Insulin resistance and impaired adipogenesis

Gustafson, Birgit; Hedjazifar, Shahram; Gogg, Silvia; Hammarstedt, Ann; Smith, Ulf

doi:10.1016/j.tem.2015.01.006

Cited by 302 publications

(277 citation statements)

References 79 publications

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“…AQP7 is considered the main glycerol channel facilitating glycerol release/uptake in adipocytes (78,117,129,199), but other glycerol channels such as AQP3, AQP5, AQP9, AQP10, and AQP11 also contribute to glycerol transport in fat cells (175,192,193,264). Insulin constitutes an important regulator of adipocyte hypertrophy, but not of hyperplasia, since low levels of insulin receptor are found in preadipocytes (112). Several mechanisms contribute to insulin-induced TG accumulation, including the increase in glucose uptake through the translocation of glucose transporter 4 (GLUT4) from the cytoplasm to the plasma membrane (116), the activation of LPL (75) and the stimulation of glycerol uptake through the upregulation of AQP3, AQP7, and AQP9 (264) in human fat cells (Fig.…”

Section: Biological and Morphological Changes Of White Adipose Tissuementioning

confidence: 99%

Revisiting the adipocyte: a model for integration of cytokine signaling in the regulation of energy metabolism

Rodrı́guez

Ezquerro

Méndez‐Giménez

et al. 2015

American Journal of Physiology-Endocrinology and Metabolism

235

186

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Adipose tissue constitutes an extremely active endocrine organ with a network of signaling pathways enabling the organism to adapt to a wide range of different metabolic challenges, such as starvation, stress, infection, and short periods of gross energy excess. The functional pleiotropism of adipose tissue relies on its ability to synthesize and release a huge variety of hormones, cytokines, complement and growth factors, extracellular matrix proteins, and vasoactive factors, collectively termed adipokines. Obesity is associated with adipose tissue dysfunction leading to the onset of several pathologies including type 2 diabetes, dyslipidemia, nonalcoholic fatty liver, or hypertension, among others. The mechanisms underlying the development of obesity and its associated comorbidities include the hypertrophy and/or hyperplasia of adipocytes, adipose tissue inflammation, impaired extracellular matrix remodeling, and fibrosis together with an altered secretion of adipokines. Recently, the potential role of brown and beige adipose tissue in the protection against obesity has been also recognized. In contrast to white adipocytes, which store energy in the form of fat, brown and beige fat cells display energy-dissipating capacity through the promotion of triacylglycerol clearance, glucose disposal, and generation of heat for thermogenesis. Identification of the morphological and molecular changes in white, beige, and brown adipose tissue during weight gain is of utmost relevance for the identification of pharmacological targets for the treatment of obesity and its associated metabolic diseases. white and brown adipogenesis; fat browning; adipocyte hypertrophy and hyperplasia; adipose tissue inflammation; extracellular matrix remodeling THE ADIPOSE ORGAN REPRESENTS a special loose connective tissue containing adipocytes and several cell types surrounded by capillary and innervation networks (47, 79, 82). Adipocytes comprise ϳ35-70% of adipose mass, and the other cell types found in the stroma-vascular fraction include preadipocytes, mesenchymal stem cells, macrophages and other immune cells, and endothelial and smooth muscle cells, among others (79). The classical functions of adipose tissue are the storage of energy in the form of triacylglycerols (TG) and as thermal insulator. Adipocytes were formerly classified into two main types: white adipocytes, which store energy in the form of fat, and brown adipocytes, which induce thermogenesis (82). The current classification scheme includes a third category of adipocytes, termed beige or brite (brown-in-white) adipocytes, which can be considered inducible brown-like cells with thermogenic properties (340). Since the identification of leptin in 1994 (359), adipose tissue has emerged as an extremely active endocrine organ that secretes a huge variety of hormones, cytokines, growth factors, and vasoactive factors that are collectively termed adipokines (67, 81,235,262). Over the last three decades, overwhelming evidence has proven that adipokines not only influence adipobiol...

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Section: Biological and Morphological Changes Of White Adipose Tissuementioning

confidence: 99%

Revisiting the adipocyte: a model for integration of cytokine signaling in the regulation of energy metabolism

Rodrı́guez

Ezquerro

Méndez‐Giménez

et al. 2015

American Journal of Physiology-Endocrinology and Metabolism

235

186

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“…1,2 The genetic analysis of gene expression by identification of expression quantitative trait loci (eQTLs) in relevant tissues has proven useful to predict candidate genes at GWAS loci and biological pathways that are perturbed in affected individuals. [3][4][5][6] Subcutaneous adipose tissue serves as a buffering system for lipid energy balance, particularly fatty acids, 7,8 and might play a protective role in metabolic and cardiovascular disease risk. 9 Subcutaneous adipose eQTL studies have implicated genes involved in obesity and metabolic traits.…”

Section: Introductionmentioning

confidence: 99%

Genetic Regulation of Adipose Gene Expression and Cardio-Metabolic Traits

Civelek

Pan

et al. 2017

The American Journal of Human Genetics

154

211

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Subcutaneous adipose tissue stores excess lipids and maintains energy balance. We performed expression quantitative trait locus (eQTL) analyses by using abdominal subcutaneous adipose tissue of 770 extensively phenotyped participants of the METSIM study. We identified cis-eQTLs for 12,400 genes at a 1% false-discovery rate. Among an approximately 680 known genome-wide association study (GWAS) loci for cardio-metabolic traits, we identified 140 coincident cis-eQTLs at 109 GWAS loci, including 93 eQTLs not previously described. At 49 of these 140 eQTLs, gene expression was nominally associated (p < 0.05) with levels of the GWAS trait. The size of our dataset enabled identification of five loci associated (p < 5 3 10 À8 ) with at least five genes located >5 Mb away. These trans-eQTL signals confirmed and extended the previously reported KLF14-mediated network to 55 target genes, validated the CIITA regulation of class II MHC genes, and identified ZNF800 as a candidate master regulator. Finally, we observed similar expression-clinical trait correlations of genes associated with GWAS loci in both humans and a panel of genetically diverse mice. These results provide candidate genes for further investigation of their potential roles in adipose biology and in regulating cardio-metabolic traits.

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“…Adipose tissuederived stem cells (ADSCs) serve as a reservoir and allow the continued renewal of precursor cells that can differentiate into adipocytes (Bowers et al, 2006). However, differentiation of adipocytes is a complex and multi-step process with many factors and signaling pathways involved (Gustafson et al, 2015b). The terminal differentiation of adipocytes has been extensively characterized with the use of hormonal cocktails that typically contains dexamethasone (DEX), insulin, indomethacin and isobutylmethylxanthin (IBMX) (Rosen andSpiegelman, 2014, Wu et al, 2010).…”

Section: Introductionmentioning

confidence: 99%

miR-450a-5p within rat adipose tissue exosome-like vesicles promotes adipogenic differentiation by targeting WISP2

Zhang

Dai

et al. 2017

Journal of Cell Science

103

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Adipose tissue is an active endocrine organ that can secrete a wide number of factors to regulate adipogenesis via paracrine signals. In addition to soluble proteins in adipose tissue, microRNAs (miRNAs) enriched in extracellular vesicles (EVs), such as exosomes or microvesicles, could modulate intercellular communications. In this study, we demonstrated that exosome-like vesicles derived from adipose tissue (Exo-AT) were internalized by adipose tissue-derived stem cells (ADSCs), and that these, in turn, induced adipogenesis. High-throughput sequencing showed that 45 miRNAs were enriched in Exo-AT, and 31.11% of them were associated with adipogenesis, compared with ADSC-derived exosome-like vesicles (Exo-ADSC). miR-450a-5p, one of the most abundant miRNAs in Exo-AT, was a proadipogenic miRNA. Further study demonstrated that miR-450a-5p promoted adipogenesis through repressing expression of WISP2 by targeting its 3′ untranslated region. Additionally, Exo-AT could also downregulate the expression of WISP2, while miR-450a-5p inhibitor reversed this effect. Moreover, inhibition of miR-450a-5p impaired adipogenesis mediated by exosome-like vesicles. In conclusion, Exo-AT mediates adipogenic differentiation through a mechanism involving transfer of miR-450a-5p.

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Insulin resistance and impaired adipogenesis

Cited by 302 publications

References 79 publications

Revisiting the adipocyte: a model for integration of cytokine signaling in the regulation of energy metabolism

Revisiting the adipocyte: a model for integration of cytokine signaling in the regulation of energy metabolism

Genetic Regulation of Adipose Gene Expression and Cardio-Metabolic Traits

miR-450a-5p within rat adipose tissue exosome-like vesicles promotes adipogenic differentiation by targeting WISP2

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