Short-term treatment with metformin reduces hepatic lipid accumulation but induces liver inflammation in obese mice

Abstract

The study aimed to evaluate the metabolic and inflammatory effects of short-term treatments (10 days) with metformin (MET) on the NAFLD caused by a high-fat diet (HFD) in C57BL/6 mice. After the treatment, histological liver slices were obtained, hepatocytes and macrophages were extracted and cultured with phosphate buffered saline, LPS (2.5 µg/mL) and MET (1 µM) for 24 h. Cytokine levels were determined by ELISA. NAFLD caused by the HFD was partially reduced by MET. The lipid accumulation induced by the HFD was not associated with liver inflammation; however, MET seemed to promote pro-inflammatory effects in liver, since it increased hepatic concentration of IL-1β, TNF-α, IL-6, MCP-1 and IFN-γ. Similarly, MET increased the concentration of IL-1β, IL-6 in hepatocyte cultures. However, in macrophages culture, MET lowered levels of IL-1β, IL-6 and TNF-α stimulated by LPS. Overall, MET reduced liver NAFLD but promoted hepatocyte increase in pro-inflammatory cytokines, thus, leading to liver inflammation.