Cellular responses to 8-methyl nonanoic acid, a degradation by-product of dihydrocapsaicin, in 3T3-L1 adipocytes

BMC Complement Med Ther. 2023 Jan 21;23(1):18. doi: 10.1186/s12906-023-03844-w.

Abstract

Background: Capsaicinoids, such as dihydrocapsaicin (DHC), exert the health-promoting effects of chili peppers on energy metabolism. The metabolic responses to capsaicinoids are primarily mediated through transient receptor potential cation channel subfamily V member 1 (TRPV1). However, the varying contributions of their metabolites to beneficial health outcomes remain unclear. 8-methyl nonanoic acid (8-MNA), a methyl-branched medium chain fatty acid (MCFA), is an in vivo degradation by-product of DHC. Since MCFAs have emerged as metabolic modulators in adipocytes, here we examined various cellular responses to 8-MNA in 3T3-L1 adipocytes.

Methods: The viability of 3T3-L1 adipocytes exposed to various concentrations of 8-MNA was assessed by the Calcein AM assay. Biochemical assays for lipid accumulation, AMP-activated protein kinase (AMPK) activity, lipolysis and glucose uptake were performed in 3T3-L1 adipocytes treated with 8-MNA during 48-h nutrient starvation or 5-day maturation.

Results: 8-MNA caused no impact on cell viability. During nutrient starvation, 8-MNA decreased lipid amounts in association with AMPK activation, a molecular event that suppresses lipogenic processes. Moreover, 3T3-L1 adipocytes that were treated with 8-MNA during 5-day maturation exhibited a reduced lipolytic response to isoproterenol and an increased glucose uptake when stimulated with insulin.

Conclusions: These results suggest that 8-MNA derived from DHC modulates energy metabolism in adipocytes and also support the idea that the metabolic benefits of chili consumption are partly attributable to 8-MNA.

Keywords: 8-methyl nonanoic acid; Adipocytes; Capsaicinoids; Metabolic function.

MeSH terms

  • 3T3-L1 Cells
  • AMP-Activated Protein Kinases* / metabolism
  • Adipocytes*
  • Animals
  • Fatty Acids / pharmacology
  • Glucose / metabolism
  • Mice

Substances

  • pelargonic acid
  • dihydrocapsaicin
  • AMP-Activated Protein Kinases
  • Fatty Acids
  • Glucose