Journal
PSYCHONEUROENDOCRINOLOGY
Volume 110, Issue -, Pages -Publisher
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.psyneuen.2019.104418
Keywords
Adipocyte CB1; Obesity; Inflammation; Hippocampus; Memory; Neurogenesis
Categories
Funding
- 7th Framework Programme of European Union [HEALTH-F2-2008-223713]
- Instituto de Salud Carlos III (ISCIII), Ministerio de Economia y Competitividad (MINECO) - ERDF-EU [CP12/03109, PI16/01374, PI16/016981]
- Consejerfa de Economia, Innovacion, Ciencia y Empleo, Junta de Andalucia, ERDF-EU [CTS-8221]
- Consejerfa de Salud, Junta de Andalucia, ERDF-EU [SAS111224]
- National System of Health, ISCIII, ERDF-EU [CPII17/00024, CD16/00067]
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Background: Obesity is a low-grade inflammation condition that facilitates the development of numerous comorbidities and the dysregulation of brain homeostasis. Additionally, obesity also causes distinct behavioral alterations both in humans and rodents. Here, we investigated the effect of inducible genetic deletion of the cannabinoid type 1 receptor (CB1) in adipocytes (Ati-CB1-KO mice) on obesity-induced memory deficits, depressive-like behavior, neuroinflammation and adult neurogenesis. Methods: Behavioral, mRNA expression and immunohistochemical studies were performed in Ati-CB1-KO mice and corresponding wild-type controls under standard and high-fat diet. Results: Adipocyte-specific CB1 deletion reversed metabolic disturbances associated with an obese condition confirming previous studies. As compared to obese mice, the metabolic amelioration in Ati-CB1-KO mice was associated with an improvement of mood-related behavior and recognition memory, concomitantly with an increase in cell proliferation in metabolic relevant neurogenic niches in hippocampus and hypothalamus. In mutant mice, these changes were related to an increased neuronal maturation/survival in the hippocampus. Furthermore, CB1 deletion in adipocytes was sufficient to reduce obesity-induced inflammation, gliosis and apoptosis in a brain region-specific manner. Conclusions: Overall our data provide compelling evidence of the physiological relevance of the adipocyte-brain crosstalk where adipocyte-specific CB1 influences obesity-related cognitive deficits and depression-like behavior, concomitantly with brain remodeling, such as adult neurogenesis and neuroinflammation in the hippocampus and hypothalamus.
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