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.