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Angiopoietin-Like Protein 4 Overexpression in Visceral Adipose Tissue from Obese Subjects with Impaired Glucose Metabolism and Relationship with Lipoprotein Lipase
Angiopoietin-like protein 4 (ANGPTL4) regulates lipid partitioning by inhibiting circulating and tissue lipoprotein lipase (LPL); ANGPTL4 loss-of-function variants improve insulin sensitivity and reduce type 2 diabetes (T2D) risk with mechanisms partially unknown. This study was designed to explore...
Autores principales: | , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7582588/ https://www.ncbi.nlm.nih.gov/pubmed/33003532 http://dx.doi.org/10.3390/ijms21197197 |
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author | Barchetta, Ilaria Chiappetta, Caterina Ceccarelli, Valentina Cimini, Flavia Agata Bertoccini, Laura Gaggini, Melania Cristofano, Claudio Di Silecchia, Gianfranco Lenzi, Andrea Leonetti, Frida Baroni, Marco Giorgio Gastaldelli, Amalia Cavallo, Maria Gisella |
author_facet | Barchetta, Ilaria Chiappetta, Caterina Ceccarelli, Valentina Cimini, Flavia Agata Bertoccini, Laura Gaggini, Melania Cristofano, Claudio Di Silecchia, Gianfranco Lenzi, Andrea Leonetti, Frida Baroni, Marco Giorgio Gastaldelli, Amalia Cavallo, Maria Gisella |
author_sort | Barchetta, Ilaria |
collection | PubMed |
description | Angiopoietin-like protein 4 (ANGPTL4) regulates lipid partitioning by inhibiting circulating and tissue lipoprotein lipase (LPL); ANGPTL4 loss-of-function variants improve insulin sensitivity and reduce type 2 diabetes (T2D) risk with mechanisms partially unknown. This study was designed to explore metabolic implications of differential ANGPTL4 and LPL expression in human adipose tissue (AT). We recruited eighty-eight obese individuals, with and without abnormal glucose metabolism (AGM), undergoing bariatric surgery; visceral AT (VAT) fragments were obtained intra-operatively and analyzed by immunohistochemistry and mRNA by rt-PCR. Data on hepatic ANGPTL4 mRNA were available for 40 participants. VAT ANGPTL4 expression was higher in AGM individuals than in those with normal glucose tolerance (NGT) and associated with VAT inflammation, insulin resistance, and presence of adipocyte size heterogeneity. Increased ANGPTL4 was associated with AGM with OR = 5.1 (95% C.I.: 1.2–23; p = 0.02) and AUROC = 0.76 (95% C.I.: 1.2–23; p < 0.001). High LPL was associated with the detection of homogeneous adipocyte size, reduced microvessel density, and higher HIF-1α levels and inversely correlated to blood transaminases. In conclusion, in obese individuals, VAT ANGPTL4 levels are increased in the presence of local inflammation and AGM. Conversely, higher LPL expression describes a condition of increased lipid storage in adipocytes, which may serve as a protective mechanism against ectopic fat accumulation and related metabolic disease in obesity. |
format | Online Article Text |
id | pubmed-7582588 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-75825882020-10-28 Angiopoietin-Like Protein 4 Overexpression in Visceral Adipose Tissue from Obese Subjects with Impaired Glucose Metabolism and Relationship with Lipoprotein Lipase Barchetta, Ilaria Chiappetta, Caterina Ceccarelli, Valentina Cimini, Flavia Agata Bertoccini, Laura Gaggini, Melania Cristofano, Claudio Di Silecchia, Gianfranco Lenzi, Andrea Leonetti, Frida Baroni, Marco Giorgio Gastaldelli, Amalia Cavallo, Maria Gisella Int J Mol Sci Article Angiopoietin-like protein 4 (ANGPTL4) regulates lipid partitioning by inhibiting circulating and tissue lipoprotein lipase (LPL); ANGPTL4 loss-of-function variants improve insulin sensitivity and reduce type 2 diabetes (T2D) risk with mechanisms partially unknown. This study was designed to explore metabolic implications of differential ANGPTL4 and LPL expression in human adipose tissue (AT). We recruited eighty-eight obese individuals, with and without abnormal glucose metabolism (AGM), undergoing bariatric surgery; visceral AT (VAT) fragments were obtained intra-operatively and analyzed by immunohistochemistry and mRNA by rt-PCR. Data on hepatic ANGPTL4 mRNA were available for 40 participants. VAT ANGPTL4 expression was higher in AGM individuals than in those with normal glucose tolerance (NGT) and associated with VAT inflammation, insulin resistance, and presence of adipocyte size heterogeneity. Increased ANGPTL4 was associated with AGM with OR = 5.1 (95% C.I.: 1.2–23; p = 0.02) and AUROC = 0.76 (95% C.I.: 1.2–23; p < 0.001). High LPL was associated with the detection of homogeneous adipocyte size, reduced microvessel density, and higher HIF-1α levels and inversely correlated to blood transaminases. In conclusion, in obese individuals, VAT ANGPTL4 levels are increased in the presence of local inflammation and AGM. Conversely, higher LPL expression describes a condition of increased lipid storage in adipocytes, which may serve as a protective mechanism against ectopic fat accumulation and related metabolic disease in obesity. MDPI 2020-09-29 /pmc/articles/PMC7582588/ /pubmed/33003532 http://dx.doi.org/10.3390/ijms21197197 Text en © 2020 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 Barchetta, Ilaria Chiappetta, Caterina Ceccarelli, Valentina Cimini, Flavia Agata Bertoccini, Laura Gaggini, Melania Cristofano, Claudio Di Silecchia, Gianfranco Lenzi, Andrea Leonetti, Frida Baroni, Marco Giorgio Gastaldelli, Amalia Cavallo, Maria Gisella Angiopoietin-Like Protein 4 Overexpression in Visceral Adipose Tissue from Obese Subjects with Impaired Glucose Metabolism and Relationship with Lipoprotein Lipase |
title | Angiopoietin-Like Protein 4 Overexpression in Visceral Adipose Tissue from Obese Subjects with Impaired Glucose Metabolism and Relationship with Lipoprotein Lipase |
title_full | Angiopoietin-Like Protein 4 Overexpression in Visceral Adipose Tissue from Obese Subjects with Impaired Glucose Metabolism and Relationship with Lipoprotein Lipase |
title_fullStr | Angiopoietin-Like Protein 4 Overexpression in Visceral Adipose Tissue from Obese Subjects with Impaired Glucose Metabolism and Relationship with Lipoprotein Lipase |
title_full_unstemmed | Angiopoietin-Like Protein 4 Overexpression in Visceral Adipose Tissue from Obese Subjects with Impaired Glucose Metabolism and Relationship with Lipoprotein Lipase |
title_short | Angiopoietin-Like Protein 4 Overexpression in Visceral Adipose Tissue from Obese Subjects with Impaired Glucose Metabolism and Relationship with Lipoprotein Lipase |
title_sort | angiopoietin-like protein 4 overexpression in visceral adipose tissue from obese subjects with impaired glucose metabolism and relationship with lipoprotein lipase |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7582588/ https://www.ncbi.nlm.nih.gov/pubmed/33003532 http://dx.doi.org/10.3390/ijms21197197 |
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