Viral Infections and Obesity

Abstract

Numerous microbial agents cause obesity in various experimental models-a phenomena known as infectobesity. Several of the same agents alter metabolic function in human cells and are associated with human obesity or metabolic dysfunction in humans. We address the evidence for a role in the genesis of obesity for viral agents in five broad categories: adenoviridae, herpesviridae, phages, transmissible spongiform encephalopathies (slow virus), and other encephalitides and hepatitides. Despite the importance of this topic area, there are many persistent knowledge gaps that need to be resolved. We discuss factors motivating further research and recommend that future infectobesity investigation should be more comprehensive, leveraged, interventional, and patient-centered.

Virome-wide serological profiling reveals association of herpesviruses with obesity

“…Currently there is compelling epidemiological data on the association between Adenovirus-36 and obesity as well as animal data on several other viruses (7,(20)(21)(22), but a broad screen for these and other infectious causes of obesity cannot be performed without a well-established, high throughput platform for comprehensive serological profiling. The establishment of the VirScan PhIP-Seq serological profiling platform (16) has created an opportunity to investigate the association between obesity and infection at an unprecedented depth.…”

“…However, epidemiological data to link infection with human cases of obesity was mostly limited to adenoviruses. Among different serotypes of adenoviruses, evidence for adipogenesis, based on results from laboratory, animal or epidemiologic investigations, exists for Adv-5, Adv-9, Adv-31, Adv-36 and Adv-37 (7,(9)(10)(11)(12).…”

Phenotype diffusion and one health: A proposed framework for investigating the plurality of obesity epidemics across many species

“…The hygiene (or “Old Friends”) hypothesis proposes inflammatory diseases are due to insufficient exposure to microbes (Yazdanbakhsh, Kremsner, & van Ree, ), which has been extensively reviewed elsewhere (Rook, ). Like other chronic diseases, obesity is associated with several markers of systemic inflammation (Voss & Dhurandhar, ). As the agricultural revolution, exposure to milk from cows was likely a large source of commensal microbes, but is currently more sterile.…”

“…This pathogen enables a gene‐centric view as these adipogenic mechanisms are caused by a single gene (E4‐ORF1) (Rogers et al., ). It seems likely that many microbes (including adenoviridae) that cause weight gain would have been selected in chickens along with their host genome over the past century, making infection among humans more likely (Voss & Dhurandhar, ). Historic seroprevalence of Ad‐36 in humans is uncertain, but two population‐based cohorts of lean individuals were available from Stockholm, Sweden, and seroprevalence paralleled the historic change in obesity prevalence (Almgren et al., ).…”

“…Despite these intriguing taxonomic connections, the overall association between gut bacterial taxa and obesity is modest (Sze & Schloss, ). Still, these bacterial analyses do not include zoonotic viruses previously associated with obesity (Ad‐5, Ad‐9, Ad‐31, Ad‐36, Ad‐37, BDV, bovine spongiform encephalopathy, gut phages, Rous‐associated virus 7, scrapie and SMAM‐1; Voss & Dhurandhar, ) (Section 2.4). Plus, taxonomy could obscure the emergence of a gene in livestock that transfers to humans through horizontal gene transfer, as shared ecology is associated with horizontal gene transfer (Smillie et al., ) and is well known to occur in antibiotic resistance (see Forslund et al., ).…”