The Extracellular Matrix Protein MAGP1 Is a Key Regulator of Adipose Tissue Remodeling During Obesity

Levin, Malin; Borén, Jan

doi:10.2337/db14-0331

Cited by 5 publications

(5 citation statements)

References 14 publications

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“…In accordance with data revealing the crucial role of ECM in AT physiology [37], we demonstrated that atECM can alter differentiation of ASCs. Previous reports showing that atECM coating stimulates osteogenesis of BM-MSCs [38] and that atECM-based scaffold stimulates chondrogenic differentiation of ASCs [39] are partly in contrast with our results as we showed that atECM inhibit osteogenic without change of chondrogenic capacity in ASCs.…”

Section: Discussionsupporting

confidence: 91%

Adipoinductive effect of extracellular matrix involves cytoskeleton changes and SIRT1 activity in adipose tissue stem/stromal cells

Trivanović

Drvenica

Кукољ

et al. 2018

Artificial Cells, Nanomedicine, and Biotechnology

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Adipose tissue (AT) homeostasis and expansion are dependent on complex crosstalk between resident adipose stromal/stem cells (ASCs) and AT extracellular matrix (ECM). Although adipose tissue ECM (atECM) is one of the key players in the stem cell niche, data on bidirectional interaction of ASCs and atECM are still scarce. Here, we investigated how atECM guides ASCs' differentiation. atECM altered shape and cytoskeleton organization of ASCs without changing their proliferation, β-galactosidase activity and adhesion. Cytoskeleton modifications occurred due to fostered parallel organization of F-actin and elevated expression of Vimentin in ASCs. After seven-day cultivation, atECM impaired osteogenesis of ASCs, simultaneously decreasing expression of Runx2. In addition, atECM accelerated early adipogenesis concomitantly with altered Vimentin organization in ASCs, slightly increasing PPARγ, while elevated Adiponectin and Vimentin mRNA expression. Early adipogenesis triggered by atECM was followed by upregulated mitochondrial activity and Sirtuin 1 (SIRT1) expression in ASCs. Proadipogenic events induced by atECM were mediated by SIRT1, indicating the supportive role of atECM in adipogenesis-related metabolic state of ASCs. These results provide a closer look at the effects of atECM on ASC physiology and may support the advancement of engineering design in soft tissue reconstruction and fundamental research of AT.

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Section: Discussionsupporting

confidence: 91%

Adipoinductive effect of extracellular matrix involves cytoskeleton changes and SIRT1 activity in adipose tissue stem/stromal cells

Trivanović

Drvenica

Кукољ

et al. 2018

Artificial Cells, Nanomedicine, and Biotechnology

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“…Several authors have shown the relationship between ECM remodeling and metabolic disturbances in obesity. Previous studies have demonstrated that several components of ECM are increased in individuals with obesity . In this sense, collagen VI‐null ob/ob mice showed better metabolic control when fed on HF diet allowing a better expansion of adipocytes.…”

Section: Discussionmentioning

confidence: 91%

Vitamin E reduces adipose tissue fibrosis, inflammation, and oxidative stress and improves metabolic profile in obesity

Alcalá

Sánchez-Vera

Sevillano

et al. 2015

Obesity

109

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Objective: To test whether enhancing the capability of adipose tissue to store lipids using antioxidant supplementation may prevent the lipotoxic effects and improve the metabolic profile of long-term obesity. Methods: C57BL/6J mice were randomized into three experimental groups for 28 weeks: control group (n 5 10) fed chow diet (10% kcal from fat), obese group (O, n 5 12) fed high-fat (HF) diet (45% kcal from fat), and obese group fed HF diet and supplemented twice a week with 150 mg of a-tocopherol (vitamin E) by oral gavage (OE, n 5 12). Results: HF diet resulted in an obese phenotype with a marked insulin resistance, hypertriglyceridemia, and hepatic steatosis in O mice. Histological analysis of obese visceral adipose tissue (VAT) revealed smaller adipocytes surrounded by a fibrotic extracellular matrix and an increased macrophage infiltration, with the consequent release of proinflammatory cytokines. Vitamin E supplementation decreased oxidative stress and reduced collagen deposition in the VAT of OE mice, allowing a further expansion of the adipocytes and increasing the storage capability. As a result, circulating cytokines were reduced and hepatic steasosis, hypertriglyceridemia, and insulin sensitivity were improved. Conclusions: Our results suggest that oxidative stress is implicated in extracellular matrix remodeling and may play an important role in metabolic regulation.

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“…MAGP-1 has been linked with complex phenotypes in multiple organ systems [18][19][20][21]. In this sense, Mfap2-deficient mice exhibited a phenotype of increased adiposity and impaired thermoregulation consistent with predisposition to metabolic dysfunction and increased TGF-β activity [22][23][24]. The treatment of Mfap2 knockout mice with antibodies neutralizing TGF-β prevented increased adiposity, proposing its role in the regulation of TGF-β in obesity and its associated comorbidities [17].…”

Section: Introductionmentioning

confidence: 99%

Decreased Levels of Microfibril-Associated Glycoprotein (MAGP)-1 in Patients with Colon Cancer and Obesity Are Associated with Changes in Extracellular Matrix Remodelling

Segura

Ahechu

Gómez-Ambrosi

et al. 2021

IJMS

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Objective: The protein microfibril-associated glycoprotein (MAGP)-1 constitutes a crucial extracellular matrix protein. We aimed to determine its impact on visceral adipose tissue (VAT) remodelling during obesity-associated colon cancer (CC). Methods: Samples obtained from 79 subjects (29 normoponderal (NP) (17 with CC) and 50 patients with obesity (OB) (19 with CC)) were used in the study. Circulating concentrations of MAGP-1 and its gene expression levels (MFAP2) in VAT were analysed. The impact of inflammation-related factors and adipocyte-conditioned media (ACM) on MFAP2 mRNA levels in colon adenocarcinoma HT-29 cells were further analysed. The effects of MAGP-1 in the expression of genes involved in the extracellular matrix (ECM) remodelling and tumorigenesis in HT-29 cells was also explored. Results: Obesity (p < 0.01) and CC (p < 0.001) significantly decreased MFAP2 gene expression levels in VAT whereas an opposite trend in TGFB1 mRNA levels was observed. Increased mRNA levels of MFAP2 after the stimulation of HT-29 cells with lipopolysaccharide (LPS) (p < 0.01) and interleukin (IL)-4 (p < 0.01) together with a downregulation (p < 0.05) after hypoxia mimicked by CoCl2 treatment was observed. MAGP-1 treatment significantly enhanced the mRNA levels of the ECM-remodelling genes collagen type 6 α3 chain (COL6A3) (p < 0.05), decorin (DCN) (p < 0.01), osteopontin (SPP1) (p < 0.05) and TGFB1 (p < 0.05). Furthermore, MAGP-1 significantly reduced (p < 0.05) the gene expression levels of prostaglandin-endoperoxide synthase 2 (COX2/PTGS2), a key gene controlling cell proliferation, growth and adhesion in CC. Interestingly, a significant decrease (p < 0.01) in the mRNA levels of MFAP2 in HT-29 cells preincubated with ACM from volunteers with obesity compared with control media was observed. Conclusion: The decreased levels of MAGP-1 in patients with obesity and CC together with its capacity to modulate key genes involved in ECM remodelling and tumorigenesis suggest MAGP-1 as a link between AT excess and obesity-associated CC development.

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The Extracellular Matrix Protein MAGP1 Is a Key Regulator of Adipose Tissue Remodeling During Obesity

Cited by 5 publications

References 14 publications

Adipoinductive effect of extracellular matrix involves cytoskeleton changes and SIRT1 activity in adipose tissue stem/stromal cells

Adipoinductive effect of extracellular matrix involves cytoskeleton changes and SIRT1 activity in adipose tissue stem/stromal cells

Vitamin E reduces adipose tissue fibrosis, inflammation, and oxidative stress and improves metabolic profile in obesity

Decreased Levels of Microfibril-Associated Glycoprotein (MAGP)-1 in Patients with Colon Cancer and Obesity Are Associated with Changes in Extracellular Matrix Remodelling

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