Journal
INFLAMMOPHARMACOLOGY
Volume 26, Issue 4, Pages 1103-1115Publisher
SPRINGER BASEL AG
DOI: 10.1007/s10787-018-0443-7
Keywords
Obesity; Metformin; Inflammation; Liver
Categories
Funding
- Fundacao de Amparo a Pesquisa do Estado de Sao Paulo (FAPESP, Brazil) [2013/09367-4, 2015/16777-0, 2016/01409-8]
- Coordenacao de Aperfeicoamento de Pessoal de Nivel Superior (CAPES, Brazil)
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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 A mu g/mL) and MET (1 A mu M) 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-1 beta, TNF-alpha, IL-6, MCP-1 and IFN-gamma. Similarly, MET increased the concentration of IL-1 beta, IL-6 in hepatocyte cultures. However, in macrophages culture, MET lowered levels of IL-1 beta, IL-6 and TNF-alpha stimulated by LPS. Overall, MET reduced liver NAFLD but promoted hepatocyte increase in pro-inflammatory cytokines, thus, leading to liver inflammation.
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