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Orexin/hypocretin immunoreactivity in the lateral hypothalamus is reduced in genetically obese but not in diet-induced obese mice

View ORCID ProfileJ. Antonio González, Jochen H. M. Prehn
doi: https://doi.org/10.1101/145508
J. Antonio González
1Department of Physiology and Medical Physics, Royal College of Surgeons in Ireland, Dublin, Ireland.
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  • For correspondence: antonio.gonzalez@crick.ac.uk
Jochen H. M. Prehn
1Department of Physiology and Medical Physics, Royal College of Surgeons in Ireland, Dublin, Ireland.
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Abstract

The mechanisms that link diet and body weight are not fully understood. A diet high in fat often leads to obesity, and this in part is the consequence of diet-induced injury to specific hypothalamic nuclei. It has been suggested that a diet high in fat leads to cell loss in the lateral hypothalamus, which contains specific populations of neurones that are essential for regulating energy homoeostasis; however, we do not know which cell types are affected by the diet. We studied the possibility that high-fat diet leads to a reduction in orexin/hypocretin (O/H) and/or melanin-concentrating hormone (MCH) immunoreactivity in the lateral hypothalamus. We quantified immuno-labelled O/H and MCH cells in brain sections of mice fed a diet high in fat for up to 12 weeks starting at 4 weeks of age and found that this diet did not modify the number of O/H- or MCH-immunoreactive neurones. By contrast, there were fewer O/H- (but not MCH-) immunoreactive cells in geneticallyobese db/db mice compared to wild-type mice. Non-obese, heterozygous db/+ mice also had fewer O/H-immunoreactive cells. Differences in the number of O/H-immunoreactive cells were only a function of the db genotype but not of diet or body weight. Our findings show that the lateral hypothalamus is affected differently in genetic and in diet-induced obesity, and support the idea that hypothalamic neurones involved in energy balance regulation are not equally sensitive to the effects of diet.

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The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY 4.0 International license.
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Posted June 02, 2017.
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Orexin/hypocretin immunoreactivity in the lateral hypothalamus is reduced in genetically obese but not in diet-induced obese mice
J. Antonio González, Jochen H. M. Prehn
bioRxiv 145508; doi: https://doi.org/10.1101/145508
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Orexin/hypocretin immunoreactivity in the lateral hypothalamus is reduced in genetically obese but not in diet-induced obese mice
J. Antonio González, Jochen H. M. Prehn
bioRxiv 145508; doi: https://doi.org/10.1101/145508

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