Omega-3 Fatty Acids: DHA Lili Belcastro PC424 March 9, 2009

What are Fatty Acids? Hydrocarbon chains of varying lengths and degrees of saturation, terminated with carboxylic acid.

Hydrocarbon chains of varying lengths and degrees of saturation, terminated with carboxylic acid.

Naming of Fatty Acids Oleic acid

Saturated vs. Unsaturated

Omega-3 Fatty Acids Polyunsaturated fatty acids (PUFA) Double bond in the n−3 position (3rd C from methyl end) Important nutritionally-essential omega-3’s are: α-linolenic acid (LNA) eicosapentaenoic acid (EPA) docosahexaenoic acid (DHA)

Polyunsaturated fatty acids (PUFA)

Double bond in the n−3 position (3rd C from methyl end)

Important nutritionally-essential omega-3’s are:

α-linolenic acid (LNA)

eicosapentaenoic acid (EPA)

docosahexaenoic acid (DHA)

Omega-3 Fatty Acids DHA, EPA, and LNA are essential fatty acids obtained from the diet; no de novo synthesis. Dietary sources include fish, flax, some fruits, nuts, and vegetables, eggs, milk, and meat.

DHA, EPA, and LNA are essential fatty acids obtained from the diet; no de novo synthesis.

Dietary sources include fish, flax, some fruits, nuts, and vegetables, eggs, milk, and meat.

Docosahexanoic Acid (DHA) Most abundant PUFA in the brain Synthesized from LNA DHA LNA

Most abundant PUFA in the brain

Synthesized from LNA

Other Fatty Acids Oleic acid (OA) Docosapentanaenoic acid (DPA) Arachidonic acid (AA)

Oleic acid (OA)

Docosapentanaenoic acid (DPA)

Arachidonic acid (AA)

Omega-3 Fatty Acids and Cardiovascular Health DHA and EPA specifically  circulation, breakdown fibrin, and  BP  triglyceride levels and  risk of heart attack.

DHA and EPA specifically

 circulation, breakdown fibrin, and  BP

 triglyceride levels and  risk of heart attack.

Omega-3 Fatty Acids and Neurological Health Account for 8% of the human brain DHA is 50% of plasma membranes Prenatal development Schizophrenia, depression, Parkinson’s, and Alzheimer’s Repair damage

Account for 8% of the human brain

DHA is 50% of plasma membranes

Prenatal development

Schizophrenia, depression, Parkinson’s, and Alzheimer’s

Repair damage

Omega-3 Fatty Acids and the Inflammatory Cascade Inflammation associated with degenerative disorders Improve inflammatory diseases The PUFA ratio of omega-6 to omega-3 fatty acids Linoleic acid  -linolenic acid

PUFA Ratio 1970s Eskimo diet observed Fewer heart disease, arthritis, diabetes, and psoriasis High fat diet of omega-3’s Healthy ratios of n-6:n-3 = 1:1 to 4:1 American diet = 10:1 to 30:1 Corn, canola, safflower, sunflower oils high omega-6

1970s Eskimo diet observed

Fewer heart disease, arthritis, diabetes, and psoriasis

High fat diet of omega-3’s

Healthy ratios of n-6:n-3 = 1:1 to 4:1

American diet = 10:1 to 30:1

Corn, canola, safflower, sunflower oils high omega-6

Neurites Any projection from the cell body of a neuron: axons and dendrites Essential for proper function of neurons

Any projection from the cell body of a neuron: axons and dendrites

Essential for proper function of neurons

Docosahexaenoic Acid Promotes Neurite Growth in Hippocampal Neurons Frances Calderon and Hee-Yong Kim Journal of Neurochemistry, 2004, Vol. 90, 979-988

Frances Calderon and Hee-Yong Kim

Journal of Neurochemistry, 2004, Vol. 90,

979-988

Assumptions DHA accumulates during perinatal period Deficiency of omega-3’s  DHA in brain by 90%  levels =  density of synaptic vesicles,  soma size in hippocampal neurons  neurite growth in PC12 cells

DHA accumulates during perinatal period

Deficiency of omega-3’s  DHA in brain by 90%

 levels =  density of synaptic vesicles,  soma size in hippocampal neurons

 neurite growth in PC12 cells

Hypothesis Deficiency causes adverse effects on hippocampus Compared to other fatty acids Promotes neuronal differentiation

Deficiency causes adverse effects on hippocampus

Compared to other fatty acids

Promotes neuronal differentiation

Methods & Results In vitro study 18 day old Sprague-Dawley rat hippocampi Naturally lose PUFA in culture Day 1 = 13.8 pmol/µg Day 6 = 7.8 pmol/µg Cells supplemented with 1.5 µM of DHA reached a concentration of 14.2 pmol/µg. Cells supplemented with 1.5 µM of OA, AA, and DPA

In vitro study

18 day old Sprague-Dawley rat hippocampi

Naturally lose PUFA in culture

Day 1 = 13.8 pmol/µg

Day 6 = 7.8 pmol/µg

Cells supplemented with 1.5 µM of DHA reached a concentration of 14.2 pmol/µg.

Cells supplemented with 1.5 µM of OA, AA, and DPA

Increase in Total Neurite Length Increased length of neurites Increased number neurites

In Vivo Study Pregnant Sprague-Dawley rats fed different diets for 16 days: Deficient = 0.1% LNA Adequate = 2.6% LNA Hippocampi removed at 18 days gestation Deficient diet  neurite growth and reversed with supplementation in culture.

Pregnant Sprague-Dawley rats fed different diets for 16 days:

Deficient = 0.1% LNA

Adequate = 2.6% LNA

Hippocampi removed at 18 days gestation

Deficient diet  neurite growth and reversed with supplementation in culture.

Discussion DHA  neurite growth in vitro Specific PUFA for growth Deficient diet  neurite growth in vivo ; reversal in culture to level of adequate diet Further study in vivo , finding the molecular mechanism - membrane synthesis, gene expression, growth factors, astroglial cells Implications for the future

DHA  neurite growth in vitro

Specific PUFA for growth

Deficient diet  neurite growth in vivo ; reversal in culture to level of adequate diet

Further study in vivo , finding the molecular mechanism - membrane synthesis, gene expression, growth factors, astroglial cells

Implications for the future

Calderon, F., Hee-Yong Kim “Docosahexaenoic acid promotes neurite growth in hippocampal neurons.” Journal of Neurochemistry . 2004: 979-988. www.wikipedia.org

Calderon, F., Hee-Yong Kim “Docosahexaenoic acid promotes neurite growth in hippocampal neurons.” Journal of Neurochemistry . 2004: 979-988.

www.wikipedia.org