TY - JOUR AU - Ferrigno, Andrea AU - Berardo, Clarissa AU - Di Pasqua, Laura Giuseppina AU - Cagna, Marta AU - Siciliano, Veronica AU - Richelmi, Plinio AU - Vairetti, Mariapia PY - 2020/11/10 Y2 - 2024/03/28 TI - The selective blockade of metabotropic glutamate receptor-5 attenuates fat accumulation in an in vitro model of benign steatosis JF - European Journal of Histochemistry JA - Eur J Histochem VL - 64 IS - 4 SE - Articles DO - 10.4081/ejh.2020.3175 UR - https://www.ejh.it/ejh/article/view/3175 SP - AB - <p>It has been previously found that the blockade of metabotropic glutamate receptor type 5 (mGluR5) protects against hepatic ischemia/reperfusion injury and acetaminophen toxicity. The role of mGluR5 in NAFLD has not yet been elucidated. Here, we evaluated the effects of mGluR5 blockade in an <em>in vitro</em> model of steatosis. HepG2 cells were pre-incubated for 12 h with an mGluR5 agonist, a negative allosteric modulator (DHPG and MPEP, respectively) or vehicle, then treated with 1.5 mM oleate/palmitate (O/P) for another 12 h. Cell viability was evaluated with the MTT assay; fat accumulation was measured using the fluorescent dye nile red; SREBP-1, PPAR-α, iNOS and Caspase-3 protein expression were evaluated by Western blot; NFkB activity was evaluated as pNFkB/NFkB ratio. mGluR5 modulation did not alter cell viability in O/P-incubated cells; MPEP prevented intracellular lipid accumulation in O/P treated cells; MPEP administration was also associated with a reversion of O/P-induced changes in SREBP-1 and PPAR-α expression, involved in free fatty acid (FFA) metabolism and uptake. No changes were observed in iNOS and Caspase-3 expression, or in NFkB activity. In conclusion, mGluR5 pharmacological blockade reduced fat accumulation in HepG2 cells incubated with O/P, probably by modulating the expression of SREBP-1 and PPAR-α.</p> ER -