Extracellular Matrix Remodeling of Adipose Tissue in Obesity and Metabolic Diseases

Ruiz‐Ojeda, Francisco Javier; Méndez-Gutiérrez, Andrea; Aguilera, Concepción M.; Plaza‐Díaz, Julio

doi:10.3390/ijms20194888

Cited by 167 publications

(159 citation statements)

References 225 publications

(271 reference statements)

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“…Adipocytes are surrounded by an extracellular matrix, which serves as mechanical support and is mainly composed of collagens, fibronectin, and elastin [122]. Cells producing ECM in adipose tissue are not clearly indentified; however, it is recognized that collagens are mostly produced by adipocytes, but also by endothelial cells and adipose stem cells in normal conditions [123]. The molecular signature of subcutaneous white adipose tissue with Egr1 deletion identifies a downregulation of ECM genes, including Col1a1, Col1a2, Col3a1, Col5a1, Col5a2, Col14a1, Fn1, Dcn, and Post (Periostin) [77].…”

Section: Egr1 Regulates Extracellular Matrix Production In Adipose Timentioning

confidence: 99%

EGR1 Transcription Factor is a Multifaceted Regulator of Matrix Production in Tendons and Other Connective Tissues

Havis

Duprez

2020

IJMS

338

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Although the transcription factor EGR1 is known as NGF1-A, TIS8, Krox24, zif/268, and ZENK, it still has many fewer names than biological functions. A broad range of signals induce Egr1 gene expression via numerous regulatory elements identified in the Egr1 promoter. EGR1 is also the target of multiple post-translational modifications, which modulate EGR1 transcriptional activity. Despite the myriad regulators of Egr1 transcription and translation, and the numerous biological functions identified for EGR1, the literature reveals a recurring theme of EGR1 transcriptional activity in connective tissues, regulating genes related to the extracellular matrix. Egr1 is expressed in different connective tissues, such as tendon (a dense connective tissue), cartilage and bone (supportive connective tissues), and adipose tissue (a loose connective tissue). Egr1 is involved in the development, homeostasis, and healing processes of these tissues, mainly via the regulation of extracellular matrix. In addition, Egr1 is often involved in the abnormal production of extracellular matrix in fibrotic conditions, and Egr1 deletion is seen as a target for therapeutic strategies to fight fibrotic conditions. This generic EGR1 function in matrix regulation has little-explored implications but is potentially important for tendon repair.

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Section: Egr1 Regulates Extracellular Matrix Production In Adipose Timentioning

confidence: 99%

EGR1 Transcription Factor is a Multifaceted Regulator of Matrix Production in Tendons and Other Connective Tissues

Havis

Duprez

2020

IJMS

338

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“…ECM components in adipose tissue consist mainly of collagens, fibronectin, and laminin [ 46 ]. Additionally, several components, such as TSP-1, MMPs, tissue inhibitors of MMPs (TIMPs), a disintegrin and metalloproteinase (ADAMs), ADAM with thrombospondin motifs (ADAMTS), osteopontin, hyaluronan, and elastin, function as the modulators of ECM remodeling and adipose tissue expansion [ 47 , 48 ]. This process also helps to form new blood vessels that are important for healthy adipose tissue expansion and allows hypoxia that induces chronic low-grade inflammation and fibrosis [ 49 ].…”

Section: Angiogenesis and Adipose Tissue Growthmentioning

confidence: 99%

Regulation of Obesity by Antiangiogenic Herbal Medicines

Shin

Yoon

2020

Molecules

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Obesity is the result of an energy imbalance caused by an increased ratio of caloric intake to energy expenditure. In conjunction with obesity, related metabolic disorders, such as dyslipidemia, atherosclerosis, and type 2 diabetes, have become global health problems. Obesity progression is thought to be associated with angiogenesis and extracellular matrix (ECM) remodeling. Angiogenesis occurs in growing adult adipose tissues, which are similar to neoplastic tissues. Adipose tissue is highly vascularized, and each adipocyte is nourished by an extensive capillary network. Adipocytes produce proangiogenic factors, such as vascular endothelial growth factor A and fibroblast growth factor 2, which promote neovascularization within the adipose tissue. Furthermore, matrix metalloproteinases (MMPs), including MMP-2 and MMP-9, play important roles in adipose tissue development and microvessel maturation by modifying the ECM. Thus, modulation of angiogenesis and MMP activity provides a promising therapeutic approach for controlling human obesity and its related disorders. Over the past decade, there has been a great increase in the use of alternative treatments, such as herbal remedies, for these diseases. This review will focus on the role of angiogenesis in adipose tissue growth and the regulation of obesity by antiangiogenic herbal medicines.

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“…At the cellular level, obesity is de ned as accelerated AT expansion and remodeling that induces either AT hypertrophy (i.e., adipocyte expansion due to excessive fat storage) or hyperplasia (i.e., increased adipogenesis from preadipocytes) through ECM remodeling and angiogenesis [7,8]. Various ECM proteins, including MMP2, ADAM, TIMP, CTSK, and CTSS, are altered in obese AT [9][10][11][12]. Angiogenic genes such as VEGF and ANGPT2 are upregulated in response to activated HIF1A (i.e., hypoxia-related transcription factor) [13,14].…”

Section: Introductionmentioning

confidence: 99%

Putative positive role of inflammatory genes in fat deposition supported by altered gene expression in purified human adipocytes and preadipocytes from lean and obese adipose tissues

Lee

Choi

Koh

et al. 2020

Preprint

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BackgroundObesity is a chronic low-grade inflammatory disease that is generally characterized by enhanced inflammation in obese adipose tissue (AT). Here, we investigated alterations in gene expression between lean and obese conditions using mRNA-Seq data derived from human purified adipocytes (ACs) and preadipocytes (preACs). ResultsWe defined four classes of differentially expressed genes (DEGs) by comparing gene expression between 1) lean and obese ACs, 2) lean and obese preACs, 3) lean ACs and lean preACs, and 4) obese ACs and obese preACs. Based on an analysis of comparison 1, numerous canonical obesity-related genes, particularly inflammatory genes including IL6, TNF- and IL-1, i.e., the genes that are expected to be upregulated in obesity conditions, were found to be expressed at significantly lower levels in obese ACs than in lean ACs. In contrast, some inflammatory genes were found to be expressed at higher levels in obese preACs than lean preACs in the analysis of comparison 2. These two results indicate that (1) up-/downregulation of genes in ACs and preACs is inversely controlled during the fat deposition process and (2) preACs rather than ACs have increased inflammatory response genes in comparisons of lean and obese conditions for each of these cell types. Analysis of comparisons 3 and 4 showed that inflammatory gene classes were expressed at higher levels in differentiated ACs than undifferentiated preACs under both lean and obese conditions; however, the degree of upregulation was greater for lean than for obese conditions.ConclusionsTaken together, our analyses may suggest that lean fat differentiation involves even greater enhancement of inflammatory responses than does obese fat differentiation.

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Extracellular Matrix Remodeling of Adipose Tissue in Obesity and Metabolic Diseases

Cited by 167 publications

References 225 publications

EGR1 Transcription Factor is a Multifaceted Regulator of Matrix Production in Tendons and Other Connective Tissues

EGR1 Transcription Factor is a Multifaceted Regulator of Matrix Production in Tendons and Other Connective Tissues

Regulation of Obesity by Antiangiogenic Herbal Medicines

Putative positive role of inflammatory genes in fat deposition supported by altered gene expression in purified human adipocytes and preadipocytes from lean and obese adipose tissues

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