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

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

Congreso; Reunión anual de sociedades de biociencias; 2023

The association between non-alcoholic fatty liver disease (NAFLD)and type 2 diabetes is strong. Up to 70% of obese patients with type2 diabetes (T2D) have NAFLD. The spectrum of NAFLD ranges fromsimple steatosis to non-alcoholic steatohepatitis with variable degrees of fibrosis and cirrhosis. Aim: the present work was designedto evaluate alterations in the liver in a model of T2D induced byhigh fat diet in mice and the possible recovery by treatment with theoligonucleotide IMT504. Materials and Methods: male C57BL/6LPmice 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 bodyweight (BW: p˂0.01). SD mice received one daily dose of IMT504 for16 consecutive days (SD-IMT: 6mg/kg, sc) or saline (SD-sal). HFDmice 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, day10) and insulin tolerance test (ITT, day 12) were performed. On day16, after 3 hours fasting, mice were weighed (BW), sacrificed, andblood, 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