Orexin-A/hypocretin-1 Immunoreactivity in the Lateral Hypothalamus is Reduced in Genetically Obese but not in Diet-induced Obese Mice. (15th January 2018)

• Record Type: Journal Article
• Authors: González, J. Antonio; Prehn, Jochen H.M.
• Is Part Of: Neuroscience. Volume 369(2018)
• Page Start: 183
• Page End: 191
• Publication Date: 2018-01-15
• Subjects: Hcrt1 hypocretin-1 (orexin-A) -- HFD high-fat diet -- Ir immunoreactive -- MCH melanin-concentrating hormone; melanin-concentrating hormone -- db/db mouse -- high-fat diet -- immunohistochemistry; Neurochemistry -- Periodicals; Neurophysiology -- Periodicals; Neurology -- Periodicals; Neurochimie -- Périodiques; Neurophysiologie -- Périodiques; Neurochemistry; Neurophysiology; Electronic journals; Periodicals; Electronic journals; 612.8
• DOI: 10.1016/j.neuroscience.2017.11.009
• Languages: English
• ISSNs: 0306-4522

Abstract

Highlights: A diet high in fat does not change the number of orexin-A/hypocretin-1 neurons. Melanin-concentrating hormone cell counts are likewise unaffected by high-fat diet. Genetically obese db/db mice have fewer hypocretin-1 cells than wild-type mice. Hypocretin-1 cell counts are related to the db genotype but not diet or body weight. 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.