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G protein-coupled receptor kinase 2 regulates: The development of non-alcoholic fatty liver disease

AuthorsCruces-Sande, Marta ; Vila-Bedmar, Rocío ; Lucas, Elisa ; González-Rodríguez, Águeda; Valverde, Ángela M.; Mayor Menéndez, Federico ; Murga, Cristina
Issue Date2014
PublisherSociedad Española de Bioquímica y Biología Molecular
CitationXXXVII Congreso SEBBM (2014)
Abstract[Background]: Insulin resistance (IR) and obesity are major health problems and important risk factors for the development of non-alcoholic fatty liver disease (NAFLD), a disease spectrum that includes hepatic steatosis, non-alcoholic steatohepatitis (NASH), fibrosis, and cirrhosis. G proteincoupled receptor kinase 2 (GRK2), fi rst identifi ed as a G protein-coupled receptor regulator, has been recently described to play a relevant role in IR and obesity in vivo. GRK2 hemizygous (GRK2+/-) mice are protected against high fat diet (HFD)-induced systemic and hepatic insulin resistance and obesity. However, the effect of GRK2 in the development of HFD-induced NAFLD has not been studied. [Materials and methods]: Given the lack of a potent and specific GRK2 inhibitor, we used a global tamoxifen (Tx)-inducible murine model in which GRK2 levels are decreased once HFD-induced IR has been established. Also, a long term chronic state of IR and obesity was triggered by feeding wild type (WT) and GRK2+/- mice a 32 week-long HFD. To discriminate the effects of the differential body weight gain, we fed mice with a methionine-choline defi cient diet (MCD), which induces NAFLD independently of fat mass accretion. [Results]: Systemic insulin sensitivity was preserved after decreasing GRK2 levels in the middle of a high fat feeding using tamoxifen, and accordingly enhanced insulin signaling was observed in the liver of HFD-fed Tx-induced GRK2-/- mice. Moreover, hepatic steatosis, a hallmark of NAFLD, was decreased in these mice. Also, different signs of infl ammation present in WT mice were absent in Tx-induced GRK2-/- animals. Nevertheless, after a long term HFD we found no differences in steatosis between WT and GRK2+/- mice, despite the decrease in body weight gain and liver weight. Finally, we found an increase in GRK2 protein levels in the liver of mice fed a MCD, a well established model of NASH, similar to what is detected during HFD feeding in WT animals, and we are further characterizing this model. [Conclusion]: Taken together, these results suggest a role for GRK2 in the establishment and development of NAFLD.
DescriptionResumen del póster presentado al XXXVII Congreso de la Sociedad Española de Bioquímica y Biología Molecular, celebrado en Granada del 9 al 12 de septiembre de 2014.-- et al.
Appears in Collections:(IIBM) Comunicaciones congresos
(CBM) Comunicaciones congresos
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