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Improved β-cell function leads to improved glucose tolerance in a transgenic mouse expressing lipoprotein lipase in adipocytes
Lipoprotein lipase (LPL) hydrolyzes the triglyceride core of lipoproteins and also functions as a bridge, allowing for lipoprotein and cholesterol uptake. Transgenic mice expressing LPL in adipose tissue under the control of the adiponectin promoter (AdipoQ-LPL) have improved glucose metabolism when...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group UK
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9789969/ https://www.ncbi.nlm.nih.gov/pubmed/36566329 http://dx.doi.org/10.1038/s41598-022-26995-1 |
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author | Memetimin, Hasiyet Zhu, Beibei Lee, Sangderk Katz, Wendy S. Kern, Philip A. Finlin, Brian S. |
author_facet | Memetimin, Hasiyet Zhu, Beibei Lee, Sangderk Katz, Wendy S. Kern, Philip A. Finlin, Brian S. |
author_sort | Memetimin, Hasiyet |
collection | PubMed |
description | Lipoprotein lipase (LPL) hydrolyzes the triglyceride core of lipoproteins and also functions as a bridge, allowing for lipoprotein and cholesterol uptake. Transgenic mice expressing LPL in adipose tissue under the control of the adiponectin promoter (AdipoQ-LPL) have improved glucose metabolism when challenged with a high fat diet. Here, we studied the transcriptional response of the adipose tissue of these mice to acute high fat diet exposure. Gene set enrichment analysis (GSEA) provided mechanistic insight into the improved metabolic phenotype of AdipoQ-LPL mice. First, the cholesterol homeostasis pathway, which is controlled by the SREBP2 transcription factor, is repressed in gonadal adipose tissue AdipoQ-LPL mice. Furthermore, we identified SND1 as a link between SREBP2 and CCL19, an inflammatory chemokine that is reduced in AdipoQ-LPL mice. Second, GSEA identified a signature for pancreatic β-cells in adipose tissue of AdipoQ-LPL mice, an unexpected finding. We explored whether β-cell function is improved in AdipoQ-LPL mice and found that the first phase of insulin secretion is increased in mice challenged with high fat diet. In summary, we identify two different mechanisms for the improved metabolic phenotype of AdipoQ-LPL mice. One involves improved adipose tissue function and the other involves adipose tissue—pancreatic β-cell crosstalk. |
format | Online Article Text |
id | pubmed-9789969 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-97899692022-12-26 Improved β-cell function leads to improved glucose tolerance in a transgenic mouse expressing lipoprotein lipase in adipocytes Memetimin, Hasiyet Zhu, Beibei Lee, Sangderk Katz, Wendy S. Kern, Philip A. Finlin, Brian S. Sci Rep Article Lipoprotein lipase (LPL) hydrolyzes the triglyceride core of lipoproteins and also functions as a bridge, allowing for lipoprotein and cholesterol uptake. Transgenic mice expressing LPL in adipose tissue under the control of the adiponectin promoter (AdipoQ-LPL) have improved glucose metabolism when challenged with a high fat diet. Here, we studied the transcriptional response of the adipose tissue of these mice to acute high fat diet exposure. Gene set enrichment analysis (GSEA) provided mechanistic insight into the improved metabolic phenotype of AdipoQ-LPL mice. First, the cholesterol homeostasis pathway, which is controlled by the SREBP2 transcription factor, is repressed in gonadal adipose tissue AdipoQ-LPL mice. Furthermore, we identified SND1 as a link between SREBP2 and CCL19, an inflammatory chemokine that is reduced in AdipoQ-LPL mice. Second, GSEA identified a signature for pancreatic β-cells in adipose tissue of AdipoQ-LPL mice, an unexpected finding. We explored whether β-cell function is improved in AdipoQ-LPL mice and found that the first phase of insulin secretion is increased in mice challenged with high fat diet. In summary, we identify two different mechanisms for the improved metabolic phenotype of AdipoQ-LPL mice. One involves improved adipose tissue function and the other involves adipose tissue—pancreatic β-cell crosstalk. Nature Publishing Group UK 2022-12-24 /pmc/articles/PMC9789969/ /pubmed/36566329 http://dx.doi.org/10.1038/s41598-022-26995-1 Text en © The Author(s) 2022 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . |
spellingShingle | Article Memetimin, Hasiyet Zhu, Beibei Lee, Sangderk Katz, Wendy S. Kern, Philip A. Finlin, Brian S. Improved β-cell function leads to improved glucose tolerance in a transgenic mouse expressing lipoprotein lipase in adipocytes |
title | Improved β-cell function leads to improved glucose tolerance in a transgenic mouse expressing lipoprotein lipase in adipocytes |
title_full | Improved β-cell function leads to improved glucose tolerance in a transgenic mouse expressing lipoprotein lipase in adipocytes |
title_fullStr | Improved β-cell function leads to improved glucose tolerance in a transgenic mouse expressing lipoprotein lipase in adipocytes |
title_full_unstemmed | Improved β-cell function leads to improved glucose tolerance in a transgenic mouse expressing lipoprotein lipase in adipocytes |
title_short | Improved β-cell function leads to improved glucose tolerance in a transgenic mouse expressing lipoprotein lipase in adipocytes |
title_sort | improved β-cell function leads to improved glucose tolerance in a transgenic mouse expressing lipoprotein lipase in adipocytes |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9789969/ https://www.ncbi.nlm.nih.gov/pubmed/36566329 http://dx.doi.org/10.1038/s41598-022-26995-1 |
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