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      Niveles plasmáticos de glucosa y triglicéridos en ratones con hígado graso inducido por DL-etionina Translated title: Variation of plasma levels of glucose and triglyceride in adult NMRI mice of both sexes with DLethionine-induced fatty liver

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          Abstract

          Resumen 16. El objetivo del presente estudio fue determinar las modificaciones plasmáticas de la glucosa (Gluc) y de los triglicéridos (TG) en el hígado graso no alcohólico (HGNA) inducido por DL-etionina en ratones IRMN (imagen por resonancia magnética nuclear) machos y hembras. Se distribuyeron en dos grupos de 10 animales de cada sexo: uno control y otro tratado con etionina (7,5 mg/20 g peso corporal). Después de un ayuno de 48 horas, por venopunción coccígea se obtuvo una muestra de sangre con anticoagulante y en los plasmas se cuantificaron las concentraciones de Gluc y de TG mediante kit comercial. La eutanasia se practicó bajo ligera anestesia con éter. Se disecó el hígado, se evaluó su aspecto macroscópico y se obtuvo el homogeneizado hepático, en el que se determinó la concentración de TG. Una pequeña porción de hígado fijado en formol tamponado al 10% fue utilizado para su estudio histopatológico. El análisis estadístico se realizó mediante el programa SPSS versión 17.0 para Windows. Tanto en los machos como en las hembras, la administración de DL-etionina indujo metamorfosis grasa hepática con vacuolas lipídicas en el citoplasma de los hepatocitos, así como un aumento de la concentración de TG en el tejido hepático (p<0,001). En las hembras se observó que el HG provoca un descenso de los niveles de TG plasmáticos (p<0,01), resultado que está de acuerdo con la aumentada glicemia que presentaron (p<0,05). Tales efectos se deberían a la resistencia a la insulina, anormalidad clave en el HGNA. En los machos no se modificó el nivel de TG circulantes, lo que respondería a la glicemia normal que mostraron. Como conclusión, la inducción de HG por acción de la DL-etionina afectó los parámetros plasmáticos estudiados en forma diferente en machos y hembras, quizás debido a variables adaptativas ante el HG, propias de cada sexo.

          Translated abstract

          Abstract 20. The objective of the present study was to determine the plasma modifications of glucose (Gluc) and triglycerides (TG) in non-alcoholic fatty liver (NAFL) induced by DL-ethionine in male and female mice NMRI (nuclear magnetic resonance imaging). They were distributed in two groups of 10 animals of each sex: one control and the other treated with ethionine (7.5 mg/20 g body weight). After fasting for 48 hours, a blood sample with anticoagulant was obtained by coccygeal venipuncture and the plasma concentrations of Gluc and TG were quantified using a commercial kit. Euthanasia was performed under light ether anesthesia. The liver was dissected, its macroscopic appearance was evaluated and the liver homogenate was obtained, in which the concentration of TG was determined. A small portion of liver fixed in 10% buffered formalin was used for histopathological study. Statistical analysis was carried out using SPSS software program version 17.0 for Windows. In both males and females, the administration of DL-ethionine induced hepatic fat metamorphosis with lipid vacuoles in the cytoplasm of hepatocytes, as well as an increase in the concentration of triglycerides in the liver tissue (p<0.001). In females, it was observed that NAFL causes a decrease in plasma TG levels (p<0.01), a result that is in agreement with the increased glycemia they presented (p<0.05). Such effects would be due to insulin resistance, a key abnormality in NAFL. In males, the level of circulating TG was not modified, which would respond to the normal glycemia they showed. In conclusion, the induction of NAFL by the action of DL-ethionine affected the plasma parameters studied differently in males and females, perhaps due to adaptive variables to NAFL, specific to each sex.

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          Most cited references25

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          AGA technical review on nonalcoholic fatty liver disease.

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            Inhibiting triglyceride synthesis improves hepatic steatosis but exacerbates liver damage and fibrosis in obese mice with nonalcoholic steatohepatitis.

            In the early stages of nonalcoholic fatty liver disease (NAFLD), triglycerides accumulate in hepatocytes. Diacylglycerol acyltransferase 2 (DGAT2) catalyzes the final step in hepatocyte triglyceride biosynthesis. DGAT2 antisense oligonucleotide (ASO) treatment improved hepatic steatosis dramatically in a previous study of obese mice. According to the 2-hit hypothesis for progression of NAFLD, hepatic steatosis is a risk factor for nonalcoholic steatohepatitis (NASH) and fibrosis. To evaluate this hypothesis, we inhibited DGAT2 in a mouse model of NASH induced by a diet deficient in methionine and choline (MCD). Six-week-old genetically obese and diabetic male db/db mice were fed either the control or the MCD diet for 4 or 8 weeks. The MCD diet group was treated with either 25 mg/kg DGAT2 ASO or saline intraperitoneally twice weekly. Hepatic steatosis, injury, fibrosis, markers of lipid peroxidation/oxidant stress, and systemic insulin sensitivity were evaluated. Hepatic steatosis, necroinflammation, and fibrosis were increased in saline-treated MCD diet-fed mice compared to controls. Treating MCD diet-fed mice with DGAT2 ASO for 4 and 8 weeks decreased hepatic steatosis, but increased hepatic free fatty acids, cytochrome P4502E1, markers of lipid peroxidation/oxidant stress, lobular necroinflammation, and fibrosis. Progression of liver damage occurred despite reduced hepatic expression of tumor necrosis factor alpha, increased serum adiponectin, and striking improvement in systemic insulin sensitivity. Results from this mouse model would suggest accumulation of triglycerides may be a protective mechanism to prevent progressive liver damage in NAFLD.
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              Contribution of de novo fatty acid synthesis to hepatic steatosis and insulin resistance: lessons from genetically engineered mice.

              Nonalcoholic fatty liver disease (NAFLD) is associated with obesity, insulin resistance, and type 2 diabetes. NAFLD represents a large spectrum of diseases ranging from (i) fatty liver (hepatic steatosis); (ii) steatosis with inflammation and necrosis; and (iii) cirrhosis. Although the molecular mechanism leading to the development of hepatic steatosis in the pathogenesis of NAFLD is complex, recent animal models have shown that modulating important enzymes in fatty acid synthesis in liver may be key for the treatment of NAFLD. This review discusses recent advances in the field.
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                Author and article information

                Journal
                revet
                Revista veterinaria
                Rev. vet.
                Universidad Nacional del Nordeste, Facultad de Ciencias Veterinarias (Corrientes, Corrientes, Argentina )
                1669-6840
                June 2022
                : 33
                : 1
                : 23-28
                Affiliations
                [1] orgnameUniversidad Centroccidental Lisandro Alvarado orgdiv1Dec. Cs. Veterinarias orgdiv2Unid. Investig. Cs. Funcionales Venezuela alopez@ 123456ucla.edu.ve
                [2] Aragón orgnameUniversidad de Zaragoza orgdiv1Facult. Vet. Aragón orgdiv2Dep. Farmacol Spain
                Article
                S1669-68402022000100023 S1669-6840(22)03300100023
                10.30972/vet.3315874
                8bdf3580-4dec-47cb-bfa4-8530be904513

                This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.

                History
                : 01 June 2021
                : 01 September 2021
                Page count
                Figures: 0, Tables: 0, Equations: 0, References: 26, Pages: 6
                Product

                SciELO Argentina

                Categories
                Trabajos de Investigación

                triglycerides,hígado graso,DL-etionina,glucosa,triglicéridos,ratones IRMN,fatty liver,DL-ethionine,glucose,NMRI mice

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