Fulvic acid inhibits the differentiation of 3T3-L1 adipocytes by activating the Ca2+/CaMKⅡ/AMPK pathway

Biochem Biophys Res Commun. 2025 Jan:743:151173. doi: 10.1016/j.bbrc.2024.151173. Epub 2024 Dec 11.

Abstract

Type 2 diabetes increases the risk of developing obesity. Although fulvic acid alleviates back fat thickness in pigs, the mechanism underlying its anti-obesity effect remains unclear. Therefore, we investigated the anti-obesity mechanism of fulvic acid using 3T3-L1 adipocytes. We examined the effects of fulvic acid on adipocyte differentiation, cell viability, and lipid accumulation using molecular techniques. Fulvic acid treatment significantly decreased intracellular lipid accumulation in 3T3-L1 cells during the differentiation compared with that in the control group. Western blotting revealed fulvic acid-induced downregulated expression of the adipocyte differentiation-related markers peroxisome proliferator-activated receptor gamma, CCAAT/enhancer-binding protein alpha, and sterol regulatory element-binding protein 1. The fulvic acid treatment decreased the expression of the lipid uptake-related markers fatty acid-binding protein 4 and the cluster of differentiation 36 in 3T3-L1 cells. Moreover, fulvic acid significantly increased cytosolic Ca2+ concentration via Ca2+ sequestration from the endoplasmic reticulum, enhanced Ca2+/calmodulin-dependent protein kinase II (CaMKII) activity, and upregulated AMP-activated protein kinase (AMPK), thereby reducing adipocyte differentiation. Conclusively, fulvic acid attenuates adipocyte differentiation by activating the Ca2+/CaMKⅡ/AMPK pathway, suggesting its anti-obesity potential.

Keywords: 3T3-L1 adipocytes; AMPK; CaMKⅡ; Cytosolic Ca(2+); Fulvic acid; Obesity.

MeSH terms

  • 3T3-L1 Cells*
  • AMP-Activated Protein Kinases* / metabolism
  • Adipocytes* / cytology
  • Adipocytes* / drug effects
  • Adipocytes* / metabolism
  • Adipogenesis / drug effects
  • Animals
  • Anti-Obesity Agents / pharmacology
  • Benzopyrans / pharmacology
  • Calcium* / metabolism
  • Calcium-Calmodulin-Dependent Protein Kinase Type 2* / metabolism
  • Cell Differentiation* / drug effects
  • Lipid Metabolism / drug effects
  • Mice
  • Signal Transduction / drug effects

Substances

  • Calcium-Calmodulin-Dependent Protein Kinase Type 2
  • AMP-Activated Protein Kinases
  • Calcium
  • Benzopyrans
  • Anti-Obesity Agents