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Omega Fatty Acid Balance Can Alter Immunity And Gene Expression
For the past century, changes in the Western diet have altered the consumption of omega-6 fatty acids (w6, found in meat and vegetable oils) compared with omega-3 fatty acids (w3, found in flax and fish oil). Many studies seem to indicate this shift has brought about an increased risk of inflammation (associated with autoimmunity and allergy), and now using a controlled diet study with human volunteers, researchers may have teased out a biological basis for these reported changes.
See Also:
Health & Medicine
* Cholesterol
* Dietary Supplement
* Immune System
* Obesity
* Genes
* Nutrition
Reference
* Saturated fat
* Oily fish
* Zone diet
* Fatty acid
Anthropological evidence suggests that human ancestors maintained a 2:1 w6/w3 ratio for much of history, but in Western countries today the ratio has spiked to as high as 10:1. Since these omega fatty acids can be converted into inflammatory molecules, this dietary change is believed to also disrupt the proper balance of pro- and anti- inflammatory agents, resulting in increased systemic inflammation and a higher incidence of problems including asthma, allergies, diabetes, and arthritis.
Floyd Chilton and colleagues wanted to examine whether theses fatty acids might have other effects, and developed a dietary intervention strategy in which 27 healthy humans were fed a controlled diet mimicking the w6/w3 ratios of early humans over 5 weeks. They then looked at the gene levels of immune signals and cytokines (protein immune messengers), that impact autoimmunity and allergy in blood cells and found that many key signaling genes that promote inflammation were markedly reduced compared to a normal diet, including a signaling gene for a protein called PI3K, a critical early step in autoimmune and allergic inflammation responses.
This study demonstrates, for the first time in humans, that large changes in gene expression are likely an important mechanism by which these omega fatty acids exert their potent clinical effects.
Effect of Dietary Fatty Acids on Inflammatory Gene Expression in Healthy Humans*
1. Kelly L. Weaver‡§,
2. Priscilla Ivester§,1,
3. Michael Seeds‡,
4. L. Douglas Case¶,
5. Jonathan P. Arm? and
6. Floyd H. Chilton§
+ Author Affiliations
1.
From the ‡Department of Internal Medicine, Section on Molecular Medicine, and
2.
Departments of §Physiology and Pharmacology and
3.
¶Public Health Sciences, Wake Forest University School of Medicine, Winston-Salem, North Carolina 27157 and the
4.
?Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts 02115
1. 1To whom correspondence should be addressed:
Wake Forest University School of Medicine, Medical Center Blvd., Winston-Salem, NC 27157.
Tel.: 336-716-7388; Fax: 336-716-8501; E-mail: ivester@wfubmc.edu.
Abstract
Over the past 100 years, changes in the food supply in Western nations have resulted in alterations in dietary fatty acid consumption, leading to a dramatic increase in the ratio of omega-6 (?6) to ?3 polyunsaturated fatty acids (PUFA) in circulation and in tissues. Increased ?6/?3 ratios are hypothesized to increase inflammatory mediator production, leading to higher incidence of inflammatory diseases, and may impact inflammatory gene expression. To determine the effect of reducing the ?6/?3 ratio on expression of inflammatory pathway genes in mononuclear cells, healthy humans were placed on a controlled diet for 1 week, then given fish oil and borage oil for an additional 4 weeks. Serum and neutrophil fatty acid composition and ex vivo leukotriene B4 production from stimulated neutrophils were measured at the start and end of the supplementation period and after a 2-week washout. RNA was isolated from mononuclear cells and expression of PI3K, Akt, NF?B, and inflammatory cytokines was measured by real-time PCR. A marked increase was seen in serum and neutrophil levels of long-chain ?3 PUFA concomitant with a reduction in the ?6/?3 PUFA ratio (40%). The ex vivo capacity of stimulated neutrophils to produce leukotriene B4 was decreased by 31%. Expression of PI3K? and PI3K? and the quantity of PI3K? protein in mononuclear cells was reduced after supplementation, as was the expression of several proinflammatory cytokines. These data reveal that PUFA may exert their clinical effects via their capacity to regulate the expression of signal transduction genes and genes for proinflammatory cytokines.
For the past century, changes in the Western diet have altered the consumption of omega-6 fatty acids (w6, found in meat and vegetable oils) compared with omega-3 fatty acids (w3, found in flax and fish oil). Many studies seem to indicate this shift has brought about an increased risk of inflammation (associated with autoimmunity and allergy), and now using a controlled diet study with human volunteers, researchers may have teased out a biological basis for these reported changes.
See Also:
Health & Medicine
* Cholesterol
* Dietary Supplement
* Immune System
* Obesity
* Genes
* Nutrition
Reference
* Saturated fat
* Oily fish
* Zone diet
* Fatty acid
Anthropological evidence suggests that human ancestors maintained a 2:1 w6/w3 ratio for much of history, but in Western countries today the ratio has spiked to as high as 10:1. Since these omega fatty acids can be converted into inflammatory molecules, this dietary change is believed to also disrupt the proper balance of pro- and anti- inflammatory agents, resulting in increased systemic inflammation and a higher incidence of problems including asthma, allergies, diabetes, and arthritis.
Floyd Chilton and colleagues wanted to examine whether theses fatty acids might have other effects, and developed a dietary intervention strategy in which 27 healthy humans were fed a controlled diet mimicking the w6/w3 ratios of early humans over 5 weeks. They then looked at the gene levels of immune signals and cytokines (protein immune messengers), that impact autoimmunity and allergy in blood cells and found that many key signaling genes that promote inflammation were markedly reduced compared to a normal diet, including a signaling gene for a protein called PI3K, a critical early step in autoimmune and allergic inflammation responses.
This study demonstrates, for the first time in humans, that large changes in gene expression are likely an important mechanism by which these omega fatty acids exert their potent clinical effects.
Effect of Dietary Fatty Acids on Inflammatory Gene Expression in Healthy Humans*
1. Kelly L. Weaver‡§,
2. Priscilla Ivester§,1,
3. Michael Seeds‡,
4. L. Douglas Case¶,
5. Jonathan P. Arm? and
6. Floyd H. Chilton§
+ Author Affiliations
1.
From the ‡Department of Internal Medicine, Section on Molecular Medicine, and
2.
Departments of §Physiology and Pharmacology and
3.
¶Public Health Sciences, Wake Forest University School of Medicine, Winston-Salem, North Carolina 27157 and the
4.
?Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts 02115
1. 1To whom correspondence should be addressed:
Wake Forest University School of Medicine, Medical Center Blvd., Winston-Salem, NC 27157.
Tel.: 336-716-7388; Fax: 336-716-8501; E-mail: ivester@wfubmc.edu.
Abstract
Over the past 100 years, changes in the food supply in Western nations have resulted in alterations in dietary fatty acid consumption, leading to a dramatic increase in the ratio of omega-6 (?6) to ?3 polyunsaturated fatty acids (PUFA) in circulation and in tissues. Increased ?6/?3 ratios are hypothesized to increase inflammatory mediator production, leading to higher incidence of inflammatory diseases, and may impact inflammatory gene expression. To determine the effect of reducing the ?6/?3 ratio on expression of inflammatory pathway genes in mononuclear cells, healthy humans were placed on a controlled diet for 1 week, then given fish oil and borage oil for an additional 4 weeks. Serum and neutrophil fatty acid composition and ex vivo leukotriene B4 production from stimulated neutrophils were measured at the start and end of the supplementation period and after a 2-week washout. RNA was isolated from mononuclear cells and expression of PI3K, Akt, NF?B, and inflammatory cytokines was measured by real-time PCR. A marked increase was seen in serum and neutrophil levels of long-chain ?3 PUFA concomitant with a reduction in the ?6/?3 PUFA ratio (40%). The ex vivo capacity of stimulated neutrophils to produce leukotriene B4 was decreased by 31%. Expression of PI3K? and PI3K? and the quantity of PI3K? protein in mononuclear cells was reduced after supplementation, as was the expression of several proinflammatory cytokines. These data reveal that PUFA may exert their clinical effects via their capacity to regulate the expression of signal transduction genes and genes for proinflammatory cytokines.
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