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 language | English |
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Pages (from-to) | 183-191 |
Number of pages | 9 |
Journal | Neuroscience |
Volume | 369 |
Early online date | 10 Nov 2017 |
DOIs | |
Publication status | Published - 15 Jan 2018 |
Bibliographical note
Work funded by a Marie Curie Intra-European Fellowship FP7-PEOPLE-2009-IEF Project number 255559 to J.A.G.). The authors declare no conflicts of interest.Keywords
- Journal Article
- melanin-concentrating hormone
- db/db mouse
- high-fat diet
- immunohistochemistry