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Background Adipose tissue dysfunction is a condition characterized by inflammation and oxidative stress able to lead metabolic disorders. Curcuma longa L. ( Cl ) is a rhizome commonly used in Indian culinary which presents anti-inflammatory and antioxidant compounds. The aim of this study was to evaluate the effect of in natura Curcuma longa L. on adipose tissue dysfunction and comorbidities in obese rats. Methods Male Wistar rats (8 weeks old, n = 16) received standard chow + fructose in drinking water (30%) ad libitum for 16 weeks. After this period, animals were randomly divided to receive placebo treatment (fructose, n = 8) or Curcuma longa L. treatment (fructose + Cl , n = 8) for more 8 weeks, totalizing 24 weeks of experiment. Curcuma longa L. was mixed in water and gave to the animals by gavage in a dose of 80 mg/kg of body weight. Body composition, systolic blood pressure, metabolic, hormonal, inflammatory, and oxidative stress analysis were performed in plasma and adipose tissue. Results Curcuma longa L. reduced adiposity index and adipocyte hypertrophy, improved insulin resistance and systolic blood pressure, and reduced inflammation and oxidative stress in adipose tissue. Conclusion Curcuma longa L. in natura is able to modulate adipose tissue dysfunction, avoiding the development of comorbidities. It can be considered a phytochemical treatment strategy against obesity-related chronic diseases.
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R E S E A R C H Open Access
Brazilian Curcuma longa L. attenuates
comorbidities by modulating adipose tissue
dysfunction in obese rats
Angelo Thompson Colombo Lo
, Fabiane Valentini Francisqueti
, Fabiana Kurokawa Hasimoto
Ana Paula Costa Rodrigues Ferraz
, Igor Otávio Minatel
, Jéssica Leite Garcia
, Klinsmann Carolo dos Santos
Pedro Henrique Rizzi Alves
, Giuseppina Pace Pereira Lima
, Fernando Moreto
, Artur Junio Togneri Ferron
and Camila Renata Corrêa
Background: Adipose tissue dysfunction is a condition characterized by inflammation and oxidative stress able to
lead metabolic disorders. Curcuma longa L. (Cl) is a rhizome commonly used in Indian culinary which presents anti-
inflammatory and antioxidant compounds. The aim of this study was to evaluate the effect of in natura Curcuma
longa L. on adipose tissue dysfunction and comorbidities in obese rats.
Methods: Male Wistar rats (8 weeks old, n= 16) received standard chow + fructose in drinking water (30%) ad
libitum for 16 weeks. After this period, animals were randomly divided to receive placebo treatment (fructose, n=8)
or Curcuma longa L. treatment (fructose + Cl,n= 8) for more 8 weeks, totalizing 24 weeks of experiment. Curcuma
longa L. was mixed in water and gave to the animals by gavage in a dose of 80 mg/kg of body weight. Body
composition, systolic blood pressure, metabolic, hormonal, inflammatory, and oxidative stress analysis were
performed in plasma and adipose tissue.
Results: Curcuma longa L. reduced adiposity index and adipocyte hypertrophy, improved insulin resistance and
systolic blood pressure, and reduced inflammation and oxidative stress in adipose tissue.
Conclusion: Curcuma longa L. in natura is able to modulate adipose tissue dysfunction, avoiding the development
of comorbidities. It can be considered a phytochemical treatment strategy against obesity-related chronic diseases.
Keywords: Adipose dysfunction, Comorbidities, Obesity
White adipose tissue (WAT) is the primary site for en-
ergy storage and is also responsible by thermal isolation
and mechanical protection. Moreover, it is considered an
important endocrine organ which secrets a large number
of adipokines responsible by the whole body metabolism
maintenance [1,2]
However, obese individuals are sus-
ceptible to adipose tissue dysfunction, which is character-
ized by altered adipokine secretion, increased reactive
oxygen species, and inability to store triacylglycerol [24].
This condition is able to lead to metabolic syndrome and
cardiovascular diseases [57].
Studies show that the excessive fructose intake is one
cause for the current epidemics of metabolic syndrome
and obesity [811]. Fructose is a sugar commonly found
in fruits. However, the industry has used corn syrup,
which is rich in fructose, to sweet beverages and foods,
increasing the intake of this sugar by the population
[12]. Although glucose and fructose present similar mo-
lecular structures, their metabolism is different. Fructose
has a lower glycemic index and does not generate an in-
sulin response, but present a higher sweetener power
[13]. Moreover, fructose is quickly absorbed by the liver
and converted into glucose, glycogen, lactate, and fat
[14]. For this reason, fructose is considered a potent
* Correspondence:
Medical School, São Paulo State University (UNESP), Avenida Professor
Montenegro, s/n- Rubião Júnior, Botucatu, SP 18618-970, Brazil
Full list of author information is available at the end of the article
© The Author(s). 2018 Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0
International License (, which permits unrestricted use, distribution, and
reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to
the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver
( applies to the data made available in this article, unless otherwise stated.
Lo et al. Nutrire (2018) 43:25
lipogenic and adipogenic nutrient, able to promote
hypertrophy in adipocyte precursor cells (APCs), other
condition related to adipose tissue dysfunction, and
metabolic disorders [15].
Considering this condition, functional foods have pre-
sented many health benefits, protecting against several
diseases such as hypertension, diabetes, and cancer [16].
Curcuma longa L. (Cl) is a cultivated and appreciated
spice since antiquity in the Mediterranean region, com-
monly used as coloring, flavoring, and seasonings [17].
This rhizome is composed mainly by curcumin (1,7-bis
(4-hidroxi-3-metoxifenil)-1,6-heptadieno-3,5-diona) but
also by bis-demethoxycurcumin and demethoxycurcumin.
Curcumin is a polyphenol very studied in the isolated
form and presents anti-inflammatory and antioxidant ac-
tivity and is able to attenuate obesity-related disorders
[1721]. Curcuma longa L. extract is another administra-
tion form with health benefit results [17]. However, most
of population ingests this food in natura in the diet, added
in the preparations. Considering that studies with
Curcuma longa L. in natura in the literature are scarce, it
is important to evaluate the action of this food on inflam-
mation and oxidative due adipose tissue dysfunction. So,
the aim of this study was to evaluate the in natura effect
of Curcuma longa L. on adipose tissue dysfunction and
comorbidities in obese rats.
Material and methods
Experimental protocol
All the experiments and procedures were approved by the
Animal Ethics Committee of Botucatu Medical School
(1065/2013) and performed in accordance with the Na-
tional Institute of Healths Guide for the Care and Use of
Laboratory Animals. Male Wistar rats (8 weeks old) were
housed in individual cages in an environmental controlled
room (22 °C ± 3 °C; 12-h light-dark cycle and relative hu-
midity of 60 ± 5%). During 16 weeks, animals (n= 16) re-
ceived standard chow + fructose in drinking water (30%)
ad libitum. After this period, animals were randomly di-
vided to receive placebo treatment (fructose, n=8) or
Curcuma longa L. treatment (fructose + Cl,n=8) for
more 8 weeks, totalizing 24 weeks of experiment. Both
groups (fructose and fructose + Cl) continued receiving
standard chow + fructose in drinking water (30%) ad libi-
tum.In order to confirm obesity in the fructose group,
additional rats of the same age, fed with a chow diet and
water, were used as control group (n=8).
Curcuma longa L. preparation and treatment
Curcuma longa L. was harvested in São Manuel city, São
Paulo, Brazil, in the Experimental Farm of Teaching,
Research and Production, belonging to the Agronomic
Sciences Faculty (FCA) - UNESP/Botucatu-SP. After the
harvest, the rhizomes were washed and sent to the
Department of Chemistry and Biochemistry of the Institute
of Biosciences (IB) - UNESP/Botucatu-SP, where they were
chopped and dried in a forced air circulation oven at 65 °C
until stabilization of pasta. The rhizomes were ground in a
knife mill and stored in amber glass bottles at room
temperature, protected from light and moisture. After this,
animals received both placebo or Curcuma longa L. (Cl)by
gavagem. Curcuma longa L. was mixed in water and ad-
ministered to the animals in a dose of 80 mg/kg of body
weight [22]. It was also added black pepper (1%) to increase
Curcuma longa L. absorption [23]. Placebo was only water.
Body composition
Body composition was evaluated by initial and final body
weight and adiposity index. Adiposity index (AI), consid-
ered an estimative of body fat, was calculated according
to the formula: [(epididymal + retroperitoneal + vis-
ceral)/body weight] × 100 [24,25].
Systolic blood pressure
Systolic blood pressure (SBP) evaluation was assessed in con-
scious rats by the non-invasive tail-cuff method with a Nar-
coBioSystems® Electro-Sphygmomanometer (International
Biomedical, Austin, TX, USA). The animals were kept in a
wooden box (50 × 40 cm) between 38 and 40 °C for 45min
to stimulate arterial vasodilation [26]. After this procedure, a
cuff with a pneumatic pulse sensor was attached to the tail
of each animal. The cuff was inflated to 200 mmHg pressure
and subsequently deflated. The blood pressure values were
recorded on a Gould RS 3200 polygraph (Gould Instrumen-
tal Valley View, OH, USA). Theaverageofthreepressure
readings was recorded for each animal.
Plasma metabolic and hormonal analysis
After 12 h of fasting, blood was collected and plasma was
used for the following analysis. An enzymatic-colorimetric
kit was used to measure glucose and triglycerides
(Bioclin®; Belo Horizonte) using an automatic enzymatic
analyzer system (Chemistry Analyzer BS-200, Mindray
Medical International Limited, Shenzhen, China). The
insulin level was measured using the enzyme-linked im-
munosorbent assay (ELISA) method using commercial
kits (EMD Millipore Corporation, Billerica, MA, USA).
The homeostatic model of insulin resistance (HOMA-IR)
was used as an insulin resistance index, calculated accord-
ing to the formula: HOMA-IR = (fasting glucose (mmol/
L) × fasting insulin (μU/mL))/22.5 [27].
Plasma inflammatory cytokines
Plasma levels of tumoral necrose factor-alpha (TNF-α)
and interleukin-6 (IL-6) were measured by ELISA kits
(R&D System, Minneapolis, USA). Reading was made in a
microplate spectrophotometer reader (SpectraMax 190;
Molecular Devices).
Lo et al. Nutrire (2018) 43:25 Page 2 of 8
Plasma extraction and identification of curcuminoids by
The extraction was made according to Asai and Miyazawa
(2000) [28]. Aliquots (20 μL) were injected into a UHPLC
Thermo Scientific Dionex UltiMate 3000 system (Thermo
Fisher Scientific Inc., MA, USA), coupled to a quaternary
pump an Ultimate 3000RS auto sampler and a diode array
detector (DAD-3000RS). The reading was performed at a
wavelength of 245 nm using an isocratic method com-
posed of ethanol: methanol (60:40) as the mobile phase
under a flow of 1.0 mL per minute. The column used was
C18, 5 μm, 150 × 4.6. The results were obtained through a
curve performed with the sigma standards (98% purity) of
curcumin (C08511), bisdemethoxycurcumin (B6938), and
demethoxycurcumin (D7696).
Epididymal adipose tissue analysis
Tissue preparation
Epididymal adipose tissue (400 mg) was homogenized
with 2 ml of PBS (pH 7.4) and then centrifuged at
3000 rpm, 4 °C, 10 min. The supernatant was used to
evaluate inflammatory cytokines, malondialdehyde, and
carbonylation. The results were corrected by the protein
amounts of each sample, quantified by the Bradford
method [29].
Inflammatory cytokines in adipose tissue
Tumoral necrosis factor-alpha (TNF-α) and interleukin 6
(IL-6) were measured by ELISA kits (R&D System, Minne-
apolis, USA) according to the manufacturers instructions.
Reading was made in a microplate spectrophotometer
reader (SpectraMax 190; Molecular Devices).
Malondialdehyde (MDA) in adipose tissue
For MDA quantification, 250 μL of epididymal adipose
tissue supernatant was mixed with 750 μL of 10%
trichloroacetic acid for protein precipitation. After cen-
trifugation (3000 rpm, 5 min; Eppendorf® Centrifuge
5804-R, Hamburg, Germany), the supernatant was re-
moved. Thiobarbituric acid (TBA, 0.67%) was added in
ratio (1: 1), and the samples were heated for 15 min at
100 °C. MDA reacts with TBA in the ratio 1: 2
MDA-TBA, absorbed at 535 nm. After cooling, the read-
ing at 535 nm was performed on Spectra Max 190 mi-
croplate reader (Molecular Devices®, Sunnyvale, CA,
USA). The MDA concentration was obtained by the
molar extinction coefficient (1.56 × 105 M
) and
the sample absorbance and the final result expressed in
nmol/g protein [30].
Protein carbonylation in adipose tissue
Epididymal adipose tissue supernatant was used to
measure protein carbonylation (PC) by an unspecific
method based on the photometric detection of DNPH
(2,4-dinitrophenyl hydrazine) derivatizing agent [31].
Briefly, 10 μL of diluted (1:10) supernatant was incu-
bated in an acid DNPH solution for 10 min. After this,
NaOH 1 M was added and the absorbance was checked.
Results were obtained according to the molecular extinc-
tion coefficient of DNPH and adjusted according to the
total tissue proteins amount (mg).
Histological analysis
Adipose tissue was fixed in 4% formaldehyde and embed-
ded in paraffin. Two consecutive sections from each sam-
ple were cut (4 μm) and stained with hematoxylin/eosin.
The entire slide was scanned using a 3DHISTECH Pano-
ramic MIDI System attached to a Hitachi HV-F22 color
camera and ten fields/slide were analyzed under × 100
magnification in a blinded manner. The inflammatory re-
actions are reported as present/absent. Using the same
slides, adipocyte mean area was calculated using a method
previously described by Osman et al. in 2013 [32].
Statistical analysis
Results are expressed as mean + standard deviation (SD).
The significance of differences was calculated by the Stu-
dentsttest, using SigmaStat version 3.5 for Windows
(Systat Software, Inc., San Jose, CA, USA). A pvalue of
0.05 was considered as statistically significant.
Effect of Curcuma longa L. on body weight and adiposity
There were no differences in BW among the groups in the
beginning of this study. At the end of the experiment, the
mean BWs of the fructose group was significantly higher
than control group (control 489 + 58 g vs. fructose 579 +
71 g, p< 0.05). Regarding the effect of Curcuma longa L.
on body weight, the treated group (fructose + Cl) did not
present difference compared to fructose group. The adi-
posity index was also significantly higher in fructose group
(control 5.3 + 1.2% vs. fructose 9.5 + 1.7%, p<0.001) com-
pared to control group, which confirms obesity in fructose
group. However, fructose + Cl group presented after the
treatment, lower adiposity index compared to fructose
group, demonstrating the positive effect of Curcuma longa
L. against obesity. In order to confirm the presence of
Curcuma longa L. in the treated group, plasma detection
of curcumin and two isoforms, bis-demethoxycurcumin
and demethoxycurcumin, were analyzed. It is possible to
verify the presence of curcuminoids only in fructose + Cl
group. All the results are presented in Table 1.
Effect of Curcuma longa L. on the adipose tissue
Adipose tissue histological analysis showed inflammatory
cells in both groups that received fructose. About the
Lo et al. Nutrire (2018) 43:25 Page 3 of 8
effect of Curcuma longa L. the treated group (fructose +
Cl) presented reduction in adipocyte area compared to
fructose group, confirming the positive result of this
food to reduce hypertrophy (Fig. 1).
Inflammatory cytokine levels are presented in Fig. 2.
Fructose + Cl group also presented reduced plasma and
adipose tissue IL-6 levels as well as reduced TNF-αcon-
centration in adipose tissue compared to fructose group.
Figure 3presents oxidative stress parameters in adi-
pose tissue. Fructose + Cl group showed lower levels of
MDA compared to fructose group. No effect on carbon-
ylation was observed.
Effect of Curcuma longa L. on comorbidities
Figure 4shows the effect of Cl on metabolic parameters.
It is possible to verify a positive effect to reduce plasma
triglycerides, HOMA-IR, and systolic blood pressure in
fructose + Cl group compared to fructose group.
The aim of this study was to evaluate the in natura effect
of Curcuma longa L. on adipose tissue dysfunction and
comorbidities in obese rats. Adipose tissue dysfunction is
characterized by an imbalanced production and release of
pro- and anti-inflammatory adipokines, increased produc-
tion of reactive oxygen species (ROS), and increased in-
flammatory cell infiltrate [33]. This condition is associated
with metabolic systemic consequences such as systemic
low-grade inflammation, hypercoagulability, hypertension,
dyslipidemia, and insulin resistance [12,15,3436].
Therefore, it is extremely important to prevent or to treat
the adipose tissue dysfunction in order to avoid the devel-
opment of diabetes and cardiovascular and renal diseases.
The consumption of bioactive compounds present in
many foods can be a treatment option for these condi-
tions. In this way, our results showed a positive effect of
Curcuma longa L. on attenuation of adipose tissue dys-
function and comorbidities.
Curcumin is the major active component of turmeric, a
yellow compound originally isolated from the plant
Table 1 BW, adiposity index, and plasma levels of curcuminoids
Variables Groups
Fructose Fructose + Cl
Initial BW (g) 257 ± 15 258 ± 14
Final BW (g) 538 ± 15 467 ± 42
Adiposity index (%) 6.59 ± 0.69 4.92 ± 1.05
Caloric intake (Kcal) 66.9 ± 8.3 70.2 ± 9.3
Feed efficiency (%) 2.64 ± 0.23 2.37 ± 0.57
Plasm total curcumin (nmol) ND 0.08 ± 0.04
Bisdemetoxicurcumin (μg/dL) ND 0.09 ± 0.03
Demetoxicurcumin (μg/dL) ND 0.066 ± 0.002
* indicates p<0.05
Fig. 1 Histological section in adipose tissue stained with hematoxilin/eosin (× 100 magnification). aControl groupno changes, bfructose groupadipocyte
hypertrophy and inflammatory infiltrate, cFructose + Cl groupdiscrete inflammatory infiltrate (n= 6 animals/group), dadipocyte area (μm
Lo et al. Nutrire (2018) 43:25 Page 4 of 8
Curcuma longa. It is a member of the curcuminoid family
and has been used for centuries in traditional medicines.
As a spice, it provides curry with its distinctive color and
flavor. Furthermore, traditional Indian medicine has con-
sidered curcumin a drug effective for many disorders in-
cluding asthma and hepatic diseases. However, evidence
from numerous literatures revealed that the major chal-
lenge about curcumin is to increase the absorption and
bioavailability [37]. Uptake and distribution of curcumin
in body tissues is obviously important for its biological ac-
tivity. Most of curcumin get metabolized in the liver and
intestine; however, a small quantity still remains detectable
in the organs [37]. In order to increase the absorption,
piperine, a constituent of pepper, is an inhibitor of hepatic
and intestinal glucuronidation. Thus, the ingestion of pip-
erine contributes to increase the serum concentration of
curcumin and thereby its bioavailability [38]. In our study,
we used in natura Curcuma longa associated with black
pepper to improve the absorption and the result was the
three main curcuminoids present in plasma of the treated
group. Aiming to increase the bioavailability, longer circu-
lation, better permeability, and resistance to metabolic
processes of curcumin several formulations have been pre-
pared which include nanoparticles, liposomes, micelles,
and phospholipid complexes. All of them show improve-
ment in the bioavailability of curcuminoids [37]. However,
these forms have not gained significant attention in hu-
man since most people find and use to cook in natura
Curcuma longa and studies show health benefits from oral
administration. The dietary treatment with curcumin im-
proved insulin sensitivity, inflammatory disorders, or pre-
vented liver fat accumulation in rodents fed with a HF
diet. It is worth noting that the beneficial effects observed
in those studies were always demonstrated after a long
period of administration (up to 8 weeks) [39]. Other in
vitro studies show that curcumin treatment for 12 weeks
could diminish expansion of adipose tissue and body
weight gain probably through inhibition of angiogenesis
Fig. 2 Adipokine levels in plasma and adipose tissue. aIL-6: interleukin-6 in plasma; bIL-6: interleukin-6 in adipose tissue; cTNF-α: tumoral
necrosis factor alpha in plasma; dTNF-α: tumoral necrosis factor alpha in adipose tissue. Values are mean ± standard deviation (SD), n-6 animals/
group. Comparison by StudentsTtest
Fig. 3 Oxidative stress parameters in adipose tissue. aCarbonylation levels. bMDA: malondialdehyde levels. Values are mean ± standard deviation
(SD), n-6 animals/group. Comparison by StudentsTtest
Lo et al. Nutrire (2018) 43:25 Page 5 of 8
and adipogenesis in adipose tissue [40]. So, to investigate
the effects of Curcuma longa in adipose tissue of animals
and humans is very important.
The adipose tissue becomes dysfunctional when the de-
mand of triglycerides is too high, and the adipocyte needs
to hypertrophy to store this excessive TG. Our results
showed that the group treated with Curcuma longa L. pre-
sented reduction of triglyceride levels. Regarding this ef-
fect, two mechanisms could explain these findings. The
first one is that Curcuma longa L. could impact on TG
synthesis and oxidation in the liver by increasing PPAR-α
expression and activation. It has been demonstrated that
PPAR-αregulates liver enzymes related to lipid synthesis
as well as beta-oxidation enzymes [41,42]. The second is
that Curcuma longa L. can upregulate fatty acid oxidation
in the skeletal muscle and/or adipose tissue in association
to a greater expression and activation of UCP-1 [43,44].
Independent of which mechanism happened in our ani-
mals, the reduced plasma TG concentrations reflected in
lower adipocyte fat deposition with consequent reduction
in adiposity index, in adipocyte area, and in IL-6,
TNF-alpha, and MDA levels in the treated group.
This improvement in adipose tissue dysfunction avoided
the manifestation of some comorbidities, among them in-
sulin resistance and type 2 diabetes, since these diseases are
closely associated with chronic inflammation. Regarding
the association of adipokines and diseases, the literature re-
ports that TNF-αwas the first link among obesity, diabetes,
and chronic inflammation in adipose tissue [45,46]. Later,
IL-6 was discovered to be also increased in obese individ-
uals. In this study, both TNF-αand IL-6 were increased in
fructose group and these animals also presented some
comorbidities, such as insulin resistance and hypertension.
nal transduction cascades, including insulin action inhib-
ition pathways. In physiological conditions, insulin
stimulates tyrosine phosphorylation by insulin-receptor
substrate(IRS),whichisacrucial event in mediating insulin
action. However, TNF-αalso targets this element of
insulin-receptor signaling through inhibitory serine phos-
phorylation of IRS-1, which interferes with the ability of
thisproteintoengageininsulin-receptor signaling and re-
sults in alterations in insulin action [45]. Hypertension in
fructose group can be explained by increased IL-6, a cyto-
kine that acts under the renin-angiotensin system (RAS) ac-
tivity leading to angiotensin II (ANGII)-mediated
hypertension [47]. On the other hand, fructose + Cl group
presented a reduction of TNF-αand IL-6 levels which can
explain insulin resistance improvement and the reduction
in systolic blood pressure.
Together with the anti-inflammatory results above de-
scribed, other studies have already showed the
anti-inflammatory and also the antioxidant effect of Cur-
cuma longa L. [4850].The treated group presented re-
duction in MDA levels compared to untreated group,
and no difference in carbonylation was found. Protein
carbonylation is an irreversible protein oxidation pro-
moted by reactive oxygen species, which leads to the loss
of protein function and considered a marker of severe
oxidative damage. This reaction can happens via the
addition of aldehydes such as those generated from lipid
peroxidation. Oxidative decomposition of polyunsatur-
ated fatty acids initiates chain reactions that lead to the
formation of a variety of carbonyl species, among them
Fig. 4 Plasma biochemical parameters and systolic blood pressure. aTG: triglycerides. bHOMA-IR: homeostasis model assessment. cSBP: systolic
blood pressure. Values are mean ± standard deviation (SD), n-6 animals/group. Comparison by StudentsTtest
Lo et al. Nutrire (2018) 43:25 Page 6 of 8
malondialdehyde [51]. Although fructose + Cl group
presented reduction in MDA levels, protein oxidation
did not present difference from fructose group. Since
the group started the treatment with Curcuma longa L.
after 16 weeks receiving fructose, protein carbonylation
have already happened, even with a reduction in MDA
levels. This reduction in MDA levels corroborates the
antioxidant effect of Curcuma longa L.; however, a pre-
ventive consumption of this food should have more
interest to avoid protein oxidation.
In summary, in obese condition, Curcuma longa L.
reduced adiposity index and adipocyte hypertrophy,
improved insulin resistance and systolic blood pressure,
and reduced inflammation and oxidative stress in the adi-
pose tissue. These results can be attributed to the modula-
tion of adipose tissue dysfunction after treatment with this
functional food. So, it is possible to conclude that
Curcuma longa L. in natura is able to modulate adipose
tissue dysfunction, avoiding the development of comor-
bidities. It can be considered a phytochemical treatment
strategy against obesity-related chronic diseases.
AI: Adiposity index; ANGII: Angiotensin II; APCs: Adipocyte precursor cells;
Cl:Curcuma longa L.; DNPH : 2,4-Dinitrophenyl hydrazine; ELISA : Enzyme-
linked immunosorbent assay; HOMA-IR: Homeostatic model of insulin
resistance; IL-6: Interleukin-6; IRS: Insulin receptor substrate;
MDA: Malondialdehyde; PC: Protein carbonylation; PPAR-α: Peroxisome
proliferator-activated receptor alpha; RAS : Renin-angiotensin system;
ROS: Reactive oxygen species; SBP: Systolic blood pressure; SD: Standard
deviation; TBA: Thiobarbituric acid; TG: Triglycerides; TNF-α: Tumoral necrose
factor-alpha; UCP1: Uncoupling protein 1; WAT: White adipose tissue
The authors thank Fundação de Amparo à Pesquisa do Estado de São Paulo
Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP-process
Availability of data and materials
The datasets used and/or analyzed during the current study are available
from the corresponding author on reasonable request.
ATCL contributed to the experimental design and data analysis. FVF
contributed to the experimental design and data analysis, and wrote and
reviewed the manuscript. FKH contributed to the experimental design and
data analysis. APCRF contributed to the experimental design. IOM
contributed to the data analysis and wrote and reviewed the manuscript.
JLG and KCS contributed to the data analysis of the manuscript. PHRA
contributed to the experimental design and data analysis. GPPL, FM and
AJTF wrote and reviewed the manuscript. CRC contributed to the
experimental design and data analysis, and wrote and reviewed the
manuscript. All authors read and approved the final manuscript.
Ethics approval
This study was approved by the Animal Ethics Committee of Botucatu
Medical School (1065/2013).
Consent for publication
Not applicable.
Competing interests
The authors declare that they have no competing interests.
Springer Nature remains neutral with regard to jurisdictional claims in
published maps and institutional affiliations.
Author details
Medical School, São Paulo State University (UNESP), Avenida Professor
Montenegro, s/n- Rubião Júnior, Botucatu, SP 18618-970, Brazil.
Institute, São Paulo State University (UNESP), Botucatu, Brazil.
Received: 19 August 2018 Accepted: 31 October 2018
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The aim of this study is to test the hypothesis that feeding trans fatty acids (TFA) (5%) along with fructose exacerbates obesity and non-alcoholic fatty liver disease (NAFLD) in rats. Male Wistar rats were randomized into four groups, i.e., standard diet, 5% TFA + standard diet, fructose + standard diet, and TFA + fructose + standard diet. All the diets were provided for 16 weeks. The body weight, body mass index, calorie intake, adiposity index, and liver index were determined. Serum glucose, insulin, lipid profile, and liver enzymes were estimated. Liver lipids, markers of oxidative stress, inflammation, and collagen were estimated in the liver. The histopathological evaluation of the adipose tissue and liver were carried out. TFA + standard diet caused an increase in body weight while TFA + fructose + standard diet caused significant body weight gain, adiposity index, and hypertrophy of adipocytes. TFA + fructose + standard diet caused insulin resistance and dyslipidemia in the rats. Rats in the TFA + standard diet group showed marked hepatic steatosis and an elevation in alanine aminotransferase, while those in the TFA + fructose + standard diet group showed oxidative stress, inflammation, and fibrosis in the liver. Feeding of TFA at a concentration of 5% along with the standard diet resulted in an increase in the body weight and hepatic steatosis, but the addition of fructose to 5% TFA and standard diet resulted in obesity and non-alcoholic steatohepatitis. Thus, the reduction in TFA content of foods must be accompanied by a significant decrease in the fructose intake in order to protect against obesity and NAFLD.
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Increasing evidence suggests a role for excessive intake of fructose in the Western diet as a contributor to the current epidemics of metabolic syndrome and obesity. Hereditary fructose intolerance (HFI) is a difficult and potentially lethal orphan disease associated with impaired fructose metabolism. In HFI, the deficiency of a particular aldolase, aldolase B, results in the accumulation of intracellular phosphorylated fructose thus leading to phosphate sequestration and depletion, increased ATP turnover and a plethora of conditions leading to clinical manifestations including fatty liver, hyperuricemia, Fanconi syndrome and severe hypoglycemia. Unfortunately, to date, there is no treatment for HFI and avoiding sugar and fructose in our society has become quite challenging. In this report, through use of genetically modified mice and pharmacological inhibitors, we demonstrate that the absence or inhibition of ketohexokinase (Khk), an enzyme upstream of aldolase B, is sufficient to prevent hypoglycemia and liver and intestinal injury associated with HFI using aldolase B knockout mice. We thus provide evidence for the first time of a potential therapeutic approach for this condition. Mechanistically, our studies suggest that it is the inhibition of the Khk C isoform, not the A isoform, that protects animals from HFI.
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Background The aim of this study is to test the hypothesis that obesity induced by a diet rich in saturated fats and balanced in carbohydrates is associated with the development of systemic complications and comorbidities. Methods Thirty-seven 60-day-old male Wistar rats were randomized into two groups: control (C, n = 18, standard diet) and obese (OB, n = 19, high-saturated fat diet), for 33 weeks. Nutritional profile: food and caloric intake, feed efficiency, body weight, and adiposity index. Complications: in plasma were analyzed dyslipidemia, insulin resistance (HOMA-IR), glucose intolerance, hyperleptinemia, hyperinsulinemia, plasmatic C-reactive protein (CRP), interleukin-6 (IL-6), and tumor necrosis factor-alpha (TNF-α); in the myocardial and epididymal adipose tissue were assessed IL-6 and TNF-α. Comorbidities: diabetes mellitus and systemic blood pressure (SBP). Student’s t test, ANOVA, and Bonferroni P < 0.05. Results The final body weight, feed efficiency, and adiposity index were higher in OB group than in control; although food intake was lower in OB group, caloric intake was similar in both groups. Specific parameters, such as LDL, cholesterol, triglycerides, HOMA-IR, CRP, TNF-α in epididymal adipose tissue, and IL-6 in the myocardium, were higher in obese rats than in controls. SBP, baseline glucose, and glucose after 2 h of overload were significantly increased in OB group; however, the severity was not enough to classify the animals as diabetic and hypertensive. Conclusion Obesity induced by a diet high in saturated fatty acids with balanced carbohydrates for 33 weeks in Wistar rats was effective in triggering complications but unable to develop comorbidities.
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We investigated the aqueous and ethanolic extracts of different forms (local names: mura and chora ) of turmeric (Curcuma longa) from the Khulna and Chittagong divisions of Bangladesh for their antioxidant properties and polyphenol, flavonoid, tannin, and ascorbic acid contents. The antioxidant activity was determined using the 1,1-diphenyl-2-picrylhydrazyl (DPPH) free radical-scavenging activity and ferric reducing antioxidant power (FRAP) values. The ethanolic extract of Chittagong’s mura contained the highest concentrations of polyphenols (16.07%), flavonoids (9.66%), and ascorbic acid (0.09 mg/100 g) and chora resulted in high yields (17.39%). The ethanolic extract of Khulna’s mura showed a higher DPPH radical-scavenging activity with the lowest 50% inhibitory concentration (IC 50 ) (1.08 μ g/mL), while Khulna’s chora had the highest FRAP value ( 4204.46±74.48 μ M Fe [II] per 100 g). Overall, the ethanolic extract had higher antioxidant properties than those in the aqueous extract. However, the tannin concentration was lower in the ethanolic extract. We conclude that the turmeric varieties investigated in this study are useful sources of natural antioxidants, which confer significant protection against free radical damage.
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The modern Western society lifestyle is characterized by a hyperenergetic, high sugar containing food intake. Sugar intake increased dramatically during the last few decades, due to the excessive consumption of high-sugar drinks and high-fructose corn syrup. Current evidence suggests that high fructose intake when combined with overeating and adiposity promotes adverse metabolic health effects including dyslipidemia, insulin resistance, type II diabetes, and inflammation. Similarly, elevated glucocorticoid levels, especially the enhanced generation of active glucocorticoids in the adipose tissue due to increased 11β-hydroxysteroid dehydrogenase 1 (11β -HSD1) activity, have been associated with metabolic diseases. Moreover, recent evidence suggests that fructose stimulates the 11β -HSD1-mediated glucocorticoid activation by enhancing the availability of its cofactor NADPH. In adipocytes, fructose was found to stimulate 11β -HSD1 expression and activity, thereby promoting the adipogenic effects of glucocorticoids. This article aims to highlight the interconnections between overwhelmed fructose metabolism, intracellular glucocorticoid activation in adipose tissue, and their metabolic effects on the progression of the metabolic syndrome. © 2017 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license.
Compared with other carbohydrates, fructose-containing caloric sweeteners (sucrose, high-fructose corn syrup, pure fructose and fructose-glucose mixtures) are characterized by: a sweet taste generally associated with a positive hedonic tone; specific intestinal fructose transporters, i.e. GLUT5; a two-step fructose metabolism, consisting of the conversion of fructose carbones into ubiquitous energy substrates in splanchnic organs where fructolytic enzymes are expressed, and secondary delivery of these substrates to extrasplanchnic tissues. Fructose is a dispensable nutrient, yet its energy can be stored very efficiently owing to a rapid induction of intestinal fructose transporters and of splanchnic fructolytic and lipogenic enzymes by dietary fructose-containing caloric sweeteners. In addition, compared with fat or other dietary carbohydrates, fructose may be favored as an energy store because it uses different intestinal absorption mechanisms and different inter-organ trafficking pathways. These specific features make fructose an advantageous energy substrate in wild animals, mainly when consumed before periods of scarcity or high energy turnover such as migrations. These properties of fructose storage are also advantageous to humans who are involved in strenuous sport activities. In subjects with low physical activity, however, these same features of fructose metabolism may have the harmful effect of favoring energy overconsumption. Furthermore, a continuous exposure to high fructose intake associated with a low energy turnover leads to a chronic overproduction of intrahepatic trioses-phosphate production, which is secondarily responsible for the development of hepatic insulin resistance, intrahepatic fat accumulation, and increased blood triglyceride concentrations. In the long term, these effects may contribute to the development of metabolic and cardiovascular diseases.
Adipose tissue is an endocrine organ which is responsible for postprandial uptake of glucose and fatty acids, consequently producing a broad range of adipokines controlling several physiological functions like appetite, insulin sensitivity and secretion, immunity, coagulation, and vascular tone, among others. Many aspects of adipose tissue pathophysiology in metabolic diseases have been described in the last years. Recent data suggest two main factors for adipose tissue dysfunction: accumulation of nonesterified fatty acids and their secondary products and hypoxia. Both of these factors are thought to be on the basis of low-grade inflammatory activation, further increasing metabolic dysregulation in adipose tissue. In turn, inflammation is involved in the inhibition of substrate uptake, alteration of the secretory profile, stimulation of angiogenesis, and recruitment of further inflammatory cells, which creates an inflammatory feedback in the tissue and is responsible for long-term establishment of insulin resistance.
The worldwide obesity epidemic has become a major health concern, because it contributes to higher mortality due to an increased risk for noncommunicable diseases including cardiovascular diseases, type 2 diabetes, musculoskeletal disorders and some cancers. Insulin resistance may link accumulation of adipose tissue in obesity to metabolic diseases, although the underlying mechanisms are not completely understood. In the past decades, data from human studies and transgenic animal models strongly suggested correlative, but also causative associations between activation of proinflammatory pathways and insulin resistance. Particularly chronic inflammation in adipose tissue seems to play an important role in the development of obesity-related insulin resistance. On the other hand, adipose tissue inflammation has been shown to be essential for healthy adipose tissue expansion and remodelling. However, whether adipose tissue inflammation represents a consequence or a cause of impaired insulin sensitivity remains an open question. A better understanding of the molecular pathways linking excess adipose tissue storage to chronic inflammation and insulin resistance may provide the basis for the future development of anti-inflammatory treatment strategies to improve adverse metabolic consequences of obesity. In this review, potential mechanisms of adipose tissue inflammation and how adipose tissue inflammation may cause insulin resistance are discussed.
Adipose tissue dysfunction is defined as an imbalance between pro- and anti-inflammatory adipokines, causing insulin resistance, systemic low-grade inflammation, hypercoagulability, and elevated blood pressure. These can lead to cardiovascular disease and diabetes mellitus type 2. Although quantity of adipose tissue is an important determinant of adipose tissue dysfunction, it can be diagnosed in both obese and lean individuals. This implies that not only quantity of adipose tissue should be used as a measure for adipose tissue dysfunction. Instead, focus should be on measuring quality of adipose tissue, which can be done with diagnostic modalities ranging from anthropometric measurements to tissue biopsies and advanced imaging techniques. In daily clinical practice, high quantity of visceral adipose tissue (reflected in high waist circumference or adipose tissue imaging), insulin resistance, or presence of the metabolic syndrome are easy and low-cost diagnostic modalities to evaluate presence or absence of adipose tissue dysfunction. © Georg Thieme Verlag KG Stuttgart · New York.