Fructose affects enzymes involved in the synthesis and degradation of hypothalamic endocannabinoids

Endocannabinoids have been implicated in the regulation of consumption of palatable food, sugar in particular. In this study, we investigated how palatable solutions would affect the hypothalamic mRNA expression of enzymes involved in the synthesis and degradation of the two main endocannabinoids, anandamide and 2-arachidonoyl-glycerol. Rats were offered sugar solutions to drink for one week, during which daily food and drink intake, and body weight gain was monitored. Rats offered sugar solutions to drink consumed less solid food but drank more of their respective sugar solution than did water-drinking control rats, resulting in increased total calorie intake. However, this increase in caloric intake did not result in increased body weight or adiposity in the rats. The mRNA expression of fatty acid amid hydrolase was up-regulated by sucrose and fructose. N-acyl phospatidyl ethanolamine phospholipase D mRNA was up-regulated by sucrose, whereas phospholipase C was down-regulated by all forms of sugar tested. The mRNA expression of monoglyceride lipase was down-regulated by all three forms of sugar. Also, the mRNA expression of diacylglycerol lipase 1alpha was down-regulated by sucrose and fructose, whereas the mRNA expression of diacylglycerol lipase 1beta was up-regulated by fructose. In this study, we show that sugars in liquid form affect enzymes involved in the degradation and synthesis of endocannabinoids in the hypothalamus and that this effect predates obesity.