Limits...
Maternal high fat diet is associated with decreased plasma n-3 fatty acids and fetal hepatic apoptosis in nonhuman primates.

Grant WF, Gillingham MB, Batra AK, Fewkes NM, Comstock SM, Takahashi D, Braun TP, Grove KL, Friedman JE, Marks DL - PLoS ONE (2011)

Bottom Line: To begin to understand the contributions of maternal obesity and over-nutrition to human development and the early origins of obesity, we utilized a non-human primate model to investigate the effects of maternal high-fat feeding and obesity on breast milk, maternal and fetal plasma fatty acid composition and fetal hepatic development.Furthermore, the HFD fetal plasma n-6:n-3 ratio was elevated and was significantly correlated to the maternal plasma n-6:n-3 ratio and maternal hyperinsulinemia.This study links chronic maternal consumption of a HFD with fetal hepatic apoptosis and suggests that a potentially pathological maternal fatty acid milieu is replicated in the developing fetal circulation in the nonhuman primate.

View Article: PubMed Central - PubMed

Affiliation: Neuroscience Graduate Program, Oregon Health & Science University, Portland, Oregon, United States of America.

ABSTRACT
To begin to understand the contributions of maternal obesity and over-nutrition to human development and the early origins of obesity, we utilized a non-human primate model to investigate the effects of maternal high-fat feeding and obesity on breast milk, maternal and fetal plasma fatty acid composition and fetal hepatic development. While the high-fat diet (HFD) contained equivalent levels of n-3 fatty acids (FA's) and higher levels of n-6 FA's than the control diet (CTR), we found significant decreases in docosahexaenoic acid (DHA) and total n-3 FA's in HFD maternal and fetal plasma. Furthermore, the HFD fetal plasma n-6:n-3 ratio was elevated and was significantly correlated to the maternal plasma n-6:n-3 ratio and maternal hyperinsulinemia. Hepatic apoptosis was also increased in the HFD fetal liver. Switching HFD females to a CTR diet during a subsequent pregnancy normalized fetal DHA, n-3 FA's and fetal hepatic apoptosis to CTR levels. Breast milk from HFD dams contained lower levels of eicosopentanoic acid (EPA) and DHA and lower levels of total protein than CTR breast milk. This study links chronic maternal consumption of a HFD with fetal hepatic apoptosis and suggests that a potentially pathological maternal fatty acid milieu is replicated in the developing fetal circulation in the nonhuman primate.

Show MeSH

Related in: MedlinePlus

Correlation of fetal plasma fatty acids with maternal insulin resistance and glucose clearance.Pair-wise correlation analysis of fetal plasma N6∶N3 fatty acid ratio with respective maternal insulin AUC (A), across CTR, HFD and REV maternal diet groups. Pair-wise correlation analysis of total fetal plasma saturated FA's with respective maternal glucose AUC (B), across CTR, HFD and REV maternal diet groups. (n = 23 maternal/fetal pairs). Fetal N6∶N3 ratio is positively correlated with maternal insulin AUC. Total fetal plasma saturated FA's are correlated with maternal glucose AUC. (CTR: white squares, HFD: dark grey circles, REV: grey diamonds).
© Copyright Policy
Related In: Results  -  Collection


getmorefigures.php?uid=PMC3045408&req=5

pone-0017261-g002: Correlation of fetal plasma fatty acids with maternal insulin resistance and glucose clearance.Pair-wise correlation analysis of fetal plasma N6∶N3 fatty acid ratio with respective maternal insulin AUC (A), across CTR, HFD and REV maternal diet groups. Pair-wise correlation analysis of total fetal plasma saturated FA's with respective maternal glucose AUC (B), across CTR, HFD and REV maternal diet groups. (n = 23 maternal/fetal pairs). Fetal N6∶N3 ratio is positively correlated with maternal insulin AUC. Total fetal plasma saturated FA's are correlated with maternal glucose AUC. (CTR: white squares, HFD: dark grey circles, REV: grey diamonds).

Mentions: Interestingly, we found that the fetal plasma n-6∶n-3 ratio was positively correlated with maternal insulin AUC (Roverall = .61, p = .002, Figure 2A). No other fetal plasma fatty acids assayed were correlated with the maternal insulin AUC. Additionally, we found that the total fetal plasma levels of saturated fatty acids (Roverall = .54, p = .007, Figure 2B) were correlated with the maternal glucose AUC, as were the individual saturated fatty acids C14:0 (myristic acid; Roverall = .43, p = .04), C16:0 (palmitic acid; Roverall = .45, p = .04). In addition, C18:1 (oleic acid; Roverall = .43, p = .04) and C18:3 (α-linolenic acid ( n-3); Roverall = .50, p = .01 ) were also positively correlated with maternal glucose AUC (Figure S1). These data extend previous associations found between maternal diet sensitivity and fetal outcomes in our model [53]. Our findings suggest that while maternal diet has been the primary predictor of fetal outcomes thus far, other maternal factors (e.g. obesity, hyperinsulinemia, etc.) may also play important roles in determining the fatty acid milieu of the developing fetus.


Maternal high fat diet is associated with decreased plasma n-3 fatty acids and fetal hepatic apoptosis in nonhuman primates.

Grant WF, Gillingham MB, Batra AK, Fewkes NM, Comstock SM, Takahashi D, Braun TP, Grove KL, Friedman JE, Marks DL - PLoS ONE (2011)

Correlation of fetal plasma fatty acids with maternal insulin resistance and glucose clearance.Pair-wise correlation analysis of fetal plasma N6∶N3 fatty acid ratio with respective maternal insulin AUC (A), across CTR, HFD and REV maternal diet groups. Pair-wise correlation analysis of total fetal plasma saturated FA's with respective maternal glucose AUC (B), across CTR, HFD and REV maternal diet groups. (n = 23 maternal/fetal pairs). Fetal N6∶N3 ratio is positively correlated with maternal insulin AUC. Total fetal plasma saturated FA's are correlated with maternal glucose AUC. (CTR: white squares, HFD: dark grey circles, REV: grey diamonds).
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3045408&req=5

pone-0017261-g002: Correlation of fetal plasma fatty acids with maternal insulin resistance and glucose clearance.Pair-wise correlation analysis of fetal plasma N6∶N3 fatty acid ratio with respective maternal insulin AUC (A), across CTR, HFD and REV maternal diet groups. Pair-wise correlation analysis of total fetal plasma saturated FA's with respective maternal glucose AUC (B), across CTR, HFD and REV maternal diet groups. (n = 23 maternal/fetal pairs). Fetal N6∶N3 ratio is positively correlated with maternal insulin AUC. Total fetal plasma saturated FA's are correlated with maternal glucose AUC. (CTR: white squares, HFD: dark grey circles, REV: grey diamonds).
Mentions: Interestingly, we found that the fetal plasma n-6∶n-3 ratio was positively correlated with maternal insulin AUC (Roverall = .61, p = .002, Figure 2A). No other fetal plasma fatty acids assayed were correlated with the maternal insulin AUC. Additionally, we found that the total fetal plasma levels of saturated fatty acids (Roverall = .54, p = .007, Figure 2B) were correlated with the maternal glucose AUC, as were the individual saturated fatty acids C14:0 (myristic acid; Roverall = .43, p = .04), C16:0 (palmitic acid; Roverall = .45, p = .04). In addition, C18:1 (oleic acid; Roverall = .43, p = .04) and C18:3 (α-linolenic acid ( n-3); Roverall = .50, p = .01 ) were also positively correlated with maternal glucose AUC (Figure S1). These data extend previous associations found between maternal diet sensitivity and fetal outcomes in our model [53]. Our findings suggest that while maternal diet has been the primary predictor of fetal outcomes thus far, other maternal factors (e.g. obesity, hyperinsulinemia, etc.) may also play important roles in determining the fatty acid milieu of the developing fetus.

Bottom Line: To begin to understand the contributions of maternal obesity and over-nutrition to human development and the early origins of obesity, we utilized a non-human primate model to investigate the effects of maternal high-fat feeding and obesity on breast milk, maternal and fetal plasma fatty acid composition and fetal hepatic development.Furthermore, the HFD fetal plasma n-6:n-3 ratio was elevated and was significantly correlated to the maternal plasma n-6:n-3 ratio and maternal hyperinsulinemia.This study links chronic maternal consumption of a HFD with fetal hepatic apoptosis and suggests that a potentially pathological maternal fatty acid milieu is replicated in the developing fetal circulation in the nonhuman primate.

View Article: PubMed Central - PubMed

Affiliation: Neuroscience Graduate Program, Oregon Health & Science University, Portland, Oregon, United States of America.

ABSTRACT
To begin to understand the contributions of maternal obesity and over-nutrition to human development and the early origins of obesity, we utilized a non-human primate model to investigate the effects of maternal high-fat feeding and obesity on breast milk, maternal and fetal plasma fatty acid composition and fetal hepatic development. While the high-fat diet (HFD) contained equivalent levels of n-3 fatty acids (FA's) and higher levels of n-6 FA's than the control diet (CTR), we found significant decreases in docosahexaenoic acid (DHA) and total n-3 FA's in HFD maternal and fetal plasma. Furthermore, the HFD fetal plasma n-6:n-3 ratio was elevated and was significantly correlated to the maternal plasma n-6:n-3 ratio and maternal hyperinsulinemia. Hepatic apoptosis was also increased in the HFD fetal liver. Switching HFD females to a CTR diet during a subsequent pregnancy normalized fetal DHA, n-3 FA's and fetal hepatic apoptosis to CTR levels. Breast milk from HFD dams contained lower levels of eicosopentanoic acid (EPA) and DHA and lower levels of total protein than CTR breast milk. This study links chronic maternal consumption of a HFD with fetal hepatic apoptosis and suggests that a potentially pathological maternal fatty acid milieu is replicated in the developing fetal circulation in the nonhuman primate.

Show MeSH
Related in: MedlinePlus