Hindawi Publishing Corporation

Journal of Obesity
Volume 2015, Article ID 846041, 8 pages
http://dx.doi.org/10.1155/2015/846041

Research Article
Protective Effects of Tamarillo (Cyphomandra betacea) Extract
against High Fat Diet Induced Obesity in Sprague-Dawley Rats

Noor Atiqah Aizan Abdul Kadir,1 Asmah Rahmat,1 and Hawa Z. E. Jaafar2
1
Department of Nutrition and Dietetics, Faculty of Medicine and Health Sciences, Universiti Putra Malaysia,
43400 Serdang, Selangor, Malaysia
2
Department of Crop Science, Faculty of Agriculture, University Putra Malaysia, 43400 Serdang, Selangor, Malaysia

Correspondence should be addressed to Asmah Rahmat; [email protected]

Received 19 April 2015; Accepted 27 May 2015

Academic Editor: Andras Hajnal

Copyright © 2015 Noor Atiqah Aizan Abdul Kadir et al. This is an open access article distributed under the Creative Commons
Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is
properly cited.

This study aims to investigate the protective effect of Cyphomandra betacea in adult male Sprague-Dawley rats fed with high fat diet.
Rats were fed on either normal chow or high fat diet for 10 weeks for obesity induction phase and subsequently received C. betacea
extract at low dose (150 mg kg−1 ), medium dose (200 mg kg−1 ), or high dose (300 mg kg−1 ) or placebo via oral gavages for another
7 weeks for treatment phase. Treatment of obese rats with C. betacea extracts led to a significant decrease in total cholesterol and
significant increase in HDL-C (𝑝 < 0.05). Also there was a trend of positive reduction in blood glucose, triglyceride, and LDL-C
with positive reduction of body weight detected in medium and high dosage of C. betacea extract. Interestingly, C. betacea treated
rats showed positive improvement of superoxide dismutase (SOD) activity and glutathione peroxidase (GPx) activity along with
a significant increase of total antioxidant status (TAS) (𝑝 < 0.05). Further, rats treated with C. betacea show significantly lower
in TNF-𝛼 and IL-6 activities (𝑝 < 0.05). This study demonstrates the potential use of Cyphomandra betacea extract for weight
maintenance and complimentary therapy to suppress some obesity complication signs.

1. Introduction Obesity is considered as a low-grade chronic inflamma-

tion. The levels of proinflammatory adipokines and protein
Obesity is currently the most common metabolic disease in such as tumour necrosis factor-𝛼 (TNF-𝛼), interleukin (IL-
the world; it is significantly associated with potentially life- 6), and inducible nitric oxide synthase (iNOS) in adipose
threatening comorbidities. Either obesity itself or comorbidi- tissues and C-reactive protein (CRP) in plasma are increased
ties of obesity are responsible for increased cardiovascular
in obese people [5]. The uncontrolled inflammatory response
risk. Obesity is associated with most of the components of
leads to a persistent proinflammatory state resulting in rising
metabolic syndrome, the leading cause of type 2 diabetes. The
blood pressure, thrombosis, dyslipidaemia, and metabolic
comorbidities of obesity and type 2 diabetes associated with
insulin-resistance syndrome include obstructive sleep apnea, disease in obesity [6–8].
hypertension, polycystic ovary syndrome, nonalcoholic fatty High fat diet induced obese rat model has been con-
liver disease, and certain forms of cancer [1]. sidered as a popular preference for its ability to mimic the
When obesity persists for a long time, therefore, the usual way of obesity in human. High fat diet is one of the
antioxidant sources can be depleted, decreasing the activity major factors causing obesity and long term intake of high fat
of enzymes such as superoxide dismutase (SOD) and catalase diet showed significant increase in abdominal fat weight in
(CAT) [2]. The activity of SOD and glutathione peroxidase mammals [9]. Woods et al. [10] reported that in high fat diet
(GPx) in individuals with obesity is significantly lower com- induced obese rat model, the high fat rats weighed more than
pared with that in healthy persons, having implications for control rats. In addition, they also developed subsequently
the development of obesity-related health problems [3, 4]. more adipose tissue than control rats and acquired the
2 Journal of Obesity

insulin resistance and hyperleptinemia typically associated Table 1: Composition of high fat diet and normal rat chow diet.
with obesity.
Interestingly, eating fruits and vegetables can ensure High fat diet Normal rat chow diet
the adequate supply of micronutrient, dietary fibres, and Nutrients %/100 g Nutrients %/100 g
phytochemicals which in turn maintain the body in healthy Carbohydrate 43 Carbohydrate 48.8
state [11]. The rationale behind the potential role of fruit in Protein 17 Protein 21
the prevention of overweight and obesity is related to special Fat 40 Fat 3
features of whole fruit which include high water content, low g/100 g 0.8
Ingredients Calcium
energy density, and high content of dietary fibres, of which
Powdered rat feed 68.0 Phosphorus 0.4
viscous dietary fibres constitute a considerable proportion
[12]. Maize oil 6.0 Fiber 5
In Malaysia, Cyphomandra betacea is locally known with Ghee 6.0 Moisture 13
various names such as “Buah Cinta,” “Moginiwang,” “Pokok Milk powder 20.0 Ash 8
Tomato,” or “Tamarillo” and cultivated in Cameron Highland Total energy Total energy
and Kundasang, Malaysia [13]. C. betacea are considerably 414.0 306.2
(kcal/100 g) (kcal/100 g)
nutritious because of their high vitamin content. C. betacea
was demonstrated to contain phytochemicals including beta-
carotene anthocyanins, flavonols, phenolic acids, and large the dried sample was homogenously ground into fine powder
amounts of ascorbic acid [14–18]. To date, C. betacea remains by using dry grinder. C. betacea extract was given at three
unexplored except for its antioxidant profile and, to the best of different doses: 150, 200, and 300 mg kg−1 . The respective
our knowledge, this is the first study to evaluate the protective treatment extracts were prepared by adding 15 g, 20 g, and
effects of Cyphomandra betacea in adult male Sprague Dawley 30 g of freeze-dried C. betacea extract to 100 mL of distilled
rats fed with high fat diet. water and given to the C. betacea treatment group.

2. Materials and Methods 2.3. Animal Study Design. All experiment protocols were
approved by the Institutional Animal Care and Use Commit-
2.1. Materials. Freshly harvested Tamarillo (Cyphomandra tee, Universiti Putra Malaysia. Male Sprague Dawley rats (𝑛 =
betacea) was collected from Cameron Highland and stored 40) at the age of 8 weeks, weighing between 200 and 250 g,
at 4∘ C in Nutrition laboratory, Faculty of Medicine and were acclimatized for one week under room temperature
Health Sciences, Universiti Putra Malaysia. Normal rat chow (28 ± 2∘ C) with regular light and dark cycle and free access
pallet was purchased from Saintik Enterprise (Malaysia). to food and water. Following acclimatization, the rats were
RANSOD kit (RANDOX Laboratory Ltd., USA), RANSEL kit randomly divided into five groups (𝑛 = 8). Four groups
(RANDOX Laboratories Ltd., USA), TAS kit (RANDOX Lab- were given 25 g/per rat high fat diet for obesity induction
oratories Ltd., Crumlin, UK), Rat TNF-𝛼 and IL-6 Platinum week. Another group noted as Negative Control (NC) was
ELISA kit (eBioscience, USA), and test kits for measuring given 25 g/per rat normal rat chow diet (Saintik Enterprise,
blood glucose (Sigma-Aldrich, USA) and lipid profile (Roche, Malaysia) throughout the study period.
Germany) were all supplied from Scientifacts Sdn. Bhd. After 10 weeks of obesity induction, the mean body
(Malaysia). weight and BMI of the high fat diet groups were compared
to those of NC group. The group with significantly higher
2.2. Diet. The high fat diet was adapted based on the com- body weight and BMI were considered as obese [20] and
position provided by Levin and Dunn-Meynell [19]. The high subsequently received C. betacea extract or placebo treatment
fat diet contains 414.0 kcal/100 g with 43% as carbohydrate, following treatment phase for 7 weeks. The high fat diet
17% as protein, and 40% as fat (Table 1). The diet consists of a was continuously given to the obese induced rats during
mixture of 68% normal rat chow pellet (Saintik Enterprise, treatment period.
Malaysia), 20% instant milk powder (Dutch Lady), 6% C. betacea supplement was given once daily to the C.
corn oil (Krystal), and 6% ghee (Crispo). Meanwhile the betacea treated rats groups: Tamarillo low dosage group
normal rat chow diet contains 306.2 kcal/100 g with 48.8% as (150 mg kg−1 ) (TLDG), Tamarillo medium dosage group
carbohydrate, 21% as protein, and 3% as fat. All ingredients (200 mg kg−1 ) (TMDG), and Tamarillo high dosage group
of high fat diet were thoroughly mixed and baked in the oven (300 mg kg−1 ) (THDG) via oral gavage (0.2 mL/100 g), while
at 65∘ C overnight. The high fat diet prepared was given to the Negative Control group (NC) and Positive Control group
obese induced rats for 10 weeks of obesity induction week. (PC) received distilled water as placebo.
The normal rat chow diet was referred to as the control diet
and given to negative control rats. 2.4. Analyses
C. betacea was used as treatment extract in the study.
Every sample was cleaned and washed to remove any residual 2.4.1. Blood Sampling. Approximately 3 mL blood was col-
compost by using tap water. These samples were cut into lected into EDTA and lithium heparin tubes via cardiac
pieces and stored at −80∘ C. Then, the samples were freeze- puncture. Intraperitoneal injection with zoletil (tiletamine
dried to remove the moisture content. After freeze-drying, 15 mg/kg and zolazepam 15 mg/kg) was performed on the
Journal of Obesity 3

Table 2: Mean of food and caloric intake of rats after the obesity induction week (week 10) and after treatment week (week 7).

Food intake (g) Caloric intake (kcal)

Group
Initial (week 10) Final (week 7) Initial (week 10) Final (week 7)
NC 18.39 ± 0.50 19.41 ± 2.12 69.89 ± 1.91 a
73.75 ± 8.06a
PC 18.48 ± 1.04 21.57 ± 0.59 80.66 ± 4.53 b
94.44 ± 2.60b
TLDG 18.61 ± 1.93 21.30 ± 0.88 81.48 ± 8.45 b
94.93 ± 4.04b
TMDG 19.35 ± 2.18 21.78 ± 1.11 84.74 ± 9.57 b
96.88 ± 4.75b
THDG 19.15 ± 1.65 21.61 ± 1.35 83.85 ± 7.09 b
96.13 ± 5.90b
Values represent the Mean ± SD (𝑛 = 8). a 𝑝 < 0.05 versus positive control group; b 𝑝 < 0.05 versus negative control group. NC: negative control; PC: positive
control; TLDG: C. betacea extract 150 mg/kg; TMDG: C. betacea extract 200 mg/kg; THDG: C. betacea extract 300 mg/kg.

rats to alleviate and minimize any pain. Then the blood status (TAS) was analysed by using a TAS kit (RANDOX
collected in the EDTA tube was centrifuged at 3000 rpm at Laboratories Ltd., Crumlin, UK); inflammatory biomarkers
4∘ C for 10 min and the plasma was stored at −80∘ C. The (TNF-𝛼 and IL-6) were analysed by using the Rat TNF-𝛼 and
blood collected in the heparinised tube was processed in the IL-6 Platinum ELISA kit (eBioscience, USA) which were all
same day for superoxide dismutase (SOD) and glutathione according to manufacturer’s instructions, respectively.
peroxidase (GPx) evaluation.
2.5. Statistical Analysis. Data were expressed as mean ±
2.4.2. Bodyweight, Food Intake, and BMI. Individual body- standard deviation. Data were analysed by using one-way
weight was recorded weekly using electrical balance. The ANOVA using SPSS for windows version 21. Duncan’s Multi-
amount of leftover food was weighed daily using electri- ple Range Test was used to test whether there were significant
cal balance and deducted from the amount of food given differences between the experimental groups. A significant
(25 g/per rat) in order to calculate daily food intake. Food difference is considered at the level of 𝑝 < 0.05.
intake was the amount of food (g) consumed by each rat
within 24 hours. Meanwhile, the body length (cm) (nose-
to-anus) was determined at week 7 to determine the BMI. 3. Result
BMI for normal adult rats ranged between 0.45 ± 0.02 and
3.1. Food Intake and Body Weight. All rats appeared to be
0.68±0.05 g/cm2 [20]. BMI was calculated using the following
healthy throughout the study and ate the food provided
formula:
during the experimental period. After obesity induction week
body weight (g) (week 10), there were no significant differences of food intake
Body mass index (BMI) = . (1)
body length2 (cm2 ) observed for all groups (𝑝 > 0.05). However, a significant
difference can be seen for the caloric intake between the
2.4.3. Biochemical Test. Blood samples were taken from negative control group and obese induced groups (𝑝 < 0.05)
the overnight unfed rats. In this study, blood glucose was (Table 2).
analysed by glucose oxidase (GO) assay kit (Sigma-Aldrich, There were significant weight differences observed
USA), lipid profile (total cholesterol, triglyceride, LDL-C, and between the negative control group and all the obese induced
HDL-C) was evaluated by using a diagnostic reagent test groups at week 10 (𝑝 < 0.05) (Table 3). Similarly, there
kit (Roche, Germany) on a Hitachi Automatic Analyzer 902 were also significant BMI differences found between the
(Tokyo, Japan). The activity of superoxide dismutase (SOD) negative control group and all the obese induced groups
was analysed by using a RANSOD kit (RANDOX Laboratory (Table 3) (𝑝 < 0.05). Since all the obese induced groups had
Ltd., USA); 0.5 mL heparinised whole blood sample was significantly higher mean bodyweight and BMI than the
centrifuged at 3000 rpm for 10 min. The plasma was then negative control group at week 10, they were all verified to
aspirated off and later was washed four times with 3 mL nor- be obese and therefore proceeded to the supplementation
mal saline (0.9% NaCl) solution for 10 min and followed by phase.
centrifugation at 3000 rpm after each wash. The washed cen- After treatment week (week 7), there was weight reduc-
trifuged erythrocyte was made up to 2 mL with cold distilled tion detected in TMDG and THDG. THDG (462.50±23.02 g)
water, mixed, and left to stand at 4∘ C for 15 min to form lysate. showed lowest bodyweight as compared to positive control
The absorbance was read spectrophotometrically at 505 nm group followed by TMDG (464.00 ± 47.15 g) and TLDG
via clinical chemistry analyzer machine (Vitalab Selectra E, (482.17±61.47 g), respectively (𝑝 > 0.05). There was also BMI
Germany). Meanwhile, the activity of glutathione peroxidase reduction detected in all C. betacea treated groups. Lowest
(GPx) was analysed by using a RANSEL kit (RANDOX BMI can be seen in THDG (0.60 ± 0.08 g/cm2 ) followed by
Laboratories Ltd., USA); 0.05 mL of heparinised whole blood TMDG (0.66 ± 0.06 g/cm2 ) and TLDG (0.67 ± 0.11 g/cm2 ),
sample was added with 2 mL of Ransel diluting agent. The respectively (𝑝 > 0.05) (Table 3).
sample was mixed well and incubated for 5 min. Absorbance
was then read at 30 nm via clinical chemistry analyzer 3.2. Blood Glucose and Lipid Profile. After obesity induction
machine (Vitalab Selectra E, Germany). Total antioxidant week (week 10), there were significant increments of glucose,
4 Journal of Obesity

Table 3: Mean of body weight and body mass index (BMI) of rats after the obesity induction week (week 10) and after treatment week (week
7).

Bodyweight (g) Body mass index (BMI) (g/cm2 )

Group
Initial (week 10) Final (week 7) Initial (week 10) Final (week 7)
NC 413.83 ± 40.46a 453.17 ± 48.22 0.56 ± 0.05a 0.62 ± 0.05
PC 465.83 ± 22.33b 508.00 ± 56.06 0.73 ± 0.05b 0.71 ± 0.08
TLDG 471.33 ± 40.54b 482.17 ± 61.47 0.71 ± 0.04b 0.67 ± 0.11
TMDG 468.50 ± 53.64b 464.00 ± 47.15 0.71 ± 0.05b 0.66 ± 0.06
THDG 470.50 ± 47.75b 462.50 ± 23.02 0.72 ± 0.08b 0.60 ± 0.08
Values represent the Mean ± SD (𝑛 = 8). a 𝑝 < 0.05 versus positive control group; b 𝑝 < 0.05 versus negative control group. NC: negative control; PC: positive
control; TLDG: C. betacea extract 150 mg/kg; TMDG: C. betacea extract 200 mg/kg; THDG: C. betacea extract 300 mg/kg.

Table 4: Mean of blood glucose and lipid profile of rats after obesity induction (week 10) and after treatment (week 7).

Group
NC PC TLDG TMDG THDG
Blood glucose
(week 10) 6.00 ± 0.80a 7.47 ± 0.69b 7.95 ± 0.88b 7.45 ± 1.32b 7.72 ± 1.8b
(week 7) 6.95 ± 0.99 7.07 ± 0.69 6.80 ± 0.88 6.30 ± 0.63 5.97 ± 0.21
TC
(week 10) 1.65 ± 0.52a 2.63 ± 0.67b 1.84 ± 0.07b 1.85 ± 0.10b 1.79 ± 0.49b
(week 7) 1.35 ± 0.31a 1.86 ± 0.43b 1.79 ± 0.37ab 1.75 ± 0.25ab 1.75 ± 0.22ab
TG
(week 10) 0.51 ± 0.13a 0.88 ± 0.30b 0.81 ± 0.07b 0.75 ± 0.08b 0.82 ± 0.12b
(week 7) 0.51 ± 0.29 0.52 ± 0.09 0.50 ± 0.13 0.48 ± 0.15 0.46 ± 0.10
LDL-C
(week 10) 0.19 ± 0.17a 0.72 ± 1.14b 0.25 ± 0.16b 0.23 ± 0.12b 0.27 ± 0.15b
(week 7) 0.16 ± 0.13 0.19 ± 0.10 0.17 ± 0.15 0.18 ± 0.04 0.18 ± 0.10
HDL-C
(week 10) 1.33 ± 0.39a 0.89 ± 0.62b 1.09 ± 0.36b 0.89 ± 0.12b 0.92 ± 0.21b
(week 7) 0.98 ± 0.33a 1.18 ± 0.06b 1.40 ± 0.16ab 1.45 ± 0.22ab 1.55 ± 0.36ab
Values represent the Mean ± SD (𝑛 = 8). a 𝑝 < 0.05 versus positive control group; b 𝑝 < 0.05 versus negative control group. NC: negative control; PC: positive
control; TLDG: C. betacea extract 150 mg/kg; TMDG: C. betacea extract 200 mg/kg; THDG: C. betacea extract 300 mg/kg.

Table 5: Effect C. betacea extract on antioxidant enzyme activities. Although there was a positive reduction in triglyceride, LDL-
C, and glucose found in the C. betacea treated groups, there
Antioxidant enzyme activities was no significant difference detected between C. betacea
Group
GPx (UL−1 ) SOD (UmL−1 ) TAS (mmolL−1 ) treated groups with positive control group or negative control
NC 1798.00 ± 2.26 7.15 ± 0.96 1.20 ± 0.11 group (𝑝 > 0.05) (Table 4).
PC 1735.02 ± 2.43 7.11 ± 1.01 1.47 ± 0.10
TLDG 2195.95 ± 5.33 7.61 ± 0.13 1.78 ± 0.16ab
3.3. Antioxidant Enzyme. Treatment of obese rats with C.
TMDG 2298.90 ± 3.01 7.62 ± 0.13 1.87 ± 0.19ab betacea extract led to positive increment of GPx and SOD
THDG 2422.07 ± 5.76 ab
7.76 ± 0.13 1.97 ± 0.48ab activity (𝑝 > 0.05) and a significant increment in TAS level
Values represent the Mean ± SD (𝑛 = 8). a 𝑝 < 0.05 versus positive control (𝑝 < 0.05) in C. betacea treated group as compared to
group; b 𝑝 < 0.05 versus negative control group. NC: negative control; PC: negative control group and positive control group (Table 5).
positive control; TLDG: C. betacea extract 150 mg/kg; TMDG: C. betacea THDG rats showed highest value for all antioxidant enzymes
extract 200 mg/kg; THDG: C. betacea extract 300 mg/kg.
activity (GPx, SOD, and TAS) followed by TMDG and TLDG,
respectively.
cholesterol, triglyceride, and LDL-C and significant decre-
ment of HDL-C in the obese induced group as compared to 3.4. Inflammatory Biomarkers. Supplementation of C.
negative control group (𝑝 < 0.05) (Table 4). betacea extracts results in decrement of TNF-𝛼 concentration
Following treatment week (week 7), there were significant in C. betacea treated group. The lowest concentration can be
decrements of cholesterol and significant HDL-C increment seen in THDG (36.67 ± 44.57 pg/mL), followed by TMDG
found in the C. betacea treated groups as compared to (43.33 ± 32.04 pg/mL) and TLDG (46.67 ± 39.33 pg/mL).
negative control and positive control group (𝑝 < 0.05). There was a significant difference of TNF-𝛼 found in
Journal of Obesity 5

Table 6: Effect C. betacea extract on inflammatory biomarkers.

Groups
NC PC TLDG TMDG THDG
TNF-𝛼 (pg/mL) 50.00 ± 3.52a 113.33 ± 7.34b 46.67 ± 3.93a 43.33 ± 3.20a 36.67 ± 4.46a
IL-6 (pg/mL) 660.00 ± 3.66 1066.67 ± 5.71 476.67 ± 5.25a 380.00 ± 2.41a 286.67 ± 3.06a
Values represent the Mean ± SD (𝑛 = 8). a 𝑝 < 0.05 versus positive control group; b 𝑝 < 0.05 versus negative control group. NC: negative control; PC: positive
control; TLDG: C. betacea extract 150 mg/kg; TMDG: C. betacea extract 200 mg/kg; THDG: C. betacea extract 300 mg/kg.

C. betacea treated group as compared with positive control leading to greater obesity showed that the fat content of the
group (𝑝 < 0.05) (Table 6). diet is an important factor in energy balance. As a result, diets
Likewise, supplementation of C. betacea extracts also containing more than 30% of total energy as fat lead to the
results in significant decrement of IL-6 concentration in development of obesity [25].
C. betacea treated group. The lowest concentration can be An increase of glucose level can be seen following obesity
seen in THDG (286.67 ± 306.38 pg/mL), followed by TMDG induction. Previous study explained elevated blood glucose
(380.00 ± 241.00 pg/mL) and TLDG (476.67 ± 524.66 pg/mL) levels in animals consuming high fat diet; it was assumed
(𝑝 < 0.05). that chronic exposure to elevated levels of fatty acids induces
an increase in fatty acid oxidation and a decrease in glucose
4. Discussion oxidation [30]. It was also reported that ingestion of high
saturated fat induced an increase in hepatic liposynthetic
Experimental obesity is usually taken as any significant gene expression and impairment in glucose metabolism,
increase in body weight or energy content relative to control which can be seen through impaired translocation of glu-
animals [21]. In most studies, the degree of obesity has cose transporter-4 activity, suppressed expression of glucose
been evaluated by comparing body weight or fat of the transporter-4, inhibited expression of hepatic glycolytic and
experimental group fed with high fat diet or energy dense lipogenic enzymes, and impaired insulin signalling [31, 32].
diet with control animals that show normal growth while As a result from high fat diet consumption, there were
being fed chow or low-fat diet [9, 10, 22]. There is a lack of increments of TG, cholesterol, and LDL; meanwhile there was
information on anthropometrical parameters in laboratory a decrease in HDL. It also can be seen that LDL and TG
rats. However, the method of verifying obese status via level were higher in obese induced rats compared to negative
BMI was demonstrated in an obesity research conducted by control group. LDL increases the rate of triacylglycerol
Novelli et al. [20] and affirms that the BMI for normal adult catabolism by mobilizing fats from the liver to adipose tissue.
rats ranged between 0.45 ± 0.02 and 0.68 ± 0.05 g/cm2 . It carries 60% to 70% of total cholesterol in the serum [33].
During the obesity induction period, the daily food intake The hypertriglyceridemia condition resulting from high fat
between groups showed no significant differences (𝑝 > 0.05); diet could be caused by enhanced liver VLDL-triglyceride
it was revealed that the amount of food intake was not affected secretion into circulation [34]. It was reported that, with
by the calories content in normal chow diet and high fat diet. unsaturated triglyceride, upregulating of LDL receptors
It was suggested that food intake was influenced by sensitivity occurred compared to saturated triglyceride. Therefore, it was
of the rats to the palatability of food in the diet. Palatable food suggested that dietary fatty acids can induced changes in cel-
such as food high in fat and sugar inhibits the satiety signal lular membrane lipids and may influence certain metabolic
and upregulates hunger sensation [11]. properties, such as receptor-mediated uptake of lipopro-
The continuous consumption of high fat diet results teins [35]. Meanwhile, the hypercholesteremia condition is
in significantly higher caloric intake compared to normal associated with enhanced oxidizability of LDL molecules.
chow diet; therefore 𝑝 < 0.05 showed positive increment The lag phase of lipid oxidation is shorter in LDL particles
of body weight thus leading to obese state. Previous liter- from obesity; rapid lipid peroxidation in the polyunsaturated
ature demonstrated that a fat-rich diet induces obesity by fatty acids of LDL particles subsequently occurs [3, 36]. The
increasing energy intake [10, 22–24]. Fat is the most energy susceptibility of lipids to oxidative modification is also shown
dense nutrient (9 kcal/g versus 4 kcal/g for carbohydrate by higher concentrations of 4-HNE per unit intramuscular
and protein); therefore, an addition of fat to food increases triglycerides in obesity [37].
calories and also energy density [25]. In this study, the antioxidants enzyme activities of GPx,
After receiving their respective diet for 10 weeks, the obese SOD, and TAS were lower in the positive control group.
induced rats gained significantly higher body weight and BMI Decrease of antioxidant enzyme may be related to rapid
than the negative control rats, thus verified to be obese. In this consumption and exhaustion of storage of this enzyme in
present study, the high fat diet consists of 40% of fat of total combating free radicals generated during development of
energy. Diet rich in fat induced obesity not only in human obesity. In addition activities of major antioxidant enzymes
but also in animals. Previous literature mentioned a positive may also be inadequate in obesity [38].
relationship between the level of fat in the diet and body Bełtowski et al. [39] demonstrated that activity of ery-
weight or weight gain [24, 26–29]. Therefore, the relationship throcyte SOD and GPx activities were lower by 29–42%
in human or animals models which have more dietary fat in the high fat, high calorie fed animals as compared to
6 Journal of Obesity

control animals after diet period. Similar lower result was C. betacea also successfully decrease the inflammatory
also found for TAS value. At the early stage of obesity, it biomarkers in the C. betacea treated groups. Previous study
has been proposed that there may be an initial elevation in showed that carotenoids in fruit and vegetable were asso-
antioxidant enzymes to counteract oxidative stress; as chronic ciated with anti-inflammatory effects [53]. The biological
obesity developed, it continually depletes the sources of mechanisms for the protective effect of greater variety in
antioxidant enzymes [40, 41]. Meanwhile, TAS has been used fruit and vegetable intake are not entirely clear but may be
as comprehensive measure of radical-squelching capacity by attributed to the singular or synergistic action of several
antioxidant in plasma. Lower TAS value was directly related bioactive compounds. Mounting evidence shows that bioac-
to lower levels of various forms of plasma carotenoids such as tive compounds such as carotenoids, flavonoids, phytoestro-
𝛼-carotene, 𝛽-carotene and 𝛼-tocopherol, 𝛽-tocopherol, and gens, dietary fibre, and resveratrol, which are present in a
Υ-tocopherol [41]. wide variety of fruits and vegetables, influence the risk of
The effect of high fat diet on proinflammatory cytokines oxidative stress [54, 55]. It was also reported that low dietary
can be seen with the increment of IL-6 and TNF-𝛼 in intake of fruits and vegetables and low serum concentration
positive control group. Numerous previous studies found of flavonoids, carotenoids, and vitamin C, which may indi-
that, compared to healthy lean individuals, overweight and rectly represent low fruit and vegetable variety, have been
obese individuals have higher proinflammatory cytokines associated with increased inflammatory status [56–59].
[42, 43]. Obesity is characterized by having a greater number Throughout the treatment period, highest dose of oral
of adipose tissues (hyperplasia) and an increase in the size of administration of C. betacea (300 mg kg−1 ) did not induce
adipocytes (hypertrophy) [44, 45]. These conditions lead to mortality. There were no toxic signs such as vomiting, fur
oxygen depletion in adipose tissue, hence causing adipocyte loss, diarrhoea, or death detected in C. betacea treated group;
cell death. In addition, the excess storage of triacylglycerol therefore, it could be considered safe [60].
(TAG) from dietary intake results in an excessive influx
of free fatty acids into blood circulation. Therefore, taken 5. Conclusion
together, this condition can lead to low-grade inflammation
characterized by the overproduction of proinflammatory Overall, treatment of obese induced rats with C. betacea
adipocytokines [46]. extract showed its potential in weight maintenance and
The supplementation of C. betacea demonstrated that the positive lipid lowering effect and demonstrated an increment
treatment groups showed lower bodyweight as compared of antioxidant activity of SOD, GPx, and TAS and exhibited
to positive control group. This finding supports C. betacea anti-inflammatory effects as showed in the decrements of
ability in maintaining the current bodyweight. Lister et al. inflammatory biomarkers. Therefore, consumption of C.
[14] stated that the amount of water for red and yellow C. betacea in daily dietary intake is a one-step action towards
betacea was 86.06 g and 86.30 g, respectively. Meanwhile the prevention of obesity and weight management principle.
value of fibre was stated to be 3.3 g. As such, C. betacea showed
high water content and considerable amount of fibre. The
rationale behind the potential role of an increased consump-
Conflict of Interests
tion of fruit in the prevention of overweight and obesity The authors have no conflict of interests.
is related to several features of whole fruit which include
high water content, low energy density, and high content
of dietary fibres, of which viscous dietary fibres constitute Acknowledgments
a considerable proportion. Dietary fibre and, in particular, The authors would like to acknowledge the Department of
viscous dietary fibre, which present in fruit in considerable Nutrition and Dietetics, Pathology Laboratory and Animal
amounts, have been shown to increase postprandial satiety House of Faculty of Medicine and Health Sciences, Universiti
and to decrease subsequent hunger in short-term studies [12]. Putra Malaysia, for the facilities, tremendous help, and
Administering C. betacea extract to the high fat diet support of this project. The study was funded by Research
rats showed positive increment of antioxidants enzyme. C. University Grant Scheme (RUGS) Universiti Putra Malaysia.
betacea has been demonstrated to have antioxidant activ-
ity and contained phenolic composition [14–18]. Dietary
nutrients and specific foods, rich in polyphenols (e.g., References
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