Effects of metformin and losartan on non-alcoholic fatty liver disease associated with mesenteric adiposity in an experimental model of metabolic syndrome in the rat

LEE HJ; CANTÚ SM; DONOSO AS; KIM G; CHOI MR; PUYÓ AM

Congreso; LXVI Reunión Anual de la Sociedad Argentina de Investigación Clínica (SAIC); 2021

Sociedad Argentina de Investigación Clínica (SAIC)

Non-alcoholic fatty liver disease (NAFLD) has been described as ahistological manifestation of metabolic syndrome (MS). Mesentericfat that drains into the portal circulation is the largest contributor tovisceral adiposity. There is great interest in the pleiotropic effects ofmetformin (M) and losartan (L) in the treatment of risk factors for MS.We studied the effects of M (500 mg/kg/day) and L (30 mg/kg/day) on NAFLD and its relationship with mesenteric vascular bed(MVB) adiposity, insulin resistance (IR) and systolic blood pressure(SBP) in an experimental model of MS for 9 weeks. Six groups ofSprague-Dawley rats were used: control (C, standard diet), highfatplus fructose-overload (HFF, 50% w/w bovine fat plus 10% w/vfructose solution), M-treated (CM), L-treated (CL), M-treated HFFdiet (HFFM) and L-treated HFF diet (HFFL). Adiposity index wascalculated as MVB adipose tissue weight/body weight x 100. Homeostasismodel of assessment of IR (HOMA-IR), SBP, hepatic steatosisand perivascular fibrosis (hematoxylin-eosin and Sirius Redtechniques) were measured.HFF diet produced significant (p<0.001) increments on MVB adiposityindex (%, 1.75±0.07 vs C: 0.81±0.04), HOMA-IR (0.50±0.06 vsC: 0.11±0.003), SBP (mmHg, 154±2 vs C: 120±2), hepatic steatosis(%, 81.5±2.5 vs C: 1.3±0.3) and perivascular fibrosis (%, 52.0±3.3vs C: 12.3±1.1). Compared with HFF rats, M and L treatments(HFFM and HFFL respectively), significantly (p<0.001) amelioratedMVB adiposity index (%, 1.23±0.02 and 1.18±0.08), HOMA-IR(0.13±0.01 and 0.20±0.03), SBP (mmHg, 127±1 and 116±3), hepaticsteatosis (%, 51.6±3.2 and 56.5±5.2) and perivascular fibrosis (%,33.4±3.4 and 31.0±2.8). Moreover, we found that both steatosis andperivascular fibrosis positively correlated with MVB adiposity index,HOMA-IR and SBP.Both M and L prevented MVB adiposity increase and consequentlyexhibited beneficial effects on the stages of NAFLD in a context ofIR and hypertension.