title: Foodborne transmission of bovine spongiform encephalopathy to non-human primates results in preclinical rapid-onset obesity.
abstract: Obesity has become one of the largest public health challenges worldwide. Recently, certain bacterial and viral pathogens have been implicated in the pathogenesis of obesity. In the present study, we retrospectively analyzed clinical data, plasma samples and post-mortem tissue specimens derived from a risk assessment study in bovine spongiform encephalopathy (BSE)-infected female cynomolgus monkeys (Macaca fascicularis). The original study design aimed to determine minimal infectious doses after oral or intracerebral (i.c.) infection of macaques to assess the risk for humans. High-dose exposures resulted in 100% attack rates and a median incubation time of 4.7 years as described previously. Retrospective analyses of clinical data from high-dosed macaques revealed that foodborne BSE transmission caused rapid weight gain within 1.5 years post infection (β = 0.915; P<0.0001) which was not seen in age- and sex-matched control animals or i.c. infected animals. The rapid-onset obesity was not associated with impaired pancreatic islet function or glucose metabolism. In the early preclinical phase of oral transmission associated with body weight gain, prion accumulation was confined to the gastrointestinal tract. Intriguingly, immunohistochemical findings suggest that foodborne BSE transmission has a pathophysiological impact on gut endocrine cells which may explain rapid weight gain. To our knowledge, this is the first experimental model which clearly demonstrates that foodborne pathogens can induce obesity.
authors.affiliation: Institute for Clinical Diabetology, German Diabetes Center, Leibniz Center for Diabetes Research, Düsseldorf, Germany.
authors.forename: Alexander
authors.initials: A
authors.lastname: Strom
authors.affiliation: Paul-Ehrlich-Institut, Federal Agency for Vaccines and Biomedicines, Langen, Germany.
authors.forename: Barbara
authors.initials: B
authors.lastname: Yutzy
authors.affiliation: Paul-Ehrlich-Institut, Federal Agency for Vaccines and Biomedicines, Langen, Germany.
authors.forename: Carina
authors.initials: C
authors.lastname: Kruip
authors.affiliation: Institute for Clinical Diabetology, German Diabetes Center, Leibniz Center for Diabetes Research, Düsseldorf, Germany.
authors.forename: Mark
authors.initials: M
authors.lastname: Ooms
authors.affiliation: Institute for Clinical Diabetology, German Diabetes Center, Leibniz Center for Diabetes Research, Düsseldorf, Germany.
authors.forename: Nanette C
authors.initials: NC
authors.lastname: Schloot
authors.affiliation: Institute for Clinical Diabetology, German Diabetes Center, Leibniz Center for Diabetes Research, Düsseldorf, Germany; Department of Endocrinology and Diabetology, Heinrich-Heine University, Düsseldorf, Germany.
authors.forename: Michael
authors.initials: M
authors.lastname: Roden
authors.affiliation: Chronic Disease Program, Ottawa Hospital Research Institute, Ottawa, Ontario, Canada.
authors.forename: Fraser W
authors.initials: FW
authors.lastname: Scott
authors.affiliation: Paul-Ehrlich-Institut, Federal Agency for Vaccines and Biomedicines, Langen, Germany.
authors.forename: Johannes
authors.initials: J
authors.lastname: Loewer
authors.affiliation: Paul-Ehrlich-Institut, Federal Agency for Vaccines and Biomedicines, Langen, Germany.
authors.forename: Edgar
authors.initials: E
authors.lastname: Holznagel
mesh_terms: D000818:Animals; D002417:Cattle; D016643:Encephalopathy, Bovine Spongiform / Q000150:complications* / Q000378:metabolism / Q000503:physiopathology / Q000635:transmission; D005260:Female; D005517:Foodborne Diseases / Q000503:physiopathology*; D006801:Humans; D008252:Macaca fascicularis; D009765:Obesity / Q000209:etiology* / Q000378:metabolism / Q000503:physiopathology; D011323:Primates; D011328:Prions / Q000235:genetics / Q000472:pathogenicity*; D015430:Weight Gain / Q000502:physiology
chemical_list: D011328:Prions
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