Hypothalamic endocannabinoids inversely correlate with the development of diet-induced obesity in male and female mice

Autor: Anna Fosch, Laura Herrero, Rosalía Rodríguez-Rodríguez, Dolors Serra, Cristina Miralpeix, Núria Casals, Miguel Baena, Josefina Casas
Přispěvatelé: Ministerio de Economía y Competitividad (España), Universitat de Barcelona
Jazyk: angličtina
Rok vydání: 2019
Předmět:
0301 basic medicine
Male
Obesidad
Adipose tissue
Ensayos clínicos
030204 cardiovascular system & hematology
Biochemistry
Energy homeostasis
Mice
0302 clinical medicine
Endocrinology
Clinical trials
Adipose Tissue
Brown
Brown adipose tissue
Research Articles
Sex Characteristics
Hipotàlem
Leptin
Endocannabinoid system
medicine.anatomical_structure
Hypothalamus
Obesitat
Female
616.4 - Patologia del sistema limfàtic
òrgans hematopoètics
endocrins
medicine.medical_specialty
Tejido adiposo
Polyunsaturated Alkamides
QD415-436
Arachidonic Acids
Biology
Diet
High-Fat
Diet and dietary lipids
Glycerides
03 medical and health sciences
Internal medicine
medicine
Dimorfisme sexual en els animals
Sexual dimorphism (Animals)
Animals
Obesity
Adipose tissues
brown adipose tissue
Cell Biology
medicine.disease
Teixit adipós
030104 developmental biology
Brain lipids
sexual dimorphism
Thermogenesis
Hipotálamo
Assaigs clínics
Endocannabinoids
Zdroj: Journal of Lipid Research
Dipòsit Digital de la UB
Universidad de Barcelona
Recercat. Dipósit de la Recerca de Catalunya
instname
Digital.CSIC. Repositorio Institucional del CSIC
Journal of Lipid Research, Vol 60, Iss 7, Pp 1260-1269 (2019)
Popis: 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 male. 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. Intracerebroventricular 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.
We thank Dr. Gemma Fabriàs and Alexandre García from the Research Unit of BioActive Molecules (Institut de Química Avançada de Catalunya, IQAC) for their technical assistance in the analysis of eCB levels. This work was supported by the Ministerio de Economía, Industria y Competitividad (MINECO), Agencia Estatal de Investigación (AEI) and Fondo Europeo de Downloaded from www.jlr.org by guest, on June 3, 2019 Desarrollo Regional (FEDER) (Grants SAF2014-52223-C2-2-R to NC, SAF2017-83813-C3-3-R to NC and RR-R, SAF2017-83813-C3-1-R to DS and LH), the Centro de Investigación Biomédica en Red Fisiopatología de la Obesidad y la Nutrición (CIBEROBN) (Grant CB06/03/0001 to DS), the Generalitat de Catalunya (2014SGR465 to DS and NC; 2017SGR152 to JC), Fundació La Marató de TV3 (Grant 87/C/2016 to DS and NC). AF is the recipient of a fellowship from the Agència de Gestió d’Ajuts Universitaris i de la Recerca (AGAUR) in Catalonia.
Databáze: OpenAIRE
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