RESUMEN
The work reported here is an extension of our previous findings in which supercritical composite particles (SCP) of alpha lipoic acid (ALA) masked with hydrogenated colza oil (HCO) named as ALA/HCO/SCP were obtained by the modified particles from gas-saturated solutions (PGSS) process in supercritical carbon dioxide in order to obscure the unpleasant taste and odor of ALA. The masking effect on ALA/HCO/SCP was compared with the widely used mechano-chemically masked formulation of ALA and HCO named as MC-50F. In the present study, ALA/HCO/SCP particles were found to have a significant improvement in regard to bitterness, numbness, and smell compared to ALA bulk powders suggesting they were well coated. The pharmacokinetic parameters for ALA/HCO/SCP and ALA bulk powder gave similar values but were significantly different from those of MC-50F. The amount of ALA absorbed into the body, in the administered ALA/HCO/SCP, was comparable to that absorbed by ALA bulk powder, whereas about half portion of ALA of the MC-50F was not absorbed, because the ALA/HCO/SCP particles were small enough and the particles of MC-50F were relatively large and had smaller specific surface area. Therefore, this study suggested a newly masked candidate may offer functional particles with maintained efficacy.
Asunto(s)
Dióxido de Carbono/química , Aceites de Plantas/química , Ácido Tióctico/administración & dosificación , Animales , Masculino , Tamaño de la Partícula , Ratas , Ratas Sprague-Dawley , Propiedades de Superficie , Ácido Tióctico/farmacocinéticaRESUMEN
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.
Asunto(s)
Ácidos Araquidónicos/química , Grasas de la Dieta , Endocannabinoides/química , Preferencias Alimentarias , Proteína Ácida Fibrilar de la Glía/metabolismo , Glicéridos/química , Hipotálamo/metabolismo , Alimentación Animal , Animales , Astrocitos/metabolismo , Conducta Animal , Conducta de Elección , Cromatografía de Gases y Espectrometría de Masas/métodos , Immunoblotting/métodos , Masculino , Ratones , Ratones Endogámicos ICR , Modelos Estadísticos , Receptor Cannabinoide CB1/metabolismo , Recompensa , Factores de TiempoRESUMEN
The aim of the present study is to examine the relationship between preference for HFD and 2-arachidonoylglycerol (2-AG), endogenous cannabinoid. The 3-day HFD intake induced preference for HFD, which was suppressed by CB1 antagonist, O-2050. Moreover, hypothalamic 2-AG was increased after 3-day HFD intake. Our results show that preference for HFD is induced by activation of CB1 receptors via an increment of 2-AG in hypothalamus.
Asunto(s)
Ácidos Araquidónicos/metabolismo , Grasas de la Dieta/administración & dosificación , Preferencias Alimentarias/fisiología , Glicéridos/metabolismo , Hipotálamo/metabolismo , Receptor Cannabinoide CB1/metabolismo , Animales , Dronabinol/análogos & derivados , Dronabinol/farmacología , Ingestión de Alimentos/efectos de los fármacos , Ingestión de Alimentos/fisiología , Endocannabinoides , Preferencias Alimentarias/efectos de los fármacos , Hipotálamo/efectos de los fármacos , Masculino , Ratones , Ratones Endogámicos ICR , Piranos/farmacología , Receptor Cannabinoide CB1/antagonistas & inhibidoresRESUMEN
Endocannabinoids have been shown to activate reward-related feeding and to promote astrocytic differentiation. We investigated whether high-fat diet (HFD) intake produced a preference for HFD via an endocannabinoid-dependent mechanism. In the conditioned place preference test, the 2-week HFD-intake group showed preference for HFD and had increased expression of a marker for reactive astrocytes, glial fibrillary acid protein (GFAP), in the hypothalamus. The cannabinoid CB(1)-receptor antagonist O-2050 reduced the preference for HFD and expression of GFAP in the hypothalamus. These results suggested that HFD intake led to the development of a preference for HFD via astrocytic CB(1) receptors in the hypothalamus.