Hypothalamic endocannabinoids inversely correlate with the development of diet-induced obesity in male and female mice
Author
Miralpeix Monclús, Cristina
Fosch, Anna
Casas, Josefina
Baena, Miguel
Herrero Rodríguez, Laura
Serra, Dolors
Rodríguez-Rodríguez, Rosalía
Casals i Farré, Núria
Publication date
2019-07ISSN
0022-2275
Abstract
The endocannabinoid (eCB) system regulates energy homeostasis and is linked to obesity development. However, the exact dynamic and regulation of eCBs in the hypothalamus during obesity progression remain incompletely described and understood. Our study examined the time course of responses in two hypothalamic eCBs, 2-arachidonoylglycerol (2-AG) and arachidonoylethanolamine (AEA), in male and female mice during diet-induced obesity and explored the association of eCB levels with changes in brown adipose tissue (BAT) thermogenesis and body weight. We fed mice a high-fat diet (HFD), which induced a transient increase (substantial at 7 days) in hypothalamic eCBs, followed by a progressive decrease to basal levels with a long-term HFD. This transient rise at early stages of obesity is considered a physiologic compensatory response to BAT thermogenesis, which is activated by diet surplus. The eCB dynamic was sexually dimorphic: hypothalamic eCBs levels were higher in female mice, who became obese at later time points than males. The hypothalamic eCBs time course positively correlated with thermogenesis activation, but negatively matched body weight, leptinemia, and circulating eCB levels. Increased expression of eCB-synthetizing enzymes accompanied the transient hypothalamic eCB elevation. Icv injection of eCB did not promote BAT thermogenesis; however, administration of thermogenic molecules, such as central leptin or a peripheral β3-adrenoreceptor agonist, induced a significant increase in hypothalamic eCBs, suggesting a directional link from BAT thermogenesis to hypothalamic eCBs. This study contributes to the understanding of hypothalamic regulation of obesity.
Document Type
Article
Document version
Accepted version
Language
English
Subject (CDU)
616.4 - Patologia del sistema limfàtic, òrgans hematopoètics, endocrins
Keywords
Obesitat
Assaigs clínics
Teixit adipós
Hipotàlem
Obesidad
Ensayos clínicos
Tejido adiposo
Hipotálamo
Obesity
Clinical trials
Adipose tissue
Hypothalamus
Pages
10
Publisher
American Society for Biochemistry and Molecular Biology
Collection
60;
Is part of
Journal of Lipid Research
Citation
Miralpeix, Cristina; Fosch, Anna; Casas, Josefina [et al.]. Hypothalamic endocannabinoids inversely correlate with the development of diet-induced obesity in male and female mice. Journal of Lipid Research, 2019, vol. 60, p. 1260-1269. Disponible en: <https://www.jlr.org/content/60/7/1260>. Fecha de acceso: 1 feb. 2020. DOI: 10.1194/jlr.M092742
Grant agreement number
info:eu-repo/grantAgreement/ES/1PE/SAF2014-52223-C2-2-R
info:eu-repo/grantAgreement/ES/2PE/SAF2017-83813- C3-3-R
info:eu-repo/grantAgreement/ES/2PE/SAF2017-83813-C3-1-R
This item appears in the following Collection(s)
- Ciències de la Salut [712]
Rights
Final version open access under the terms of the Creative Commons CC-BY license (https://creativecommons.org/licenses/by/4.0/).
Except where otherwise noted, this item's license is described as https://creativecommons.org/licenses/by/4.0/