Files
Document type
ArticleVersion
Published versionPublication date
All rights reserved
Please use this identifier to cite or link to this item: https://hdl.handle.net/2445/143720
Hypothalamic endocannabinoids inversely correlate with the development of diet-induced obesity in male and female mice
Journal Title
Director/Tutor
Journal ISSN
Volume Title
Related resource
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. Keywords: hypothalamus, sexual dimorphism, brown adipose tissue
Subject (English)
Citation
Citation
MIRALPEIX, Cristina, 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, num. 1260-1269. ISSN 0022-2275. [consulted: 20 of August of 2026]. Available at: https://hdl.handle.net/2445/143720