Vaccenic Acid
Introduction
Section titled “Introduction”Vaccenic acid is a monounsaturated fatty acid (MUFA) that plays various roles in human metabolism. As a type of unsaturated fatty acid characterized by a single double bond, vaccenic acid is both synthesized within the body and obtained through diet.[1]Endogenously, it is an elongation product primarily derived from palmitoleic or oleic acid.[1]MUFAs, including vaccenic acid, are essential components of cell membranes and serve as vital energy sources, for example, in skeletal muscle during exercise.[1]
Biological Basis
Section titled “Biological Basis”The circulating levels of vaccenic acid are influenced by a combination of genetic and environmental factors. Genetic studies, particularly genome-wide association studies (GWASs), have identified specific genetic loci associated with vaccenic acid levels. For instance, variants within theFADS1/2gene cluster have been linked to higher vaccenic acid levels.[1]These genes encode Δ5 and Δ6 desaturases, enzymes predominantly involved in the biosynthesis of polyunsaturated fatty acids (PUFAs), but also capable of producing other unsaturated fatty acids from precursors like palmitic and stearic acid, which are substrates for MUFA synthesis.[1] Another locus, PKD2L1, contains the variant rs603424 , which is associated with lower vaccenic acid levels.[1] This SNP is located near the SCDgene, which encodes Δ-9 desaturase, an enzyme critical for MUFA metabolism that catalyzes the conversion of palmitic and stearic acid to palmitoleic and oleic acid, respectively.[1] Research suggests that rs603424 may influence vaccenic acid levels by regulatingSCD transcription in adipose tissue.[1]Vaccenic acid levels in research are typically expressed as a percentage of total fatty acids.[1]
Clinical Relevance
Section titled “Clinical Relevance”Abnormal levels of vaccenic acid have been implicated in various health conditions. Elevated levels of specific plasma and erythrocyte membrane MUFAs, including vaccenic acid, have been associated with an increased risk of cardiometabolic disorders such as Type 2 Diabetes (T2D), metabolic abnormalities, and Cardiovascular Disease (CVD) in European populations.[1]These associations highlight the significant role of vaccenic acid in cardiometabolic health.[1]Specific genetic variants associated with vaccenic acid levels, such asrs102275 in FADS1/2, have also shown associations with T2D, and rs603424 in PKD2L1has suggestive evidence for an association with Coronary Artery Disease (CAD).[1]
Social Importance
Section titled “Social Importance”Understanding the genetic and metabolic factors influencing vaccenic acid levels holds considerable social importance. Given its associations with prevalent cardiometabolic diseases like T2D, CVD, and metabolic syndrome, insights into vaccenic acid biology can contribute to public health strategies aimed at prevention and management.[1] Genetic research, particularly trans-ethnic meta-analyses involving diverse populations like Chinese and European ancestries, helps to elucidate the genetic architecture of MUFA metabolism, providing a broader understanding that can inform personalized medicine and nutritional recommendations across different populations.[1] This foundational knowledge supports future genetic and functional investigations, paving the way for potential therapeutic targets or dietary interventions.[1]
Methodological and Cohort Heterogeneity
Section titled “Methodological and Cohort Heterogeneity”The analysis of vaccenic acid levels involved a diverse set of cohorts, which, while increasing overall sample size, introduced heterogeneity in both participant demographics and fatty acid methodologies. Fatty acid levels were consistently expressed as a percentage of total fatty acids, which provides relative rather than absolute concentrations and may obscure insights into total fatty acid metabolism or dietary intake effects.[1] Furthermore, the specific techniques for measuring fatty acids varied, including quantification in fasting plasma phospholipids, total plasma, or erythrocyte fatty acids using gas chromatography or gas-liquid chromatography across different studies.[1] Although the research indicates these differences did not significantly alter association results, they represent a source of underlying variability that could influence the precision and comparability of data across cohorts.
The study population comprised primarily middle-aged to older individuals, with mean ages ranging from 45.8 to 75.0 years across the cohorts.[1] Additionally, some cohorts were sex-specific, such as the Nurses’ Health Study (female only) and the Health Professionals Follow-Up Study (male only).[1]This demographic specificity, while inherent to the contributing studies, limits the direct generalizability of the findings to younger populations or to individuals outside these specific age and sex ranges. The findings may not fully capture genetic influences on vaccenic acid levels that manifest differently across the lifespan or in more diverse demographic contexts.
Generalizability and Environmental Confounders
Section titled “Generalizability and Environmental Confounders”While the trans-ethnic meta-analysis enhanced power and fine-mapping resolution by combining data from Chinese and European populations, the findings are primarily limited to these two ancestral groups.[1]The genetic architecture and environmental influences on vaccenic acid levels may differ substantially in other ethnic populations, restricting the broader applicability of the identified loci and their effect sizes. Further research involving a wider range of global ancestries is necessary to fully understand the generalizability of these genetic associations.
Vaccenic acid levels are influenced not only by endogenous synthesis but also by dietary intake.[1]Despite adjustments for basic demographic factors like age and sex, the study did not extensively account for specific dietary patterns, lifestyle factors, or other environmental exposures that could confound the genetic associations. These unmeasured or unadjusted environmental variables could interact with genetic predispositions, leading to a complex interplay that is not fully elucidated by the current genetic analysis, thus representing a potential source of residual confounding.
Incomplete Functional Understanding and Replication Gaps
Section titled “Incomplete Functional Understanding and Replication Gaps”Although novel genetic associations were identified and fine-mapping resolution improved for some loci, the precise functional variants and the underlying biological mechanisms through which these genetic loci influence vaccenic acid levels remain largely to be fully characterized.[1]The credible sets, even after fine-mapping, often contain multiple single nucleotide polymorphisms (SNPs), meaning that the definitive causal variant for each association has not been pinpointed. A comprehensive understanding of the molecular pathways linking these genetic variants to vaccenic acid metabolism requires further functional investigations beyond statistical association.
The study aimed to replicate previously reported associations for other monounsaturated fatty acids (MUFAs) and observed instances where some failed to replicate in Chinese populations or the trans-ethnic meta-analysis.[1]For example, associations of 2p13 with palmitoleic acid andTRIM58with oleic acid were not consistently replicated.[1] This highlights the potential for variability in genetic effects across different populations and fatty acids, suggesting that the genetic landscape of MUFA metabolism may be more complex and population-specific than currently understood, implying limitations in drawing universal conclusions from specific findings.
Variants
Section titled “Variants”The genetic landscape influencing vaccenic acid levels involves several key variants and genes, with significant implications for lipid metabolism and cardiometabolic health. Among these,*rs603424 * within the _PKD2L1_ gene has been identified as a particularly strong associate. The _PKD2L1_ gene encodes a protein belonging to the polycystin family, which are known for their roles as transient receptor potential (TRP) channels involved in various cellular signaling processes. The *rs603424 * variant is located in the second intron of the _PKD2L1_ gene.[1]Its minor allele A is significantly associated with lower circulating vaccenic acid levels, an observation consistently found in both European-specific and trans-ethnic genome-wide association studies.[1]This variant also shows an association with decreased palmitoleic acid levels.[1] Furthermore, *rs603424 * has been observed to overlap with enhancer histone marks, such as H3K4me1, H3K27ac, and H3K9ac, in adipose tissue, suggesting a potential role in regulating gene expression.[1] The mechanism by which *rs603424 *influences vaccenic acid levels appears to be mediated through the_SCD_ gene, which encodes stearoyl-CoA desaturase. Cis-eQTL analysis has shown that the minor allele A of *rs603424 * is significantly associated with decreased RNA levels of _SCD_ in adipose tissue.[1] _SCD_plays a critical role in endogenous fatty acid synthesis, catalyzing the desaturation of saturated fatty acids like palmitic and stearic acid into monounsaturated fatty acids (MUFAs), including palmitoleic and oleic acid, which are precursors to vaccenic acid.[1] Therefore, *rs603424 *likely exerts its effect on vaccenic and palmitoleic acid levels by modulating_SCD_ transcription.[1]Elevated levels of vaccenic acid have been epidemiologically linked to an increased risk of cardiometabolic disorders, such as Type 2 Diabetes and cardiovascular disease.[1] and *rs603424 *itself shows suggestive evidence of association with Coronary Artery Disease.[1] Another variant, *rs174528 *, is associated with the _MYRF_ and _TMEM258_genes, although its precise functional impact on these genes and their direct link to vaccenic acid levels requires further investigation._MYRF_ (Myelin Regulatory Factor) is a transcription factor primarily recognized for its role in central nervous system development, particularly myelin formation, but transcription factors can also broadly regulate genes involved in metabolic pathways throughout the body. _TMEM258_ (Transmembrane Protein 258) is a less characterized transmembrane protein, which generally participates in various cellular functions like transport or signaling. *rs174528 * is located in a genomic region implicated in fatty acid metabolism, and as a non-coding variant, it may influence the expression or activity of nearby genes, including _MYRF_ or _TMEM258_, through effects on regulatory elements like enhancers or promoters. Vaccenic acid itself is a vital monounsaturated fatty acid that forms part of cell membranes and serves as an energy source.[1]with its levels being influenced by both diet and endogenous synthesis.
The intricate interplay between genes like _MYRF_ and _TMEM258_ and lipid metabolism, potentially mediated by variants such as *rs174528 *, highlights the complexity of fatty acid regulation. While the direct mechanisms linking these specific genes to vaccenic acid are still being elucidated, their roles in cellular regulation or membrane biology could indirectly contribute to the maintenance of lipid homeostasis. Disruptions in these pathways, influenced by genetic variations, can lead to altered vaccenic acid levels. High levels of vaccenic acid, along with other specific monounsaturated fatty acids, have been associated with increased risk of metabolic abnormalities, Type 2 Diabetes, and cardiovascular disease.[1] Therefore, understanding the impact of *rs174528 * on _MYRF_ and _TMEM258_, and their subsequent effects on vaccenic acid, is crucial for gaining insights into the genetic underpinnings of cardiometabolic health.
Key Variants
Section titled “Key Variants”| RS ID | Gene | Related Traits |
|---|---|---|
| rs603424 | PKD2L1 | fatty acid amount metabolite phospholipid amount heel bone mineral density coronary artery disease |
| rs174528 | MYRF, TMEM258 | phosphatidylcholine ether serum metabolite level vaccenic acid gondoic acid kit ligand amount |
Definition and Biological Significance of Vaccenic Acid
Section titled “Definition and Biological Significance of Vaccenic Acid”Vaccenic acid is precisely defined as a monounsaturated fatty acid (MUFA) characterized by a single double bond within its carbon chain.[1]It is an important naturally occurring lipid in human metabolism, primarily produced through endogenous synthesis as an elongation product of other fatty acids like palmitoleic or oleic acid.[1]Functionally, vaccenic acid, along with other MUFAs, is a vital component of cellular membranes, contributing to their structural integrity and fluidity. Furthermore, MUFAs serve as essential energy sources for the body, undergoing β-oxidation within mitochondria to generate ATP, particularly notable in tissues such as skeletal muscle during physical activity.[1]The conceptual framework surrounding vaccenic acid emphasizes its significant role in human health, particularly its association with cardiometabolic diseases. Elevated levels of vaccenic acid in plasma and erythrocyte membranes have been epidemiologically linked to an increased risk of Type 2 Diabetes (T2D), various metabolic abnormalities, and Cardiovascular Disease (CVD) in diverse populations.[1]This makes the precise and understanding of vaccenic acid levels critical for assessing metabolic health and disease risk, underscoring its importance in lipid biology and clinical research.
Approaches and Operational Definitions
Section titled “Approaches and Operational Definitions”The quantification of vaccenic acid levels relies on standardized analytical methods and operational definitions to ensure consistency and comparability across studies. Vaccenic acid levels are typically expressed as a percentage of total fatty acids (FAs) within a given biological sample.[1] Operational definitions for sample collection often involve fasting conditions to minimize dietary influence on circulating FA levels. approaches vary depending on the tissue matrix; for instance, fasting plasma phospholipids are commonly isolated via Thin-Layer Chromatography (TLC), with subsequent quantification of FAs performed using gas chromatography.[1] Alternatively, total plasma FAs or erythrocyte FAs can be directly measured using gas chromatography or gas-liquid chromatography.[1]Despite variations in protocols across different cohorts—such as quantifying vaccenic acid in plasma phospholipids, total plasma, or erythrocyte membranes—studies indicate that these differences do not introduce significant noise or bias into genetic association results.[1] For research purposes, particularly in Genome-Wide Association Studies (GWAS), linear regression models are applied to test associations between genetic variants and individual FA levels. These models are rigorously adjusted for confounding factors such as age, sex, site of recruitment, and principal components to account for population stratification, thereby ensuring robust and reliable criteria.[1]
Genetic and Clinical Classification of Vaccenic Acid Levels
Section titled “Genetic and Clinical Classification of Vaccenic Acid Levels”The classification of vaccenic acid levels extends beyond mere quantitative measures to include its genetic determinants and clinical implications. Genetic studies have identified specific loci significantly associated with circulating vaccenic acid concentrations, providing a molecular basis for understanding inter-individual variability. Notably, genome-wide significant associations for vaccenic acid levels have been found at theFADS1/2 and PKD2L1 loci.[1] For example, the minor allele A of PKD2L1-rs603424 is consistently associated with lower vaccenic acid levels, whereas minor alleles ofFADS1/2 variants are linked to higher levels.[1]These genetic insights contribute to a more nuanced classification of an individual’s predisposition to certain vaccenic acid profiles.
Clinically, the classification of vaccenic acid levels often involves thresholds or cut-off values, although specific diagnostic criteria for disease based solely on vaccenic acid are still evolving. Elevated vaccenic acid levels are broadly categorized as a biomarker associated with an increased risk of cardiometabolic diseases such as T2D, metabolic abnormalities, and CVD.[1]Pathway-based analyses further refine this classification by linking vaccenic acid levels to broader metabolic processes, including the biosynthesis of unsaturated FAs, α-linolenic acid metabolism, glycerophospholipid metabolism, and the PPAR signaling pathway.[1]Such comprehensive genetic and metabolic classifications help elucidate the complex interplay between genetic factors, lipid metabolism, and disease risk.
Monounsaturated Fatty Acid Metabolism and Vaccenic Acid Biosynthesis
Section titled “Monounsaturated Fatty Acid Metabolism and Vaccenic Acid Biosynthesis”Vaccenic acid (18:1n-7) is a monounsaturated fatty acid (MUFA) characterized by a single double bond in its carbon chain.[1]These fatty acids are essential components of cell membranes and serve as vital energy sources, particularly through β-oxidation in mitochondria, which is active in tissues like skeletal muscle during exercise.[2]While MUFAs can be obtained from diet, vaccenic acid is primarily an elongation product of other MUFAs, specifically palmitoleic acid (16:1n-7) or oleic acid (18:1n-9), through endogenous synthesis pathways within the body.[1]The synthesis of these foundational MUFAs, palmitoleic and oleic acid, largely occurs via de novo lipogenesis (DNL) in key metabolic organs such as the liver and adipose tissue.[3] This process involves the Δ-9 desaturase enzyme, encoded by the SCDgene, which catalyzes the introduction of a double bond into saturated fatty acids like palmitic and stearic acid, converting them into their monounsaturated counterparts.[4]The elongation of these initial MUFAs then leads to the formation of longer-chain MUFAs such as vaccenic acid, gondoic acid (20:1n-9), erucic acid (22:1n-9), and nervonic acid (24:1n-9).[1]
Genetic Regulation of Fatty Acid Desaturation and Elongation
Section titled “Genetic Regulation of Fatty Acid Desaturation and Elongation”Genetic factors significantly influence the circulating levels of vaccenic acid and other MUFAs, with several genes playing critical roles in their metabolic pathways. Variants within theFADS1/2gene cluster, which encode Δ5 and Δ6 desaturases, have been consistently associated with higher vaccenic acid levels.[1]While these desaturases are primarily known for their involvement in polyunsaturated fatty acid (PUFA) biosynthesis, recent research indicates that Δ6 desaturase can also modify saturated fatty acid substrates like palmitic and stearic acid, thereby potentially influencing MUFA levels through substrate availability or direct catalytic action.[5]Another key genetic locus influencing vaccenic acid isPKD2L1, where the minor allele A of PKD2L1-rs603424 has been linked to lower vaccenic acid levels.[1] This genetic association appears to be mediated through the regulation of SCD transcription, as PKD2L1-rs603424 has been found to correlate with SCD RNA levels in adipose tissue.[1] This suggests a regulatory network where genetic variation outside of the primary desaturase genes can indirectly impact fatty acid profiles by modulating the expression of key metabolic enzymes. Other genes such as HIF1AN, LPCAT3, FEN1, WNT8B, and NDUFB8 have also been implicated in broader MUFA metabolism through gene-based analyses.[1]
Glucokinase Regulation and Systemic Lipid Homeostasis
Section titled “Glucokinase Regulation and Systemic Lipid Homeostasis”The GCKRgene, encoding the glucokinase regulator protein, plays a central role in maintaining systemic lipid and glucose homeostasis by inhibiting glucokinase (GCK) activity in the liver and pancreas.[1]Glucokinase is a crucial enzyme in glucose metabolism, initiating glycolysis, and its regulation byGCKR directly impacts glycolytic flux and the rate of de novo lipogenesis (DNL).[1] A specific missense variant, GCKR-rs1260326 (p.P446L), has been identified as a likely driver of associations between GCKRand MUFA levels, including palmitoleic acid, by modifyingGCK activity and consequently altering the DNL pathway.[1]Disruptions in these finely tuned metabolic pathways can have systemic consequences, affecting various tissues and organs involved in fatty acid metabolism, such as adipose tissue, liver, and skeletal muscle.[6] For instance, LPCAT3, which encodes lysophosphatidylcholine acyltransferase 3, is involved in lysophospholipid esterification, another process that contributes to overall lipid homeostasis.[1] The interconnectedness of these genetic and metabolic factors highlights the complexity of maintaining balanced fatty acid profiles and their broad impact on physiological function.
Pathophysiological Implications of Vaccenic Acid Levels
Section titled “Pathophysiological Implications of Vaccenic Acid Levels”The regulation of vaccenic acid and other MUFA levels is critical for cardiometabolic health, as imbalances are frequently associated with adverse health outcomes. Elevated plasma and erythrocyte membrane levels of specific MUFAs, including vaccenic acid, palmitoleic acid, erucic acid, and nervonic acid, have been consistently linked to an increased risk of Type 2 Diabetes (T2D), metabolic abnormalities, and Cardiovascular Disease (CVD).[7] These associations underscore the importance of MUFAs in the pathogenesis of common chronic diseases.
Further supporting these links, studies in Chinese populations have also observed that higher levels of erythrocyte palmitoleic and oleic acid are associated with an increased risk of metabolic syndrome (MS) and T2D.[8] Genetic evidence also points to these pathophysiological connections, with suggestive associations found between PKD2L1-rs603424 and Coronary Artery Disease (CAD), and betweenGCKR-rs780094 and T2D.[1]These findings collectively emphasize that understanding the biological pathways governing vaccenic acid levels is crucial for elucidating the mechanisms underlying cardiometabolic disorders and developing targeted interventions.
Endogenous Biosynthesis and Metabolic Flux Control
Section titled “Endogenous Biosynthesis and Metabolic Flux Control”Vaccenic acid is a monounsaturated fatty acid (MUFA) primarily generated through endogenous synthesis within the body.[5]Its production pathway involves the elongation of shorter-chain MUFAs, specifically palmitoleic acid or oleic acid, which are themselves products of desaturation reactions.[5] This entire process is intricately linked to the broader de novo lipogenesis (DNL) pathway, which synthesizes fatty acids from non-lipid precursors like carbohydrates.
Key enzymes in this pathway include stearoyl-CoA desaturase (SCD), which catalyzes the introduction of a double bond into saturated fatty acids such as palmitic and stearic acid to form palmitoleic and oleic acid, respectively.[4]These desaturated products serve as essential precursors for subsequent elongation steps leading to vaccenic acid. Furthermore, the glucokinase regulator (GCKR) plays a pivotal role in metabolic flux control by inhibiting glucokinase (GCK) activity in the liver and pancreas.[1]This inhibition directly impacts glycolytic flux, thereby modulating the availability of substrates for DNL and, consequently, the endogenous production of vaccenic acid and its precursors.[1]
Genetic Regulation of Fatty Acid Desaturation
Section titled “Genetic Regulation of Fatty Acid Desaturation”The levels of vaccenic acid are subject to significant genetic regulation, particularly through genes encoding fatty acid desaturases. For instance, the minor allele A ofPKD2L1-rs603424 is significantly associated with lower vaccenic acid levels.[1] This genetic variant is hypothesized to exert its effect by influencing the RNA expression levels of SCD in adipose tissue, thereby modulating the transcriptional activity of this critical desaturase enzyme.[1] Altered SCDactivity directly impacts the availability of palmitoleic and oleic acids, which are direct precursors to vaccenic acid.
Another crucial genetic locus is FADS1/FADS2, where variants are associated with higher vaccenic acid levels.[1] While FADS1 and FADS2primarily encode Δ5 and Δ6 desaturases involved in polyunsaturated fatty acid (PUFA) biosynthesis, studies suggest that Δ6 desaturase can also catalyze the desaturation of saturated fatty acids like palmitic and stearic acid to produce other unsaturated fatty acids.[1] This mechanism implies that FADS1/FADS2 variants may influence specific MUFA levels not just through direct desaturation, but potentially by altering the substrate pool available for elongation, highlighting a complex regulatory interplay within fatty acid metabolism.[1]
Cross-Pathway Metabolic Integration and Allosteric Control
Section titled “Cross-Pathway Metabolic Integration and Allosteric Control”The regulation of vaccenic acid levels is not an isolated process but is intricately integrated within a broader network of metabolic pathways. Pathway-based analyses have highlighted associations with diverse processes such as the biosynthesis of unsaturated fatty acids, alpha-linolenic acid metabolism, glycerophospholipid metabolism, and thePPAR signaling pathway.[1]This demonstrates significant pathway crosstalk, where changes in one lipid or glucose metabolic route can have cascading effects on vaccenic acid synthesis or degradation.
A prime example of this integration and regulatory mechanism is the role of GCKRin allosteric control. The glucokinase regulator (GCKR) protein directly inhibits the activity of glucokinase (GCK), an enzyme central to glucose phosphorylation and glycolytic flux.[1] A specific missense variant, rs1260326 , within the GCKR locus has been identified as a key driver affecting GCK activity, thereby influencing the rate of de novo lipogenesis.[1] This allosteric regulation of GCK by GCKRrepresents a hierarchical control point, linking carbohydrate metabolism to fatty acid synthesis pathways and ultimately impacting the substrate availability for vaccenic acid production.
Vaccenic Acid in Cardiometabolic Disease
Section titled “Vaccenic Acid in Cardiometabolic Disease”Dysregulation in vaccenic acid metabolism and its associated pathways is closely linked to the pathogenesis of several cardiometabolic diseases. Elevated levels of vaccenic acid in plasma and erythrocyte membranes have been consistently associated with an increased risk of Type 2 Diabetes (T2D), various metabolic abnormalities, and cardiovascular disease (CVD).[1]These associations underscore the functional significance of vaccenic acid beyond its roles as an energy source or membrane component.
The genetic loci influencing vaccenic acid levels also exhibit disease-relevant mechanisms. For instance, variants inFADS1/FADS2 have been significantly associated with T2D, while GCKR variants show associations with BMI.[1] Additionally, PKD2L1-rs603424 , which influences SCDtranscription and vaccenic acid levels, has suggestive associations with coronary artery disease (CAD) and T2D.[1]These findings suggest that alterations in the pathways governing vaccenic acid synthesis and regulation contribute to the development and progression of these complex diseases, potentially by affecting overall lipid homeostasis, insulin sensitivity, or inflammatory responses, thus identifying these genes as potential therapeutic targets for cardiometabolic disorders.
Role in Cardiometabolic Health and Risk Assessment
Section titled “Role in Cardiometabolic Health and Risk Assessment”Vaccenic acid, as an endogenously synthesized monounsaturated fatty acid (MUFA) and an important component of cell membranes, plays a significant role in human metabolism. Research indicates that elevated levels of vaccenic acid, alongside other specific plasma and erythrocyte membrane MUFAs, are associated with an increased risk of Type 2 Diabetes (T2D), various metabolic abnormalities, and cardiovascular disease (CVD) in European populations. These associations highlight vaccenic acid’s potential as a valuable biomarker for assessing an individual’s susceptibility to these widespread cardiometabolic conditions. Its could contribute to early risk stratification, enabling clinicians to identify individuals who may benefit from targeted lifestyle interventions or more intensive monitoring to prevent disease onset or progression.
Genetic Determinants and Comorbidity Links
Section titled “Genetic Determinants and Comorbidity Links”Genetic studies have shed light on the inherited factors influencing circulating vaccenic acid levels and their connections to broader health outcomes. Trans-ethnic meta-analyses, involving Chinese and European populations, have identified novel genome-wide significant associations for vaccenic acid at loci such asPKD2L1, FADS1/FADS2, and GCKR. For instance, a minor allele of PKD2L1-rs603424 is linked to lower vaccenic acid levels, while minor alleles ofFADS1/FADS2variants are associated with higher levels of vaccenic acid in both European and Chinese populations. These genetic insights are crucial for understanding the underlying biological pathways of vaccenic acid metabolism, including its endogenous synthesis from palmitoleic or oleic acid.[5] and how these pathways interact with other metabolic processes.
Furthermore, these genetic associations extend to various comorbidities, suggesting overlapping biological mechanisms. Specifically, the FADS1/FADS2 variant rs102275 has been associated with T2D, and GCKR-rs780094 shows suggestive associations with T2D and a significant association with BMI. There is also suggestive evidence linking PKD2L1-rs603424 to coronary artery disease (CAD). These findings indicate that genetic variations influencing vaccenic acid levels are often implicated in the broader spectrum of cardiometabolic disorders, offering potential avenues for understanding complex disease etiologies and identifying individuals at risk through genetic profiling.
Prognostic Value and Personalized Medicine Approaches
Section titled “Prognostic Value and Personalized Medicine Approaches”The established associations between vaccenic acid levels and cardiometabolic diseases impart significant prognostic value to its . Monitoring vaccenic acid levels, potentially alongside an individual’s genetic profile at loci likeFADS1/FADS2, PKD2L1, and GCKR, could aid in predicting an individual’s long-term risk for T2D, CVD, and metabolic syndrome. This comprehensive approach allows for more precise risk stratification, moving beyond traditional risk factors to incorporate molecular and genetic predispositions.
Such insights are foundational for developing personalized medicine strategies, where treatment selection and prevention strategies can be tailored to an individual’s unique metabolic and genetic landscape. By identifying high-risk individuals through vaccenic acid levels and associated genetic markers, clinicians can implement targeted interventions, monitor treatment response more effectively, and potentially mitigate disease progression. The understanding of pathways like the biosynthesis of unsaturated fatty acids and PPAR signaling, which are associated with vaccenic acid levels, further supports the development of precision health interventions aimed at optimizing lipid profiles and improving overall cardiometabolic health.
Frequently Asked Questions About Vaccenic Acid
Section titled “Frequently Asked Questions About Vaccenic Acid”These questions address the most important and specific aspects of vaccenic acid based on current genetic research.
1. My family has heart issues; am I at risk for certain fats?
Section titled “1. My family has heart issues; am I at risk for certain fats?”Yes, your family history can play a role. Genetic variations, such as those near the PKD2L1 gene (like *rs603424 *), have been linked to lower vaccenic acid levels, with suggestive evidence for an association with Coronary Artery Disease. Conversely, higher vaccenic acid levels in general have been associated with an increased risk of cardiovascular disease. Understanding these genetic influences can help assess your personal risk.
2. If I eat a healthy diet, can my body still make unhealthy fat levels?
Section titled “2. If I eat a healthy diet, can my body still make unhealthy fat levels?”Yes, it’s possible. While diet influences your vaccenic acid levels, your body also synthesizes it internally, and this process is influenced by genetics. For example, variants within theFADS1/2gene cluster have been linked to higher vaccenic acid levels. This means genetic factors can predispose you to certain fat levels even with good dietary habits.
3. Does my age affect how my body processes certain fats?
Section titled “3. Does my age affect how my body processes certain fats?”The current research on vaccenic acid primarily involved middle-aged to older individuals, suggesting that age could be a factor in how these genetic influences manifest. While the study didn’t detail age-specific metabolic changes, it highlights that findings might not fully capture genetic influences that differ across the lifespan. More research is needed to understand the full impact of age.
4. Would my ethnic background change how my body handles fats?
Section titled “4. Would my ethnic background change how my body handles fats?”Yes, your ethnic background can influence how your body handles fats like vaccenic acid. Research has shown that genetic influences on these fat levels can differ across various populations. While studies have combined data from Chinese and European ancestries, the findings are primarily limited to these groups, meaning other ethnic populations may have different genetic architectures and environmental influences.
5. Why do some people naturally have lower levels of certain unhealthy fats than me?
Section titled “5. Why do some people naturally have lower levels of certain unhealthy fats than me?”It often comes down to genetics. Variants in genes like FADS1/2can lead to higher vaccenic acid levels in some individuals. Conversely, a specific variant,*rs603424 *, located near the SCDgene, has been associated with lower vaccenic acid levels. These genetic differences influence how your body produces and regulates these fats.
6. Can a blood test tell me if my fat metabolism is off?
Section titled “6. Can a blood test tell me if my fat metabolism is off?”Yes, a blood test can measure your vaccenic acid levels, typically expressed as a percentage of your total fatty acids. Abnormal levels of vaccenic acid have been implicated in various health conditions, including Type 2 Diabetes and Cardiovascular Disease. This can provide insight into your cardiometabolic health.
7. Could what I eat actually make my body produce more unhealthy fats?
Section titled “7. Could what I eat actually make my body produce more unhealthy fats?”Yes, dietary intake is a significant factor. Vaccenic acid is both synthesized in your body and obtained through your diet. If your diet contributes to higher levels, and especially if you have certain genetic predispositions like variants inFADS1/2linked to higher vaccenic acid, it could contribute to levels associated with health risks.
8. Could my fat levels be linked to my risk for type 2 diabetes?
Section titled “8. Could my fat levels be linked to my risk for type 2 diabetes?”Absolutely. Elevated levels of vaccenic acid have been directly associated with an increased risk of Type 2 Diabetes (T2D) and metabolic abnormalities. Furthermore, specific genetic variants, such as*rs102275 * in the FADS1/2gene, which influence vaccenic acid levels, have also shown associations with T2D risk.
9. Can knowing about my specific fat levels help me prevent future health issues?
Section titled “9. Can knowing about my specific fat levels help me prevent future health issues?”Yes, understanding your vaccenic acid levels can be valuable. Given its association with prevalent cardiometabolic diseases like Type 2 Diabetes and Cardiovascular Disease, insights into your personal levels can inform public health strategies and personalized nutritional recommendations. This knowledge supports proactive management and potential interventions.
10. If I have specific fat risks, can exercise and lifestyle changes overcome them?
Section titled “10. If I have specific fat risks, can exercise and lifestyle changes overcome them?”While genetic factors certainly influence your vaccenic acid levels, environmental and lifestyle factors are also very important. Vaccenic acid levels are influenced by diet, and exercise is a vital energy source for muscles. Although specific details on how exercisechangesvaccenic acid weren’t fully detailed in this research, a healthy lifestyle generally plays a crucial role in managing overall cardiometabolic health, even with genetic predispositions.
This FAQ was automatically generated based on current genetic research and may be updated as new information becomes available.
Disclaimer: This information is for educational purposes only and should not be used as a substitute for professional medical advice. Always consult with a healthcare provider for personalized medical guidance.
References
Section titled “References”[1] Hu Y, et al. Discovery and fine-mapping of loci associated with MUFAs through trans-ethnic meta-analysis in Chinese and European populations. J Lipid Res. 2017 Mar;58(3):599-611. PMID: 28298293.
[2] Kremmyda, L. S., E. Tvrzicka, B. Stankova, and A. Zak. “Fatty acids as biocompounds: their role in human metabolism, health and disease: a review. Part 2: fatty acid physiological roles and applications in human health and disease.”Biomedical Papers of the Medical Faculty of the University Palacky Olomouc Czech Republic, vol. 155, 2011, pp. 195–218.
[3] Calder, P. C. “Functional roles of fatty acids and their effects on human health.” Journal of Parenteral and Enteral Nutrition, vol. 39, 2015, pp. 18S–32S.
[4] Paton, C. M., and J. M. Ntambi. “Biochemical and physiological function of stearoyl-CoA desaturase.” Am. J. Physiol. Endocrinol. Metab., vol. 297, 2009, pp. E28–E37.
[5] Tvrzicka, E., L. S. Kremmyda, B. Stankova, and A. Zak. “Fatty acids as biocompounds: their role in human metabolism, health and disease–a review. Part 1: classification, dietary sources and biological functions.”Biomed. Pap. Med. Fac. Univ. Palacky Olomouc Czech Repub., vol. 155, 2011, pp. 117–130.
[6] Frayn, K. N., P. Arner, and H. Yki-Jarvinen. “Fatty acid metabolism in adipose tissue, muscle and liver in health and disease.”Essays in Biochemistry, vol. 42, 2006, pp. 89–103.
[7] Wang, L., et al. “Genome-wide association study identifies novel loci associated with concentrations of four plasma phospholipid fatty acids in the de novo lipogenesis pathway: results from the Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) consortium.”Circulation: Cardiovascular Genetics, vol. 6, 2013, pp. 171–183.
[8] Zheng, Y., et al. “Erythrocyte membrane fatty acid composition and the risk of metabolic syndrome in Chinese adults.” Journal of Atherosclerosis and Thrombosis, vol. 19, 2012, pp. 554–562.