Adipocyte cannabinoid CB1 receptor deficiency alleviates high fat diet-induced memory deficit, depressive-like behavior, neuroinflammation and impairment in adult neurogenesis. (December 2019)

• Record Type: Journal Article
• Authors: Suárez, Juan; Rivera, Patricia; Aparisi Rey, Alejandro; Pérez-Martín, Margarita; Arrabal, Sergio; Rodríguez de Fonseca, Fernando; Ruiz de Azua, Inigo; Lutz, Beat
• Is Part Of: Psychoneuroendocrinology. Volume 110(2019)
• Publication Date: 2019-12
• Subjects: ARC arcuate nucleus of hypothalamus -- Ati-CB1-KO mice mice with conditional adipocyte-specific CB1 gene deletion induced by tamoxifen administration -- BrdU 5-bromo-2′-deoxyuridine -- CA1/3 field 1/3 of Cornu Ammonis -- CB1 cannabinoid type 1 receptor -- DIO diet-induced obesity -- DG dentate gyrus -- gcl granular cell layer -- FS forced swim test -- GFAP glial fibrillary acidic protein -- HFD high-fat diet -- Iba-1 ionized calcium-binding adapter molecule 1 -- IL-6 interleukin-6 -- ml molecular layer -- NeuN (Rbfox-3) RNA binding protein fox-1 homolog 3 -- NOR novel object recognition pcl polymorphic cell layer -- PVH paraventricular nucleus of hypothalamus -- SGZ subgranular zone of dentate gyrus -- SL-M stratum lacunosum-moleculare -- SO stratum oriens -- SP stratum pyramidale -- SR stratum radiatum -- SD standard diet -- VMH ventromedial nucleus of hypothalamus; Adipocyte CB1 -- Obesity -- Inflammation -- Hippocampus -- Memory -- Neurogenesis; Psychoneuroendocrinology -- Periodicals; Endocrinology -- Periodicals; Neurology -- Periodicals; Psychiatry -- Periodicals; Neuropsychoendocrinologie -- Périodiques; 616.8
• DOI: 10.1016/j.psyneuen.2019.104418
• Languages: English
• ISSNs: 0306-4530

Abstract

Highlights: Obesity induces low-grade inflammation and impairs cognition and emotions. CB1 deletion in adipocytes (Ati-CB1-KO) reverses obesity-induced metabolic disturbances. Adipocyte CB1 alleviates obesity-induced memory deficits and depressive-like behaviors. Adipocyte CB1 modulates neurogenesis and neuroinflammation in diet-induced obesity. Abstract: 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.