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Beneficial effects of oxyntomodulin in the treatment of hepatic regeneration in non alcoholic fatty liver disease

AuthorsValdecantos, M. P.; Pardo, Virginia; Álvarez, Carmen; Grimsby, J.; Rondinone, Cristina M.; Valverde, Ángela M.
Issue Date2014
CitationCNIC Conference: Energy homeostasis and metabolic disease (2014)
Abstract[Objectives]: Partial hepatectomy (PH) is a common surgical intervention to treat liver diseases, particularly hepatocellular carcinoma. Since, a number of epidemiologic and clinical studies have shown a close association between non-alcoholic fatty liver disease (NAFLD) and response to PH, we designed a pharmacological intervention protocol with a PEGylated derivated of oxyntomodulyn aimed to investigate the effect of this drug on hepatic regeneration in a NAFLD model. [Methods]: 8 week-old male mice on the C57BU6 background were divided in 4 groups. Groups 1 and 2 were maintained on a chow diet (CHD) and groups 3 and 4 were fed with choline-methionine-deficient (MCD) diet. After 1 week, groups 2 and 4 were injected (S.C.) with oxyntomodulyn at 4 mg/kg every 2 days. Then, PH was performed and mice were maintained with the same diet and pharmacological intervention until they were sacrificed at several time-periods. Parameters that assess liver function and hepatic regeneration were analyzed. [Results]:S urvival rate following PW was increased with oxyntomodulyn in both dietary groups. Higher rate of DNA synthesis was found in the CHD and MCD oxyntomodulyn treated animals after 48 h post-PH. Hepatic regeneration index, analyzed 2 weeks after PH, was significantly improved in mice receiving CHD or MCD diet plus oxyntomodulyn as compared with not treated animals. In addition, oxyntomodulyn treatment was associated with decreased transaminase levels and improved liver histology in mice to receiving MCD diet. Moreover, several parameters that assessed hepatic inflammation, oxidative stress, fibrosis and apoptosis were increased by the MCD diet and ameliorated by oxyntomodulyn treatment. [Conclusions]: Taken together, these results strongly suggest a novel role of an oxyntomodulin-like dual acting GLPl R and GCGR co-agonist in alleviating NASH, improving liver regeneration following PH and may offer a potential therapeutic application in patients with NASH.
DescriptionResumen del póster presentado a la Conferencia del Centro Nacional de Investigaciones Cardiovasculares (CNIC) titulada: "Energy homeostasis and metabolic disease", celebrada en Madrid del 7 al 8 de noviembre de 2014.
Appears in Collections:(IIBM) Comunicaciones congresos
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