Cardiovascular disease(CVD)remains the leading cause of mortality worldwide despite major advances in prevention and treatment.The odd-chain saturated fatty acid pentadecanoic acid(C15:0),primarily obtained from dairy...Cardiovascular disease(CVD)remains the leading cause of mortality worldwide despite major advances in prevention and treatment.The odd-chain saturated fatty acid pentadecanoic acid(C15:0),primarily obtained from dairy fat,has been associated with cardiometabolic benefits.To summarize recent advances in understanding the role of pentadecanoic acid(C15:0)in CVD biology and risk,and to identify knowledge gaps and future research priorities.A narrative review was conducted,drawing on 115 PubMed-indexed studies on odd-chain fatty acids(OCFAs)and cardiovascular outcomes,as well as illustrative mechanistic studies of C15:0.This narrative review synthesized evidence from approximately 115 PubMed-indexed studies on OCFAs and cardiovascular outcomes,along with mechanistic studies of C15:0,identified through targeted searches in PubMed,Scopus,and Web of Science from January 2000 through May 2025.展开更多
Pentadecanoic acid(C15:0)is an odd-chain fatty acid,theβ-oxidation of which yields propionyl-CoA that replenishes succinyl-CoA and tricarboxylic acid cycle flux;higher circulating levels are associated with reduced t...Pentadecanoic acid(C15:0)is an odd-chain fatty acid,theβ-oxidation of which yields propionyl-CoA that replenishes succinyl-CoA and tricarboxylic acid cycle flux;higher circulating levels are associated with reduced type 2 diabetes,cardiovascular disease,metabolic dysfunction-associated steatotic liver disease,and mortality.Summarize the cellular and molecular mechanisms underlying these associations.A comprehensive literature search(2000-2025)identified studies of C15:0’s mechanistic actions in vitro and in vivo,and multi-omics studies focused on receptor binding,signaling cascades,gene expression,and comparative pharmacology.C15:0 is a dual partial peroxisome proliferator-activated receptorα/δagonist.It activates AMP-activated protein kinase,suppresses mechanistic target of rapamycin,and selectively inhibits histone deacetylase 6.It augments succinate-driven complex II respiration,preserves mitochondrial membrane potential,limits reactive oxygen species,and attenuates interleukin-6(IL-6)–triggered Janus kinase 2/signal transducer and activator of transcription 3 and nuclear factor kappa B p65 signaling,lowering monocyte chemoattractant protein-1,tumor necrosis factor-alpha,and IL-6.Across the BioMAP®human-primarycell platform–which tests 12 distinct primary human cell systems such as endothelial cells,fibroblasts,macrophages,and T-cells–C15:0(17μM)produced statistically significant changes in 36 mechanistically diverse biomarkers.This broad,multipathway modulation mirrors the phenotype produced by metformin and rapamycin,yet occurred with no detectable cytotoxicity,paralleling metformin and rapamycin with negligible cytotoxicity.C15:0 engages receptor targets that converge on enhanced lipid oxidation,cellular energetics,and inflammation resolution.Although prospective clinical outcomes are still lacking,the pleiotropic mechanism profile positions C15:0 as a potentially unique nutraceutical or adjunct therapeutic candidate.Further research is warranted to confirm its clinical impacts,optimize dosing,and clarify long-term safety as an essential fatty acid supporting metabolic and immune homeostasis.展开更多
文摘Cardiovascular disease(CVD)remains the leading cause of mortality worldwide despite major advances in prevention and treatment.The odd-chain saturated fatty acid pentadecanoic acid(C15:0),primarily obtained from dairy fat,has been associated with cardiometabolic benefits.To summarize recent advances in understanding the role of pentadecanoic acid(C15:0)in CVD biology and risk,and to identify knowledge gaps and future research priorities.A narrative review was conducted,drawing on 115 PubMed-indexed studies on odd-chain fatty acids(OCFAs)and cardiovascular outcomes,as well as illustrative mechanistic studies of C15:0.This narrative review synthesized evidence from approximately 115 PubMed-indexed studies on OCFAs and cardiovascular outcomes,along with mechanistic studies of C15:0,identified through targeted searches in PubMed,Scopus,and Web of Science from January 2000 through May 2025.
文摘Pentadecanoic acid(C15:0)is an odd-chain fatty acid,theβ-oxidation of which yields propionyl-CoA that replenishes succinyl-CoA and tricarboxylic acid cycle flux;higher circulating levels are associated with reduced type 2 diabetes,cardiovascular disease,metabolic dysfunction-associated steatotic liver disease,and mortality.Summarize the cellular and molecular mechanisms underlying these associations.A comprehensive literature search(2000-2025)identified studies of C15:0’s mechanistic actions in vitro and in vivo,and multi-omics studies focused on receptor binding,signaling cascades,gene expression,and comparative pharmacology.C15:0 is a dual partial peroxisome proliferator-activated receptorα/δagonist.It activates AMP-activated protein kinase,suppresses mechanistic target of rapamycin,and selectively inhibits histone deacetylase 6.It augments succinate-driven complex II respiration,preserves mitochondrial membrane potential,limits reactive oxygen species,and attenuates interleukin-6(IL-6)–triggered Janus kinase 2/signal transducer and activator of transcription 3 and nuclear factor kappa B p65 signaling,lowering monocyte chemoattractant protein-1,tumor necrosis factor-alpha,and IL-6.Across the BioMAP®human-primarycell platform–which tests 12 distinct primary human cell systems such as endothelial cells,fibroblasts,macrophages,and T-cells–C15:0(17μM)produced statistically significant changes in 36 mechanistically diverse biomarkers.This broad,multipathway modulation mirrors the phenotype produced by metformin and rapamycin,yet occurred with no detectable cytotoxicity,paralleling metformin and rapamycin with negligible cytotoxicity.C15:0 engages receptor targets that converge on enhanced lipid oxidation,cellular energetics,and inflammation resolution.Although prospective clinical outcomes are still lacking,the pleiotropic mechanism profile positions C15:0 as a potentially unique nutraceutical or adjunct therapeutic candidate.Further research is warranted to confirm its clinical impacts,optimize dosing,and clarify long-term safety as an essential fatty acid supporting metabolic and immune homeostasis.
