Longitudinal investigation of adenovirus 36 seropositivity and human obesity: the Cardiovascular Risk in Young Finns Study

Sabin, Matthew A.; Burgner, David; Atkinson, Richard L.; Lee, Z Pei-Lun; Magnussen, Costan G.; Cheung, Manyee; Kähönen, Mika; Lehtimäki, Terho; Jokinen, Eero; Laitinen, Tomi; Hutri‐Kähönen, Nina; Viikari, Jorma; Juonala, Markus; Raitakari, Olli T.

doi:10.1038/ijo.2015.108

Cited by 23 publications

(21 citation statements)

References 47 publications

(33 reference statements)

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“…In Italy, the odds ratio for the risk of obesity due to Ad36 antibody seropositivity was 6.879 . The association of human obesity with Ad36 antibody presence could not be confirmed in several studies including a US military personnel study, in individuals of Netherlands and Belgium, in Korean adults, in US children from Georgia and Indiana, Chinese Han population, and in Young Finns study . Nonetheless, a meta‐analysis of studies about the association of Ad36 antibody presence with human obesity shows that the odds ratio of having obesity is 1.60 for those exposed to Ad36 infection .…”

Section: Resultsmentioning

confidence: 98%

Twenty‐five years of research about adipogenic adenoviruses: A systematic review

2018

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Infectious etiology is implicated in chronic diseases such as gastric ulcer or atherosclerosis. However, "infection" is a recent term in the field of obesity. Since the first report in 1982 of obesity due to infection, several microbes have been linked to obesity. Among the adipogenic microbes, avian adenovirus SMAM-1 and human adenovirus Ad36 have been studied most extensively for the past 25 years. Here, we present a systematic review of literature about SMAM-1 and Ad36. Reports from North America, Europe, and Asia reveal strong evidence that Ad36 causes obesity in animals and paradoxically improves glycemic control, and in vitro data provides mechanistic explanation. Considering that experimental Ad36 infection of humans is unlikely, its causative role in human obesity or glycemic control has not been demonstrated unequivocally. Nonetheless, most, but not all, observational studies in children and adults link Ad36 infection to obesity and improvement in glycemic control. The E4orf1 gene of Ad36 was identified as responsible for better glycemic control. Overall, 25 years have considerably advanced knowledge about the role of infection in obesity. Potential translational benefits include the development of vaccines to prevent Ad36-induced obesity and drug development based on the E4orf1 protein to improve glycemic control.

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Section: Resultsmentioning

confidence: 98%

Twenty‐five years of research about adipogenic adenoviruses: A systematic review

2018

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“…The first cross-sectional survey was conducted in 1980. The original targeted cohort comprised 4,326 children and adolescents aged 3,6,9,12,15, and 18 years, of whom 3,596 (83.2% of the invited) participated in the baseline study. The cohort has been followed-up for 31 years in [3][4][5][6][7][8][9] year intervals (follow-up years 1983, 1986, 1989, 2001, 2007 and 2011).…”

Section: Study Design and Subjectsmentioning

confidence: 99%

“…Venous blood samples were drawn after a 12-h fast. Standard enzymatic methods were used to assess plasma glucose and serum total cholesterol (15). Low-density lipoprotein cholesterol concentration was calculated using Friedewald formula (16).…”

Section: Laboratory Analysesmentioning

confidence: 99%

“…Glycated hemoglobin fraction in whole blood was measured by an Abbott Architect ci8200 analyzer (Abbott Laboratories and Hemoglobin A1c reagent, Fisher Diagnostics). Serum insulin concentration was analyzed using microparticle enzyme immunoassay kit (Abbott Laboratories, Chicago, IL, USA) (15). The homeostasis model assessment of insulin resistance (HOMA-IR) was calculated using the equation [(fasting insulin mU/mL X fasting glucose mmol/L)/22.5](17) and was used to estimate insulin resistance.…”

Section: Laboratory Analysesmentioning

confidence: 99%

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Physical Inactivity from Youth to Adulthood and Risk of Impaired Glucose Metabolism

Kallio

Pahkala

Heinonen

et al. 2018

Medicine &Amp; Science in Sports &Amp; Exercise

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“…Ad36 infection and its association with human obesity is reported in >14 countries and Ad36 is known to cause adipogenesis in in vitro and in vivo models 7 . Although Ad36 is linked with greater adipogenesis in naturally infected humans and experimentally infected animals, paradoxically, it also provides favorable metabolic features, such as improved glycemic control, better serum lipid profile, and reduced hepatic steatosis [8][9][10][11][12] . Subsequently, the E4orf1 protein of Ad36 was identified to have a similar anti-diabetic effect and reduced hepatic steatosis in high-fat (HF) diet-fed mice 13,14 .…”

Section: Introductionmentioning

confidence: 99%

Reducing endogenous insulin is linked with protection against hepatic steatosis in mice

et al. 2020

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Background: Obesity and type 2 diabetes (T2D) are closely associated with hepatic steatosis (HS), which if untreated can advance to serious liver conditions. Since insulin promotes hepatic lipogenesis, reducing hyperinsulinemia may help in treating HS. E4orf1 is an adenovirus-derived protein that improves glucose clearance independent of insulin, lowers insulin amount required for glucose disposal, and reduces HS. As a next step, we evaluated the mechanism for E4orf1-induced reduction in HS and tested that E4orf1 does not induce hypoglycemia, an important attribute for its application as a potential anti-diabetic agent.Methods: C57Bl/6J mice that transgenically express E4orf1 in adipose tissue (E4orf-Tg) and wild-type (WT) mice received a chow diet for 6 weeks, followed by a high-fat (HF) diet for additional 10 weeks. Body composition, blood glucose, and serum insulin levels upon glucose load were measured at 0, 6, 7, and 16 weeks. Serum free fatty acid (FFA), triglyceride (TG), and hepatic TG were measured at study termination. We compared histology and the mRNA/ protein markers of hepatic and adipose tissue lipid metabolism between the two groups of mice.Results: On chow diet, both groups remained normoglycemic, but E4orf1 expression reduced insulin response. On HF diet, glycemic control in WT deteriorated, whereas E4orf1 significantly enhanced glycemic control, lowered insulin response, reduced hepatic triglycerides, and serum FFA. Overall, a comparison of hepatic mRNA and/or protein expression suggested that E4orf1 expression significantly decreased de novo lipogenesis (DNL) and intracellular lipid transport and increased fat oxidation and TG export. Adipose tissue mRNA and protein markers suggested that E4orf1 expression lowered DNL and increased lipolysis. Conclusion:Considering that E4orf1 is not secreted in circulation, we postulate that reduced endogenous insulin in E4orf1 mice indirectly contributes to reduce HS by altering hepatic lipid metabolism, including lipogenesis. This study underscores the possibility of indirectly impacting HS by manipulating adipose tissue metabolism. Nutrition and Diabetes1234567890():,; 1234567890():,; 1234567890():,; 1234567890():,;

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Longitudinal investigation of adenovirus 36 seropositivity and human obesity: the Cardiovascular Risk in Young Finns Study

Cited by 23 publications

References 47 publications

Twenty‐five years of research about adipogenic adenoviruses: A systematic review

Twenty‐five years of research about adipogenic adenoviruses: A systematic review

Physical Inactivity from Youth to Adulthood and Risk of Impaired Glucose Metabolism

Reducing endogenous insulin is linked with protection against hepatic steatosis in mice

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