Cell Models and Their Application for Studying Adipogenic Differentiation in Relation to Obesity: A Review

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Abstract

Over the last several years, the increasing prevalence of obesity has favored an intense study of adipose tissue biology and the precise mechanisms involved in adipocyte differentiation and adipogenesis. Adipocyte commitment and differentiation are complex processes, which can be investigated thanks to the development of diverse in vitro cell models and molecular biology techniques that allow for a better understanding of adipogenesis and adipocyte dysfunction associated with obesity. The aim of the present work was to update the different animal and human cell culture models available for studying the in vitro adipogenic differentiation process related to obesity and its co-morbidities. The main characteristics, new protocols, and applications of the cell models used to study the adipogenesis in the last five years have been extensively revised. Moreover, we depict co-cultures and three-dimensional cultures, given their utility to understand the connections between adipocytes and their surrounding cells in adipose tissue.

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Molecular Regulation of Adipogenesis and Potential Anti-Adipogenic Bioactive Molecules

Dorothy Moseti, Alemu Regassa, Woo-Kyun Kim (2016)

Adipogenesis is the process by which precursor stem cells differentiate into lipid laden adipocytes. Adipogenesis is regulated by a complex and highly orchestrated gene expression program. In mammalian cells, the peroxisome proliferator-activated receptor γ (PPARγ), and the CCAAT/enhancer binding proteins (C/EBPs) such as C/EBPα, β and δ are considered the key early regulators of adipogenesis, while fatty acid binding protein 4 (FABP4), adiponectin, and fatty acid synthase (FAS) are responsible for the formation of mature adipocytes. Excess accumulation of lipids in the adipose tissue leads to obesity, which is associated with cardiovascular diseases, type II diabetes and other pathologies. Thus, investigating adipose tissue development and the underlying molecular mechanisms is vital to develop therapeutic agents capable of curbing the increasing incidence of obesity and related pathologies. In this review, we address the process of adipogenic differentiation, key transcription factors and proteins involved, adipogenic regulators and potential anti-adipogenic bioactive molecules.

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β-Aminoisobutyric acid induces browning of white fat and hepatic β-oxidation and is inversely correlated with cardiometabolic risk factors.

Lee D. Roberts, Pontus Boström, John F. O’Sullivan … (2014)

The transcriptional coactivator peroxisome proliferator-activated receptor-gamma coactivator-1α (PGC-1α) regulates metabolic genes in skeletal muscle and contributes to the response of muscle to exercise. Muscle PGC-1α transgenic expression and exercise both increase the expression of thermogenic genes within white adipose. How the PGC-1α-mediated response to exercise in muscle conveys signals to other tissues remains incompletely defined. We employed a metabolomic approach to examine metabolites secreted from myocytes with forced expression of PGC-1α, and identified β-aminoisobutyric acid (BAIBA) as a small molecule myokine. BAIBA increases the expression of brown adipocyte-specific genes in white adipocytes and β-oxidation in hepatocytes both in vitro and in vivo through a PPARα-mediated mechanism, induces a brown adipose-like phenotype in human pluripotent stem cells, and improves glucose homeostasis in mice. In humans, plasma BAIBA concentrations are increased with exercise and inversely associated with metabolic risk factors. BAIBA may thus contribute to exercise-induced protection from metabolic diseases. Copyright © 2014 Elsevier Inc. All rights reserved.

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Evidence for two types of brown adipose tissue in humans.

Martin E. Lidell, Matthias J Betz, Olof Dahlqvist Leinhard … (2013)

The previously observed supraclavicular depot of brown adipose tissue (BAT) in adult humans was commonly believed to be the equivalent of the interscapular thermogenic organ of small mammals. This view was recently disputed on the basis of the demonstration that this depot consists of beige (also called brite) brown adipocytes, a newly identified type of brown adipocyte that is distinct from the classical brown adipocytes that make up the interscapular thermogenic organs of other mammals. A combination of high-resolution imaging techniques and histological and biochemical analyses showed evidence for an anatomically distinguishable interscapular BAT (iBAT) depot in human infants that consists of classical brown adipocytes, a cell type that has so far not been shown to exist in humans. On the basis of these findings, we conclude that infants, similarly to rodents, have the bona fide iBAT thermogenic organ consisting of classical brown adipocytes that is essential for the survival of small mammals in a cold environment.

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Contributors

Toshiro Arai: Role: Academic Editor

Journal

Journal ID (nlm-ta): Int J Mol Sci

Journal ID (iso-abbrev): Int J Mol Sci

Journal ID (publisher-id): ijms

Title: International Journal of Molecular Sciences

Publisher: MDPI

ISSN (Electronic): 1422-0067

Publication date (Electronic): 30 June 2016

Publication date Collection: July 2016

Volume: 17

Issue: 7

Electronic Location Identifier: 1040

Affiliations

[1 ]Department of Biochemistry and Molecular Biology II, School of Pharmacy, Campus de Cartuja s/n, 18071, Institute of Nutrition and Food Technology “José Mataix”, Center of Biomedical Research, Avenida del Conocimiento s/n, 18016, University of Granada, Granada 18071, Spain; fruizojeda@ 123456ugr.es (F.J.R.-O.); azahararuperez@ 123456ugr.es (A.I.R.); gomezll@ 123456ugr.es (C.G.-L.); agil@ 123456ugr.es (A.G.)

[2 ]Instituto de Investigación Biosanitaria ibs, Complejo Hospitalario Universitario de Granada/Universidad de Granada, Granada 18014, Spain

[3 ]CIBEROBN (Physiopathology of Obesity and Nutrition CB12/03/30038), Instituto de Salud Carlos III (ISCIII), Madrid 28029, Spain

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[* ]Correspondence: caguiler@ 123456ugr.es ; Tel.: +34-958-241-000 (ext. 20314)

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Publisher ID: ijms-17-01040

DOI: 10.3390/ijms17071040

PMC ID: 4964416

PubMed ID: 27376273

SO-VID: ebbf02a0-d421-4af1-8306-24c69d97b406

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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/).

Cell Models and Their Application for Studying Adipogenic Differentiation in Relation to Obesity: A Review

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Abstract

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Higher order chromatin architecture

Most cited references 145

Molecular Regulation of Adipogenesis and Potential Anti-Adipogenic Bioactive Molecules

β-Aminoisobutyric acid induces browning of white fat and hepatic β-oxidation and is inversely correlated with cardiometabolic risk factors.

Evidence for two types of brown adipose tissue in humans.

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