1. Hypothalamic 2-Arachidonoylglycerol Regulates Multistage Process of High-Fat Diet Preferences
- Author
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Keiichi Irie, Kenichi Mishima, Michihiro Fujiwara, Sei Higuchi, Yoshiharu Akitake, Ryuji Yamaguchi, Kenji Mishima, Shohei Mishima, Katsunori Iwasaki, Makiko Ohji, Kazuhide Hayakawa, Kiyoshi Matsuyama, Maiko Araki, and Mai Katsuki
- Subjects
Male ,Time Factors ,Animal Nutrition ,Mouse ,medicine.medical_treatment ,2-Arachidonoylglycerol ,lcsh:Medicine ,Social and Behavioral Sciences ,Biochemistry ,Choice Behavior ,chemistry.chemical_compound ,Behavioral Neuroscience ,Mice ,Receptor, Cannabinoid, CB1 ,Psychology ,Receptor ,lcsh:Science ,Animal Management ,Mice, Inbred ICR ,Multidisciplinary ,Glial fibrillary acidic protein ,Animal Behavior ,Behavior, Animal ,digestive, oral, and skin physiology ,food and beverages ,Agriculture ,Neurochemistry ,Animal Models ,Endocannabinoid system ,Hypothalamus ,Medicine ,lipids (amino acids, peptides, and proteins) ,Public Health ,Neurochemicals ,Behavioral and Social Aspects of Health ,psychological phenomena and processes ,hormones, hormone substitutes, and hormone antagonists ,Research Article ,medicine.medical_specialty ,Immunoblotting ,Arachidonic Acids ,Biology ,Gas Chromatography-Mass Spectrometry ,Glycerides ,Reward system ,Food Preferences ,Model Organisms ,Reward ,Internal medicine ,Glial Fibrillary Acidic Protein ,medicine ,Animals ,Nutrition ,Behavior ,Models, Statistical ,lcsh:R ,nutritional and metabolic diseases ,Animal Feed ,Dietary Fats ,Endocrinology ,chemistry ,Astrocytes ,biology.protein ,lcsh:Q ,Veterinary Science ,Cannabinoid ,Attention (Behavior) ,Zoology ,Immunostaining ,Endocannabinoids ,Neuroscience - Abstract
Background In this study, we examined alterations in the hypothalamic reward system related to high-fat diet (HFD) preferences. We previously reported that hypothalamic 2-arachidonoylglycerol (2-AG) and glial fibrillary acid protein (GFAP) were increased after conditioning to the rewarding properties of a HFD. Here, we hypothesized that increased 2-AG influences the hypothalamic reward system. Methods The conditioned place preference test (CPP test) was used to evaluate HFD preferences. Hypothalamic 2-AG was quantified by gas chromatography-mass spectrometry. The expression of GFAP was examined by immunostaining and western blotting. Results Consumption of a HFD over either 3 or 7 days increased HFD preferences and transiently increased hypothalamic 2-AG levels. HFD consumption over 14 days similarly increased HFD preferences but elicited a long-lasting increase in hypothalamic 2-AG and GFAP levels. The cannabinoid 1 receptor antagonist O-2050 reduced preferences for HFDs after 3, 7, or 14 days of HFD consumption and reduced expression of GFAP after 14 days of HFD consumption. The astrocyte metabolic inhibitor Fluorocitrate blocked HFD preferences after 14 days of HFD consumption. Conclusions High levels of 2-AG appear to induce HFD preferences, and activate hypothalamic astrocytes via the cannabinoid system. We propose that there may be two distinct stages in the development of HFD preferences. The induction stage involves a transient increase in 2-AG, whereas the maintenance stage involves a long lasting increase in 2-AG levels and activation of astrocytes. Accordingly, hypothalamic 2-AG may influence the development of HFD preferences.
- Published
- 2012