Role of Oxidized Fatty Acids on Plasma Lipids Metabolism
Gregory Ainsworth MS, Mahdi Garelnabi, PhD, MSc,FAHA
Department of Clinical Lab and Nutritional Sciences
College of Health Sciences
Introduction
Fatty acid and Oxidation
Experimental Design
Results & Conclusion
Overwhelming evidence suggest that
oxidized fatty acids seeds the oxidation
of low density lipoprotein (LDL) which is
known to contribute to the arterial
cardiovascular
diseases.
Dietary
oxidized lipids have been suggested to
contribute to atherosclerosis. We have
previously shown that oxidized linoleic
acid (OxLA) modulates plasma lipids.
Feeding C57BL mice oxidized linoleic
acid resulted in decreased plasma
triglycerides and increased HDL. The
current study is designed to investigate
the mechanisms involved in the
regulation of plasma lipids by the OxLA
Polyunsaturated fatty acids (PUFA)
linoleic acid is the major constituent of
our fatty acid dietary intake. This fatty
acid readily undergoes oxidation forming
couple of oxidized derivatives among
this derivatives is 13HODE which is
known
to
promote
arterial
atherosclerosis through foam cell
formation and inflammatory modulator
responses
C57BL6 male mice (N=40) were
divided into four groups (n = 10
each): Animals were fed for two
months three different formulated diet
except for the plain control (P) which
was kept on normal mouse. The other
three groups were as follows: control
group
supplemented
with
18
mg/animal/day of linoleic acid (LA)
(C); experimental group feed low
concentration (9 mg/animal/day) of
OxLA (A), and experimental group fed
high
dose
of
OxLA
(18
mg/animal/day). After two months of
feeding mice were sacrificed, blood,
liver, and adipose tissues were
collected for the analysis of plasma
lipids, and related analyts and gene
expressions for genes associated
with lipoproteins metabolism.
The plasma total cholesterol and
LDL have significantly (P<0.007)
decreased in the high concentration
OxLA compared to the group fed
LA; this was accompanied with
decreases in the high concentration
OxLA plasma TG although is not
significant. There were no observed
significant differences in the plasma
lipids between the plain control and
the OxLA high dose, and between
the controls on LA and the low
concentration OxLA. We have
observed
a
significant
dose
dependent decreases in plasma
ApoC3 in mice fed low OxLA
(P<0.01) and high OxLA (P<0.003)
compared to the control group on
LA. Plasma lipase levels have
shown similar trends; decreasing
significantly (P<0.04) in the OxLA
groups compared to the plain
controls. Plasma ApoA5 levels on
the other hand greatly increased in
high OxLA, LA, and low OxLA
compared to plain group although is
not
significant.
This
study
demonstrate that oxidized linoleic
acid modulate plasma lipoprotein
metabolism in mice through a likely
ApoC3/lipase
dependent
mechanism(s).
Garelnabi et al, Clinical Biochemistry 46 (2013) 12–19
Oxidized forms of linoleic acid
Linoleic acid (C18:2)
COOH
C57BL mice
used in the
study
13- hydroperoxy-octadecadienoic acid (HPODE)
13
OOH
COOH
LDL
35.00
13- hydroxy-octadecadienoic acid (HODE)
30.00
13
OH
25.00
COOH
20.00
mg/dL
Fig. 1. (A) PPAR gene expression. Mice PPAR gene expression have not
shown significant difference between the control and 13-HPODE fed mice.
Values are means±S.D. (B) Western blot analysis of PPAR in the liver
is shown. Gels were immunoblotted by using anti-PPAR and anti- -actin
(used as an internal control) antibodies. Control mice on oleic acid mixed
chow (n = 9) were compared to experimental mice on 13-HPODE mixed
chow (n = 9), results did not show significant difference between the two
groups; data is represented by three mice from control group, and four from
experimental mice.
Fig.
15.00
10.00
5.00
0.00
Plain
-5.00
-10.00
Fig. 4. Mice APOA5 and APOClll gene expression. APOA5 was significantly
upregulated (P≤0.001) among mice supplemented with diet
containing 13-HPODE; however APOClllwas significantly (P≤0.04) down
regulated in this group compared to the control mice fed diet containing
oleic acid. Data expressed as means±S.D. Open bars represent control
group whereas the black bars represent the experimental mice on 13HPODE
supplemented diet.
M. Garelnabi et al. / Atherosclerosis 199 (2008) 304–309
Linoleic Acid
Oxidized LA- Low
Oxidized LA- High