Hypothalamic endocannabinoids inversely correlate with the development of diet-induced obesity in male and female mice
Journal of Lipid Research. 2019-07-01; 60(7): 1260-1269
DOI: 10.1194/jlr.M092742
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Miralpeix C(1), Fosch A(1), Casas J(2)(3), Baena M(1), Herrero L(4)(5), Serra D(4)(5), Rodríguez-Rodríguez R(6), Casals N(6)(4).
Author information:
(1)Basic Sciences Department, Faculty of Medicine and Health Sciences Universitat
Internacional de Catalunya, 08195 Sant Cugat del Vallès, Spain.
(2)Department on Biomedical Chemistry, Research Unit of BioActive Molecules
Institut de Química Avançada de Catalunya, 08034 Barcelona, Spain.
(3)Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y
Digestivas Instituto de Salud Carlos III, E-28029 Madrid, Spain.
(4)Centro de Investigación Biomédica en Red de Fisiopatología de la Obesidad y la
Nutrición, Instituto de Salud Carlos III, E-28029 Madrid, Spain.
(5)Department of Biochemistry and Physiology, School of Pharmacy Institut de
Biomedicina de la Universitat de Barcelona, Universitat de Barcelona, E-08028
Barcelona, Spain.
(6)Basic Sciences Department, Faculty of Medicine and Health Sciences Universitat
Internacional de Catalunya, 08195 Sant Cugat del Vallès, Spain
.
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.
Copyright © 2019 Miralpeix et al. Published by The American Society for
Biochemistry and Molecular Biology, Inc.