Hypothalamic 2-arachidonoylglycerol regulates multistage process of high-fat diet preferences.
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.
Department of Neuropharmacology, Faculty of Pharmaceutical Sciences, Fukuoka University, Fukuoka, Japan.
Sei
S
Higuchi
Keiichi
K
Irie
Ryuji
R
Yamaguchi
Mai
M
Katsuki
Maiko
M
Araki
Makiko
M
Ohji
Kazuhide
K
Hayakawa
Shohei
S
Mishima
Yoshiharu
Y
Akitake
Kiyoshi
K
Matsuyama
Kenji
K
Mishima
Kenichi
K
Mishima
Katsunori
K
Iwasaki
Michihiro
M
Fujiwara
D000821:Animal Feed; D000818:Animals; D001095:Arachidonic Acids / Q000737:chemistry*; D001253:Astrocytes / Q000378:metabolism; D001522:Behavior, Animal; D002755:Choice Behavior; D004041:Dietary Fats; D063388:Endocannabinoids / Q000737:chemistry*; D005518:Food Preferences; D008401:Gas Chromatography-Mass Spectrometry / Q000379:methods; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism*; D005989:Glycerides / Q000737:chemistry*; D007031:Hypothalamus / Q000378:metabolism*; D015151:Immunoblotting / Q000379:methods; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D015233:Models, Statistical; D043884:Receptor, Cannabinoid, CB1 / Q000378:metabolism; D012201:Reward; D013997:Time Factors
D001095:Arachidonic Acids; D004041:Dietary Fats; D063388:Endocannabinoids; D005904:Glial Fibrillary Acidic Protein; D005989:Glycerides; D043884:Receptor, Cannabinoid, CB1; C094503:glyceryl 2-arachidonate