DİSCUSSİON AND CONCLUSİON
Obesity is defined as excessive weight gain resulting from the
accumulation of fat in the body, and it is a rapidly spreading health
problem worldwide. Factors such as increased consumption of processed
foods, sedentary lifestyle, and processed food habits brought about by
modern life are effective in the formation of obesity. Additionally,
various factors such as nutritional and psychological disorders,
endocrine system disorders, medication use, and genetic factors can
contribute to obesity (2). In recent years, studies have been conducted
on the concept of ”infectobesity,” suggesting that some microorganisms
may also contribute to obesity. According to this theory, certain
infections can alter fat regulation in the body through various
mechanisms and increase body mass index (4). This theory is supported by
numerous pieces of evidence. Many reports investigating this issue have
explained how infections caused by pathogens alter adipose tissue
structure and support the role of infected adipocytes in obesity by
disrupting components such as fat tissue signaling pathways (7).
Understanding these microorganisms as etiological factors is essential
for effective management of obesity. Viral agents that are likely to
play a role in fat regulation in the body have been found in human and
animal studies conducted since 1982, including Canine Distemper Virus
(CDV), Borna Disease Virus, Scrapie Agent, Rous-associated virus-7,
SMAM-1, and Adenoviruses (8). Adenoviruses generally cause various
infections in humans, primarily respiratory tract infections. Studies
have shown that Ad-5, Ad-36, and Ad-37 may also cause obesity in humans.
It is believed that these adenovirus serotypes have a negative effect on
leptin production in infected adipocytes, leading to increased fat
storage (9, 10).
The metabolic effects of adenoviruses have attracted more attention
since it was shown in the 1990s that SMAM1 increases fat cell counts in
chickens and that antibodies against SMAM-1 are associated with human
obesity. Since then, a total of nine adenoviruses, including Ad-2, Ad-5,
Ad-8, Ad-9, Ad-36, and Ad-37, have been investigated for their metabolic
effects in cell cultures, animal studies, and human epidemiological
studies. Among these, Ad-36 is the most studied serotype and has been
most strongly associated with human obesity. While the association
between Ad-2, Ad-8, and Ad-9 serotypes and fat accumulation in cells was
not found in most studies, Ad-5 and Ad-37 have been identified as
potentially related to obesity in different studies (11).
In a study investigating the effects of different adenovirus serotypes
(Ad-36, Ad-2, Ad-9, and Ad-37) on leptin secretion and fat accumulation
in 3T3-L1 preadipocyte cells, it was observed that leptin secretion in
cells infected with Ad-36 was 50% lower than in uninfected cells, while
lipid accumulation was significantly higher in cells infected with Ad-9,
Ad-36, and Ad-37, with lower leptin secretion. Ad-2 was found not to
affect lipid accumulation or leptin secretion (12). The decrease in
leptin, also known as the appetite-suppressing hormone, is thought to be
associated with weight gain at this level.
In our study, Ad-5 and Ad-37 serotypes were investigated in serum
samples collected from obese patients and normal-weight control groups
using ELISA kits. Ad-37 was found to be positive in 39 out of 48 obese
patients and in 24 out of 42 individuals in the control group, while
Ad-5 was positive in 26 individuals in both the patient and control
groups. According to the statistical analysis results, a significant
difference was found between the patient and control groups in terms of
Ad-37 positivity, supporting our hypothesis. The positivity of Ad-37
serotype was interpreted as a possible contribution to the development
of obesity. However, no significant difference was found for Ad-5,
contrary to our hypothesis.
In a study by Whigham et al., chickens were inoculated with Adenovirus
2, 31, and 37, and food intake and weight were monitored for three and a
half weeks. It was observed that chickens infected with Ad-37 had over
three times the visceral fat and over twice the total body fat compared
to the uninfected control group, despite consuming the same amount of
feed (13).
In a study conducted on 268 patients with non-alcoholic fatty liver
disease, the seropositivity of Ad-36 and Ad-37 was investigated. Ad-37
was positive in 65 patients, while both Ad-37 and Ad-36 were negative in
82 patients. The prevalence of obesity defined as a body mass index ≥30
did not differ significantly between patients positive for Ad-37 (11/65;
16.9%) and those negative for Ad-37 (15/82; 18.2%) (14).
In a two-stage study, antibodies for Ad-2, Ad-31, Ad-36, and Ad-37 were
searched for in the serum of 502 obese and non-obese individuals, and no
difference in antibody status was found between obese and non-obese
individuals. In the second stage, the body mass index and body fat of
twins discordant for Ad-36 antibody were compared between obese and
normal-weight individuals, and it was found that the twin positive for
Ad-36 antibody was heavier than their sibling. However, this
relationship could not be established for Ad-2, Ad-31, and Ad-37
serotypes (15).
In the molecular-level investigation of epithelial cells infected with
Ad-5, it was observed that Ad-5 has a metabolic effect similar to Ad-36
in triggering adiposity-related intracellular signaling mechanisms (11).
In a study by Cakmaklıoğulları in 2011 investigating the seropositivity
of Ad-5, Ad-8, and Ad-36 in obese and non-obese children, the positivity
of Ad-36 and Ad-5 antibodies in the obese group was found to be
statistically significant compared to the non-obese group. The study
concluded that there was an association between Ad-5 and Ad-36 serotypes
and obesity in children (8).
In a study by So et al., mice injected with Ad-5 showed significantly
greater weight gain than the control group after 21 weeks. Additionally,
there was no significant difference in food intake between the study and
control groups, indicating that the weight difference was due to
adenovirus infection (16).
In a study investigating the effect of Ad-5 on hamsters fed a balanced
diet and a high-calorie diet, the experimental group was inoculated with
Ad-5, and body weight was measured weekly for short-term (22 weeks) and
long-term (44 weeks) periods. Adenovirus infection was shown to induce
hyperglycemia and hyperlipidemia in animals fed a balanced diet. After
44 weeks, a 30% increase in body weight was reported compared to
unvaccinated animals, along with morphological changes associated with
non-alcoholic fatty liver disease. Similar but more severe changes were
observed in animals fed a high-calorie diet, with the animals with the
most morphological and functional changes having the lowest body weight
(17).
Studies investigating the relationship between Ad-5 and Ad-37 and human
obesity are limited worldwide. A definitive conclusion about whether
these serotypes can cause obesity has not been reached. Our study found
significant Ad-37 IgG positivity in obese individuals compared to the
control group. This result will contribute to the literature by
demonstrating the relationship between Ad-37 and obesity. However, Ad-5
IgG yielded insignificant results in both the obese and control groups.
The presence of twenty-four Ad-37 positive individuals in the control
group suggests previous exposure to this virus due to consumption under
unhygienic conditions.
Further research on this topic in different geographical areas could
provide clearer epidemiological information on viral obesity and
infectobesity in general. As our knowledge of the relationship between
microorganisms and obesity increases, the inclusion of antimicrobials in
the treatment options for obesity seems likely in the near future.