Orexin-A/hypocretin-1 Immunoreactivity in the Lateral Hypothalamus is Reduced in Genetically Obese but not in Diet-induced Obese Mice

J Antonio González, Jochen H M Prehn

Research output: Contribution to journalArticle

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 neurons 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-A/hypocretin-1 (Hcrt1) and/or melanin-concentrating hormone (MCH) immunoreactivity in the lateral hypothalamus. We quantified immuno-labeled Hcrt1 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 Hcrt1- or MCH-immunoreactive neurons. By contrast, there were fewer Hcrt1- (but not MCH-) immunoreactive cells in genetically obese db/db mice compared to wild-type mice. Non-obese, heterozygous db/+ mice also had fewer Hcrt1-immunoreactive cells. Differences in the number of Hcrt1-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 the db genotype and in diet-induced obesity, and support the idea that not all hypothalamic neurons involved in energy balance regulation are sensitive to the effects of diet.

Original languageEnglish
Pages (from-to)183-191
Number of pages9
JournalNeuroscience
Volume369
Early online date10 Nov 2017
DOIs
Publication statusPublished - 15 Jan 2018

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Lateral Hypothalamic Area
Obese Mice
Diet
High Fat Diet
Neurons
Obesity
Genotype
Body Weight
Orexins
Homeostasis
melanin-concentrating hormone
Wounds and Injuries
Brain

Keywords

  • Journal Article
  • melanin-concentrating hormone
  • db/db mouse
  • high-fat diet
  • immunohistochemistry

Cite this

Orexin-A/hypocretin-1 Immunoreactivity in the Lateral Hypothalamus is Reduced in Genetically Obese but not in Diet-induced Obese Mice. / González, J Antonio; Prehn, Jochen H M.

In: Neuroscience, Vol. 369, 15.01.2018, p. 183-191.

Research output: Contribution to journalArticle

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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 neurons 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-A/hypocretin-1 (Hcrt1) and/or melanin-concentrating hormone (MCH) immunoreactivity in the lateral hypothalamus. We quantified immuno-labeled Hcrt1 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 Hcrt1- or MCH-immunoreactive neurons. By contrast, there were fewer Hcrt1- (but not MCH-) immunoreactive cells in genetically obese db/db mice compared to wild-type mice. Non-obese, heterozygous db/+ mice also had fewer Hcrt1-immunoreactive cells. Differences in the number of Hcrt1-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 the db genotype and in diet-induced obesity, and support the idea that not all hypothalamic neurons involved in energy balance regulation are sensitive to the effects of diet.",
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