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.

Isolation of Fatty Acids from the Enzymatic Hydrolysis of Capsaicinoids and Their Use in Enzymatic Acidolysis of Coconut Oil

“…Hydrolysis of capsaicin and dihydrocapsaicin, which is biologically relevant, produces 8-methyl-6-trans-nonenoic and 8-methylnonanoic acids, respectively. These MCFAs have been shown to possess beneficial biological properties of their own 37) . Thus, we undertook this work, to investigate the possibility to obtain these fatty acids from enzymatic hydrolysis of purified capsaicinoids and to incorporate them into a triglyc-Fig.…”

“…In addition, their metabolism leads to the formation of ketone bodies, which are thought of as having beneficial biological properties, for example as potential energy source for the central nervous system 34,36) . A recent publication studying in detail the effects of 8-methylnonanoic acid on 3T3-L1 pre adipocytes has shown the ability of this fatty acid to inhibit the differentiation of these cells into adipocytes 37) . Interesting-ly, our initial results have shown that the mixture of fatty acids obtained from the enzymatic hydrolysis of purified capsaicinoids exhibits similar properties.…”