Comparing the effects of tumor necrosis factor alpha, lipopolysaccharide and palmitic acid on lipid metabolism and inflammation in murine 3T3-L1 adipocytes

Life Sci. 2022 May 15:297:120422. doi: 10.1016/j.lfs.2022.120422. Epub 2022 Feb 19.

Abstract

Aims: This study aimed to develop a model of dysregulated lipid metabolism and inflammation by treating 3T3-L1 adipocytes with tumor necrosis factor alpha (TNFα), lipopolysaccharide (LPS), and palmitic acid (PA) individually or in combination to assess their effects and mechanism of action.

Main methods: Differentiated 3T3-L1 adipocytes were treated with TNFα (10 ng/mL), LPS (100 ng/mL), and PA (0.75 mM) individually or in combination for 24 h. Lipolysis, lipid content, inflammation, and the expression of lipid metabolism and inflammation genes were assessed by glycerol release quantification, Oil Red O staining, enzyme-linked immunosorbent assays, and quantitative reverse transcription-polymerase chain reaction, respectively.

Key findings: Exposure of 3T3-L1 adipocytes to TNFα stimulated lipolysis, reduced lipid accumulation, decreased adiponectin (ADIPOQ) secretion, and increased secretion of pro-inflammatory adipokines, monocyte chemoattractant protein 1 (MCP-1), interleukin 6 (IL-6), and interleukin 1 beta (IL-1β). These changes were accompanied by decreased expression of lipid metabolism genes, increased expression of pro-inflammatory genes (MCP-1 and IL-6), and decreased expression of the anti-inflammatory gene, ADIPOQ. Exposure to LPS and PA, alone or in combination did not affect these parameters, while co-treatment with TNFα, LPS, and PA enhanced lipolysis and decreased ADIPOQ secretion compared to TNFα treatment.

Significance: Dysregulation of lipid metabolism and inflammation in 3T3-L1 adipocytes is attributed to TNFα rather than LPS and PA. We propose that exposing 3T3-L1 adipocytes to TNFα presents a suitable in vitro model of adipocyte dysfunction that closely resembles the complexity of obesity in vivo.

Keywords: 3T3-L1 adipocytes; Inflammation; LPS; Lipid metabolism; Palmitic acid; TNFα.

MeSH terms

  • 3T3-L1 Cells
  • Adipocytes / metabolism
  • Animals
  • Inflammation / chemically induced
  • Inflammation / metabolism
  • Lipid Metabolism
  • Lipopolysaccharides* / metabolism
  • Lipopolysaccharides* / pharmacology
  • Mice
  • Palmitic Acid / metabolism
  • Palmitic Acid / pharmacology
  • Tumor Necrosis Factor-alpha* / metabolism
  • Tumor Necrosis Factor-alpha* / pharmacology

Substances

  • Lipopolysaccharides
  • Tumor Necrosis Factor-alpha
  • Palmitic Acid