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

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. ? 2023 The Author(s).