Effects of metformin on lipopolysaccharide induced inflammation by activating fibroblast growth factor 21

Ezgi Kar1, Özkan Alataş2, Varol Şahıntürk3

  • 1Department of Medical Biochemistry, Çanakkale Onsekiz Mart University, Çanakkale, Turkey.

Insights

Metformin (MET) partially protected male rats against liver inflammation caused by lipopolysaccharide (LPS) induced endotoxemia. MET may enhance the production of anti-inflammatory Fibroblast Growth Factor 21 (FGF21).

Area of Science:

  • Biochemistry
  • Pharmacology
  • Pathology

Background:

  • Lipopolysaccharide (LPS) from Gram-negative bacteria causes endotoxemia and potentially septic shock.
  • Metformin (MET), a hypoglycemic drug, has demonstrated anti-inflammatory effects.
  • Fibroblast Growth Factor 21 (FGF21) is an endocrine polypeptide involved in metabolic regulation and inflammation.

Purpose of the Study:

  • To investigate the protective effects of Metformin (MET) and Fibroblast Growth Factor 21 (FGF21) against lipopolysaccharide (LPS)-induced endotoxemia in male rats.
  • To assess the impact of MET on liver inflammation markers and FGF21 production.

Main Methods:

  • Male rats were divided into control, LPS-induced endotoxemia, and various MET treatment groups (pre-treatment, 1-hour post-treatment, 3-hour post-treatment).
  • Serum levels of liver enzymes (ALT, AST), cytokines (IL-10, TNF-α), and FGF2 were measured.
  • Liver tissue analysis included malondialdehyde, myeloperoxidase, FGF21 levels, and histopathology (H&E staining).

Main Results:

  • LPS administration resulted in significant inflammatory liver damage.
  • Metformin (MET) treatment demonstrated a partial protective effect, significantly reducing inflammation.
  • FGF21 levels increased in the liver following inflammation, and MET appeared to enhance its production.

Conclusions:

  • Metformin (MET) offers partial protection against LPS-induced endotoxemia and associated liver inflammation in male rats.
  • The anti-inflammatory effects of MET may be partly mediated by an increase in hepatic Fibroblast Growth Factor 21 (FGF21) production.

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