Article

Human adenovirus Ad-36 promotes weight gain in male rhesus and marmoset monkeys.

Department of Nutrition and Food Science and the Center for Molecular Medicine and Genetics, Wayne State University, Detroit, MI, USA.
Journal of Nutrition (Impact Factor: 4.23). 10/2002; 132(10):3155-60.
Source: PubMed

ABSTRACT Although obesity has multiple etiologies, an overlooked possibility is an infectious origin. We previously identified two viruses, SMAM-1, an avian adenovirus (Ad), and Ad-36, a human adenovirus, that produce a syndrome of visceral obesity, with paradoxically decreased serum cholesterol and triglycerides in chickens and mice. In the two studies presented in this paper, we used nonhuman primates to investigate the adiposity-promoting potential of Ad-36. In study 1, we observed spontaneously occurring Ad-36 antibodies in 15 male rhesus monkeys, and a significant longitudinal association of positive antibody status with weight gain and plasma cholesterol lowering during the 18 mo after viral antibody appearance. In study 2, which was a randomized controlled experiment, three male marmosets inoculated with Ad-36 had a threefold body weight gain, a greater fat gain and lower serum cholesterol relative to baseline (P <0.05) than three uninfected controls at 28 wk postinoculation. These studies illustrate that the adiposity-promoting effect of Ad-36 occurs in two nonhuman primate species and demonstrates the usefulness of nonhuman primates for further evaluation of Ad-36-induced adiposity.

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    ABSTRACT: T he prevalence of obesity is increasing worldwide. According to the Canadian Health Measures Survey, in 2011, one in four Canadians was obese (25% of women; 27% of men) (1). In addition to the imbal-ance between energy intake and expenditure, sedentary lifestyle, a diet high in saturated fats and sugars, and genetic predisposition, many other factors may be involved in obesity. The presence of either sym-biotic or pathogenic microorganisms may contribute to the develop-ment of obesity. With the progress of metagenomics and molecular techniques in recent years was born an interest in the microorganisms living on and inside us (2). More than 10 14 microorganisms, which represent up to 1150 different species and a total genome comprising 150-fold more genes than the human genome, live in our gastrointes-tinal tracts (3). The gut microbiota is known to play a role in protec-tion against pathogenic bacteria, immune function and digestion by degrading nondigestible carbohydrates such as cellulose, pectin and starch (4,5). Over the past decade, several prominent publications have led to an intriguing hypothesis that links differences in gut microbial ecology to energy homeostasis. In simpler words, some indi-viduals harbouring a microbiota more efficient at extracting energy from the diet (eg, through the ability to degrade indigestible compon-ents) may be at higher risk for obesity. This hypothesis is interesting but controversial, and raises several questions. The bacterial phyla Firmicutes (which include genera Clostridium, Ruminococcus and Lactobacillus) and Bacteroidetes (including genera Prevotella and Bacteroides) account for 90% of the gut microbiota (6). The balance of these populations is essential for the maintenance of a healthy microbiota. The microbiota of genetically obese mice was associated with a 50% reduction in Bacteroidetes and a proportional increase in Firmicutes compared with lean animals (7). An interesting observation was made when colonizing germ-free mice with the gut microbiota of normal mice. This transplantation led to a 60% increase in body fat and insulin resistance within two weeks, in spite of reduced food consumption (8). Findings about the implication of the proportion of Firmicutes and Bacteroidetes in human obesity are contradictory because some studies have found no difference in the Firmicutes and Bacteroidetes ratio (9,10), while others have (11). A diet-induced weight loss in obese individuals was associated with a reduction in the Firmicutes: Bacteroidetes ratio, which was similar to the lean controls (11). Recently, a decrease in specific species (Bifidobacterium animalis and Methanobrevibacter smithii) and an increase in others, such as Staphylococcus aureus, Escherichia coli and Lactobacillus reuteri, have been associated with obesity (12). Normal-weight children had greater bifidobacteria counts and fewer fecal numbers of S aureus compared with overweight/obese children (13). These findings propose that gut microbiota in infancy may predict obesity, reinforcing the importance of prevention. Conflicting findings provide evidence of variability among individuals and in one individual over time. Some changes in gut microbiota may influence individuals to a different extent, and more studies involving large obese populations are required to draw more precise conclusions. Although their exact contribution remains unclear, microorganisms in the gut are believed to be involved in the development of obesity by two different and complementary mechanisms. They can extract energy from nondigestible polysaccharides and produce low-grade inflammation (14). Because many Firmicutes are major butyrate pro-ducers, an abundance of bacteria from this phylum could be associated with an increase in genes encoding enzymes that enable the degrada-tion of complex polysaccharides and, in turn, increase the production of monosaccharides and short-chain fatty acids (SCFAs) (15). Up to 10% of the total energy extracted from food corresponds to SCFA production (10). In a mouse model, the obese microbiome was found to be richer in enzymes involved in the digestion of complex polysac-charides. Consequently, higher concentrations of butyrate and acetate were found in these mice cecum (16). This increased capacity for extracting energy was also transferred to germ-free mice when they were colonized with an obese microbiota (16). In a cross-sectional study, overweight and obese individuals also exhibited higher fecal levels of end products of colonic fermentation (butyrate, acetate and SCFAs) than normal-weight individuals, thus suggesting a more effi-cient energy extraction process (10). Obesity has been associated with chronic low-grade inflammation; however, how they are linked remains unclear (17). The potential implication of bacterial lipopolysaccharide (LPS) in obesity was high-lighted in a mouse model. Interestingly, food was found to modulate plasma LPS levels (endotoxemia) and these levels were related to fat content. In addition, these concentrations were sufficient to induce the development of metabolic disorders (essentially, diabetes and obes-ity) (18). Later, an association was reported between endotoxemia and energy intake in humans, but not between LPS and weight or body mass index (19). More studies are needed to elucidate the role of endo-toxemia in human obesity. Over the past several years, studies investi-gating gut microbiota and obesity have accumulated. Even in the absence of consensus, researchers agree that there is undoubtedly a link between gut microbiota and metabolic diseases such as obesity. In addition to the interaction between microbiota and obesity, some studies have also attempted to show a direct relationship with some pathogenic microorganisms. The concept of 'infectobesity' (obesity of infectious origin) has recently become more popular. Nevertheless, over the past 30 years, approximately 10 microorganisms (including canine distemper virus, avian adenovirus [SMAM-1] and human adenoviruses) have been linked with obesity in either humans or animals (20). Currently, studies are focusing on adenoviruses, especially adeno-virus 36 (Ad36), which is associated with adiposity and inflammation. Although Ad36 has been reported to induce obesity in animal models (21,22), results have been contradictory in humans. A greater preva-lence of neutralizing antibodies was observed in obese individuals com-pared with nonobese individuals in both adults (23-25) and children (26-29). However, some studies did not achieve the same results in adults (30-32) or children (33). In a meta-analysis of 10 studies (34), Ad36 infection was associated with an increased risk for obesity (OR 1.9 [95% CI 1.01 to 3.56]; P=0.047) and weight gain (increase in body mass index of 3.19 kg/m 2). These variable results are questionable because positive associations were essentially reported by a limited group of authors from similar institutions and because Ad36 was identified using serology in these studies. Discrepancies in detection and specificity This open-access article is distributed under the terms of the Creative Commons Attribution Non-Commercial License (CC BY-NC) (http:// creativecommons.org/licenses/by-nc/4.0/), which permits reuse, distribution and reproduction of the article, provided that the original work is properly cited and the reuse is restricted to noncommercial purposes. For commercial reuse, contact support@pulsus.com
    The Canadian journal of infectious diseases & medical microbiology = Journal canadien des maladies infectieuses et de la microbiologie medicale / AMMI Canada 11/2014; 25(6). · 0.49 Impact Factor

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