage to the ventromedial nucleus of the hypothalamus has been linked to obesity syndromes in humans (Bray and Gallagher, 1975;Carmel, 1980;Lustig, 2002;Swaab, 2006). The infundibular nucleus plays a key role in relaying peripheral information to the metabolic and the reproductive brain (Dudas and Merchenthaler, 2006;Morton et al, 2006;Hill et al, 2008;Simpson et al, 2009). The ventromedial hypothalamus, which comprises both the ventromedial nucleus of the hypothalamus and the infundibular nucleus, might be an interesting site to target for body weight control in morbidly obese patients (Halpern et al, 2008).…”

Section: Discussionmentioning

confidence: 99%

MRI atlas of the human hypothalamus

et al. 2012

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Gaining new insights into the anatomy of the human hypothalamus is crucial for the development of new treatment strategies involving functional stereotactic neurosurgery. Here, using anatomical comparisons between histology and magnetic resonance images of the human hypothalamus in the coronal plane, we show that discrete gray and white hypothalamic structures are consistently identifiable by MRI. Macroscopic and microscopic images were used to precisely annotate the MRI sequences realized in the coronal plane in twenty healthy volunteers. MRI was performed on a 1.5T scanner, using a protocol including T1-weighted 3D fast field echo, T1-weighted inversionrecovery, turbo spin echo and T2-weighted 2D fast field echo imaging. For each gray matter structure as well as for white matter bundles, the different MRI sequences were analyzed in comparison to each other. The anterior commissure and the fornix were often identifiable, while the mammillothalamic tract was more difficult to spot. Qualitative analyses showed that MRI could also highlight finer structures such as the paraventricular nucleus, the ventromedial nucleus of the hypothalamus and the infundibular (arcuate) nucleus, brain nuclei that play key roles in the regulation of food intake and energy homeostasis. The posterior hypothalamic area, a target for deep brain stimulation in the treatment of cluster headaches, was readily identified, as was the lateral hypothalamic area, which similar to the aforementioned hypothalamic nuclei, could be a putative target for deep brain stimulation in the treatment of obesity. Finally, each of the identified structures was mapped to Montreal Neurological Institute (MNI) space. Please find enclosed the revised version of our manuscript "MRI atlas of the human hypothalamus" which we have modified according to the minor comment made by the reviewer#3.We appreciated the careful and incisive evaluation of our data made by the reviewers throughout the reviewing process. We hope that the manuscript is now in suitable form for publication in Neuroimage.  New insights into the anatomy of the human hypothalamus  Specific 1.5T MRI sequences approach histological resolution within the hypothalamus  White matter bundles within the hypothalamus can be identified using 1.5T MRI  Hypothalamic gray structures can be identified using 1.5T MRI *4. HighlightsWe have revised our manuscript to address the minor point raised by reviewer 3.In the "Data analysis" paragraph of the materials and methods section it now reads: "Structures were identified visually based on our knowledge of specific landmarks obtained from anatomical-histological cross sections and with reference to previously published atlases (Swaab et al., 1993;Koutcherov et al., 2000Koutcherov et al., , 2004Koutcherov et al., 2007;Mai et al., 2008); the landmarks used, such as the optic tract, the floor of the diencephalon, the third ventricle, and the fornix, were readily and reliably identifiable in MR scans." AbstractGaining new insights into the anatomy of the hu...

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Section: Discussionmentioning

confidence: 99%

MRI atlas of the human hypothalamus

et al. 2012

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“…The hypothalamus is the main brain region integrating peripheral metabolic information controlling the homeostatic regulation of appetite and food intake 70,71 . The hippocampus is a brain structure involved in learning and memory function and has recently been linked with food intake control 72 .…”

Section: Co-localization Of the 5-ht2c Receptor And Fluorescein-ghrelmentioning

confidence: 99%

Ghrelin’s Orexigenic Effect Is Modulated via a Serotonin 2C Receptor Interaction

Schellekens¹,

Francesco²,

Kandil³

et al. 2015

ACS Chem. Neurosci.

108

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Understanding the intricate pathways modulating appetite and subsequent food intake is of particular importance considering the rise in obesity incidence across the globe. The serotonergic system, specifically the 5-HT2C receptor, has shown to be of critical importance in the regulation of appetite and satiety. The GHS-R1a receptor is another key receptor wellknown for its role in the homeostatic control of food intake and energy balance. We recently showed compelling evidence for an interaction between the GHS-R1a receptor and the 5-HT2C receptor in an in vitro cell line system heterologously expressing both receptors. Here, we investigated this interaction further. First, we show that the GHS-R1a/5-HT2C dimer-induced attenuation of calcium signalling is not due to coupling to GαS, as no increase in cAMP signalling is observed. Next, flowcytometry fluorescence resonance energy transfer (fcFRET) is used to further demonstrate the direct interaction between the GHS-R1a receptor and 5-HT2C receptor.In addition, we demonstrate co-localized expression of the 5-HT2C and GHS-R1a receptor in cultured primary hypothalamic-and hippocampal rat neurons, supporting the biological relevance of a physiological interaction. Furthermore, we demonstrate that when 5-HT2C receptor signalling is blocked, ghrelin's orexigenic effect is potentiated in vivo. In contrast, the specific 5-HT2C receptor agonist lorcaserin, recently approved for the treatment of obesity, attenuates ghrelin-induced food intake. This underscores the biological significance of our in vitro findings of 5-HT2C receptor-mediated attenuation of GHS-R1a receptor activity. Together, this study demonstrates, for the first time, that the GHS-R1a/5-HT2C receptor interaction translates into biological significant modulation of ghrelin's orexigenic effect. This data highlights the potential development of a combined GHS-R1a and 5-HT2C receptor treatment strategy in weight management. ACS Paragon Plus Environment ACS Chemical Neuroscience 5

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“…The ARC in the hypothalamus is known to regulate food intake and energy expenditure [7,8]. It contains two populations of neurons that show an opposite effect to one another.…”

Section: Overview Of Neuroendocrine Regulation In Food Intakementioning

confidence: 99%

Role of gastrointestinal hormones in feeding behavior and obesity treatment

et al. 2015

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Food intake regulation is generally evaluated by many aspects consisting of complex mechanisms, including homeostatic regulatory mechanism, which is based on negative feedback, and hedonic regulatory mechanism, which is driven by a reward system. One important aspect of food intake regulation is the peripheral hormones that are secreted from the gastrointestinal tract. These hormones are secreted from enteroendocrine cells as feedback to nutrient and energy intake, and will communicate with the brain directly or via the vagus nerve. Gastrointestinal hormones are very crucial in maintaining a steady body weight, despite variations in nutrient intake and energy expenditure. In this review, we provide an overview of the regulation of feeding behavior by gut hormones, and its role in obesity treatments.

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Hypothalamic regulation of food intake and clinical therapeutic applications

Cited by 115 publications

References 76 publications

MRI atlas of the human hypothalamus

MRI atlas of the human hypothalamus

Ghrelin’s Orexigenic Effect Is Modulated via a Serotonin 2C Receptor Interaction

Role of gastrointestinal hormones in feeding behavior and obesity treatment

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