Dietary Omega-3 Fatty Acid Supplementation Reduces Inflammation in Obese Pregnant Women: A Randomized Double-Blind Controlled Clinical Trial.
OBJECTIVE
Long-chain omega 3 fatty acids, eicosapentaenoic acid (EPA, 20:5n-3) and docosahexaenoic acid (DHA, 22:6n-3) exert potent anti-inflammatory properties in humans. This study characterized the effects of omega-3 ω-3 fatty acids supplements (ω-3 FA) on the inflammatory status in the placenta and adipose tissue of overweight/obese pregnant women.


METHODS
A randomized, double-masked controlled trial was conducted in overweight/obese pregnant women that were randomly assigned to receive DHA plus EPA (2 g/day) or the equivalent of a placebo twice a day from week 10-16 to term. Inflammatory pathways were characterized in: 1) adipose tissue and placenta of treated vs. untreated women; and 2) adipose and trophoblast cells cultured with long chain FAs.


RESULTS
The sum of plasma DHA and EPA increased by 5.8 fold and ω-3 FA/ω-6 FA ratio was 1.5 in treated vs. untreated women (p< 0.005). Plasma CRP concentrations were reduced (p<0.001). The adipose tissue and placenta of treated women exhibited a significant decrease in TLR4 adipose and placental expression as well as IL6, IL8, and TNFα In vitro, EPA and DHA suppressed the activation of TLR4, IL6, IL8 induced by palmitate in culture of adipose and trophoblast cells.


CONCLUSIONS
Supplementation of overweight/obese pregnant women with dietary ω-3 FAs for >25 weeks reduced inflammation in maternal adipose and the placental tissue. TLR4 appears as a central target of the anti-inflammatory effects at the cellular level.


BACKGROUND
ClinicalTrials.gov NCT00957476.
Department of Reproductive Biology, Center for Reproductive Health, MetroHealth Medical Center, Cleveland, Ohio, United States of America.
Maricela
M
Haghiac
Department of Reproductive Biology, Center for Reproductive Health, MetroHealth Medical Center, Cleveland, Ohio, United States of America.
Xiao-hua
XH
Yang
Department of Reproductive Biology, Center for Reproductive Health, MetroHealth Medical Center, Cleveland, Ohio, United States of America.
Larraine
L
Presley
Department of Reproductive Biology, Center for Reproductive Health, MetroHealth Medical Center, Cleveland, Ohio, United States of America.
Shoi
S
Smith
Department of Reproductive Biology, Center for Reproductive Health, MetroHealth Medical Center, Cleveland, Ohio, United States of America.
Shirley
S
Dettelback
Department of Reproductive Biology, Center for Reproductive Health, MetroHealth Medical Center, Cleveland, Ohio, United States of America.
Judi
J
Minium
Department of Human Nutrition, College of Education and Human Ecology, Ohio State University, Columbus, Ohio, United States of America.
Martha A
MA
Belury
Department of Reproductive Biology, Center for Reproductive Health, MetroHealth Medical Center, Cleveland, Ohio, United States of America.
Patrick M
PM
Catalano
Department of Reproductive Biology, Center for Reproductive Health, MetroHealth Medical Center, Cleveland, Ohio, United States of America.
Sylvie
S
Hauguel-de Mouzon
D000273:Adipose Tissue / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D000328:Adult; D004032:Diet; D019587:Dietary Supplements; D004281:Docosahexaenoic Acids / Q000008:administration & dosage*; D004311:Double-Blind Method; D015118:Eicosapentaenoic Acid / Q000008:administration & dosage*; D005260:Female; D005786:Gene Expression Regulation; D006801:Humans; D007249:Inflammation; D015850:Interleukin-6 / Q000235:genetics / Q000276:immunology; D016209:Interleukin-8 / Q000235:genetics / Q000276:immunology; D009765:Obesity / Q000178:diet therapy* / Q000235:genetics / Q000276:immunology / Q000473:pathology; D010920:Placenta / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D011247:Pregnancy; D061251:Primary Cell Culture; D015398:Signal Transduction; D051197:Toll-Like Receptor 4 / Q000235:genetics / Q000276:immunology; D014327:Trophoblasts / Q000187:drug effects / Q000378:metabolism / Q000473:pathology
C508600:IL6 protein, human; D015850:Interleukin-6; D016209:Interleukin-8; C495345:TLR4 protein, human; D051197:Toll-Like Receptor 4; D004281:Docosahexaenoic Acids; D015118:Eicosapentaenoic Acid