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

Akheruzzaman,; Hegde, Vijay; Dhurandhar, Nikhil V.

doi:10.1111/obr.12808

Cited by 24 publications

(13 citation statements)

References 105 publications

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“…E4orf1 gene of adenovirus Ad36 was identified as necessary and sufficient for the virus to improve glucose disposal in vitro and in vivo 32 . Independent of the virus, E4orf1 protein promotes glucose uptake in adipocytes, myoblasts and reduces glucose output from hepatocytes 8,9,11–13,17 , and in vivo, it improves high fat induced hyperglycemia, and reduces the response of endogenous insulin to glucose load 14–16 .…”

Section: Discussionmentioning

confidence: 99%

E4orf1 protein reduces the need for endogenous insulin

et al. 2019

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Background E4orf1 protein derived from adenovirus-36 reduces glucose excursion in mice, and lowers endogenous insulin response, suggesting a reduced need for insulin. We tested if the E4orf1-mediated lowering of insulin response is due to increased tissue sensitivity to insulin, reduced ability to produce or release insulin, or a reduced need for insulin release. Methods Experiment 1 : hyperinsulinemic–euglycemic clamps (HEC) and glucose tolerance test (GTT) were performed in high fat fed transgenic mice expressing E4orf1 or non-transgenic littermates ( n = 12 each), for 4 weeks. Experiments 2, 3, and 4 : E4orf1 or null vectors were expressed in rat-pancreatic β-cell line (INS-1) for 72 h, and cells were exposed to varying levels of glucose. Cell lysates and media were collected. Experiment 5 : 3T3L1-preadipocytes that express E4orf1 upon doxycycline induction, or null vector were induced with doxycycline and then exposed to protein transport inhibitor. Supernatant and cell lysate were collected. Experiment 6 : 3T3L1-preadipocytes that express E4orf1 upon doxycycline induction, or null vector were co-cultured with INS-1 cells for 24 h. Media was collected. Results Experiment 1 : E4orf1 transgenic mice cleared glucose faster compared to non-transgenic mice during GTT. HEC showed that E4orf1 did not alter tissue sensitivity to exogenous insulin in mice. Experiments 2, 3, and 4 : in INS1 cells, E4orf1 did not alter Glut2 abundance or Akt activation, suggesting no reduction in glucose sensing or insulin synthesis, respectively. E4orf1 did not influence glucose-stimulated insulin secretion in media by INS1 cells. Experiment 5 : E4orf1 was present in cell lysate, but not in media, indicating it is not a secretory protein. Experiment 6 : INS1 cells released less insulin in media when co-cultured in the presence of E4orf1-expressing 3T3-L1 cells. Conclusions Our studies support the working hypothesis that the E4orf1-mediated lowering of insulin response is not due to increased tissue sensitivity to insulin, or reduced ability to produce or release insulin, but likely to be due to a reduced need for insulin release.

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Section: Discussionmentioning

confidence: 99%

E4orf1 protein reduces the need for endogenous insulin

et al. 2019

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“…In 2018, Akheruzzaman et al [88] conducted a systematic review of articles published in the last 25 years, since the first study that linked adenovirus with animal obesity [28]. They evaluated the different types of studies, including biochemical and cellular aspects.…”

Section: Aldhoonmentioning

confidence: 99%

Adenovirus 36 prevalence and association with human obesity: a systematic review

et al. 2021

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Introduction Obesity has numerous etiologies and includes biological factors. Studies have demonstrated that the human adenovirus subtype 36 (Adv36) is an adipogenic agent and causes metabolic alterations. Study results on the prevalence of Adv36 and clinical effects in humans vary substantially. This was a systematic review to summarize the studies on the prevalence of Adv36 infection and its association with human obesity. Methods A systematic literature review was conducted using the preferred reporting items for systematic reviews and metaanalysis (PRISMA). Observational or experimental studies found in the Medline, Embase, LILACS, Science Direct and SciELO databases that presented results on the prevalence of Adv36 in humans were included. Results Thirty-seven studies were screened. A total of 10,300 adults aged 18-70 years and 4585 children and adolescents aged 3-18 years were assessed. The average prevalence of Adv36 among adults was 22.9%, ranging from 5.5% to 49.8%. Among children and adolescents, the average prevalence of Adv36 was 28.9%, ranging from 7.5% to 73.9%. There was a positive statistical relationship between Adv36 and weight gain, obesity, or metabolic changes in 31 studies. However, in four studies there was no association with obesity, and in one, no association was described. One of the studies showed an inverse correlation, i.e., Adv36 was a protective factor against obesity. Conclusion Strong evidence suggested a positive association between viral infection and obesity. However, due to the multicausality of obesity and heterogeneity of studies, diagnostic tests should be standardized and easily accessible by the population to estimate the overall prevalence of Adv36 infection and its association with obesity.

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“…1,2 The relationship of avian adenovirus SMAM-1 and human adenovirus 36 (HAd36) with obesity has been extensively studied, and adenovirus 36 has been consistently associated with obesity in both in vitro and in vivo assays and human studies. 3 The first studies that analyzed the association between Human Adenovirus 36 (HAd36) and obesity were performed in animal models (mice, chickens, and nonhuman primates), reporting that infection with the virus was associated with the increase in body weight, fat mass gain, and a decrease in serum cholesterol and triglyceride levels. [4][5][6] In human studies, the relationship between HAd36 and the development of obesity has also been analyzed; however, observational serological studies have shown contradictory results.…”

Section: Introductionmentioning

confidence: 99%

Presence of Adenovirus-36 DNA in Adipose Tissue of Women: Relationship with Adipocyte Morphology and the Expression of C/EBPβ and HIF-1α

Barrera-Alcocer

García-Benavides

Muñoz‐Valle

et al. 2021

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Background Human adenovirus 36 (HAd36) infection has been associated with obesity. Experiments using 3T3-L1 adipocyte cultured cells and human adipose stem cells (hASCc) have shown that HAd36 stimulates the expression of genes implicated in cell differentiation and increased lipid accumulation. The presence of HAd36 in adipose tissue of overweight and obese women has also been confirmed. This study aims to analyze the presence of HAd36 DNA in the adipose tissue of women undergoing surgery for weight reduction and its relationship with obesity through changes in adipocyte morphology as well as the expression of C/EBPβ and HIF-1α. Methods Fifty-two subcutaneous adipose tissue biopsies were collected. The anthropometric parameters measured were weight, height, skin folds, body circumferences, and body fat percentage. Biochemical measures were performed for glucose, cholesterol, triglycerides, cholesterol HDL-c, and LDL-c. The presence of HAd36 DNA was performed by conventional PCR. Adipocyte morphology was analyzed in H&E-stained sections using ImageJ/Fiji software. The expression of genes C/EBPβ, HIF-1α and β-actin was determined using TaqMan probes. Results HAd36 DNA was detected in 31% of adipose tissue samples. The presence of viral DNA was not significantly associated with anthropometric, clinical, or metabolic measurements, or with changes in adipose tissue morphology. The levels of mRNA expression for C/EBPβ and HIF-1α did not show significant differences between positive and negative samples for HAd36 (p>0.05). Conclusion The presence of HAd36 DNA in adipose tissue was identified, but it was not related to morphological changes of adipocytes, or the expression of C/EBPβ and HIF-1α. Further studies are needed to confirm these findings.

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

Cited by 24 publications

References 105 publications

E4orf1 protein reduces the need for endogenous insulin

E4orf1 protein reduces the need for endogenous insulin

Adenovirus 36 prevalence and association with human obesity: a systematic review

Presence of Adenovirus-36 DNA in Adipose Tissue of Women: Relationship with Adipocyte Morphology and the Expression of C/EBPβ and HIF-1α

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