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Diet-gene interactions and PUFA metabolism: a potential contributor to health disparities and human diseases.

Chilton FH, Murphy RC, Wilson BA, Sergeant S, Ainsworth H, Seeds MC, Mathias RA - Nutrients (2014)

Bottom Line: Recent studies have uncovered population-related genetic variation in the LCPUFA biosynthetic pathway (especially within the fatty acid desaturase gene (FADS) cluster) that is associated with levels of circulating and tissue PUFAs and several biomarkers and clinical endpoints of cardiovascular disease (CVD).Importantly, populations of African descent have higher frequencies of variants associated with elevated levels of arachidonic acid (ARA), CVD biomarkers and disease endpoints.These observations raise important questions of whether gene-PUFA interactions are differentially driving the risk of cardiovascular and other diseases in diverse populations, and contributing to health disparities, especially in African American populations.

View Article: PubMed Central - PubMed

Affiliation: The Center for Botanical Lipids and Inflammatory Disease Prevention, Wake Forest School of Medicine, Winston-Salem, NC 27157, USA. schilton@wakehealth.edu.

ABSTRACT
The "modern western" diet (MWD) has increased the onset and progression of chronic human diseases as qualitatively and quantitatively maladaptive dietary components give rise to obesity and destructive gene-diet interactions. There has been a three-fold increase in dietary levels of the omega-6 (n-6) 18 carbon (C18), polyunsaturated fatty acid (PUFA) linoleic acid (LA; 18:2n-6), with the addition of cooking oils and processed foods to the MWD. Intense debate has emerged regarding the impact of this increase on human health. Recent studies have uncovered population-related genetic variation in the LCPUFA biosynthetic pathway (especially within the fatty acid desaturase gene (FADS) cluster) that is associated with levels of circulating and tissue PUFAs and several biomarkers and clinical endpoints of cardiovascular disease (CVD). Importantly, populations of African descent have higher frequencies of variants associated with elevated levels of arachidonic acid (ARA), CVD biomarkers and disease endpoints. Additionally, nutrigenomic interactions between dietary n-6 PUFAs and variants in genes that encode for enzymes that mobilize and metabolize ARA to eicosanoids have been identified. These observations raise important questions of whether gene-PUFA interactions are differentially driving the risk of cardiovascular and other diseases in diverse populations, and contributing to health disparities, especially in African American populations.

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Related in: MedlinePlus

LCPUFA Biosynthetic Pathways. LCPUFA are derived from C18PUFAs (LA and ALA obtained from the mammalian diet) by alternate desaturation (red/orange enzymes) and elongation (blue enzymes) steps. These enzymes utilize both n-6 and n-3 substrates. n-3 LCPUFAs undergo further metabolism through a β-oxidation step (green box) to the generate DHA.
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nutrients-06-01993-f001: LCPUFA Biosynthetic Pathways. LCPUFA are derived from C18PUFAs (LA and ALA obtained from the mammalian diet) by alternate desaturation (red/orange enzymes) and elongation (blue enzymes) steps. These enzymes utilize both n-6 and n-3 substrates. n-3 LCPUFAs undergo further metabolism through a β-oxidation step (green box) to the generate DHA.

Mentions: For the purposes of this review, we will discuss the metabolism, genetics and biology of the most abundant n-6 or n-3 18 carbon (C18) PUFAs and the n-6 or n-3 long chain (LC; 20–24 carbon) PUFAs. Two C18 PUFAs, linoleic acid (LA, 18:2, n-6) and α-linolenic acid (ALA, 18:3, n-3) are considered essential fatty acids because they cannot be synthesized by mammals including humans and thus must be obtained from the diet (Figure 1). LA is found in vegetable oil products (soybean, corn, palm, and canola oils as well as margarine and shortenings), and is by far the most abundant PUFA in today’s MWD, contributing more than 90% of ingested PUFAs and 7%–8% of food energy consumed [16]. ALA is found in green plants, nuts and botanical oils, such as flax seed oil, and represents ~1% of food energy.


Diet-gene interactions and PUFA metabolism: a potential contributor to health disparities and human diseases.

Chilton FH, Murphy RC, Wilson BA, Sergeant S, Ainsworth H, Seeds MC, Mathias RA - Nutrients (2014)

LCPUFA Biosynthetic Pathways. LCPUFA are derived from C18PUFAs (LA and ALA obtained from the mammalian diet) by alternate desaturation (red/orange enzymes) and elongation (blue enzymes) steps. These enzymes utilize both n-6 and n-3 substrates. n-3 LCPUFAs undergo further metabolism through a β-oxidation step (green box) to the generate DHA.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4042578&req=5

nutrients-06-01993-f001: LCPUFA Biosynthetic Pathways. LCPUFA are derived from C18PUFAs (LA and ALA obtained from the mammalian diet) by alternate desaturation (red/orange enzymes) and elongation (blue enzymes) steps. These enzymes utilize both n-6 and n-3 substrates. n-3 LCPUFAs undergo further metabolism through a β-oxidation step (green box) to the generate DHA.
Mentions: For the purposes of this review, we will discuss the metabolism, genetics and biology of the most abundant n-6 or n-3 18 carbon (C18) PUFAs and the n-6 or n-3 long chain (LC; 20–24 carbon) PUFAs. Two C18 PUFAs, linoleic acid (LA, 18:2, n-6) and α-linolenic acid (ALA, 18:3, n-3) are considered essential fatty acids because they cannot be synthesized by mammals including humans and thus must be obtained from the diet (Figure 1). LA is found in vegetable oil products (soybean, corn, palm, and canola oils as well as margarine and shortenings), and is by far the most abundant PUFA in today’s MWD, contributing more than 90% of ingested PUFAs and 7%–8% of food energy consumed [16]. ALA is found in green plants, nuts and botanical oils, such as flax seed oil, and represents ~1% of food energy.

Bottom Line: Recent studies have uncovered population-related genetic variation in the LCPUFA biosynthetic pathway (especially within the fatty acid desaturase gene (FADS) cluster) that is associated with levels of circulating and tissue PUFAs and several biomarkers and clinical endpoints of cardiovascular disease (CVD).Importantly, populations of African descent have higher frequencies of variants associated with elevated levels of arachidonic acid (ARA), CVD biomarkers and disease endpoints.These observations raise important questions of whether gene-PUFA interactions are differentially driving the risk of cardiovascular and other diseases in diverse populations, and contributing to health disparities, especially in African American populations.

View Article: PubMed Central - PubMed

Affiliation: The Center for Botanical Lipids and Inflammatory Disease Prevention, Wake Forest School of Medicine, Winston-Salem, NC 27157, USA. schilton@wakehealth.edu.

ABSTRACT
The "modern western" diet (MWD) has increased the onset and progression of chronic human diseases as qualitatively and quantitatively maladaptive dietary components give rise to obesity and destructive gene-diet interactions. There has been a three-fold increase in dietary levels of the omega-6 (n-6) 18 carbon (C18), polyunsaturated fatty acid (PUFA) linoleic acid (LA; 18:2n-6), with the addition of cooking oils and processed foods to the MWD. Intense debate has emerged regarding the impact of this increase on human health. Recent studies have uncovered population-related genetic variation in the LCPUFA biosynthetic pathway (especially within the fatty acid desaturase gene (FADS) cluster) that is associated with levels of circulating and tissue PUFAs and several biomarkers and clinical endpoints of cardiovascular disease (CVD). Importantly, populations of African descent have higher frequencies of variants associated with elevated levels of arachidonic acid (ARA), CVD biomarkers and disease endpoints. Additionally, nutrigenomic interactions between dietary n-6 PUFAs and variants in genes that encode for enzymes that mobilize and metabolize ARA to eicosanoids have been identified. These observations raise important questions of whether gene-PUFA interactions are differentially driving the risk of cardiovascular and other diseases in diverse populations, and contributing to health disparities, especially in African American populations.

Show MeSH
Related in: MedlinePlus