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Role of Chitinase 3-Like 1 Protein in the Pathogenesis of Hepatic Insulin Resistance in Nonalcoholic Fatty Liver Disease
A recently discovered human glycoprotein, chitinase 3-like 1 (Chi3L1), may play a role in inflammation, tissue remodeling, and visceral fat accumulation. We hypothesize that Chi3L1 gene expression is important in the development of hepatic insulin resistance characterized by the generation of pAKT,...
Autores principales: | , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7909438/ https://www.ncbi.nlm.nih.gov/pubmed/33498326 http://dx.doi.org/10.3390/cells10020201 |
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author | Zhang, Songhua Sousa, Aryanna Lin, Mengqui Iwano, Ayako Jain, Rishubh Ma, Bing Lee, Chang Min Park, Jin Wook Kamle, Suchitra Carlson, Rolf Lee, Ghun Geun Elias, Jack A. Wands, Jack R. |
author_facet | Zhang, Songhua Sousa, Aryanna Lin, Mengqui Iwano, Ayako Jain, Rishubh Ma, Bing Lee, Chang Min Park, Jin Wook Kamle, Suchitra Carlson, Rolf Lee, Ghun Geun Elias, Jack A. Wands, Jack R. |
author_sort | Zhang, Songhua |
collection | PubMed |
description | A recently discovered human glycoprotein, chitinase 3-like 1 (Chi3L1), may play a role in inflammation, tissue remodeling, and visceral fat accumulation. We hypothesize that Chi3L1 gene expression is important in the development of hepatic insulin resistance characterized by the generation of pAKT, pGSK, and pERK in wild type and Chi3L1 knockout (KO) murine liver following insulin stimulation. The Chi3L1 gene and protein expression was evaluated by Real Time PCR and ELISA; lipid accumulation in hepatocytes was also assessed. To alter Chi3L1 function, three different anti-Chi3L1 monoclonal antibodies (mAbs) were administered in vivo and effects on the insulin signaling cascade and hepatic lipid deposition were determined. Transmission of the hepatic insulin signal was substantially improved following KO of the CHi3L1 gene and there was reduced lipid deposition produced by a HFD. The HFD-fed mice exhibited increased Chi3L1 expression in the liver and there was impaired insulin signal transduction. All three anti-Chi3L1 mAbs partially restored hepatic insulin sensitivity which was associated with reduced lipid accumulation in hepatocytes as well. A KO of the Chi3L1 gene reduced lipid accumulation and improved insulin signaling. Therefore, Chi3L1 gene upregulation may be an important factor in the generation of NAFLD/NASH phenotype. |
format | Online Article Text |
id | pubmed-7909438 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-79094382021-02-27 Role of Chitinase 3-Like 1 Protein in the Pathogenesis of Hepatic Insulin Resistance in Nonalcoholic Fatty Liver Disease Zhang, Songhua Sousa, Aryanna Lin, Mengqui Iwano, Ayako Jain, Rishubh Ma, Bing Lee, Chang Min Park, Jin Wook Kamle, Suchitra Carlson, Rolf Lee, Ghun Geun Elias, Jack A. Wands, Jack R. Cells Article A recently discovered human glycoprotein, chitinase 3-like 1 (Chi3L1), may play a role in inflammation, tissue remodeling, and visceral fat accumulation. We hypothesize that Chi3L1 gene expression is important in the development of hepatic insulin resistance characterized by the generation of pAKT, pGSK, and pERK in wild type and Chi3L1 knockout (KO) murine liver following insulin stimulation. The Chi3L1 gene and protein expression was evaluated by Real Time PCR and ELISA; lipid accumulation in hepatocytes was also assessed. To alter Chi3L1 function, three different anti-Chi3L1 monoclonal antibodies (mAbs) were administered in vivo and effects on the insulin signaling cascade and hepatic lipid deposition were determined. Transmission of the hepatic insulin signal was substantially improved following KO of the CHi3L1 gene and there was reduced lipid deposition produced by a HFD. The HFD-fed mice exhibited increased Chi3L1 expression in the liver and there was impaired insulin signal transduction. All three anti-Chi3L1 mAbs partially restored hepatic insulin sensitivity which was associated with reduced lipid accumulation in hepatocytes as well. A KO of the Chi3L1 gene reduced lipid accumulation and improved insulin signaling. Therefore, Chi3L1 gene upregulation may be an important factor in the generation of NAFLD/NASH phenotype. MDPI 2021-01-20 /pmc/articles/PMC7909438/ /pubmed/33498326 http://dx.doi.org/10.3390/cells10020201 Text en © 2021 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Zhang, Songhua Sousa, Aryanna Lin, Mengqui Iwano, Ayako Jain, Rishubh Ma, Bing Lee, Chang Min Park, Jin Wook Kamle, Suchitra Carlson, Rolf Lee, Ghun Geun Elias, Jack A. Wands, Jack R. Role of Chitinase 3-Like 1 Protein in the Pathogenesis of Hepatic Insulin Resistance in Nonalcoholic Fatty Liver Disease |
title | Role of Chitinase 3-Like 1 Protein in the Pathogenesis of Hepatic Insulin Resistance in Nonalcoholic Fatty Liver Disease |
title_full | Role of Chitinase 3-Like 1 Protein in the Pathogenesis of Hepatic Insulin Resistance in Nonalcoholic Fatty Liver Disease |
title_fullStr | Role of Chitinase 3-Like 1 Protein in the Pathogenesis of Hepatic Insulin Resistance in Nonalcoholic Fatty Liver Disease |
title_full_unstemmed | Role of Chitinase 3-Like 1 Protein in the Pathogenesis of Hepatic Insulin Resistance in Nonalcoholic Fatty Liver Disease |
title_short | Role of Chitinase 3-Like 1 Protein in the Pathogenesis of Hepatic Insulin Resistance in Nonalcoholic Fatty Liver Disease |
title_sort | role of chitinase 3-like 1 protein in the pathogenesis of hepatic insulin resistance in nonalcoholic fatty liver disease |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7909438/ https://www.ncbi.nlm.nih.gov/pubmed/33498326 http://dx.doi.org/10.3390/cells10020201 |
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