Ad36 adipogenic adenovirus in human non-alcoholic fatty liver disease

Trovato, Guglielmo M.; Martines, Giuseppe Fabio; Garozzo, A; Tonzuso, Antonia; Timpanaro, R.; Pirri, Clara; Trovato, Francesca M.; Catalano, Daniela

doi:10.1111/j.1478-3231.2009.02127.x

Cited by 71 publications

(63 citation statements)

References 27 publications

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“…In both cohorts, Ad36 infection was associated with significantly lower IHL ( Table 1). These findings agree well with a recent report of protection from nonalcoholic fatty liver disease (NAFLD) in Ad36 seropositive people (60). These findings suggest that Ad36 infection may protect individuals from impaired glucose tolerance (IGT) and HS, two key risk factors associated with type 2 diabetes and serious liver diseases.…”

Section: Experiments 3: Ad36 Is Associated With Better Glycemic Controsupporting

confidence: 92%

Template to improve glycemic control without reducing adiposity or dietary fat

Krishnapuram

Dhurandhar

Dubuisson

et al. 2011

American Journal of Physiology-Endocrinology and Metabolism

117

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Drugs that improve chronic hyperglycemia independently of insulin signaling or reduction of adiposity or dietary fat intake may be highly desirable. Ad36, a human adenovirus, promotes glucose uptake in vitro independently of adiposity or proximal insulin signaling. We tested the ability of Ad36 to improve glycemic control in vivo and determined if the natural Ad36 infection in humans is associated with better glycemic control. C57BL/6J mice fed a chow diet or made diabetic with a high-fat (HF) diet were mock infected or infected with Ad36 or adenovirus Ad2 as a control for infection. Postinfection (pi), systemic glycemic control, hepatic lipid content, and cell signaling in tissues pertinent to glucose metabolism were determined. Next, sera of 1,507 adults and children were screened for Ad36 antibodies as an indicator of past natural infection. In chow-fed mice, Ad36 significantly improved glycemic control for 12 wk pi. In HF-fed mice, Ad36 improved glycemic control and hepatic steatosis up to 20 wk pi. In adipose tissue (AT), skeletal muscle (SM), and liver, Ad36 upregulated distal insulin signaling without recruiting the proximal insulin signaling. Cell signaling suggested that Ad36 increases AT and SM glucose uptake and reduces hepatic glucose release. In humans, Ad36 infection predicted better glycemic control and lower hepatic lipid content independently of age, sex, or adiposity. We conclude that Ad36 offers a novel tool to understand the pathways to improve hyperglycemia and hepatic steatosis independently of proximal insulin signaling, and despite a HF diet. This metabolic engineering by Ad36 appears relevant to humans for developing more practical and effective antidiabetic approaches.

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Section: Experiments 3: Ad36 Is Associated With Better Glycemic Controsupporting

confidence: 92%

Template to improve glycemic control without reducing adiposity or dietary fat

Krishnapuram

Dhurandhar

Dubuisson

et al. 2011

American Journal of Physiology-Endocrinology and Metabolism

117

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“…Straight, discrete, and significant mutual linear relationships between insulin resistance, obesity, and severity of fatty liver involvement are reported, and the possibility that the Ad36 adenovirus can interfere in the pathogenesis of fat storage in hepatocytes with mechanisms different from those operating in adipose cells was suggested [13]. A higher prevalence of human adenovirus Ad36 antibodies seropositivity is present in obese people [34]; nonetheless, Ad36 seropositivity in our previous study is associated with a lower occurrence of NAFLD and bright liver in subjects with the same grade of obesity [43]. Moreover, Ad36 ?…”

Section: Introductionmentioning

confidence: 66%

“…The liver is assessed for size, contour, echogenicity, structure, penetration of the US beam, i.e., posterior beam attenuation and portal vessel wall distinction. The degrees of bright liver considered for statistical evaluation are classified by combining three subscale grades focused on echogenicity, beam penetration, and portal vessel wall distinction: grade 0 -normal or slightly reduced in comparison with right kidney echogenicity; grade 1 -slightly increased in comparison with right kidney echogenicity; grade 2 -clearly increased, with a decline in echo amplitude (i.e., posterior beam attenuation owing to the high reflectivity of the fat liver parenchyma); and grade 3 -markedly increased with a decline in echo amplitude and impaired portal vessel wall distinction, i.e., loss of echoes from the walls of the portal vein [13,43,[45][46][47]. All US procedures to be used for data analysis are performed and assessed by a single senior specialist (DC) not informed of any clinical detail including the Ad36 serological status and the previous US examination reports and results.…”

Section: Methodsmentioning

confidence: 99%

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Adenovirus-36 Seropositivity Enhances Effects of Nutritional Intervention on Obesity, Bright Liver, and Insulin Resistance

et al. 2011

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Ad36 previous infection is significantly associated with enhanced weight loss, bright liver disappearance, and recovery of insulin sensitivity through the chosen tailored nutritional interventional treatment. Nonetheless, Ad36 seronegative NAFLD patients' fatty liver pattern improves, at a lower extent, also without significant weight loss: an effect of dietary changes profile, Mediterranean diet, not only of lowered food caloric intake, is conceivably operating.

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“…6,7 In addition, other studies using the Italian and the US children and adolescents demonstrated the association between the Ad-36 antibody and obesity. 8,9 Currently, little is known about the cellular and molecular mechanisms underlying Ad-36-induced obesity. Recently, Ad-36 E4 orf-1 was identified as a novel inducer of the rodent and human adipocyte differentiation process.…”

Section: Introductionmentioning

confidence: 99%

Novel genes and cellular pathways related to infection with adenovirus-36 as an obesity agent in human mesenchymal stem cells

Kim

2011

Int J Obes

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Objective: The objective of this study was to investigate the molecular mechanisms underlying adenovirus-36 (Ad-36)-induced obesity by the identification of novel genes and cellular pathways. Design: Viral growth, intracellular lipid accumulation and gene expression profiles were determined in human mesenchymal stem cells (hMSCs) infected with Ad-36 or Ad-2. A microarray assay and gene set enrichment analysis (GSEA) were performed to assess alterations in global gene expression profiles. Results: Ad-36, but not Ad-2, induced lipid accumulation and upregulated adipogenesis-related genes. There was no difference in viral growth between Ad-36 infection and Ad-2 infection in hMSCs. GSEA revealed that Ad-36 infection was more frequently associated with activation of novel pathways, including the PPAR-gamma signaling pathway, and inflammation compared with Ad-2 infection, raising the possibility that these pathways may be key regulators of Ad-36-induced adipogenesis. Conclusion: This study may help foster a better understanding of the roles of several cellular factors in Ad-36-induced obesity.

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Ad36 adipogenic adenovirus in human non-alcoholic fatty liver disease

Abstract: Ad36 seropositivity is not associated with a significant difference of IR in NAFLD patients, but is associated with a greater adiposity. Ad36 seropositivity is associated with a lower occurrence of NAFLD and bright liver, which, conceivably, is not directly mediated by IR.

Cited by 71 publications

References 27 publications

Template to improve glycemic control without reducing adiposity or dietary fat

Template to improve glycemic control without reducing adiposity or dietary fat

Adenovirus-36 Seropositivity Enhances Effects of Nutritional Intervention on Obesity, Bright Liver, and Insulin Resistance

Novel genes and cellular pathways related to infection with adenovirus-36 as an obesity agent in human mesenchymal stem cells

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