FADS1

Fatty Acid Desaturase 1 (FADS1) encodes the delta-5 desaturase enzyme, a key regulator of long-chain polyunsaturated fatty acid (LC-PUFA) synthesis from essential dietary fats.

Variants in FADS1 can impair this conversion process, influencing inflammation, cardiometabolic risk, and neurological health—making it a critical focus in personalized nutrition and disease prevention.

What is Fatty Acid Desaturase 1 (FADS1)?

The FADS1 gene encodes the delta-5 desaturase (D5D) enzyme, which catalyzes key steps in the conversion of essential dietary fatty acids into long-chain polyunsaturated fatty acids (LC-PUFAs). 

These products—such as arachidonic acid (AA) and eicosapentaenoic acid (EPA)—are vital for regulating inflammation, immunity, cardiovascular function, and neural development.

The Role of FADS1 in Fatty Acid Metabolism

The following section outlines the importance of FADS1 and its relevant protein, D5D. 

The Desaturase Enzyme Family: FADS1's Place

FADS1 is part of the fatty acid desaturase family, which includes FADS2 (delta-6/desaturase) and FADS3 (function less well understood). Together, they form a critical enzymatic axis converting essential fatty acids into bioactive lipids. 

FADS1 specifically controls the delta-5-desaturation step.

Conversion of Essential Fatty Acids

D5D specifically catalyzes important events in the following PUFA pathways:

• omega-6 pathway: Dihomo-gamma-linolenic acid, DGLA (20:3n-6) → AA (20:4n-6)
• omega-3 pathway: Eicosatetraenoic acid, ETA (20:4n-3) → EPA (20:5n-3)

These conversions are rate-limiting and essential for generating signaling molecules like prostaglandins, leukotrienes, and resolvins.

Importance of PUFAs in Human Health

LC-PUFAs derived from FADS1 activity influence:

Inflammation Resolution and Immune Regulation

LC-PUFAs serve as precursors to eicosanoids and specialized pro-resolving mediators (SPMs), which help modulate immune cell function and inflammation without suppressing immune defense.

Cardiovascular Health

EPA and DHA, key products of FADS1-mediated metabolism, reduce triglyceride levels, improve endothelial function, and help regulate blood pressure and heart rhythm through anti-inflammatory and anti-thrombotic effects.

Neurodevelopment and Cognitive Function

DHA is a major structural component of neuronal membranes and is essential for brain growth, synaptic plasticity, and neurotransmission, particularly during fetal and early childhood development.

Cell Membrane Structure and Signaling

LC-PUFAs are incorporated into phospholipid bilayers, affecting membrane fluidity and the function of membrane-bound receptors and signaling proteins involved in metabolic and immune processes.

Genetic Variations and FADS1 Activity

Single Nucleotide Polymorphisms (SNPs) in the FADS Gene Cluster

Common SNPs, such as rs174550 or rs174570, within the FADS1/2/3 gene cluster on chromosome 11q12-q13.1 modulate FADS1 expression and function. These variants can have a big impact on lipid status, especially in liver tissue.

Single nucleotide polymorphisms (SNPs) in the FADS gene cluster can alter FADS1 function by reducing its gene expression, desaturase enzyme activity (D5D), and the conversion of essential fatty acids into long-chain polyunsaturated fatty acids like AA, EPA, and DPA. 

These effects are often mediated through changes in DNA methylation, where promoter methylation typically suppresses FADS1 expression, and intragenic methylation may enhance it. 

Impact on PUFA Levels

Minor alleles of these SNPs are associated with:

• Decreased FADS1 mRNA and protein levels
• Reduced conversion of dietary LA and ALA into AA, EPA, and DHA
• Accumulation of precursor fatty acids (e.g., DGLA, ETA)
• Lower levels of downstream anti-inflammatory PUFAs (e.g., EPA, DHA)

Influence on Health Outcomes

Altered PUFA balance is associated with increased risk of:

• Nonalcoholic fatty liver disease (NAFLD)
• Cardiovascular disease
• Insulin resistance and metabolic syndrome
• Inflammatory and autoimmune conditions
• Neuropsychiatric and neurodevelopmental disorders

Who Should Get FADS1 Activity or PUFA Testing?

Individuals with Suspected Fatty Acid Metabolism Disorders

Patients with conditions including NAFLD, neurological symptoms, or developmental delays may benefit from testing FADS1-related activity or PUFA levels.

Family History of Related Conditions

A significant family history of cardiometabolic, inflammatory, or psychiatric disease may warrant investigation into FADS1 SNPs or fatty acid status.

Nutritional Studies and Interventions

Researchers and clinicians assessing responses to omega-3 or omega-6 supplementation may consider FADS1 genotyping or lipidomic analysis.

Patients with Specific Conditions

Certain conditions have been associated with altered PUFA levels:

• Inflammatory conditions: e.g., various autoimmune conditions
• Cardiometabolic disease: e.g., NAFLD, diabetes, dyslipidemia
• Neurological and psychiatric disorders: where EPA/DHA levels are relevant

Test Procedure and Interpretation

Testing for FAAH is often performed as a genetic test to look for mutations in the gene that would alter functional protein availability. 

PUFA levels can also be tested directly in blood samples. 

The following section outlines the testing procedures and interpretation.

Genetic Testing Procedure and Preparation

Genetic testing involves blood, saliva, or cheek swab samples, although specialized laboratories may recommend different sample types. 

A cheek swab or saliva sample is easily obtained from the comfort of home, while blood samples typically require a blood draw.

Normal Reference Ranges

Normal reference ranges for FADS1 genetic testing are considered to be without mutations that can alter the activity of the FADS1 proteins.

Blood Testing for PUFA Levels

Testing PUFA levels in blood typically involves collecting a sample via venipuncture or dried blood spot (DBS). 

The sample is then analyzed to measure specific fatty acid concentrations, including omega-3 and omega-6 polyunsaturated fatty acids, expressed as a percentage of total fatty acids.

What Do Altered PUFA Levels Mean?

Altered PUFA levels may have the following meanings:

High Precursor Levels (DGLA, ETA)

Suggest reduced FADS1 activity, indicating a bottleneck in the conversion to AA and EPA.

Low Product Levels (AA, EPA, DHA)

Reflect impaired desaturation and may compromise inflammation resolution, immune response, and cardiovascular function.

Imbalance in Omega-6/Omega-3 Ratios

Skewed ratios may lead to:

• Increased pro-inflammatory eicosanoids (from AA)
• Decreased anti-inflammatory mediators (from EPA/DHA)

What Do Low Precursor Levels Indicate?

Reduced Substrate Availability

Low DGLA or ALA may reflect poor dietary intake or impaired upstream conversion (e.g., low FADS2 activity), not necessarily FADS1 dysfunction.

Need for Comprehensive Assessment

Always interpret PUFA levels in the context of:

• Diet
• Enzyme function upstream of FADS1
• Overall fatty acid pathway activity

Clinical Takeaways

FADS1 is a central regulator of PUFA synthesis, linking dietary essential fatty acids to inflammation and metabolic health.

SNPs in the FADS1 gene can significantly impair the conversion of LA and ALA into downstream LC-PUFAs, increasing disease risk.

Testing FADS1 function or genotype may guide personalized dietary strategies (e.g., direct EPA/DHA supplementation).

Consider FADS1-related testing in patients with metabolic disorders, inflammatory conditions, or poor response to omega-3 interventions.

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