Hypothalamic 2-arachidonoylglycerol regulates multistage process of high-fat diet preferences

• Published in: PloS one 2012-06, Vol.7 (6), p.e38609-e38609
• Main Authors: Higuchi, Sei, Irie, Keiichi, Yamaguchi, Ryuji, Katsuki, Mai, Araki, Maiko, Ohji, Makiko, Hayakawa, Kazuhide, Mishima, Shohei, Akitake, Yoshiharu, Matsuyama, Kiyoshi, Mishima, Kenji, Mishima, Kenichi, Iwasaki, Katsunori, Fujiwara, Michihiro
• Format: Article
• Language: English
• Subjects: 2-Arachidonoylglycerol; Aging; Agriculture; Animal Feed; Animals; Appetite; Arachidonic Acids - chemistry; Astrocytes; Astrocytes - metabolism; Behavior, Animal; Biology; Brain; Cannabinoids; Chemical engineering; Choice Behavior; Chromatography; Conditioning; Consumption; Developmental stages; Diet; Dietary Fats; Dopamine; Endocannabinoid system; Endocannabinoids - chemistry; Food Preferences; Gas chromatography; Gas Chromatography-Mass Spectrometry - methods; Glial fibrillary acidic protein; Glial Fibrillary Acidic Protein - metabolism; Glycerides - chemistry; High fat diet; Hypothalamus; Hypothalamus - metabolism; Immunoblotting - methods; Male; Mass spectrometry; Mass spectroscopy; Medicine; Metabolism; Mice; Mice, Inbred ICR; Models, Statistical; Neurons; Pharmaceutical sciences; Place preference conditioning; Preferences; Receptor, Cannabinoid, CB1 - metabolism; Reinforcement; Reward; Rodents; Scientific imaging; Social and Behavioral Sciences; Time Factors; Trends; Veterinary Science; Western blotting
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0038609

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. 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. 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. 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.