Plasma total, low density lipoprotein (LDL) and high density lipoprotein (HDL)
cholesterol concentrations increase immediately following birth. Interestingly, this
increase is greater in breast-fed infants than in infants fed formula. The reason(s) why
there are differences in plasma cholesterol concentrations between breast-fed and
formula-fed infants is not known. However, this difference may be a consequence of
the variations in lipid composition between milk and infant formula. Little is known
regarding the specific effects of the lipid component(s) of infant diets on the expression
of genes involved in hepatic lipid metabolism. The studies presented in this thesis
determined whether the addition of cholesterol, arachidonic acid [20:4(n-6)] and
docosahexaenoic acid [22:6(n-3)] to formula, and the positional distribution of fatty acids
in formula triglycerides increases plasma cholesterol in formula-fed piglets to levels
observed in milk-fed piglets. In study #1, piglets were fed from birth to 18 days of age
with either a conventional infant formula (conventional formula) or a formula with
synthesized triglycerides (TG) (synthesized TG formula). The conventional infant
formula had 70% of the total 16:0, representing 23% of total fatty acids, esterified at the
sn-1 and 3 positions of the formula triglyceride. The synthesized TG formula contained
a similar percentage of 16:0, representing 23% of total fatty acids, but had 47% of the
total 16:0 esterified at the centre (sn-2) position of the formula triglyceride. Each of the
conventional and synthesized TG formulae were provided either without (<0.10 mM) or
with 0.65mM cholesterol added to formula, 0.52mmol/L as unesterified cholesterol and
0.13 mmol/L as cholesterol oleate. A reference group of piglets was also fed sow milk. In study #1, the levels of hepatic HMG-CoA reductase mRNA, 7-a-hydroxylase
(C7H) mRNA, and acetyl CoA carboxylase (ACC) mRNA were higher in the formula-fed
than milk-fed piglets, irrespective of the formula cholesterol content or the positional
distribution of fatty acids in the formula triglyceride. This was accompanied by lower
plasma total and HDL cholesterol concentrations, lower hepatic triglyceride
concentrations and lower concentrations of bile acids, cholesterol and phospholipid in
bile of the formula-fed than milk-fed piglets. Adding cholesterol to the formula increased
hepatic cholesterol concentrations and decreased hepatic levels of fatty acid synthase
(FAS) mRNA, but had no effect on the plasma cholesterol concentrations of the
formula-fed piglets. Directing 16:0 to the sn-2 position of the formula triglyceride led to
lower plasma total cholesterol and triglyceride concentrations, lower concentrations of
bile acids in bile, lower hepatic levels of FAS mRNA and activity, and higher hepatic
levels of ACC mRNA than in piglets fed the conventional formula.
In study #2, piglets were fed the conventional formula either without or with egg
phospholipid (9.5g/L) to provide 0.8% 20:4(n-6) and 0.3% 22:6(n-3) of total fatty acids,
or sow milk from birth to 15 days of age. Supplementing the conventional formula with
egg phospholipid resulted in higher levels of 20:4(n-6) and 22:6(n-3) in liver and bile
phospholipid, higher plasma HDL concentrations, higher bile acid and phospholipid
concentrations in bile and lower hepatic ACC mRNA levels in the formula-fed piglets.
The levels of 20:4(n-6) and 22:6(n-4) in liver and bile phospholipid were also higher in
the piglets fed the supplemented formula than in the piglets fed milk. A significant
inverse relation was found between the levels of hepatic ACC mRNA and the percentage
of 20:4(n-6) in liver triglyceride and the percentage of 22:6(n-3) in liver phospholipid. Egg phospholipid supplementation of formula had no effect on hepatic LDL receptor mRNA
or hepatic FAS activity and mRNA in the formula-fed piglets. The piglets fed either the
supplemented or the conventional formula had lower levels of plasma cholesterol and
higher levels of hepatic HMG-CoA reductase activity and mRNA and C7H mRNA than
piglets fed milk.
These studies show that early diet, that is, milk compared to formula feeding,
results in lower levels of hepatic HMG-CoA reductase activity and mRNA and C7H mRNA
accompanied by higher plasma cholesterol concentrations in piglets. Supplementing
formula with cholesterol or the preferential esterification of 16:0 at the sn-2 position of the
formula triglyceride did not raise plasma cholesterol concentrations and had no effect on
hepatic HMG-CoA reductase activity and mRNA or C7H mRNA in formula-fed piglets.
Supplementing formula with egg phospholipid, increased bile and liver phospholipid
20:4(n-6) and 22:6(n-3), decreased the levels of hepatic ACC mRNA and increased the
concentrations of bile acids and phospholipid in bile. These findings suggest that milk-fed
piglets have lower rates of hepatic cholesterol synthesis, lower rates of conversion of
cholesterol to bile acids and the lipid present in sow milk and formula may be metabolized
differently. These findings are significant in that they raise the question as to whether or
not this effect of early diet will continue through to adulthood and influence metabolic
response to diet fat.
| Identifer | oai:union.ndltd.org:LACETR/oai:collectionscanada.gc.ca:BVAU.2429/9455 |
| Date | 11 1900 |
| Creators | Devlin, Angela Marie |
| Source Sets | Library and Archives Canada ETDs Repository / Centre d'archives des thèses électroniques de Bibliothèque et Archives Canada |
| Language | English |
| Detected Language | English |
| Type | Electronic Thesis or Dissertation |
| Relation | UBC Retrospective Theses Digitization Project [http://www.library.ubc.ca/archives/retro_theses/] |
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