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Metabolically Favorable Remodeling of Human Adipose Tissue by Human Adenovirus Type 36

OBJECTIVE—Experimental infection of rats with human adenovirus type 36 (Ad-36) promotes adipogenesis and improves insulin sensitivity in a manner reminiscent of the pharmacologic effect of thiozolinediones. To exploit the potential of the viral proteins as a therapeutic target for treating insulin r...

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Autores principales: Rogers, Pamela M., Mashtalir, Nazar, Rathod, Miloni A., Dubuisson, Olga, Wang, Zhong, Dasuri, Kumar, Babin, Scott, Gupta, Alok, Markward, Nathan, Cefalu, William T., Dhurandhar, Nikhil V.
Formato: Texto
Lenguaje:English
Publicado: American Diabetes Association 2008
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2518483/
https://www.ncbi.nlm.nih.gov/pubmed/18599527
http://dx.doi.org/10.2337/db07-1311
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author Rogers, Pamela M.
Mashtalir, Nazar
Rathod, Miloni A.
Dubuisson, Olga
Wang, Zhong
Dasuri, Kumar
Babin, Scott
Gupta, Alok
Markward, Nathan
Cefalu, William T.
Dhurandhar, Nikhil V.
author_facet Rogers, Pamela M.
Mashtalir, Nazar
Rathod, Miloni A.
Dubuisson, Olga
Wang, Zhong
Dasuri, Kumar
Babin, Scott
Gupta, Alok
Markward, Nathan
Cefalu, William T.
Dhurandhar, Nikhil V.
author_sort Rogers, Pamela M.
collection PubMed
description OBJECTIVE—Experimental infection of rats with human adenovirus type 36 (Ad-36) promotes adipogenesis and improves insulin sensitivity in a manner reminiscent of the pharmacologic effect of thiozolinediones. To exploit the potential of the viral proteins as a therapeutic target for treating insulin resistance, this study investigated the ability of Ad-36 to induce metabolically favorable changes in human adipose tissue. RESEARCH DESIGN AND METHODS—We determined whether Ad-36 increases glucose uptake in human adipose tissue explants. Cell-signaling pathways targeted by Ad-36 to increase glucose uptake were determined in the explants and human adipose–derived stem cells. Ad-2, a nonadipogenic human adenovirus, was used as a negative control. As a proof of concept, nondiabetic and diabetic subjects were screened for the presence of Ad-36 antibodies to ascertain if natural Ad-36 infection predicted improved glycemic control. RESULTS—Ad-36 increased glucose uptake by adipose tissue explants obtained from nondiabetic and diabetic subjects. Without insulin stimulation, Ad-36 upregulated expressions of several proadipogenic genes, adiponectin, and fatty acid synthase and reduced the expression of inflammatory cytokine macrophage chemoattractant protein-1 in a phosphotidylinositol 3-kinase (PI3K)-dependent manner. In turn, the activation of PI3K by Ad-36 was independent of insulin receptor signaling but dependent on Ras signaling recruited by Ad-36. Ad-2 was nonadipogenic and did not increase glucose uptake. Natural Ad-36 infection in nondiabetic and diabetic subjects was associated with significantly lower fasting glucose levels and A1C, respectively. CONCLUSIONS—Ad-36 proteins may provide novel therapeutic targets that remodel human adipose tissue to a more metabolically favorable profile.
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spelling pubmed-25184832009-09-01 Metabolically Favorable Remodeling of Human Adipose Tissue by Human Adenovirus Type 36 Rogers, Pamela M. Mashtalir, Nazar Rathod, Miloni A. Dubuisson, Olga Wang, Zhong Dasuri, Kumar Babin, Scott Gupta, Alok Markward, Nathan Cefalu, William T. Dhurandhar, Nikhil V. Diabetes Signal Transduction OBJECTIVE—Experimental infection of rats with human adenovirus type 36 (Ad-36) promotes adipogenesis and improves insulin sensitivity in a manner reminiscent of the pharmacologic effect of thiozolinediones. To exploit the potential of the viral proteins as a therapeutic target for treating insulin resistance, this study investigated the ability of Ad-36 to induce metabolically favorable changes in human adipose tissue. RESEARCH DESIGN AND METHODS—We determined whether Ad-36 increases glucose uptake in human adipose tissue explants. Cell-signaling pathways targeted by Ad-36 to increase glucose uptake were determined in the explants and human adipose–derived stem cells. Ad-2, a nonadipogenic human adenovirus, was used as a negative control. As a proof of concept, nondiabetic and diabetic subjects were screened for the presence of Ad-36 antibodies to ascertain if natural Ad-36 infection predicted improved glycemic control. RESULTS—Ad-36 increased glucose uptake by adipose tissue explants obtained from nondiabetic and diabetic subjects. Without insulin stimulation, Ad-36 upregulated expressions of several proadipogenic genes, adiponectin, and fatty acid synthase and reduced the expression of inflammatory cytokine macrophage chemoattractant protein-1 in a phosphotidylinositol 3-kinase (PI3K)-dependent manner. In turn, the activation of PI3K by Ad-36 was independent of insulin receptor signaling but dependent on Ras signaling recruited by Ad-36. Ad-2 was nonadipogenic and did not increase glucose uptake. Natural Ad-36 infection in nondiabetic and diabetic subjects was associated with significantly lower fasting glucose levels and A1C, respectively. CONCLUSIONS—Ad-36 proteins may provide novel therapeutic targets that remodel human adipose tissue to a more metabolically favorable profile. American Diabetes Association 2008-09 /pmc/articles/PMC2518483/ /pubmed/18599527 http://dx.doi.org/10.2337/db07-1311 Text en Copyright © 2008, American Diabetes Association https://creativecommons.org/licenses/by-nc-nd/3.0/Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered. See http://creativecommons.org/licenses/by-nc-nd/3.0/ for details.
spellingShingle Signal Transduction
Rogers, Pamela M.
Mashtalir, Nazar
Rathod, Miloni A.
Dubuisson, Olga
Wang, Zhong
Dasuri, Kumar
Babin, Scott
Gupta, Alok
Markward, Nathan
Cefalu, William T.
Dhurandhar, Nikhil V.
Metabolically Favorable Remodeling of Human Adipose Tissue by Human Adenovirus Type 36
title Metabolically Favorable Remodeling of Human Adipose Tissue by Human Adenovirus Type 36
title_full Metabolically Favorable Remodeling of Human Adipose Tissue by Human Adenovirus Type 36
title_fullStr Metabolically Favorable Remodeling of Human Adipose Tissue by Human Adenovirus Type 36
title_full_unstemmed Metabolically Favorable Remodeling of Human Adipose Tissue by Human Adenovirus Type 36
title_short Metabolically Favorable Remodeling of Human Adipose Tissue by Human Adenovirus Type 36
title_sort metabolically favorable remodeling of human adipose tissue by human adenovirus type 36
topic Signal Transduction
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2518483/
https://www.ncbi.nlm.nih.gov/pubmed/18599527
http://dx.doi.org/10.2337/db07-1311
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