MAJOR ARTICLE
Adenovirus 36 as an Obesity Agent Maintains the
Obesity State by Increasing MCP-1 and Inducing
Inflammation
Ha-Na Na and Jae-Hwan Nam
Department of Biotechnology, The Catholic University of Korea, Wonmi-gu, Bucheon, Gyeonggi-do, Korea
Background. Although it is well known that adenovirus 36 (Ad36) is associated with obesity in humans as well
as in animals, the detailed cellular mechanism is unclear.
Methods. Wild-type (WT) mice and monocyte chemoattractant protein-1 knockout (MCP-12/2) mice were
infected with Ad36, and their weights and inflammatory status were measured. Macrophage infiltration was
examined in their reproductive fat pads and in a coculture system. The correlation between Ad36 antibody presence
and MCP-1 levels was tested in human samples.
Results. We have shown that Ad36 infection stimulated an inflammatory state by increasing the level of MCP-1
through the activation of nuclear factor jB, which in turn induced the infiltration of macrophages into adipocytes.
This induced inflammation resulted in viral obesity, which caused chronic inflammation and affected lipid
metabolism. In contrast to WT mice, MCP-12/2 mice were protected from Ad36-induced inflammation and
obesity. The MCP-1 levels in Ad36-antibody-positive human group were higher than those in the antibodynegative group.
Conclusions. These findings support the proposition that virus-induced inflammation is the cellular
mechanism underlying Ad36-induced obesity. These results also suggest that MCP-1 plays a critical role in
Ad36-induced obesity and that MCP-1 may be a therapeutic target in preventing virus-induced obesity.
Obesity has become the number one public health
problem worldwide. The etiology of obesity is considered to be multifactorial, including endocrine, pharmacological, nutritional, environmental, and genetic agents.
Over the past 30 years, studies of ‘‘infectobesity,’’
a new term to describe obesity of infectious origin,
have identified 10 different pathogens that cause
obesity in animal models such as mice, chickens, and
nonhuman primates [1–3]. Several pathogens have
been implicated as the cause of obesity in animal
models; these include canine distemper virus, Rous-
Received 20 July 2011; accepted 30 September 2011; electronically published
24 January 2012.
Correspondence: Jae-Hwan Nam, PhD, Department of Biotechnology, The
Catholic University of Korea, 43-1 Yeokgok 2-dong, Wonmi-gu, Bucheon, Gyeonggido, 420-743, Korea ([email protected]).
The Journal of Infectious Diseases 2012;205:914–22
Ó The Author 2012. Published by Oxford University Press on behalf of the Infectious
Diseases Society of America. All rights reserved. For Permissions, please e-mail:
[email protected]
DOI: 10.1093/infdis/jir864
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associated virus-7, Borna disease virus, SMAM-1 (an
avian adenovirus), adenovirus 5 (Ad5), and Ad37.
However, their role in human obesity has not been
established fully [1]. Interestingly, only adenovirus
36 (Ad36) has been clearly associated with human
obesity [4].
Ad36 is a nonenveloped icosahedral virus comprising
double-stranded DNA and is one of 56 serotypes in
7 subgroups of human adenoviruses [5]. Generally,
adenovirus infection causes coldlike symptoms, gastroenteritis, and conjunctivitis [6]. Recent reports
from North America, Korea, Denmark, and Italy
suggest that Ad36 is related to obesity in adults and
children [7–13]. Ad36 infection accelerates the differentiation of preadipocytes to adipocytes in 3T3-L1
cells and human preadipocytes [14]. Ad36 infection
also increases glucose uptake in human adiposederived stem cells and human skeletal muscle cells, and
this uptake is dependent on Ras signaling [15, 16]. One
of the Ad36 viral genes, E4 orf-1, is thought to be involved in the mechanism underlying virus-induced
obesity by increasing adipocyte differentiation factors such as
CCAAT-enhancer binding proteins b, peroxisome proliferatoractivated receptor c2, and glycerol 3-phosphate dehydrogenase
[17]. Although some effects of Ad36 on human obesity are
known, the cellular mechanisms responsible for virus-induced
chronic obesity remain unknown. Recent reports have revealed
that inflammation contributes to the maintenance of the obesity state [18, 19]. Ad36 infection also increases interleukin 6
(IL-6) expression in adipocytes in vitro, which may contribute
to chronic low-grade inflammation [20]. Thus, we hypothesize
that Ad36 infection up-regulates inflammation in adipose
tissue and induces the progression to chronic obesity. Interestingly, adipose tissue in obese subjects is characterized by
macrophage infiltration, which is stimulated by monocyte
chemoattractant protein-1 (MCP-1) [21, 22]. Macrophages in
adipose tissue are a source of proinflammatory factors [21, 23].
To identify whether Ad36 is involved in chronic inflammatory
obesity, we assessed proinflammatory cytokines and infiltrated
macrophages, and monitored the obesity state by measuring
body weight, reproductive fat pad weight, and metabolic factors in wild-type (WT) and MCP-1 knockout (MCP-12/2)
mice. We found that MCP-12/2 mice were protected against
Ad36-induced inflammation and obesity, suggesting that
MCP-1 plays an important role in the inflammatory response
to Ad36 infection in reproductive fat pads.
METHODS
The methods used for virus preparation, the migration assay, the
polymerase chain reaction (PCR) assay, the enzyme-linked immunosorbent assay (ELISA), immunohistochemistry, analysis of
metabolic parameters, flow cytometry, and Western blotting are
described in the Supplementary Methods.
Animals, Food Intake, and Body Weight
Five-week-old female C57BL/6 (WT) and MCP-12/2 mice were
used in this study. WT mice were obtained from Orient
Company, and MCP-12/2 mice were purchased from Jackson
Laboratory. In total, 1 3 107 plaque-forming units of Ad36
were used to infect WT and MCP-12/2 mice by intraperitoneal injection. Mice were maintained at 22–24°C
under a constant 12-hour light/dark cycle in the animal facility
at the Catholic University according to the institutional
guidelines. They were fed a normal chow diet for 14 weeks.
Food intake and body weight were measured once a week at
15:00–16:00.
Human Subjects
To identify the relationship between Ad36 antibody presence
and MCP-1 levels in humans, we used 80 human samples
that were analyzed in a previously published study [13].
These samples were collected from participants at the
Health Promotion Center of the Ewha Womans University
Medical Center (EWUMC). From 540 samples collected from
equal numbers of normal, overweight, and obese subjects
(each group contained 90 men and 90 women; mean age,
44.3 6 7.04 years; age range, 30–59 years), we randomly selected samples from 20 subjects in the normal group, 30 in
the overweight group, and 30 in the obese group. Informed
written consent for their participation was obtained from each
individual, and the study design was approved by the Institutional Review Board of EWUMC. A peripheral venous
blood sample was collected from each subject after a 12-hour
fast. After centrifugation, the serum was collected and stored
frozen at 280°C until analysis.
Statistical Analysis
All data are expressed as means 6 SD. The data were analyzed
using Student t-test (SAS Institute Inc). Differences of P , .05
were regarded as significant.
RESULTS
Wild-Type (WT) Mice
C57BL/6 WT mice were infected with phosphate-buffered saline
(PBS) (mock) or Ad36 at age 5 weeks. The mice were killed 1, 3,
7, 30, and 90 days after infection, the reproductive fat pads were
weighed, and MCP-1 and tumor necrosis factor a (TNF-a)
messenger RNA (mRNA) levels were measured. Ninety days
after infection, body weight did not differ between mock- and
Ad36-infected mice (Figure 1A). However, the weight and size of
the reproductive fat pads were significantly greater in the Ad36infected mice than in the mock-infected mice (Figure 1B), even
though the food and water intake did not differ between the
groups in our study (data not shown). Supplementary Data
1A–B also show that Ad36 can infect the reproductive fat pads,
so Ad36 may directly affect the reproductive fat pads. One day
after infection, the mRNA levels of the proinflammatory cytokines MCP-1 and TNF-a were 3 times and 2 times higher, respectively, in reproductive fat pads of Ad36-infected mice
compared with mock-infected mice. At 90 days, the MCP-1
mRNA level was twice as high in Ad36-infected WT mice
compared with mock-infected WT mice, and the TNF-a mRNA
level was 6 times higher in Ad36-infected mice (Figure 1C).
Similar results were obtained in Balb/C mice (see Supplementary data 1C–D). Moreover, the MCP-1 protein levels in the
reproductive fat pads were higher in the Ad36-infected WT
mice than in the mock-infected WT mice. TNF-a protein levels
were also higher in the Ad36-infected WT mice than in the
mock-infected WT mice (Figure 1D).
MCP-1 Knockout (MCP-12/2) Mice
Ninety days after infection, body weight and the weight of
reproductive fat pads did not differ significantly between
Ad36-infected and mock-infected MCP-12/2 mice (Figure 2A
and 2B). The weight and size of fat pads were slightly lower
Role of MCP-1 in Ad36-Induced Obesity
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Figure 1. Ad36 infection increased the weight of reproductive fat pads and monocyte chemoattractant protein-1 (MCP-1) and tumor necrosis factor a
(TNF-a) messenger RNA (mRNA) levels in wild-type C57BL/6 mice. A, Body weight was recorded each week during the 90-day experiment (mock: PBStreated group, black lozenge-shaped symbol; Ad36: Ad36-infected group, gray square-shaped symbol). B, Reproductive fat pads were weighed 1, 3, and
90 days after infection. Values are expressed as mean 6 SD (n 5 10, scale bar 5 1 cm). C, The mRNA levels of MCP-1 and TNF-a in reproductive fat
pads were analyzed by quantitative real-time PCR (AU, arbitrary unit; *P , .05, **P , .01, àP , .001). D, Protein levels of cytokines in reproductive fat
pads were measured using ELISA (àP , .001).
in Ad36-infected MCP-12/2 mice than in mock-infected
MCP-12/2 mice (Figure 2B). At 90 days, the mRNA levels of
MCP-1 and TNF-a were lower in Ad36-infected MCP-12/2
mice than in mock-infected MCP-12/2 mice (Figure 2C).
Moreover, the MCP-1 protein levels appeared to be lower in the
Ad36-infected MCP-12/2 mice than in the mock-infected
mice. TNF-a protein levels were also significantly lower in the
Ad36-infected MCP-12/2 mice than in the mock-infected
MCP-12/2 mice (Figure 2D).
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Inflammatory Status of WT and MCP-12/2 Mice
To determine whether the protection against Ad36-induced
obesity observed in MCP-12/2 mice was caused by the absence of MCP-1, WT mice and MCP-12/2 mice were killed,
and immunohistochemical studies were performed to identify
inflammation 90 days after infection. The inflammatory state
was verified by hematoxylin and eosin (H&E) staining, and
infiltrated macrophages were detected using F4/80 antibody. Infiltration of immune cells and macrophages into
Figure 2. Ad36 infection did not increase the weight of reproductive fat pads or levels of monocyte chemoattractant protein-1 (MCP-1) and tumor
necrosis factor a (TNF-a) in MCP-12/2 mice. A, Body weight was recorded each week during the 90-day experiment (n 5 5 per group). B, Mice were
killed 1, 3, and 90 days after infection, and the weight of reproductive fat pads was measured (mock: PBS-treated group, black bars; Ad36,: Ad36-infected
group gray bars; scale bar 5 1 cm). C, The messenger RNA (mRNA) levels of MCP-1 and TNF-a in reproductive fat pads were analyzed by quantitative
real-time PCR 90 days after infection in MCP-12/2 mice (AU, arbitrary unit; *P , .05). D, Protein levels of cytokines in reproductive fat pads were
identified using ELISA (**P , .01, àP , .001).
reproductive fat pads was greater in Ad36-infected WT mice
than in mock-infected WT mice (Figure 3A and 3B). Similar
results were obtained in Balb/c mice infected with Ad36
(see Supplementary Data 1E). However, Ad36-infected
MCP-12/2 mice did not show an increased infiltration of inflammatory cells in reproductive fat pads (Figure 3A and 3B).
Macrophage infiltration in reproductive fat pads was also
confirmed by real-time PCR. The F4/80 mRNA level was
3.5 times higher in Ad36-infected WT mice than in mock-
infected WT mice, whereas no increase was observed in
MCP-12/2 mice (Figure 3C).
Macrophages were classified into M1 and M2 types according
to their function. M1 macrophages produce proinflammatory
cytokines, such as MCP-1, TNF-a, and IL-6. CD64 on M1 macrophages increases in the inflammatory state [24]. By contrast, M2
macrophages, which are the major resident macrophages in lean
adipose tissue, are characterized by relatively high expression of
interleukin 10 (IL-10), MG-1, and CD206, which are involved
Role of MCP-1 in Ad36-Induced Obesity
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Figure 3. Ad36 infection increased the inflammatory state through infiltration of macrophages in reproductive fat pads of wild-type (WT) mice but not
MCP-12/2 mice 90 days after infection. A, Inflammation patterns in reproductive fat pads were identified by hematoxylin and eosin (H&E) staining, and
macrophage infiltration was revealed by immunohistochemical staining with F4/80 antibody. The arrows in panel A indicate infiltrated lymphocytes
and macrophages found in reproductive fat pads (mock: PBS-treated group; Ad36: Ad36-infected group; WT, wild-type mice; K/O, MCP-12/2 mice).
B, Infiltrated macrophages were quantified by the AxioVision Rel 4.8.2 program (Zeiss, àP , .001). C, The messenger RNA (mRNA) level of F4/80, which
represents macrophages, in reproductive fat pads was measured by quantitative real-time PCR (AU, arbitrary unit; *P ,.05). D, The mRNA levels of CD64
(M1) and CD206 (M2) macrophages were measured in reproductive fat pads by quantitative real-time PCR (*P , .05, **P , .01).
in the repair or remodeling of tissues and the resolution of
inflammation [25]. The mRNA levels of M1 macrophages,
which cause a proinflammatory state, and M2 macrophages,
which cause an anti-inflammatory state, were identified by realtime PCR (Figure 3D). The mRNA level of M1 macrophages
(CD64) was 2 times higher in Ad36-infected WT mice than in
mock-infected WT mice. By contrast, the mRNA level of M2
macrophages (CD206) was significantly lower in Ad36-infected
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WT mice than in mock-infected WT mice. The mRNA levels of
both CD64 and CD206 were lower in Ad36-infected MCP-12/2
mice (Figure 3D).
Function of MCP-1 On Lipid Metabolism in Ad36-Induced
Obesity
We assumed that MCP-1 regulates lipid metabolism in Ad36induced obesity through inflammation. Thus, we analyzed
Table 1. Metabolic Parameters Analyzed in WT Mice and
MCP-12/2 Mice
WT Mice
Parameter
NEFA
Glu
mock
Ad36
K/O Mice
mock
Ad36
420.0 6 2.1 382.5 6 2.1** 380.0 6 2.8 496.0 6 7.1**
85.5 6 0.7
59.0 6 1.4**
58.5 6 2.1
77.0 6 1.4**
HDL
LDL
53.9 6 0.4 48.9 6 0.6*
51.3 6 0.5 55.8 6 0.5*
123.5 6 0.7 104.5 6 0.7** 119.0 6 2.8 128.5 6 2.1
TC
88.5 6 0.7
80.5 6 2.1*
62.0 6 2.2
94.5 6 2.1**
TG
48.0 6 2.8
52.5 6 0.7
66.5 6 0.7
64.0 6 2.9
2.6 6 0.2
2.9 6 0.2
Insulin
3.6 6 0.1
3.0 6 0.2*
Abbreviations: Ad36, Ad36-infected group; Glu, glucose (mg/dL); HDL, highdensity lipoprotein-cholesterol (mg/dL); insulin (lU/mL); K/O, MCP-12/2 mice;
LDL, low-density lipoprotein-cholesterol (mg/dL); mock, PBS-treated group;
NEFA, neutral free fatty acid (lEq/l); TC, total cholesterol (mg/dL); TG,
triglyceride (mg/dL); WT, wild-type mice. *P , .05, **P , .01.
metabolic parameters in WT mice and MCP-12/2 mice (Table 1).
Serum was obtained from the mice via heart puncture 90 days
after infection. In WT mice, Ad36 infection significantly
decreased nonesterified fatty acids (NEFA), glucose, and insulin concentrations, indicating increased insulin sensitivity.
Lipid parameters such as HDL-C, LDL-C, and total cholesterol concentrations were lower in Ad36-infected WT
mice than in mock-infected WT mice. Interestingly, the
changes in metabolic parameters in MCP-12/2 mice were
opposite the pattern observed in WT mice (Table 1). For
example, NEFA and glucose levels increased and insulin
levels increased slightly in Ad36-infected MCP-12/2 mice.
Ad36-infected MCP-12/2 mice also had higher HDL-C,
LDL-C, and total cholesterol concentrations than did mockinfected MCP-12/2 mice (Table 1).
Macrophage Migration and Activation of Nuclear Factor kB
Ad36 infection increased the weight of reproductive fat pads
and the in vivo macrophage infiltration into mouse adipocytes
such as reproductive fat pads (Figures 1 and 3). To confirm
this infiltration into adipose tissue, we used a coculture system
of 3T3-L1 cells (as adipocytes) and RAW264.7 cells (as macrophages). In this in vitro system, Ad36 infection of 3T3-L1
cells led to an 8-fold increase in the migration of RAW264.7
cells (Figure 4A). Macrophage migration was required for
the induction of proinflammatory cytokines, such as MCP-1 by
nuclear factor jB (NFjB) activation [26]. To study this NFjB
activation further, the degradation of IjB-a, an inhibitor of
nuclear localization of NFjB [27], was measured in cocultured 3T3-L1 cells. Figure 4B shows that IjB-a level was reduced in 3T3-L1 cells 48 hours after Ad36 infection. Thus,
Ad36 infection increased the nuclear localization of NFjB in
the activated state, and NFjB in the nucleus induced expression of inflammatory cytokines. The mRNA expression of
the proinflammatory cytokine genes MCP-1 and TNF-a was
up-regulated in 3T3-L1 cells after Ad36 infection (Figure 4C).
MCP-1 Concentration and Ad36 Antibody Presence in Human
Samples
The mouse data described above show that Ad36 infection
stimulates MCP-1 induction and induces macrophage infiltration into adipocytes. To confirm this, we compared
MCP-1 concentrations with Ad36 antibody presence (positive vs negative) in human samples that had been used in
a previous study [13]. Figure 5 shows that the mean
concentration of MCP-1 was statistically significantly higher
in Ad36-antibody-positive samples than in antibody-negative
samples (3.5-fold higher in obese subjects [Figure 5A] and
2.5-fold higher in the total sample [Figure 5B]). This indicates that there is some relationship between Ad36 infection
and MCP-1 induction in humans as well as in animals.
DISCUSSION
Here, we provide evidence that Ad36-induced obesity can be
maintained as a chronic state through inflammation. The correlation between obesity and inflammation has been known for
decades from epidemiological and cellular studies [28, 29]. Recent epidemiological studies have confirmed and extended these
findings by showing increased inflammation in obese subjects
[14]. In addition, hypertrophic adipocytes may make proinflammatory cytokines such as MCP-1, TNF-a, resistin, and
plasminogen activator inhibitor-1 [30, 31]. We found previously
that Ad36 infection triggers the inflammatory pathway in human mesenchymal stem cells, which was confirmed by microarray analysis [32]. Therefore, on the basis of the above data, we
assumed that there is a relationship between Ad36-induced
obesity and inflammation. In this study, as in dietary obesity,
Ad36-infected mice showed an increase in weight of reproductive fat pads and an inflammatory state that was maintained by macrophages driven by increased MCP-1 level. Our
findings suggest that Ad36 infection induces obesity through
inflammation and that MCP-1 may be a key regulator of Ad36induced obesity.
It has previously been reported that MCP-1 is responsible
for obesity, insulin resistance, and steatosis in MCP-1 transgenic mice and obese mice [21, 33], and inhibition of MCP-1
ameliorates insulin resistance and hepatic steatosis in obese
mice [21]. Moreover, MCP-1–induced protein (MCPIP) can
increase the expression of the C/EBPa family in 3T3-L1 cells
[34]. MCP-1 also recruits macrophage colony-stimulating
factors (MCSFs), which affect adipocyte hyperplasia and adipose tissue growth [35]. It is well known that MCP-1 plays
a role in the recruitment of monocytes and macrophages into adipose tissue [21, 36], and that TNF-a increases the
number of macrophages in adipose tissue and the stromal
Role of MCP-1 in Ad36-Induced Obesity
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Figure 4. Ad36 infection increased the migration of macrophages into adipocytes through NFjB activation in an in vitro coculture system with 3T3-L1
and RAW264.7 cells. A, Infiltrated macrophages (RAW264.7 cells) in cocultured 3T3-L1 cells were quantified by flow cytometry with F4/80 antibody.
(mock, serum-free media-treated group; Ad36, Ad36-infected group; *P , .05, àP , .001). B, The protein levels of F4/80 and IjB-a were measured by
western blotting, and the intensity of each band was normalized to that of a-tubulin using the ImageJ program (àP , .001). C, The messenger RNA
(mRNA) levels of monocyte chemoattractant protein-1 (MCP-1) and tumor necrosis factor (TNF-a) as proinflammatory cytokines in cocultured 3T3-L1 cells
were measured by quantitative real-time PCR (AU, arbitrary unit; *P , .05, **P , .01).
vascular fraction [21, 37]. In the present study, the mRNA
levels of MCP-1 and TNF-a increased in the early stages of
viral infection (Figure 1C), and the cytokine levels decreased
with time. Ad36-induced obesity and inflammation in the
early stage of infection might have induced further increases
in MCP-1 and TNF-a mRNA and protein levels at later stages
(Figure 1C and 1D). These proinflammatory cytokines may
trigger the recruitment of macrophages. We found that more
immune cells, especially macrophages, were recruited to reproductive fat pads of Ad36-infected WT mice (Figure 3).
Interestingly, Ad36 infection increased M1 macrophage
(‘‘classically activated’’ macrophages) accumulation, whereas
M2 macrophage (‘‘alternatively activated’’ macrophages) accumulation decreased despite the Ad36 infection in WT mice
(Figure 3D) [37]. M1 macrophages are involved in the Th1
pathway in the inflammatory state, and M2 macrophages are
involved in anti-inflammatory responses [24, 25]. However,
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in Ad36-infected MCP-12/2 mice, body weight, reproductive
fat pad weight (Figure 2A and 2B), and proinflammatory
cytokine levels (Figure 2C and 2D) did not increase, and
macrophage recruitment was not observed (Figure 3). In addition, there was a larger decrease in M1 and M2 macrophages
in Ad36-infected MCP-12/2 mice compared with mockinfected MCP-12/2 mice (Figure 3D). Consistent with the in
vivo data, our in vitro data also showed that Ad36 infection
increased macrophage migration into adipocytes by activating NFjB, which induced the release of proinflammatory
cytokines (Figure 4). Taking these data together, we conclude
that Ad36 infection increases MCP-1, and this MCP-1 might
function to induce adipogenesis via MCP-1-related factors,
such as MCPIP and MCSF, in adipocytes. Furthermore,
increased MCP-1 triggers macrophage infiltration into adipocytes and then induces inflammation. Finally, this inflammation may play a role in maintaining obesity.
Figure 5. Monocyte chemoattractant protein-1 (MCP-1) concentration correlated with Ad36 antibody presence in human samples.
A, A statistically significant correlation between Ad36 antibody presence
and MCP-1 concentration was observed in the obese group (**P , .01).
B, The Ad36-antibody-positive group had higher MCP-1 concentrations
in the total human sample (àP ,.001). All human samples tested (n 5 80)
were selected randomly from 540 human samples that have been
reported elsewhere [13].
activity in the liver, which may improve the metabolic parameters (data not published). However, further research is required
to explain the differences in the metabolic parameters of WT
mice and MCP-12/2 mice. Bottom linedour results suggest
that MCP-1 is involved in the induction of obesity and the
changes in lipid parameters initiated by Ad36 infection.
Because MCP-1 has some function in Ad36-infected mice, we
also confirmed relationship between Ad36 infection and MCP-1
levels in human serum. It has previously been reported that
levels of circulating MCP-1 are elevated in obese human subjects
[40] and that an increase in the concentration of circulating
MCP-1 induces insulin resistance in mice [41]. This study has
shown that there is a close correlation between Ad36 antibody positivity and MCP-1 concentrations in human samples
(Figure 5). These human data imply that Ad36-induced
obesity increases the circulating levels of MCP-1 and maintains the inflammatory status.
In conclusion, our results suggest that Ad36 infection induces
early inflammation by recruiting macrophages to reproductive
fat pads by increasing MCP-1, which is activated by NFjB. This
induced inflammation causes obesity, which in turn induces
chronic inflammation and affects lipid metabolism in viral
obesity. In addition to the viral obesity mechanism, which involves the viral gene E4 orf-1 [17], these results provide some
insight into one of the cellular mechanisms responsible for
Ad36-induced obesity, in which the host immune responses to
the viral infection, such as inflammation, may contribute to
Ad36-induced obesity. Future progress in decoding the fundamental cellular mechanisms underlying the relationship between
Ad36 and obesity may lead to new strategies and therapeutics for
preventing and treating obesity.
Supplementary Data
Considering the above data, we also assumed that MCP-1
might affect lipid metabolic parameters, thus influencing the
inflammatory state. Previous studies showed that Ad-36 decreases insulin and cholesterol levels, and the homeostatic model
assessment (HOMA) index, and also decreases triglyceride and
leptin levels [7, 38, 39]. Our data (Table 1) showed that Ad36
infection decreased NEFA, glucose, insulin, and cholesterol
levels but did not decrease triglyceride level. These results suggest that Ad36 infection increases insulin sensitivity and reduces
lipid concentrations in WT mice. By contrast, Ad36 infection
slightly up-regulated HDL-C, LDL-C, and total cholesterol levels
in MCP-12/2 mice (Table 1). Thus, surprisingly, opposite results were seen in WT mice and MCP-12/2 mice, although we
did not identify the biological reasons for this. As mentioned
above, it has previously been reported that MCP-1 increases
insulin resistance [21, 33]. However, our data show contrary
results, insofar as after Ad36 infection, MCP-12/2 mice showed
increases in glucose, total cholesterol, and so forth (as shown in
Table 1). Recently, we noted that Ad36 triggers mitochondrial
Supplementary materials are available at The Journal of Infectious Diseases
online (http://www.oxfordjournals.org/our_journals/jid/). Supplementary
materials consist of data provided by the author that are published to benefit
the reader. The posted materials are not copyedited. The contents of all
supplementary data are the sole responsibility of the authors. Questions or
messages regarding errors should be addressed to the author.
Notes
Financial support. This work was supported by a grant from GRRC of
the Catholic University of Korea, the Next-generation Biogreen21 Program
(PJ007186) of Rural Development of Administration, and MKE and
KOTEF through the Human Resource Training Project for Strategic
Technology. H.-N. N. was supported by Hi Seoul Science (Humanities)
Fellowship funded by Seoul Scholarship Foundation.
Potential conflicts of interest. All authors: No reported conflicts.
All authors have submitted the ICMJE Form for Disclosure of Potential
Conflicts of Interest. Conflicts that the editors consider relevant to the
content of the manuscript have been disclosed.
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