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Cardiac Remodeling in Obesity-Resistance Model is not Related to Collagen I and III Protein Expression

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Background: As some individuals present resistance to obesity development, experiments have been trying to understand their susceptibility to cardiometabolic diseases. Objective: To evaluate if the cardiac remodeling was related to collagen protein expression change. Methods: Male Wistar rats were randomized into two experimental groups: control diet (CD, n=15) or high-fat diet (HFD, n=15) for 30 weeks. Rats fed with HFD were ranked based on their adiposity indexes and classified as obese (Ob, n = 8) or obesity-resistant (ROb, n = 6). Rats that failed to present the normal characteristic of the control group while fed with CD were excluded (Control, n = 8). Nutritional profile, comorbidities (dyslipidemia, hypertension, glucose metabolism, hyperleptinemia), cardiac remodeling, and collagen protein expression were evaluated. The groups were compared by One-Way ANOVA, together the Tukey post hoc test, with p<0.05 considered significant.Results: The Ob rats presented an increased adiposity index when compared to C and ROb. Both groups Ob and ROb presented increased low-density lipoprotein (LDL), insulin, homeostatic model assessment of insulin resistance (HOMA- IR) and systolic blood pressure (SBP), and low high-density lipoprotein (HDL) levels when compared to the control group. The levels of triglycerides, non-esterified fatty acid (NEFA), and leptin were lower in ROb as compared to Ob, but higher than the control group. The Ob and ROb groups presented cardiac remodeling, evidenced by echocardiographic and post-mortem analysis. The collagen protein expression did not differ among the groups. Conclusion: The ROb animals present cardiac remodeling that is not related to collagen type I and III protein expression change. (1) (PDF) Cardiac Remodeling in Obesity-Resistance Model is not Related to Collagen I and III Protein Expression. Available from: https://www.researchgate.net/publication/353256712_Cardiac_Remodeling_in_Obesity-Resistance_Model_is_not_Related_to_Collagen_I_and_III_Protein_Expression [accessed Jul 15 2021].
Introduction
Obesity is a chronic metabolic disease characterized
by an excessive adipose tissue accumulation.1 It is
considered a global epidemic and a major public health
problem,2 since this disease can lead to nutritional,
metabolic, hormonal, and cardiovascular changes,
increasing the population’s morbidity and mortality, and
reducing life expectancy.3–5
The literature reports that the cause of main obesity,
currently, is the inadequate dietary habits, with increased
carbohydrate and/or fat consumption.6,7 However,
some individuals seem to present resistance to the
development of obesity. Within this context, experiments
using animals fed with a high-fat diet try to understand
the pathophysiological susceptibility of obesity-resistant
individuals to cardiometabolic diseases.8–10
Int J Cardiovasc Sci. 2021; [online].ahead print, PP.0-0
ORIGINAL ARTICLE
Cardiac Remodeling in Obesity-Resistance Model is not Related to Collagen I and III
Protein Expression
ScarletMarques de Oliveira,1 Jéssica Leite Garcia,1 Danielle Fernandes Vileigas,1 Dijon Henrique Salomé de
Campos,1 Fabiane Valentini Francisqueti-Ferron,1 Artur Junio Togneri Ferron,1 Danielle Cristina Tomaz da
Silva-Bertani,1 Carlos Roberto Padovani,2 Camila Renata Corrêa,1 Antonio Carlos Cicogna1
São Paulo State University (UNESP), Botucatu Medical School, Botucatu,1 SP - Brazil
São Paulo State University (UNESP), Institute of Bioscience,2 Botucatu, SP - Brazil
DOI: https://doi.org/10.36660/ijcs.20200058
Mailing Address: Artur Junio Togneri Ferron
Av. Prof. Mário Rubens Guimarães Montenegro, s/n – UNESP. Postal Code: 18618-687, Botucatu, SP – Brazil.
E-mail: artur.ferron@gmail.com
Manuscript received March 09, 2020; revised manuscript October 15, 2020; accepted April 26, 2021.
Abstract
Background: As some individuals present resistance to obesity development, experiments have been trying to
understand their susceptibility to cardiometabolic diseases.
Objetive: To evaluate if the cardiac remodeling was related to collagen protein expression change.
Methods: Male Wistar rats were randomized into two experimental groups: control diet (CD, n=15) or high-fat diet
(HFD, n=15) for 30 weeks. Rats fed with HFD were ranked based on their adiposity indexes and classified as obese
(Ob, n = 8) or obesity-resistant (ROb, n = 6). Rats that failed to present the normal characteristic of the control group
while fed with CD were excluded (Control, n = 8). Nutritional profile, comorbidities (dyslipidemia, hypertension,
glucose metabolism, hyperleptinemia), cardiac remodeling, and collagen protein expression were evaluated. The
groups were compared by One-Way ANOVA, together the Tukey post hoc test, with p<0.05 considered significant.
Results: The Ob rats presented an increased adiposity index when compared to C and ROb. Both groups Ob and
ROb presented increased low-density lipoprotein (LDL), insulin, homeostatic model assessment of insulin resistance
(HOMA- IR) and systolic blood pressure (SBP), and low high-density lipoprotein (HDL) levels when compared
to the control group. The levels of triglycerides, non-esterified fatty acid (NEFA), and leptin were lower in ROb
as compared to Ob, but higher than the control group. The Ob and ROb groups presented cardiac remodeling,
evidenced by echocardiographic and post-mortem analysis. The collagen protein expression did not differ among
the groups.
Conclusion: The ROb animals present cardiac remodeling that is not related to collagen type I and III protein
expression change.
Keywords: Obesity; Adiposity; Diet.
The CD contained 31.0% of kcal from protein, 51.6% from
carbohydrates, and 17.4% from fat. The HFD contained
18.7% of kcal from protein, 41.6% from carbohydrates,
and 39.7% from fat. The content of saturated/unsaturated
fatty acids was 61.5% / 38.5% in CD and 64.8% / 35.2% in
HFD. The energetic densities from the diets were: HFD =
3.85 kcal/g and CD = 3.10 kcal/g.
Nutritional profile
The nutritional profile was determined by food and
calorie intake, feed efficiency, final body weight, and
adiposity index. Dietary intake and body weight were
measured weekly. The calorie intake was determined
by the following formula: weekly food intake multiplied
by the energy value of each diet (g × kcal). To analyze
the animal’s capacity to convert the consumed food
energy in body weight, feed efficiency was calculated
by dividing the total body weight gain (g) by the total
energy intake (kcal). The total body fat was obtained
by the sum of epididymal, retroperitoneal, and visceral
deposits. The adiposity index was calculated by the total
body fat divided by the final body weight and multiplied
by 100.15,16
Determination of Obesity and Obesity Resistance
A criterion based on the adiposity index was used
to determine the occurrence of obesity and obesity
resistance according to several authors.10,17-19 After 30
weeks, the rats that consumed HFD were ranked based
on their adiposity indexes. Therefore, the animals that
received HFD and presented the highest adiposity
indexes were classified as obese (Ob, n = 8); the animals
that consumed a high-fat diet and presented adiposity
indexes similar to control animals were classified as
obesity-resistant (ROb, n = 6). Rats that failed to present
the normal characteristic of the control group, while fed
with a standard diet, were excluded (n = 8).
Metabolic and hormonal evaluation
The metabolic evaluation included plasma lipid and
glucose levels, as well as insulin resistance, whereas the
hormonal evaluation was assessed by the concentrations
of leptin and insulin.
The triglycerides, total cholesterol (TC), high- and
low-density lipoprotein (HDL and LDL) levels were
determined using a specific kit (BIOCLIN®, Belo
Horizonte, MG, Brazil) and analyzed by the automated
Cardiac remodeling is well established in obesity
conditions, since research has shown the relationship
between time of obesity and myocardial collagen type I
and III expression.11 However, no studies have evaluated
the contribution of collagen expression to cardiac
remodeling in obesity-resistant animal models, and the
few studies that evaluated the cardiac changes in this
condition found divergent results. Sá et al.9 found isolated
papillary muscle contraction impairment, while Carroll
et al.10 found cardiac no abnormalities in obesity-resistant
animals fed with a high-fat diet.
Considering this situation, the primary aim of this
study was to verify the presence of cardiac remodeling
in obesity-resistant animals fed with a high-fat diet.
An additional aim was to evaluate if the cardiac
remodeling was related to collagen I and III protein
expression change.
Methods
Animals and experimental protocol
Male Wistar rats (60-day-old) were randomly divided
into two experimental groups to receive a control diet
(CD, n=15) or a high-fat diet (HFD, n=15) for 30 weeks.
The sample size and the experimental period were
based on previous studies conducted by our research
group.9,11,12 Animals were kept in individual cages with
controlled temperature (24 ± 2 ºC), humidity (55 ± 5%),
and light (12-h light/dark cycle). The diet and water
were ad libitum. The experimental procedures were
performed according to the “Guide for the Care and
Use of Laboratory Animals”9,13 and approved by the
Animal Ethics Committee of the Botucatu Medical School
(991/2012). At the end of the experimental protocol, after
8h fasting, the animals were euthanized by decapitation
after intraperitoneal anesthesia with a mixture of
ketamine (1 mg/kg) and xylazine (100 mg/kg) (Syntec,
Rhobifarma Indústria Farmacêutica Ltda., Hortolândia,
São Paulo, Brazil). The blood and the cardiac samples
were collected and stored at −20°C for further analysis.
Diet composition
The diets used in this study have been described
elsewhere11,12,14,15 and the composition followed AIN93
recommendations, consisting of the following ingredients:
corn bran, soybean hull, soybean bran, dextrin, salt, vitamin
and mineral complex, palm kernel oil, and soybean oil.
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Obesity-resistance and cardiac collagenOriginal Article
enzymatic colorimetric method (Chemistry Analyzer
BS-200, Mindray Medical International Limited,
Shenzhen, China). The non-esterified fatty acid (NEFA)
concentrations were evaluated by colorimetric kit
(WAKO Pure Chemical Industries Ltd., Osaka, Japan).
Glycemia was analyzed in blood samples collected
from the tails of the animals, using a handheld glucometer
(Accu-Chek Go Kit, Roche Diagnostic Brazil Ltda, São
Paulo, SP, Brazil). The homeostatic model assessment
of insulin resistance (HOMA-IR) was used as an insulin
resistance index, calculated according to the formula:
HOMA-IR = [fasting glucose (mmol/L) x fasting insulin
(µU/mL)]/22.57.
The insulin and leptin levels were analyzed by the
enzyme-linked immunosorbent assay (ELISA) method
(EMD Millipore Corporation, Billerica, MA, USA). The
reading was performed using a microplate reader (Spectra
MAX 190, Molecular Devices, Sunnyvale, CA, USA).
Echocardiographic Study
The analysis was performed with live animals by
transthoracic echocardiography, using a Vivid S6 system
equipped with a multifrequency ultrasonic transducer
5.0 to 11.5 MHz (General Electric Medical Systems, Tirat
Carmel, Israel). The animals were lightly anesthetized
by intraperitoneal injection with a mixture of ketamine
(50mg/kg) and xylazine (1mg/kg) and put in left
decubitus position. Only one examiner performed all
of the exams. The heart image structural measurements
were obtained in one-dimensional mode (M-mode)
guided by the images in two-dimensional mode with
the transducer in the parasternal position, minor axis.
Left ventricular (LV) evaluation was performed with the
cursor M-mode just below the mitral valve plane at the
level of the papillary muscles. The echocardiographic
analysis was performed according to that established in
prior studies.19-21
Morphometric variables
• Maximum left atrium diameter (LA, cm);
Left ventricular diastolic and systolic diameters of the
left ventricle (LV, mm): LVDD and LVSD, respectively;
Interventricular septum diastolic thickness (IVSDT)
and posterior wall diastolic thickness (PWDT) of the
LV (mm): IVSDT and PWDT, respectively;
Relative thickness of the LV (LVRT) = (2 × PWDT)/
LVDD;
Left ventricular mass (LVM, g) = 0.8 × {1.04 × [(IVSDT
+ PWDT + LVDD)3 − LVDD3]} + 0.6;
LVM index (LVMI, g/m2.7) = LVM/Height2.7 where LVMI
is LV mass indexed to height.
Systolic function variables
Cardiac output (CO) was calculated by multiplying
the systolic volume by the heart rate.
Diastolic function variables
Maximum early ventricular filling velocity (E wave
peak, cm/s): obtained by spectral Doppler recording
of the transmitral diastolic flow;
Maximum late filling velocity during atrial contraction
(A wave peak, cm/s): obtained by spectral Doppler
recording of the transmitral diastolic flow;
E-wave deceleration time (ms) corresponding to the
time between the initial velocity peak of the mitral
transvalvular flow and its extrapolation to the baseline.
Systolic blood pressure
The Systolic blood pressure (SBP) was measured by tail
plethysmography, using a Narco Bio-System® Electro-
Sphygmomanometer, model 709-0610 (International
Biomedical, Austin, TX, USA). The animals were warmed
in a wooden box (50 × 40 cm) between 38–40°C for 4–5 min
to stimulate arterial vasodilation. After this procedure, a
cuff with a sensor was placed in the proximal region of the
tail, coupled to the electro-sphygmomanometer. The cuff
was inflated to 200 mmHg pressure and subsequently
deflated.15,16 The arterial pulsations were recorded in a
computerized data acquisition system (AcqKnowledge
® MP100, Biopac Systems Inc., Santa Barbara, CA).
The average of two readings was recorded for each
measurement.
Post-Death Morphological Analysis
After euthanasia, the animals were submitted to
thoracotomy, and the hearts, ventricles, and tibia were
separated, dissected, weighed, and measured. Cardiac
remodeling was determined by analyzing the weight of
the heart and the left (LV) and right (RV) ventricles, and
their correlation with the tibial length.
Myocardial collagen types I and III protein expression
The Western Blot analysis was performed to evaluate
the types I and III collagen protein expression. Briefly,
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Obesity-resistance and cardiac collagen Original Article
the LV samples were rapidly frozen in liquid nitrogen
and subsequently homogenized in a solution containing
RIPA buffer (Amresco LLC, Solon, OH, USA), together
with protease (Sigma-Aldrich, St. Louis, MO) and
phosphatase (Roche Diagnostics, Indianapolis, IN, USA)
inhibitors. The samples were subjected to SDS-PAGE in
10% polyacrylamide gel and were then electrotransferred
to a nitrocellulose membrane (Amersham Biosciences,
Piscataway, NJ, USA). The blotted membrane was
blocked (5% nonfat dry milk, 20 mmol/L Tris-HCl
pH 7.4, 137 mmol/L NaCl and 1% Tween 20) for 2h at
room temperature and then incubated overnight at
4–8°C with primary antibody against collagen type
I (1:10000) and collagen type III (1:10000) (Abcam,
Cambridge, MA, USA). The immunoblots were
washed three times with TBS-T and incubated for 1.5h
with peroxidase-conjugated anti-rabbit secondary
antibody (1:2000) (Abcam, Cambridge, MA, USA),
and then washed again three times with TBS-T and
incubated with ECL (Enhanced Chemi-Luminescence,
Amersham Biosciences, Piscataway, NJ, USA) for
chemiluminescence detection. Blots were analyzed on
Scion Image software (Scion Corporation, Frederick,
MD, USA) and protein expressions were normalized to
β-actin expression (1:1000) (Santa Cruz Biotechnology,
Santa Cruz, CA, USA).
Statistical analysis
The data were submitted to Kolmogorov-Smirnov
normality test. Parametric variables were compared
by One-Way analysis of variance (ANOVA) and
complemented with the Tukey post hoc test for multiple
comparisons when significant differences were found (p<
0.05). All the results are presented as mean ± standard
deviation. Statistical analyses were performed using
Sigma Stat for Windows Version 3.5. (Systat Software,
Inc., San Jose, CA, USA). The level of significance
considered was 5%.
Results
Table 1 presents the nutritional profile of the groups.
It is possible to verify that both Ob and ROb groups
presented lower food intake compared to the control
group. Feed efficiency, final body weight, weight gain,
and adiposity index were higher in the Ob group when
compared to the control group. The ROb presented only
a reduced adiposity index when compared to the Ob
group, with no difference in the other variables.
The metabolic, cardiovascular, and hormonal
parameters are presented in Table 2. Both groups, Ob and
Rob, presented increased LDL, insulin, HOMA- IR and
SBP, and low HDL levels when compared to the control
group. The triglycerides, NEFA, and leptin levels were
lower in the Rob group when compared to the Ob group,
but higher than the control group.
The echocardiographic parameters are presented in
the Figure 1. The Ob and ROb groups presented cardiac
remodeling, characterized by increased LVDD, LVSD, left
atrium, and estimated LV mass when compared to the
control group. The systolic dysfunction, characterized by
reduced cardiac output, was detected in both the Ob and
Table 1 – Nutritional profile
Variables C (n=8) Ob (n=8) ROb (n=6)
Food intake (g/day) 25.1 ± 2.3 21.1 ± 1.8* 20.2 ± 1.4*
Calorie intake (kcal/day) 74.2 ± 7.1 76.9 ± 6.7 73.9 ± 5.1
Feed efficiency (%) 1.45 ± 0.08 1.82 ± 0.20* 1.64 ± 0.14
Final body weight (g) 506 ± 46.9 592 ± 60.2* 546 ± 36.4
Weight gain (g) 226 ± 21,3 296 ± 51,2* 255 ± 24,3
Adiposity index (%) 5.91 ± 0.59 10.21 ± 1.41* 6.31 ± 0.51#
Data presented as mean ± standard deviation. n: Number of animals; C: control; Ob: obese; ROb: obesity-resistant. *versus C; p < 0.05; #versus Ob, p<
0.05; One-way ANOVA for independent samples and Tukey’s post hoc test.
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Obesity-resistance and cardiac collagenOriginal Article
Table 2 – Metabolic, cardiovascular, and hormonal parameters
Variables C (n=8) Ob (n=8) ROb (n=6)
Triglycerides (mg/dL) 50.1 ± 10.3 99.6 ± 19.8* 73.1 ± 10.6*#
NEFA (mmol/L) 0.345 ± 0.033 0.642 ± 0.037* 0.462 ± 0.034*#
HDL (mg/dL) 28.7 ± 2.2 22.1 ± 2.6* 22.3 ± 2.9*
LDL (mg/dL) 19.9 ± 2.1 33.4 ± 5.1* 30.9 ± 3.7*
Glucose (mg/dL) 117 ± 13 169 ± 13* 136 ± 17#
Insulin (ng/mL) 3.39 ± 0.49 9.18 ± 2.14* 7.91 ± 2.12*
HOMA-IR 18.6 ± 4.5 75.1 ± 14.2* 21.1 ± 8.6*
Leptin (ng/mL) 4.23 ± 1.11 27.34 ± 3.36* 10.76 ± 3.21*#
SBP (mmHg) 116 ± 7 135 ± 3* 133 ± 12*
Data presented as mean ± standard deviation. n: Number of animals; C: control; Ob: obese; ROb: obesity-resistant. TC: total cholesterol; HDL: high-
density lipoprotein; LDL: low-density lipoprotein; NEFA: non-esterified fatty acids; HOMA-IR: Homeostatic Model Assessment - Insulin Resistance;
SBP: Systolic blood pressure. *versus C; p < 0.05; #versus Ob, p< 0.05; One-way ANOVA for independent samples and Tukey’s post hoc test.
Figure 1 – Echocardiographic parameters. LVDD: left ventricular diastolic diameter (A), LVSD: left ventricular systolic diameter (B),
Left atrium (C); Estimated left ventricular mass (D), Deceleration time (E), and Cardiac output (F). Control (C, n=8), Obese (Ob, n=8)
and Obesity-resistant (ROb, n=6). Data presented as mean ± standard deviation. *versus C; p < 0.05; #versus Ob, p< 0.05; One-way
ANOVA for independent samples and Tukey’s post hoc test.
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Obesity-resistance and cardiac collagen Original Article
ROb groups. The diastolic dysfunction appeared only in
the Ob group (increased deceleration time).
Cardiac remodeling was also confirmed in both the Ob
and ROb groups by the cardiac post-mortem analysis, as
these animals presented higher heart weight, LV weight,
RV weight, heart/ tibia length, LV/ tibia length, and RV/
tibia length when compared to the control group (Figure 2).
Figure 3 shows the collagen type I (figure 3A) and
the collagen type III (figure 3B) protein expression. No
difference was found among the groups.
Discussion
Since obesity and its related disorders are becoming
increasingly prevalent, several researchers have been
using high-fat diet models to induce obesity, typically
characterized by weight gain and increased body
fat.7,15,22,23 In the present study, we chose ~40% of kcal
from fat, as we believe this is closer to what is consumed
by humans. However, some individuals remain resistant
to becoming obese, a condition also observed in some
animals’ fed with high-fat diets, which are defined as
obesity-resistant animals.8-10,24,25 Within this context, some
authors have reported that around 40% of the animals
fed with a high-fat diet are classified as ROb.8-10,23 Some
possible pathways to explain the obesity resistance
include: increased expression of some thermogenic
enzymes and decreased expression of lipogenic enzymes
in adipose tissues of ROb rats, as well as the suppression
of lipogenesis and the acceleration of fatty-acid oxidation
in visceral fat.8
Several experiments have demonstrated that obese
rats due to a high-fat diet intake develop obesity-related
disorders that are similar to human disorders, such as
glucose intolerance, insulin resistance, hypertension,
and dyslipidemia.16,22,26 However, in ROb models,
there are controversies regarding the presence of
comorbidities.9,10,23,27 In the current study, the ROb
group presented relevant metabolic, hormonal, and
cardiovascular changes commonly found in obesity and
associated with increased adiposity.28 As the ROb group
presented a weight gain and an adiposity index similar
to the C group, it demonstrates that all the disorders
were independent of adiposity gain. According to the
literature, the intake of processed foods rich in fats,
especially saturated fat, is one of the main causes for
Figure 2 – Cardiac remodeling. Heart weight (A), LV: left ventricle weight (B), RV: right ventricle weight (C); Heart/tibia length (D), LV/
tibia length (E), and RV/tibia length (F). Control (C, n=8), Obese (Ob, n=8), and Obesity-resistant (ROb, n=6). Data presented as mean ±
standard deviation. *versus C; p < 0.05; #versus Ob, p< 0.05; One-way ANOVA for independent samples and Tukey’s post hoc test.
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Obesity-resistance and cardiac collagenOriginal Article
obesity and is considered an isolated cause of metabolic
disorder development due the pro-inflammatory effect
of this nutrient.29 Corroborating this finding, the ROb
group presented increased an HOMA-IR index when
compared to the control group, indicating impairment
in carbohydrate metabolism as well as dyslipidemia,
characterized by increased triglycerides and LDL, and
reduced HDL.
Increased leptin and insulin are common in obesity.16,22
However, the present study also observed this condition
in the ROb animals. Increased insulin can be due to insulin
resistance or elevated gastric inhibitory polypeptide
levels induced by high-saturated fatty acid intake.30 At the
same time, hyperinsulinemia stimulates and increases the
leptin secretion by adipose tissue through the PI3K/Akt/
mTOR pathway, which can explain the increased leptin
levels in the ROb animals that did not present increased
body fat.31
The metabolic responses to hyperinsulinemia and
hyperleptinemia are well established in the literature.22,26
Nevertheless, these conditions also promote responses
in other target organs, such as the heart.16,32 In obesity,
the high hormone levels trigger hypertrophic responses
in the heart by activating specific signaling pathways.33-36
However, in obesity-resistance models, the establishment
of cardiac remodeling seems controversial.
Our results confirm the primary aim of this experiment,
since the presence of cardiac remodeling in the ROb
animals was verified by both echocardiographic and
morphological post-mortem analysis,. The majority
of cardiac diseases are followed by heart mass and
morphologic changes. Due to the cardiac cell’s incapacity
to divide into the adult phase, the remodeling process
usually occurs because of cardiomyocytes hypertrophy
in response to a hemodynamic overload.37
Hemodynamic and hormonal changes promote
extracellular matrix remodeling, altering its gene
expression.38,39 There are two main types of collagen
in the heart, types I and III, which are responsible by
cardiac rigidity.40 However, different obesity models
have demonstrated controversial results about collagen
synthesis and degradation in the heart.38,39,41 In this
sense, this study had as secondary aim to evaluate if
the cardiac remodeling was related to collagen I and III
protein expression changes. Our results showed that no
difference was found in the collagen protein expression
among the groups. Thus, other pathways that influence
cardiac remodeling and should be addressed in future
studies include insulin/ PI3k/Akt/ PKB,33,37 leptin/ RhoA/
ROCK/ p38,34,35 oxidative stress,42 and inflammation.43
Study Limitations
Limitations of this study include the absence of
histological analysis for collagen evaluation and the
small sample size.
Conclusion
Considering the results presented in this study, it
is possible to conclude that obesity-resistant animals
present cardiac remodeling that is not related to collagen
type I and III protein expressions.
Figure 3 – Western blot analysis of collagen type I (A) and type III (B) in the hearts of the control (C, n=4) and obese I (Ob, n=4) and II
(ROb, n=4) rats. Western blot bands were normalized by β‐actin. Data presented as mean ± standard deviation. n: Number of animals;
C: control; Ob: obese; ROb: obesity-resistant. *versus C; p < 0.05; #versus Ob, p< 0.05; One-way ANOVA for independent samples and
Tukey’s post hoc test.
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Obesity-resistance and cardiac collagen Original Article
Author contributions
Conception and design of the research: Oliveira SM and
Cicogna AC. Acquisition of data: Oliveira SM, Campos
DHS, Silva-Bertani DCT and Vileigas DF. Analysis and
interpretation of the data: Oliveira SM, Vileigas DF, Ferron
AJT, Silva-Bertani DCT and Corrêa CR. Statistical analysis:
Francisqueti-Ferron FV, Ferron AJT and Padovani CR.
Obtaining financing: Oliveira SM and Cicogna AC. Writing
of the manuscript: Oliveira SM, Garcia JL, Francisqueti-
Ferron FV, Ferron AJT and Cicogna AC. Critical revision of
the manuscript for intellectual content: Ferron AJT, Corrêa
CR and Cicogna AC.
Potential Conflict of Interest
No potential conflict of interest relevant to this article
was reported.
Sources of Funding
This study was funded by Fundação de Amparo
à Pesquisa do Estado de São Paulo - FAPESP (grants:
2013/23954-0 and 2012/21024-2).
Study Association
This study is not associated with any thesis or
dissertation work.
Ethics approval and consent to participate
This study was approved by the Ethics Committee
on Animal Experiments of the FMB-UNESP under the
protocol number 991/2012.
1. World Health Organization. [Internet]. Obesity and overweight. Geneva:
World Health Organization; 2020. [cited 2021 Jun 02]. Available from: https://
www.who.int/news-room/fact-sheets/detail/obesity-and-overweight
2. NCD Risk Factor Collaboration (NCD-RisC). Worldwide trends in body-
mass index, underweight, overweight, and obesity from 1975 to 2016: a
pooled analysis of 2416 population-based measurement studies in 128·9
million children, adolescents, and adults. Lancet. 2017;390(10113):2627-
42. doi: 10.1016/S0140-6736(17)32129-3.
3. Popkin BM. Relationship between shifts in food system dynamics and
acceleration of the global nutrition transition. Nutr Rev. 2017;75(2):73-82.
doi: 10.1093/nutrit/nuw064.
4. Elagizi A, Kachur S, Lavie CJ, Carbone S, Pandey A, Ortega FB, Milani
RV. An Overview and Update on Obesity and the Obesity Paradox in
Cardiovascular Diseases. Prog Cardiovasc Dis. 2018;61(2):142-50. doi:
10.1016/j.pcad.2018.07.003.
5. Popkin BM, Adair LS, Ng SW. Global nutrition transition and the
pandemic of obesity in developing countries. Nutr Rev. 2012;70(1):3-21.
doi: 10.1111/j.1753-4887.2011.00456.x.
6. Francisqueti FV, Minatel IO, Ferron AJT, Bazan SGZ, Silva VDS, Garcia
JL, et al. Effect of gamma-oryzanol as therapeutic agent to prevent
cardiorenal metabolic syndrome in animals submitted to high sugar-fat
diet. Nutrients. 2017;9(12):1299. doi: 10.3390/nu9121299.
7. Ferron AJT, Aldini G, Francisqueti-Ferron FV, Silva CCVA, Bazan SGZ,
Garcia JL, et al. Protective effect of tomato-oleoresin supplementation on
oxidative injury recoveries cardiac function by improving β-adrenergic
response in a diet-obesity induced model. Antioxidants. 2019;8(9):368.
doi: 10.3390/antiox8090368.
8. Akieda-Asai S, Koda S, Sugiyama M, Hasegawa K, Furuya M, Miyazato
M, et al. Metabolic features of rats resistant to a high-fat diet. Obes Res
Clin Pract. 2013;7(4):e243-50. doi: 10.1016/j.orcp.2013.01.004.
9. Sá FG, Lima-Leopoldo AP, Jacobsen BB, Ferron AJ, Estevam WM,
Campos DH, et al. Obesity resistance promotes mild contractile
dysfunction associated with intracellular Ca2+ handling. Arq Bras
Cardiol. 2015;105(6):588-96. doi: 10.5935/abc.20150134.
10. Carroll JF, Zenebe WJ, Strange TB. Cardiovascular function in a rat model
of diet-induced obesity. Hypertension. 2006;48(1):65-72. doi: 10.1161/01.
HYP.0000224147.01024.77.
11. Silva DC, Lima-Leopoldo AP, Leopoldo AS, Campos DH, Nascimento
AF, Oliveira SA Jr, et al. Influence of term of exposure to high-fat diet-
induced obesity on myocardial collagen type I and III. Arq Bras Cardiol.
2014;102(2):157-63. doi: 10.5935/abc.20130232
12. Silva-Bertani DCTD, Vileigas DF, Mota GAF, Souza SLB, Tomasi
LC, Campos DHS, et al. Decreased collagen type i is associated with
increased metalloproteinase-2 activity and protein expression of leptin
in the myocardium of obese rats. Arq Bras Cardiol. 2020;115(1):61-70.
doi: 10.36660/abc.20180143.
13. Canadian Council on Animal Care. Conseil canadien de protection des
animaux. Guide to the Care and Use of Experimental Animals. 2nd ed.
Ottawa: CCAC; 2020.
14. Adorni CS, Corrêa CR, Vileigas DF, Campos DHS, Padovani CR, Minatel
IO, et al. The influence of obesity by a diet high in saturated fats and
carbohydrates balance in the manifestation of systemic complications
and comorbidities. Nutrire. 2017;42:16. doi: 10.1186/s41110-017-0042-1.
15. Vileigas DF, Deus AF, Silva DC, Tomasi LC, Campos DH, Adorni CS, et
al. Saturated high-fat diet-induced obesity increases adenylate cyclase
of myocardial β-adrenergic system and does not compromise cardiac
function. Physiol Rep. 2016;4(17):e12914. doi: 10.14814/phy2.12914.
16. Ferron AJ, Jacobsen BB, Sant'Ana PG, Campos DH, Tomasi LC, Luvizotto
RA, et al. Cardiac dysfunction induced by obesity is not related to
β-adrenergic system impairment at the receptor-signalling pathway.
PLoS One. 2015;10(9):e0138605. doi: 10.1371/journal.pone.0138605.
17. Boustany-Kari CM, Gong M, Akers WS, Guo Z, Cassis LA. Enhanced
vascular contractility and diminished coronary artery flow in rats made
hypertensive from diet-induced obesity. Int J Obes. 2007;31(11):1652-9.
doi: 10.1038/sj.ijo.0803426.
18. Levin BE, Keesey RE. Defense of differing body weight set points in
diet-induced obese and resistant rats. Am J Physiol. 1998;274(2):412-9.
doi: 10.1152/ajpregu.1998.274.2.R412.
19. Rodrigues JCS, Luvizutto GJ, Costa RDM, Prudente RA, Silva TR, Souza
JT, et al. Influence of an exercise program on cardiac remodeling and
functional capacity in patients with stroke (CRONuS trial): study protocol
for a randomized controlled trial. Trials. 2019;20(1):298. doi: 10.1186/
s13063-019-3328-1.
References
Int J Cardiovasc Sci. 2021; [online].ahead print, PP.0-0 Oliveira et al.
Obesity-resistance and cardiac collagenOriginal Article
20. Lang RM, Bierig M, Devereux RB, Flachskampf FA, Foster E, Pellikka
PA, et al. Recommendations for chamber quantification: a report from
the American Society of Echocardiography's Guidelines and Standards
Committee and the Chamber Quantification Writing Group, developed
in conjunction with the European Association of Echocardiography, a
branch of the European Society of Cardiology. J Am Soc Echocardiogr.
2005;18(12):1440-63. doi: 10.1016/j.echo.2005.10.005.
21. Nagueh SF, Appleton CP, Gillebert TC, Marino PN, Oh JK, Smiseth OA,
et al. Recommendations for the evaluation of left ventricular diastolic
function by echocardiography. J Am Soc Echocardiogr. 2009;22(2):107-33.
doi: 10.1016/j.echo.2008.11.023.
22. Francisqueti FV, Ferron AJT, Hasimoto FK, Alves PHR, Garcia JL, Santos
KC, et al. Gamma oryzanol treats obesity-induced kidney injuries by
modulating the adiponectin receptor 2/PPAR-α axis. Oxid Med Cell
Longev. 2018;2018:1278392. doi: 10.1155/2018/1278392.
23. Oliveira SA Jr, Dal Pai-Silva M, Martinez PF, Campos DH, Lima-
Leopoldo AP, Leopoldo AS, et al. Differential nutritional, endocrine,
and cardiovascular effects in obesity-prone and obesity-resistant rats fed
standard and hypercaloric diets. Med Sci Monit. 2010;16(7):BR208-17.
24. Madsen AN, Hansen G, Paulsen SJ, Lykkegaard K, Tang-Christensen M,
Hansen HS, et al. Long-term characterization of the diet-induced obese
and diet-resistant rat model: a polygenetic rat model mimicking the
human obesity syndrome. J Endocrinol. 2010;206(3):287-96. doi: 10.1677/
JOE-10-0004.
25. Nascimento AP, Monte-Alto-Costa A. Both obesity-prone and obesity-
resistant rats present delayed cutaneous wound healing. Br J Nutr.
2011;106(4):603-11. doi: 10.1017/S0007114511000468.
26. Ferron AJT, Francisqueti FV, Minatel IO, Silva CCVA, Bazan SGZ,
Kitawara KAH, et al. Association between cardiac remodeling and
metabolic alteration in an experimental model of obesity induced by
western diet. Nutrients. 2018;10(11):1675. doi: 10.3390/nu10111675.
27. Tulipano G, Vergoni AV, Soldi D, Muller EE, Cocchi D. Characterization
of the resistance to the anorectic and endocrine effects of leptin in
obesity-prone and obesity-resistant rats fed a high-fat diet. J Endocrinol.
2004;183(2):289-98. doi: 10.1677/joe.1.05819.
28. Fruh SM. Obesity: risk factors, complications, and strategies for
sustainable long-term weight management. J Am Assoc Nurse Pract.
2017;29(S1):3-14. doi: 10.1002/2327-6924.12510.
29. Minihane AM, Vinoy S, Russell WR, Baka A, Roche HM, Tuohy KM,
et al. Low-grade inflammation, diet composition and health: current
research evidence and its translation. Br J Nutr. 2015;114(7):999-1012.
doi: 10.1017/S0007114515002093.
30. Itoh K, Moriguchi R, Yamada Y, Fujita M, Yamato T, Oumi M, et al.
High saturated fatty acid intake induces insulin secretion by elevating
gastric inhibitory polypeptide levels in healthy individuals. Nutr Res.
2014;34(8):653-60. doi: 10.1016/j.nutres.2014.07.013.
31. Garcia JL, Francisqueti FV, Ferraz APCR, Ferron AJT, Costa MR, Gregolin
CS. High sugar-fat diet induces metabolic-inflammatory disorders
independent of obesity development. Food Nutr Sci. 2019;10(6):664-77.
doi: 10.4236/fns.2019.106049.
32. Lima-Leopoldo AP, Leopoldo AS, Sugizaki MM, Bruno A, Nascimento
AF, Luvizotto RA, et al. Myocardial dysfunction and abnormalities
in intracellular calcium handling in obese rats. Arq Bras Cardiol.
2011;97(3):232-40. doi: 10.1590/s0066-782x2011005000061.
33. Dhanasekaran A, Gruenloh SK, Buonaccorsi JN, Zhang R, Gross GJ, Falck
JR, et al. Multiple antiapoptotic targets of the PI3K/Akt survival pathway
are activated by epoxyeicosatrienoic acids to protect cardiomyocytes from
hypoxia/anoxia. Am J Physiol Heart Circ Physiol. 2008;294(2):724-35. doi:
10.1152/ajpheart.00979.2007.
34. Zeidan A, Hunter JC, Javadov S, Karmazyn M. mTOR mediates RhoA-
dependent leptin-induced cardiomyocyte hypertrophy. Mol Cell
Biochem. 2011;352(1-2):99-108. doi: 10.1007/s11010-011-0744-2.
35. Leifheit-Nestler M, Wagner NM, Gogiraju R, Didié M, Konstantinides S,
Hasenfuss G, et al. Importance of leptin signaling and signal transducer
and activator of transcription-3 activation in mediating the cardiac
hypertrophy associated with obesity. J Transl Med. 2013;11:170. doi:
10.1186/1479-5876-11-170.
36. Rider OJ, Francis JM, Ali MK, Byrne J, Clarke K, Neubauer S, et al.
Determinants of left ventricular mass in obesity; a cardiovascular
magnetic resonance study. J Cardiovasc Magn Reson. 2009;11(1):9. doi:
10.1186/1532-429X-11-9.
37. Francischi RPP, Pereira LO, Freitas CS, Klopfer M, Santos RC, Vieira P, et
al. Obesidade: atualização sobre sua etiologia, morbidade e tratamento.
Rev Nutr. 2000:13(1):17-28. doi: 10.1590/S1415-52732000000100003.
38. Schram K, Girolamo S, Madani S, Munoz D, Thong F, Sweeney G. Leptin
regulates MMP-2, TIMP-1 and collagen synthesis via p38 MAPK in
HL-1 murine cardiomyocytes. Cell Mol Biol Lett. 2010;15(4):551-63. doi:
10.2478/s11658-010-0027-z.
39. Madani S, De Girolamo S, Muñoz DM, Li RK, Sweeney G. Direct effects
of leptin on size and extracellular matrix components of human pediatric
ventricular myocytes. Cardiovasc Res. 2006;69(3):716-25. doi: 10.1016/j.
cardiores.2005.11.022.
40. Mill JG, Vassallo DV. Hipertrofia cardíaca. Rev Bras Hipertens.
2001;8(1):63-75.
41. Schram K, Ganguly R, No EK, Fang X, Thong FS, Sweeney G. Regulation
of MT1-MMP and MMP-2 by leptin in cardiac fibroblasts involves
Rho/ROCK-dependent actin cytoskeletal reorganization and leads
to enhanced cell migration. Endocrinology. 2011;152(5):2037-47. doi:
10.1210/en.2010-1166).
42. Rababa'h AM, Guillory AN, Mustafa R, Hijjawi T. Oxidative stress and
cardiac remodeling: an updated edge. Curr Cardiol Rev. 2018;14(1):53-59.
doi: 10.2174/1573403X14666180111145207.
43. Abel ED, Litwin SE, Sweeney G. Cardiac remodeling in obesity. Physiol
Rev. 2008;88(2):389-419. doi: 10.1152/physrev.00017.2007.
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Obesity-resistance and cardiac collagen Original Article
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