TYPE 2 DIABETES-ASSOCIATED FATTY LIVER DISEASE: EFFECTS OF OLIGONUCLEOTIDE IMT504

CONVERTI A; RIAÑO GÓMEZ JM; MENDEZ L; BECÚ-VILLALOBOS D; SORIANELLO E; LUX-LANTOS VAR; BIANCHI MS

Mar del Plata

Congreso; Reunión Anual de Sociedade de Biociencias: LXVIII Reunión Anual de la SAIC, XXV Jornadas Anuales de la SAB, LV Reunión Anual de la AAFE, VIII Reunión Científica Regional de la AACyTAL; 2023

SAIC, SAB, AAFE, AACyTAL

The association between non-alcoholic fatty liver disease (NAFLD) and type 2 diabetes is strong. Up to 70% of obese patients with type 2 diabetes (T2D) have NAFLD. The spectrum of NAFLD ranges from simple steatosis to non-alcoholic steatohepatitis with variable degrees of fibrosis and cirrhosis. Aim: the present work was designed to evaluate alterations in the liver in a model of T2D induced by high fat diet in mice and the possible recovery by treatment with the oligonucleotide IMT504.Materials and Methods: male C57BL/6LP mice were fed either a standard diet (SD) or a high-fat diet (HFD: ResearchDiet, D12492, 60% fat content) for 12 weeks. HFD animals showed higher non-fasting glycemia (Gly: p˂0.01) and body weight (BW: p˂0.01). SD mice received one daily dose of IMT504 for 16 consecutive days (SD-IMT: 6mg/kg, sc) or saline (SD-sal). HFD mice received one daily dose of IMT504 for 16 consecutive days (HFD-IMT: 6mg/kg, sc), a control polyC oligonucleotide (HFD-PolyC: 6mg/kg, sc, to evaluate the specificity of the IMT504 effects), or saline (HFD-sal). Intraperitoneal glucose tolerance test (ipGTT, day 10) and insulin tolerance test (ITT, day 12) were performed. On day 16, after 3 hours fasting, mice were weighed (BW), sacrificed, and blood, white adipose tissue (WAT) and liver samples were collected. Results: Alterations GTT, ITT and BW induced by HFD were all reversed by IMT treatment but not by PolyC (p