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Abstract
BackgroundIn 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.MethodsThe 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.ResultsConsumption 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.ConclusionsHigh 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.
Highlights
Subjects often choose to consume a high-fat diet (HFD) over other diets; this is called a HFD preference
Animals that had consumed a HFD for 14, 28 and 42 days exhibited higher 2-AG levels before the test compared with animals that had not consumed a HFD, regardless of whether they had undergone the Conditioned place preference (CPP) test
The levels of astrocytes were examined to evaluate the effects of HFD consumption on the hypothalamus using the anti-glial fibrillary acid protein (GFAP) antibody
Summary
Subjects often choose to consume a high-fat diet (HFD) over other diets; this is called a HFD preference. We reported that the brain levels of the endocannabinoid 2-arachidonoylglycerol (2-AG), which is a full agonist of cannabinoid 1 (CB1) receptors, are increased in mice with HFD preferences [14]. 2-AG may be intimately involved in the relationship between HFD preferences and the brain reward system. From these findings, in this study we hypothesized that 2AG may influence the hypothalamic reward system and the process of developing a HFD preference. 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. We hypothesized that increased 2-AG influences the hypothalamic reward system
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