Abstract

Introduction: Diacylglycerol lipase alpha (DAGLα) is a 2-AG-producing enzyme, an endocannabinoid able to moduate food intake and the main endogenous ligand of CB1 receptors in the central nervous system. DAGLα is expressed in the hypothalamus, a critical region for the cerebral glucosensing. This process is carried out mainly by a group of glial cells present in the wall of third ventricle (3v) denominated tanycytes, which take contact with the cerebrospinal fluid (CSF) and relevant neuronal circuits in the arcuate nucleus (AN). Therefore, these cells metabolically coupled this cerebral region with the levels of peripheral molecules, like glucose and others that reach the CSF in response to the energetic state. We previously demonstrated that tanycytes expressed DAGLα and respond to glucose increasing DALGα expression and here we shown the effect of glucose on subcellular localization of DAGLα in tanycytes. Materials and methods: Western blot and immunohistochemistry (IHC) were performed in basal hypothalamus sections of adult rats under several glycemic conditions to evaluate the sublocalization of DAGLα. Additionally, cell fractionation and immunocytochemistry (ICC) were performed in tanycyte cultures incubated at 2, 5 and 15 mM glucose to evaluate the protein expression. Results: Using in vitro and in situ approaches we demonstrated that variations in extracellular glucose concentration produce significant changes in the subcellular localization of DAGLα, increasing its nuclear localization under high glucose conditions. Discussion: The modification of the subcellular localization of DAGLα in response to glucose in the tanycyte, the main glucosensor cell of the hypothalamus, could establish the bases of the mechanism by which the endocannabinoids or the enzyme itself mediates a response to affect the energy balance.