Deciphering the cellular interplays underlying obesity-induced adipose tissue fibrosis

Marcelin, Geneviève; Silveira, Ana Letícia Malheiros; Martins, Laís Bhering; Ferreira, Adaliene Versiani Matos; Clément, Karine

doi:10.1172/jci129192

Cited by 196 publications

(171 citation statements)

References 139 publications

(158 reference statements)

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“…Collagen VI is secreted by adipocytes, and collagen VI secretion increases during adipose differentiation ( 27 ). Although adipocytes can secrete ECM proteins directly, other factors such as TGFβ can activate other cells such as myofibroblasts or macrophages to synthesize ECM proteins ( 28 ). In the Seo et al ( 18 ) study, adipose stromal cells were isolated and those isolated from obese tissue were found to have myofibroblast-like characteristics, as indicated by α-SMA (smooth muscle actin) staining.…”

Section: Discussionmentioning

confidence: 99%

Decellularized extracellular matrix scaffolds identify full-length collagen VI as a driver of breast cancer cell invasion in obesity and metastasis

et al. 2020

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The extracellular matrix (ECM), a major component of the tumor microenvironment, promotes local invasion to drive metastasis. Here, we describe a method to study whole-tissue ECM effects from disease states associated with metastasis on tumor cell phenotypes and identify the individual ECM proteins and signaling pathways that are driving these effects. We show that decellularized ECM from tumor-bearing and obese mammary glands drives TNBC cell invasion. Proteomics of the ECM from the obese mammary gland led us to identify full-length collagen VI as a novel driver of TNBC cell invasion whose abundance in tumor stroma increases with body mass index in human TNBC patients. Last, we describe the mechanism by which collagen VI contributes to TNBC cell invasion via NG2-EGFR cross-talk and MAPK signaling. Overall, these studies demonstrate the value of decellularized ECM scaffolds obtained from tissues to identify novel functions of the ECM.

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Section: Discussionmentioning

confidence: 99%

Decellularized extracellular matrix scaffolds identify full-length collagen VI as a driver of breast cancer cell invasion in obesity and metastasis

et al. 2020

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“…There are two morphologically and functionally distinct AT types: white adipose tissue (WAT) and brown adipose tissue (BAT) [8]. WAT accumulates fat during nutrient abundance and releases fatty acids during fasting.…”

Section: Introductionmentioning

confidence: 99%

Non-invasive investigation of adipose tissue by time domain diffuse optical spectroscopy

Lanka

Segala

Farina

et al. 2020

Biomed. Opt. Express

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The human abdominal region is very heterogeneous and stratified with subcutaneous adipose tissue (SAT) being one of the primary layers. Monitoring this tissue is crucial for diagnostic purposes and to estimate the effects of interventions like caloric restriction or bariatric surgery. However, the layered nature of the abdomen poses a major problem in monitoring the SAT in a non-invasive way by diffuse optics. In this work, we examine the possibility of using multi-distance broadband time domain diffuse optical spectroscopy to assess the human abdomen non-invasively. Broadband absorption and reduced scattering spectra from 600 to 1100 nm were acquired at 1, 2 and 3 cm source-detector distances on ten healthy adult male volunteers, and then analyzed using a homogeneous model as an initial step to understand the origin of the detected signal and how tissue should be modeled to derive quantitative information. The results exhibit a clear influence of the layered nature on the estimated optical properties. Clearly, the underlying muscle makes a relevant contribution in the spectra measured at the largest source-detector distance for thinner subjects related to blood and water absorption. More unexpectedly, also the thin superficial skin layer yields a direct contamination, leading to higher water content and steeper reduced scattering spectra at the shortest distance, as confirmed also by simulations. In conclusion, provided that data analysis properly accounts for the complex tissue structure, diffuse optics may offer great potential for the continuous non-invasive monitoring of abdominal fat.

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“…besity is a serious health problem as it is a strong risk factor for the development of type-2 diabetes, cardiovascular diseases, and cancer [1][2][3][4][5][6] . In obesity, the adipose tissue undergoes dynamic remodeling including an increase in size (hypertrophy) and number of adipocytes (hyperplasia), an infiltration by immune cells, and the development of tissue fibrosis [7][8][9][10][11][12] . In the obese adipose tissue, adipocytes are exposed to different forms of stress.…”

mentioning

confidence: 99%

YAP and TAZ protect against white adipocyte cell death during obesity

Wang

Shi

et al. 2020

Nat Commun

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The expansion of the white adipose tissue (WAT) in obesity goes along with increased mechanical, metabolic and inflammatory stress. How adipocytes resist this stress is still poorly understood. Both in human and mouse adipocytes, the transcriptional co-activators YAP/TAZ and YAP/TAZ target genes become activated during obesity. When fed a high-fat diet (HFD), mice lacking YAP/TAZ in white adipocytes develop severe lipodystrophy with adipocyte cell death. The pro-apoptotic factor BIM, which is downregulated in adipocytes of obese mice and humans, is strongly upregulated in YAP/TAZ-deficient adipocytes under HFD, and suppression of BIM expression reduces adipocyte apoptosis. In differentiated adipocytes, TNFα and IL-1β promote YAP/TAZ nuclear translocation via activation of RhoA-mediated actomyosin contractility and increase YAP/TAZ-mediated transcriptional regulation by activation of c-Jun N-terminal kinase (JNK) and AP-1. Our data indicate that the YAP/TAZ signaling pathway may be a target to control adipocyte cell death and compensatory adipogenesis during obesity.

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Deciphering the cellular interplays underlying obesity-induced adipose tissue fibrosis

Cited by 196 publications

References 139 publications

Decellularized extracellular matrix scaffolds identify full-length collagen VI as a driver of breast cancer cell invasion in obesity and metastasis

Decellularized extracellular matrix scaffolds identify full-length collagen VI as a driver of breast cancer cell invasion in obesity and metastasis

Non-invasive investigation of adipose tissue by time domain diffuse optical spectroscopy

YAP and TAZ protect against white adipocyte cell death during obesity

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