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Open AccessArticle

Role of Chitinase 3-Like 1 Protein in the Pathogenesis of Hepatic Insulin Resistance in Nonalcoholic Fatty Liver Disease

1
Liver Research Center, Rhode Island Hospital and the Warren Alpert Medical School of Brown University, Providence, RI 02903, USA
2
Department of Molecular Microbiology and Immunology, Brown University, Providence, RI 02912, USA
3
Department of Medicine, Warren Alpert Medical School of Brown University, Providence, RI 02912, USA
*
Author to whom correspondence should be addressed.
Academic Editor: Marc Basson
Cells 2021, 10(2), 201; https://doi.org/10.3390/cells10020201
Received: 15 December 2020 / Revised: 15 January 2021 / Accepted: 17 January 2021 / Published: 20 January 2021
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. View Full-Text
Keywords: nonalcoholic steatosis (NASH); Chi3L1; hepatic insulin resistance; anti-Chi3L1 monoclonal antibody nonalcoholic steatosis (NASH); Chi3L1; hepatic insulin resistance; anti-Chi3L1 monoclonal antibody
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MDPI and ACS Style

Zhang, S.; Sousa, A.; Lin, M.; Iwano, A.; Jain, R.; Ma, B.; Lee, C.M.; Park, J.W.; Kamle, S.; Carlson, R.; Lee, G.G.; Elias, J.A.; Wands, J.R. Role of Chitinase 3-Like 1 Protein in the Pathogenesis of Hepatic Insulin Resistance in Nonalcoholic Fatty Liver Disease. Cells 2021, 10, 201. https://doi.org/10.3390/cells10020201

AMA Style

Zhang S, Sousa A, Lin M, Iwano A, Jain R, Ma B, Lee CM, Park JW, Kamle S, Carlson R, Lee GG, Elias JA, Wands JR. Role of Chitinase 3-Like 1 Protein in the Pathogenesis of Hepatic Insulin Resistance in Nonalcoholic Fatty Liver Disease. Cells. 2021; 10(2):201. https://doi.org/10.3390/cells10020201

Chicago/Turabian Style

Zhang, Songhua; Sousa, Aryanna; Lin, Mengqui; Iwano, Ayako; Jain, Rishubh; Ma, Bing; Lee, Chang M.; Park, Jin W.; Kamle, Suchitra; Carlson, Rolf; Lee, Ghun G.; Elias, Jack A.; Wands, Jack R. 2021. "Role of Chitinase 3-Like 1 Protein in the Pathogenesis of Hepatic Insulin Resistance in Nonalcoholic Fatty Liver Disease" Cells 10, no. 2: 201. https://doi.org/10.3390/cells10020201

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