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Life Science Archives (LSA)

ISSN: 2454-1354
Volume 1; Issue - 4; Year 2015; Page: 240 - 245

Research Article

INFLUENCE OF ATORVASTATIN ON LIPID PROFILE IN HIGH FAT

DIET INDUCED HYPERLIPIDEMIC RATS
Arunachalam Seenipandi* and Perumal Subramanian
Department of Biochemistry and Biotechnology, Faculty of Science, Annamalai University,
Annamalainagar-608 002, Tamil Nadu, India.
Abstract
This study was aimed to evaluate the antioxidant effects of atorvastatin on high fat diet induced
hyperlipidemic rats. Hyperlipidemia was induced in rats by administering 2% cholesterol, 20% coconut oil
and 0.125% cholic acid daily for a period of 10 weeks. Atorvastatin (0.8 mg/kg b.w.) was administered
orally into rats along with high fat diet for daily for a period of 10 weeks. The levels of cholesterol,
phospholipids, triglycerides, free fatty acids (FFA), low density lipoprotein cholesterol (LDL-C), very low
density lipoprotein cholesterol (VLDL-C) and high density lipoprotein cholesterol (HDL-C)) were analyzed
in plasma. High fat diet fed rats showed increased levels in cholesterol, phospholipids, triglycerides, FFA,
LDL, and VLDL and decreased levels of HDL. Further oral administration of atorvastatin restored the
normal lipid metabolism in rats. The antihyperlipidemic potential of atorvastatin might be due to the
modulation of lipid profile in high fat diet induced hyperlipidemic rats.
Key words: Antioxidant effect, atorvastatin, fatty
acids and hyperlipidermic rats.

Article History
Received : 22.08.2015
Revised : 29.08.2015
Accepted : 08.09.2015
1. Introduction

Obesity is the major risk factor for

hyperlipidemia, type 2 diabetes, atherosclerosis,
cardiovascular diseases and certain cancers (Niimi
et al., 2013). It is characterized by excess
accumulation of fats inside the body and
alterations in lipid metabolism (Ok et al., 2013).
High fat diet fed rats increasing the risk of
developing
diabetes,
hypertension
and
dyslipidemia, which are the key components of the
metabolic syndrome. Type 2 diabetes and
cardiovascular diseases are currently major causes
of morbidity and mortality all over the world
(Brownlee, 2005). High fat diet intake leads to
lipid accumulation in the liver and skeletal
* Corresponding author: Arunachalam Seenipandi
E-mail: seenipandi27@yahoo.com

muscles. Altered lipid metabolism has been

prevailed in patients with type 1 diabetes
including elevated levels of total serum cholesterol
(TC), triglycerides (TG) (Dullaart, 1995), lowdensity lipoprotein cholesterol (LDL-C) (Erciyas
et al., 2004), very low-density lipoprotein
cholesterol (VLDL-C) with decreased levels of
high density lipoprotein (HDL-c) (Verg`es, 2009).
Hepatic lipid metabolism is influenced by the
balance between the degradation and synthesis
and/or import and export of triglyceride (TG) and
fatty acids (FA). Fatty acids are important for
many biological functions and they are degraded
through - oxidation or esterified and then stored
as TG in the liver and its excessive storage results
in hepatic steatosis (Nishikawa et al., 2008).
Moreover, the FA transport process appears to be
disturbed in obesity and diabetes mellitus (Bonen

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Arunachalam Seenipandi / Life Science Archives (LSA), Volume 1, Issue 4, Page: 240 - 245, 2015

2. Materials and Methods

Adult male albino Wistar rats weighing
180-200 g were used for the study. The animals
were obtained from Faculty of Medicine,
Annamalai University and were housed in
polypropylene cages at temperature (252C). The
experimental animals were divided into four
groups (n = 6 in each group) during the
experimental period of 10 weeks. Group I control
rats received food ad libitum, group II rats orally
treated with high fat diet (HFD), (2% cholesterol,
20% coconut oil and 0.125% cholic acid) (Aubin
et al., 2010 and Rathod et al., 2011), group III rats
treated HFD and were orally treated with
atorvastatin (0.8 mg/ kg) (Ito et al., 2007), group
IV rats were orally treated with atorvastatin
(ATO). The experimental protocol was approved
by the committee for Research and Animal Ethics,
Annamalai University (Proposal No: 892/2012)
and were in accordance with the guidelines of the
National Institute of Nutrition (NIN) and Indian
Council of Medical Research (ICMR), India.
Biochemical Assays
After the experimental period, animals
were fasted overnight and sacrificed. Blood
samples were collected for the biochemical
estimations. Levels of triglycerides (Wahlfield,
1974), FFA (Falholt et al., 1973), LDL-C (Okada
et al., 1998), VLDL-C and HDL-C (Gordon et al.,
1977) were estimated in plasma and Cholesterol

(Allain et al., 1974), phospholipids (Zilversmit et

al., 1950) were estimated in serum.
Statistical analysis
The data for various biochemical
parameters were analyzed using analysis of
variance (ANOVA) and the group means were
compared by Duncans Multiple Range Test
(DMRT) (Duncan, 1957). Values were considered
statistically significant when p < 0.05.
3. Results
HFD induced rats revealed significantly
(p<0.05) increased levels of serum cholesterol,
phospholipids and plasma triglycerides, FFA,
VLDL-C, LDL-C and decreased levels HDL-C.
Treatment with atorvastatin (0.8 mg/kg)
significantly (p<0.05) reduced the levels of
cholesterol, phospholipids, triglycerides, FFA,
VLDL-C, LDL-C and increased the levels HDL-C
in HFD induced hyperlipidemic rats. Control and
atorvastatin alone treated rats showed no
significant effects (Figure 1-7).

Cholesterol
160
a
b

120
mg/dl

et al., 2004). Atorvastatin is a 3-hydroxy-3methyl-glutaryl-CoA (HMG-CoA) reductase

inhibitor, a key enzyme for the hepatic cholesterol
biosynthesis pathway (Ludwig et al 2005).
Cholesterol incorporates mostly in LDL-C which
is directly correlated with atherosclerosis (Bisgaier
et al., 1997 and Davidson, 2005). Our present
study evaluates the high fat diet induced
hyperlipidemia and the treatment of atorvastatin
on the lipid profile (cholesterol, phospholipids,
triglycerides, free fatty acids (FFA), low density
lipoprotein cholesterol (LDL-C), very low density
lipoprotein cholesterol (VLDL-C) and high
density lipoprotein cholesterol (HDL-C)) in
control and experimental rats were analyzed.

241

80
40
0
Control

HFD

HFD+ATO ATO alone

Fig- 1: Values are mean SD of six rats from each

group. HFD- high fat diet; HFD+ATO- high fat diet
treated with atorvastatin (0.8 mg/kg b.w/day); ATO
alone- atorvastatin alone. a- Significant as compared to
control (p<0.05; ANOVA followed by DMRT). bSignificant as compared to HFD (p<0.05; ANOVA
followed by DMRT).

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Arunachalam Seenipandi / Life Science Archives (LSA), Volume 1, Issue 4, Page: 240 - 245, 2015

180
160
140
120
100
80
60
40
20
0

FFA

a
b

mg/dl

mg/dl

Triglycerides

Control

HFD

180
160
140
120
100
80
60
40
20
0

HFD+ATO ATO alone

Fig- 2: Values are mean SD of six rats from each

group. HFD- high fat diet; HFD+ATO- high fat diet
treated with atorvastatin (0.8 mg/kg b.w/day); ATO
alone- atorvastatin alone. a- Significant as compared to
control (p<0.05; ANOVA followed by DMRT). bSignificant as compared to HFD (p<0.05; ANOVA
followed by DMRT).

Control

mg/dl

120
90
60
30
0
Control

HFD

HFD+ATO

HFD+ATO ATO alone

LDL-C

150

HFD

Fig. 4: Values are mean SD of six rats from each

group. FFA- free fatty acids; HFD- high fat diet;
HFD+ATO- high fat diet treated with atorvastatin (0.8
mg/kg b.w/day); ATO alone- atorvastatin alone. aSignificant as compared to control (p<0.05; ANOVA
followed by DMRT). b- Significant as compared to
HFD (p<0.05; ANOVA followed by DMRT).

Phospholipids
180

242

ATO alone

50
45
40
35
30
25
20
15
10
5
0

Control

Fig. 3: Values are mean SD of six rats from each

group. HFD- high fat diet; HFD+ATO- high fat diet
treated with atorvastatin (0.8 mg/kg b.w/day); ATO
alone- atorvastatin alone. a- Significant as compared to
control (p<0.05; ANOVA followed by DMRT). bSignificant as compared to HFD (p<0.05; ANOVA
followed by DMRT).

HFD

HFD+ATO ATO alone

Fig. 5: Values are mean SD of six rats from each

group. LDL-C- low density lipoprotein cholesterol;
HFD- high fat diet; HFD+ATO- high fat diet treated
with atorvastatin (0.8 mg/kg b.w/day); ATO aloneatorvastatin alone. a- Significant as compared to control
(p<0.05; ANOVA followed by DMRT). b- Significant
as compared to HFD (p<0.05; ANOVA followed by
DMRT).

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Arunachalam Seenipandi / Life Science Archives (LSA), Volume 1, Issue 4, Page: 240 - 245, 2015

50

mg/dl

4. Discussion

VLDL-C

60

40
30
20
10
0
Control

HFD

HFD+ATO ATO alone

Fig- 6: Values are mean SD of six rats from each

group. VLDL-C- very low density lipoprotein
cholesterol; HFD- high fat diet; HFD+ATO- high fat
diet treated with atorvastatin (0.8 mg/kg b.w/day);
ATO alone- atorvastatin alone. a- Significant as
compared to control (p<0.05; ANOVA followed by
DMRT). b- Significant as compared to HFD (p<0.05;
ANOVA followed by DMRT).

60

mg/dl

50
40
a
30
20
10
0
Control

HFD

Lipid accumulation and inflammation have

been proposed to play significant roles in the
dysfunction of liver because of its diverse array of
metabolic activities. Accumulation of lipids in
HFD induced diabetes mellitus and insulin
deficiency leads to hyperglycemia
and
hyperlipidemia
(Gylling
et
al.,
2004).
Hyperlipidemia is associated with specific diabetic
complications and disturbances in various tissues,
such as diabetic nephropathy and cardiovascular
diseases and liver dysfunction (Arkkila et al.,
2001). Regulation of lipid metabolism is mainly
coordinated by liver, which actively metabolizes
fatty acids as fuel and continuously produces very
low-density lipoprotein (VLDL) particles to
provide a constant supply of fatty acids to
peripheral tissues. Disturbances in these pathways
are the basis for hepatic steatosis and alterations in
plasma lipoprotein levels.
The liver is responsible for regulating the
endogenous glucose production (Stumvoll et al.,
1997) and holds other key roles in regulating lipid
and protein metabolism, lipoprotein metabolism,
and detoxification (Fisher et al., 2009). Hepatic
lipid content and IR are associated with increased
levels of triglycerides, VLDL-C, which contribute
heavily to
cardiovascular
diseases
and
atherosclerosis (Adiels et al., 2005).

HDL-C

70

243

HFD+ATO ATO alone

Fig- 7: Values are mean SD of six rats from each

group. HDL-C- high density lipoprotein cholesterol;
HFD- high fat diet; HFD+ATO- high fat diet treated
with atorvastatin (0.8 mg/kg b.w/day); ATO aloneatorvastatin alone. a- Significant as compared to control
(p<0.05; ANOVA followed by DMRT). b- Significant
as compared to HFD (p<0.05; ANOVA followed by
DMRT).

Hyperlipidemia is a common risk factor of

diabetes
which
can
range
from
hypercholesterolemia to hyperlipoproteinemia
(Gylling et al., 2004). Hyperlipidemia might be a
factor for fatty liver formation (Zafar et al., 2009).
Free fatty acids are a major component of blood
lipids and play a key role in regulating blood lipid
levels, especially in triglyceride metabolism
(Julius, 2003). Elevated levels of plasma fatty acid
is a risk factor for metabolic syndrome, which can
lead to hyperlipidemia, fatty liver, and insulin
resistance (Boden, 1999, Kovacs and Stumvoll,
2005). In the present study, the levels of plasma
cholesterol, triglycerides, FFA, Phospholipids,
LDL-C and VLDL-C were significantly decreased
in the atorvastatin treated group than in the HFD
group. This is found in line with the previous

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Arunachalam Seenipandi / Life Science Archives (LSA), Volume 1, Issue 4, Page: 240 - 245, 2015
studies on HFD fed rats (Gauthier et al., 2006,
Yang et al., 2010). These results suggest that
atorvastatin may have beneficial effects on
hyperlipidemia induced by HFD. These results
demonstrate that atorvastatin has strong effects on
obesity-related hyperlipidemia (Dullaart, 1995 and
Erciyas et al., 2004). However, the elevated levels
of serum triglycerides in HFD rats were
significantly decreased after treatment with
atorvastatin. This is in agreement with the
evidence that atorvastatin decrease the high levels
of TG. It has been suggested that atorvastatin have
acute antihyperlipidemic properties, inhibiting
inflammatory pathways and promoting fatty acids
oxidation.
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