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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...

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Autores principales: 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
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2020
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.
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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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