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Beneficial effects of a dual acting GLP-1R/glucagon receptor co-agonist in the treatment of hepatic regeneration in NAFLD

AuthorsValdecantos, M. P.; Pardo, Virginia; Álvarez, Carmen; Grimsby, J.; Rondinone, Cristina M.; Valverde, Ángela M.
Issue Date2014
Citation74th Scientific Sesions of ADA (2014)
AbstractA number of epidemiologic and clinical studies have shown an close between non-alcoholic fatty Iiver disease (NAFLD), insulin resistance and impaired Iiver function Since partial hepatectomy (PH) is a common surgical intervention to treat Iiver diseases, we designed a phamacological intervention with a PEGylated dual acting GLPlR and GCGR co-agonist to investigate the effect of this drug on hepatic regeneration in NAFLD. Eight week-old male mice on the C57BL/6 background were divided in 4 groups. Groups 1 and 2 were maintained on a chow diet (CHD) and groups 3 and 4 with choline-methionine-deficient (MCD) diet, an established model of steatohepatitis (NASH). After 1 week, groups 2 and 4 were injected with the co-agonist at 4 mg/kg every 2 days for 2 weeks Then, PH was performed and mice were maintained with similar intervention until sacrifice. Survival rate following PH increased with co-agonist treatment in CHD and MCD groups compared with vehicle-treated mice. In mice sacrificed at 48 h post-PH, higher DNA synthesis was found in the CHD and MCD plus co-agonist groups compared to mice receiving vehicle. Two weeks after PH, hepatic regeneration index significantly improved in mice with CHD or MCD diet plus co-agonist compared to the same groups treated with vehicle. Coagonist treatment in mice receiving MCD diet decreased transaminases and improved Iiver histology. Serum tryglicerides (TG) decreased in the MCD compared to CHD mice, reflecting lower capacity of the Iiverto export VLDL during NASH. However, the MCD plus co-agonist group restored TG to near levels of CHD mice. Parameters that assessed hepatic inflammation, oxidative stress, fibrosis and apoptosis were increased by the MCD diet and ameliorated by co-agonist treatment These data suggest a novel role of an Dxyntomodulin-like dual acting GLPlR and GCGR co-agonist in alleviating NASH and improving Iiver regeneration following PH and may offer potential therapeutic application in patients with NASH.
DescriptionResumen del póster presentado a la 74th Scientific Sesions of American Diabetes Association, celebrada en San Francisco-California (US) del 13 al 17 de junio de 2104.
Appears in Collections:(IIBM) Comunicaciones congresos
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