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A Direct Comparison of Metabolic Responses to High-Fat Diet in C57BL/6J and C57BL/6NJ Mice

Although nicotinamide nucleotide transhydrogenase (NNT)–deficient C57BL/6J (6J) mice are known to be highly susceptible to diet-induced metabolic disease, this notion stems primarily from comparisons of 6J mice to other inbred strains. To date, very few studies have directly compared metabolic disea...

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Autores principales: Fisher-Wellman, Kelsey H., Ryan, Terence E., Smith, Cody D., Gilliam, Laura A.A., Lin, Chien-Te, Reese, Lauren R., Torres, Maria J., Neufer, P. Darrell
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Diabetes Association 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5079634/
https://www.ncbi.nlm.nih.gov/pubmed/27495226
http://dx.doi.org/10.2337/db16-0291
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author Fisher-Wellman, Kelsey H.
Ryan, Terence E.
Smith, Cody D.
Gilliam, Laura A.A.
Lin, Chien-Te
Reese, Lauren R.
Torres, Maria J.
Neufer, P. Darrell
author_facet Fisher-Wellman, Kelsey H.
Ryan, Terence E.
Smith, Cody D.
Gilliam, Laura A.A.
Lin, Chien-Te
Reese, Lauren R.
Torres, Maria J.
Neufer, P. Darrell
author_sort Fisher-Wellman, Kelsey H.
collection PubMed
description Although nicotinamide nucleotide transhydrogenase (NNT)–deficient C57BL/6J (6J) mice are known to be highly susceptible to diet-induced metabolic disease, this notion stems primarily from comparisons of 6J mice to other inbred strains. To date, very few studies have directly compared metabolic disease susceptibility between NNT-deficient 6J mice and NNT-competent C57BL/6 substrains. In this study, comprehensive profiling of the metabolic response to a high-fat/high-sucrose diet (HFD) were compared across time in 6J and C57BL/6NJ (6N) mice. Given that increased peroxide exposure drives insulin resistance, coupled with the fact that NNT regulates peroxide detoxification, it was hypothesized that 6J mice would experience greater derangements in redox homeostasis/metabolic disease upon HFD exposure. Contrary to this, both lines were found to be highly susceptible to diet-induced metabolic disease, as evidenced by impairments in glucose tolerance as early as 24 h into the HFD. Moreover, various markers of the metabolic syndrome, as well as peroxide stress, were actually blunted, rather than exacerbated, in the 6J mice, likely reflecting compensatory increases in alterative redox-buffering pathways. Together, these data provide evidence that the susceptibility to HFD-induced metabolic disease is similar in the 6J and 6N substrains. Given the numerous genetic variances in the 6J stain, including loss of NNT function, these findings suggest that the 6N substrain is the more logical and representative genetic background model for metabolic studies.
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spelling pubmed-50796342017-11-01 A Direct Comparison of Metabolic Responses to High-Fat Diet in C57BL/6J and C57BL/6NJ Mice Fisher-Wellman, Kelsey H. Ryan, Terence E. Smith, Cody D. Gilliam, Laura A.A. Lin, Chien-Te Reese, Lauren R. Torres, Maria J. Neufer, P. Darrell Diabetes Metabolism Although nicotinamide nucleotide transhydrogenase (NNT)–deficient C57BL/6J (6J) mice are known to be highly susceptible to diet-induced metabolic disease, this notion stems primarily from comparisons of 6J mice to other inbred strains. To date, very few studies have directly compared metabolic disease susceptibility between NNT-deficient 6J mice and NNT-competent C57BL/6 substrains. In this study, comprehensive profiling of the metabolic response to a high-fat/high-sucrose diet (HFD) were compared across time in 6J and C57BL/6NJ (6N) mice. Given that increased peroxide exposure drives insulin resistance, coupled with the fact that NNT regulates peroxide detoxification, it was hypothesized that 6J mice would experience greater derangements in redox homeostasis/metabolic disease upon HFD exposure. Contrary to this, both lines were found to be highly susceptible to diet-induced metabolic disease, as evidenced by impairments in glucose tolerance as early as 24 h into the HFD. Moreover, various markers of the metabolic syndrome, as well as peroxide stress, were actually blunted, rather than exacerbated, in the 6J mice, likely reflecting compensatory increases in alterative redox-buffering pathways. Together, these data provide evidence that the susceptibility to HFD-induced metabolic disease is similar in the 6J and 6N substrains. Given the numerous genetic variances in the 6J stain, including loss of NNT function, these findings suggest that the 6N substrain is the more logical and representative genetic background model for metabolic studies. American Diabetes Association 2016-11 2016-08-05 /pmc/articles/PMC5079634/ /pubmed/27495226 http://dx.doi.org/10.2337/db16-0291 Text en © 2016 by the American Diabetes Association. http://www.diabetesjournals.org/content/licenseReaders 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. More information is available at http://www.diabetesjournals.org/content/license.
spellingShingle Metabolism
Fisher-Wellman, Kelsey H.
Ryan, Terence E.
Smith, Cody D.
Gilliam, Laura A.A.
Lin, Chien-Te
Reese, Lauren R.
Torres, Maria J.
Neufer, P. Darrell
A Direct Comparison of Metabolic Responses to High-Fat Diet in C57BL/6J and C57BL/6NJ Mice
title A Direct Comparison of Metabolic Responses to High-Fat Diet in C57BL/6J and C57BL/6NJ Mice
title_full A Direct Comparison of Metabolic Responses to High-Fat Diet in C57BL/6J and C57BL/6NJ Mice
title_fullStr A Direct Comparison of Metabolic Responses to High-Fat Diet in C57BL/6J and C57BL/6NJ Mice
title_full_unstemmed A Direct Comparison of Metabolic Responses to High-Fat Diet in C57BL/6J and C57BL/6NJ Mice
title_short A Direct Comparison of Metabolic Responses to High-Fat Diet in C57BL/6J and C57BL/6NJ Mice
title_sort direct comparison of metabolic responses to high-fat diet in c57bl/6j and c57bl/6nj mice
topic Metabolism
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5079634/
https://www.ncbi.nlm.nih.gov/pubmed/27495226
http://dx.doi.org/10.2337/db16-0291
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