Effects of gadilinum chloride treatment on metabolism in insulin resistant rats

WISZNIEWSKI, MORENA; MORI D; CYMERYNG, CORA B.; REPETTO, EM

Mar del Plata

Congreso; REUNIÓN CONJUNTA SAIC SAB AAFE AACYTAL 2023; 2023

Sociedad Argentina de Investigación Clínica

Non-Alcoholicfatty liver disease (NAFLD) is the most prevalent chronic liver disease.Although of yet unknown origin, several factors such as inflammation arepostulated to contribute to its etiology Previous results from our laboratoryshowed that rats fed a sucrose rich diet (SRD) for 12 weeks developsteatohepatitis and metabolic dysfunction. It has been described thatinflammation perpetuates metabolic syndrome. Taking this into account, thepurpose of the present study was to assess the effect of systemic macrophageinhibition in central tissues involved in energy metabolism: adipose tis- sueand the liver. Male Wistar rats were fed a normal diet and either tap water(control, n=12) or a SRD (n=12) for 12 weeks. A subgroup of SRD treated animalsreceived gadolinium chloride (GdCl3 10mg/ kg ip every 3 days) for the last twoweeks of the dietary modification (SRD+Gd, n=8). Gd treatment had no effect onbody weight, caloric consumption or triglyceridemia compared to the SRD group.However, it was associated with a reduction in glycemia and a restoration ofperipheral insulin resistance (assessed by an insulin tolerance test, p<0.01vs SRD, in both cases), with no changes in hepatic glucose production(evaluated by a pyruvate tolerance test). In the liver, GdCl3 treatment wasassociated with less inflammatory tissue injury with no changes in steatosis orin the expression of lipogenic enzymes induced by SRD. Macrophage inhibitionwas associated with a restoration of insulin signaling in the epididymaladipose tissue (EAT), as assessed by the phosphorylation of AKT1 (p<0.001 vsSRD). As expected, Gd treatment attenuated tissular damage associated withinflammation. While we can’t disregard possible effects of Gd treatment inother tissues, our results suggest that the restoration of peripheric insulinsensitivity could be, at least in part, due to an improvement in insulinsignaling in the EAT.