Fibrosis and Adipose Tissue Dysfunction

Sun, Kai; Tordjman, Joan; Clément, Karine; Scherer, Philipp E.

doi:10.1016/j.cmet.2013.06.016

Cited by 720 publications

(685 citation statements)

References 59 publications

Supporting

Mentioning

647

Contrasting

Unclassified

Order By: Relevance

“…Similar alterations have also been described in adipose tissue (Sun, Tordjman, Clement, & Scherer, 2013). Interestingly, undifferentiated adipogenic progenitor cells are a major source of ECM components in AT (Kubo, Kaidzu, Nakajima, Takenouchi, & Nakamura, 2000; Nakajima, Yamaguchi, Ozutsumi, & Aso, 1998), suggesting that alterations in progenitor cell function with increased age may contribute to homeostatic changes in the tissue matrix (Tchkonia et al, 2010).…”

Section: Discussionsupporting

confidence: 76%

Loss of periostin occurs in aging adipose tissue of mice and its genetic ablation impairs adipose tissue lipid metabolism

et al. 2018

View full text Add to dashboard Cite

Remodeling of the extracellular matrix is a key component of the metabolic adaptations of adipose tissue in response to dietary and physiological challenges. Disruption of its integrity is a well‐known aspect of adipose tissue dysfunction, for instance, during aging and obesity. Adipocyte regeneration from a tissue‐resident pool of mesenchymal stem cells is part of normal tissue homeostasis. Among the pathophysiological consequences of adipogenic stem cell aging, characteristic changes in the secretory phenotype, which includes matrix‐modifying proteins, have been described. Here, we show that the expression of the matricellular protein periostin, a component of the extracellular matrix produced and secreted by adipose tissue‐resident interstitial cells, is markedly decreased in aged brown and white adipose tissue depots. Using a mouse model, we demonstrate that the adaptation of adipose tissue to adrenergic stimulation and high‐fat diet feeding is impaired in animals with systemic ablation of the gene encoding for periostin. Our data suggest that loss of periostin attenuates lipid metabolism in adipose tissue, thus recapitulating one aspect of age‐related metabolic dysfunction. In human white adipose tissue, periostin expression showed an unexpected positive correlation with age of study participants. This correlation, however, was no longer evident after adjusting for BMI or plasma lipid and liver function biomarkers. These findings taken together suggest that age‐related alterations of the adipose tissue extracellular matrix may contribute to the development of metabolic disease by negatively affecting nutrient homeostasis.

show abstract

Section: Discussionsupporting

confidence: 76%

Loss of periostin occurs in aging adipose tissue of mice and its genetic ablation impairs adipose tissue lipid metabolism

et al. 2018

View full text Add to dashboard Cite

show abstract

“…The excessive accumulation of ECM components (tenascins, collagens, or fibrin, among others) damages AT homeostasis and reduces tissue plasticity leading to adipocyte dysfunction, ectopic lipid deposition in peripheral tissues, tissue inflammation, and metabolic disorders 15,16 . One important feature of AT expansion and the subsequent accumulation of ECM components is AT hypoxia, which ultimately leads to fibrosis 17 .…”

Section: Introductionmentioning

confidence: 99%

“…In the context of obesity, the AT ECM undergoes considerable pathological and dynamic remodeling associated with fibrotic deposition, infiltration of proinflammatory macrophages, and increased angiogenesis 14,15 . The excessive accumulation of ECM components (tenascins, collagens, or fibrin, among others) damages AT homeostasis and reduces tissue plasticity leading to adipocyte dysfunction, ectopic lipid deposition in peripheral tissues, tissue inflammation, and metabolic disorders 15,16 .…”

Section: Introductionmentioning

confidence: 99%

Targeted disruption of the iNOS gene improves adipose tissue inflammation and fibrosis in leptin-deficient ob/ob mice: role of tenascin C

et al. 2018

View full text Add to dashboard Cite

Background/Objectives: Obesity is related to a dynamic extracellular matrix (ECM) remodeling, which involves the synthesis and degradation of different proteins, such as tenascin C (TNC) in the adipose tissue (AT). Given the functional relationship between leptin and inducible nitric oxide synthase (iNOS), our aim was to analyze the impact of the absence of the iNOS gene in AT inflammation and ECM remodeling in ob/ob mice. Subjects/Methods: The expression of genes involved in inflammation and ECM remodeling was evaluated in 10-week-old male double knockout (DBKO) mice simultaneously lacking the ob and iNOS genes as well as in ob/ob mice classified into three groups [control, leptin-treated (1 mg kg −1 day −1 ) and pair-fed]. Results: Leptin deficiency increased inflammation and fibrosis in AT. As expected, leptin treatment improved the obesity phenotype. iNOS deficiency in ob/ob mice improved insulin sensitivity, AT inflammation, and ECM remodeling, as evidenced by lower AT macrophage infiltration and collagen deposition, a downregulation of proinflammatory and profibrogenic genes Tnf, Emr1, Hif1a, Col6a1, Col6a3, and Tnc, as well as lower circulating TNC levels. Interestingly, leptin upregulated TNC expression and release in 3T3-L1 adipocytes, and iNOS knockdown in 3T3-L1 fat cells produced a significant decrease in basal and leptin-induced Tnc expression. Conclusions: Ablation of iNOS in leptin-deficient mice improved AT inflammation and ECM remodeling-related genes, attenuating fibrosis, and metabolic dysfunction. The activation of iNOS by leptin is necessary for the synthesis and secretion of TNC in adipocytes, suggesting an important role of this alarmin in the development of AT inflammation and fibrosis.

show abstract

“…In obese patients, the expression and secretion of ECM components are highly upregulated, suggesting that the altered microenvironment may play an important role in obesity and metabolic disease. 15,22 Thus, it's becoming clear that the ECM, which orchestrates mechanical signals, cell morphology and cytoskeleton dynamics, can affect the fate of white and beige adipocytes.…”

Section: Extracellular Matrixmentioning

confidence: 99%

Morphogenetics in brown, beige and white fat development

Lin

Farmer

2016

Adipocyte

View full text Add to dashboard Cite

Brown and beige (or brite) fat cells are capable of evoking non-shivering thermogenesis in response to cold and b-adrenergic stimulation. By metabolizing lipids and carbohydrate via uncoupled respiration these cells directly convert energy to heat. The discovery of brown and brown-like adipocytes in adult humans has reinvigorated interest in stimulating brown and beige fat development to combat the obesity epidemic. This review focuses on the role that cytoskeleton dynamics play in the regulation of adipocyte biology, specifically beige and brown fat development and how newly discovered adipogenic morphogens affect these processes.

show abstract

Fibrosis and Adipose Tissue Dysfunction

Cited by 720 publications

References 59 publications

Loss of periostin occurs in aging adipose tissue of mice and its genetic ablation impairs adipose tissue lipid metabolism

Loss of periostin occurs in aging adipose tissue of mice and its genetic ablation impairs adipose tissue lipid metabolism

Targeted disruption of the iNOS gene improves adipose tissue inflammation and fibrosis in leptin-deficient ob/ob mice: role of tenascin C

Morphogenetics in brown, beige and white fat development

Contact Info

Product

Resources

About