Influence of dietary long-chain PUFA on premature baboon lung FA and dipalmitoyl PC composition.

One of the major survival challenges of premature birth is production of lung surfactant. The lipid component of surfactant, dipalmitoyl PC (DPPC), increases in concentration in the period before normal term birth via a net shift in FA composition away from unsaturates. We investigated the influence of dietary DHA and arachidonic acid (AA) on lung FA composition and DPPC concentration in term and preterm baboons. Pregnant animals/neonates were randomized to one of four groups: breast-fed (B), term formula-fed (T-, preterm formula-fed (P-, and preterm fed formula supplemented with DHA-AA (P+). Breast milk contained 0.68%wt DHA and the P+ group formula contained 0.61%wt DHA. In the preterm groups (P- and P+), pregnant females received a course of antenatal corticosteroids. At the adjusted age of 4 wk, neonate lung tissue was harvested, and FA composition and DPPC were analyzed. Palmitate was approximately 28%wt of lung total FA and no significant differences were found among the four treatment groups. In contrast, DPPC in the B group lung tissue was significantly greater than DPPC in the unsupplemented groups, but not compared with the P+ group. The B and P+ groups were not significantly different in DHA and AA, but were different compared with the unsupplemented (T, P-) groups. These results indicate that LCP supplementation increases lung DHA and AA, without compromising overall lung 16:0 or DPPC. The shift in FA composition toward greater unsaturation in the groups consuming LCP supported improved surfactant lipid concentration in preterm neonate lungs.

Differential tissue dose responses of (n-3) and (n-6) PUFA in neonatal piglets fed docosahexaenoate and arachidonoate.

Docosahexaenoic acid (DHA) and arachidonic acid (ARA) are commonly added to infant formula worldwide; however, dietary concentrations needed to obtain optimal tissue levels have not been established. Hence, we studied tissue responses in piglets fed various doses of DHA and ARA. Doses were 0, 1, 2, and 5 times those used in U.S. infant formulas and DHA/ARA in Diet 0, Diet 1, Diet 2, and Diet 5 were 0, 4.1/8.1, 8.1/16.2, and 20.3/40.6 mg/100 kJ formula, respectively. Supplementation of dietary DHA and ARA increased DHA in brain, retina, liver, adipose tissue, plasma, and erythrocyte by 1.1- to 25.8-fold of Diet 0 (P-trend < 0.01). Tissue ARA (1.1- to 6.0-fold of Diet 0) responded to dietary ARA in liver, adipose tissue, plasma, and erythrocytes (P-trend < 0.05); brain and retina ARA was, however, unresponsive to dietary DHA and ARA. Plasma and erythrocyte DHA were positively associated with DHA in neural (brain and retina) and visceral (liver and adipose) tissues (r(2) = 0.11-0.56; P < 0.001-P = 0.042). Plasma and erythrocyte ARA did not correlate with neural ARA. Only plasma ARA was associated with liver ARA (r(2) = 0.222; P = 0.02) and adipose ARA (r(2) = 0.867; P < 0.001) and erythrocyte ARA correlated with adipose ARA (r(2) = 0.470; P < 0.001). We conclude that dietary DHA supplementation affords an effective strategy for enhancing tissue DHA, ARA in visceral but not neural tissues is sensitive to dietary ARA, and erythrocyte and plasma DHA can be used as proxies for tissue DHA, although blood-borne ARA is not an indicator of neural ARA.

Formula feeding potentiates docosahexaenoic and arachidonic acid biosynthesis in term and preterm baboon neonates.

Infant formulas supplemented with docosahexaenoic acid (DHA) and arachidonic acid (ARA) are now available in the United States; however, little is known about the factors that affect biosynthesis. Baboon neonates were assigned to one of four treatments: term, breast-fed; term, formula-fed; preterm (155 of 182 days gestation), formula-fed; and preterm, formula+DHA/ARA-fed. Standard formula had no DHA/ARA; supplemented formula had 0.61%wt DHA (0.3% of calories) and 1.21%wt ARA (0.6% of calories), and baboon breast milk contained 0.68 +/- 0.22%wt DHA and 0.62 +/- 0.12%wt ARA. At 14 days adjusted age, neonates received a combined oral dose of [U-13C]alpha-linolenic acid (LNA*) and [U-13C]linoleic acid (LA*), and tissues were analyzed 14 days after dose. Brain accretion of linolenic acid-derived DHA was approximately 3-fold greater for the formula groups than for the breast-fed group, and dietary DHA partially attenuated excess DHA synthesis among preterms. A similar, significant pattern was found in other organs. Brain linoleic acid-derived ARA accretion was significantly greater in the unsupplemented term group but not in the preterm groups compared with the breast-fed group. These data show that formula potentiates the biosynthesis/accretion of DHA/ARA in term and preterm neonates compared with breast-fed neonates and that the inclusion of DHA/ARA in preterm formula partially restores DHA/ARA biosynthesis to lower, breast-fed levels. Current formula DHA concentrations are inadequate to normalize long-chain polyunsaturated fatty acids synthesis to that of breast-fed levels.

The influence of prematurity and long chain polyunsaturate supplementation in 4-week adjusted age baboon neonate brain and related tissues.

Clinical studies show that docosahexaenoic acid (DHA) and arachidonic acid (ARA) supplemented formula improve visual function in preterm infants, however improved fatty acid status is known only for plasma and red blood cells (RBC) since target organs cannot be sampled from humans. Baboons were randomized to one of four groups: Term breast-fed (B); Term formula-fed (T-); Preterm formula-fed (P-); and Preterm DHA/ARA-supplemented formula-fed (P+). The P+ contained 0.61 +/- 0.03% DHA and 1.21 +/- 0.09% ARA, and breast milk had 0.68 +/- 0.22% and 0.62 +/- 0.12% as DHA and ARA, respectively. The B and P+ groups had significantly higher DHA concentration in all tissues than T- and P-. The P- group showed dramatically lower DHA content of 35%, 27%, 66%, and 75% in the brain, retina, liver, and plasma, respectively, compared with B. Supplementation prevented declines in DHA levels in the retina, and liver, and attenuated the decline in brain, plasma and RBC of preterm animals. In contrast, ARA was not significantly lower compared with B in any group in any tissue but was significantly elevated in liver and brain. RBC and plasma DHA were correlated with DHA in tissues; RBC/plasma ARA were uncorrelated with tissue ARA. We conclude that 1) DHA drops precipitously in term and preterm primates consuming formula without long chain polyunsaturates, while 22:5n-6 concentration rises; 2) tissue ARA levels are insensitive to dietary LCP supplementation or prematurity, 3) plasma and RBC levels of ARA are uncorrelated with total ARA levels; 4) DHA levels are correlated with group effects and are uncorrelated within groups.