TGFBI remodels adipose metabolism by regulating the Notch-1 signaling pathway
2
조회
0
다운로드
1
인용
0
참고문헌
초록
Extracellular matrix proteins are associated with metabolically healthy adipose tissue and regulate inflammation, fibrosis, angiogenesis, and subsequent metabolic deterioration. In this study, we demonstrated that transforming growth factor-beta (TGFBI), an extracellular matrix (ECM) component, plays an important role in adipose metabolism and browning during high-fat diet-induced obesity. TGFBI KO mice were resistant to adipose tissue hypertrophy, liver steatosis, and insulin resistance. Furthermore, adipose tissue from TGFBI KO mice contained a large population of CD11b+ and CD206+ M2 macrophages, which possibly control adipokine secretion through paracrine mechanisms. Mechanistically, we showed that inhibiting TGFBI-stimulated release of adipsin by Notch-1-dependent signaling resulted in adipocyte browning. TGFBI was physiologically bound to Notch-1 and stimulated its activation in adipocytes. Our findings revealed a novel protective effect of TGFBI deficiency in obesity that is realized via the activation of the Notch-1 signaling pathway.
Abstract
Extracellular matrix proteins are associated with metabolically healthy adipose tissue and regulate inflammation, fibrosis, angiogenesis, and subsequent metabolic deterioration. In this study, we demonstrated that transforming growth factor-beta (TGFBI), an extracellular matrix (ECM) component, plays an important role in adipose metabolism and browning during high-fat diet-induced obesity. TGFBI KO mice were resistant to adipose tissue hypertrophy, liver steatosis, and insulin resistance. Furthermore, adipose tissue from TGFBI KO mice contained a large population of CD11b+ and CD206+ M2 macrophages, which possibly control adipokine secretion through paracrine mechanisms. Mechanistically, we showed that inhibiting TGFBI-stimulated release of adipsin by Notch-1-dependent signaling resulted in adipocyte browning. TGFBI was physiologically bound to Notch-1 and stimulated its activation in adipocytes. Our findings revealed a novel protective effect of TGFBI deficiency in obesity that is realized via the activation of the Notch-1 signaling pathway.
참고문헌 (50)
- Kaila, B., "Obesity : A Review of Pathogenesis and Management Strategies", Can. J. Gastroenterol, 22, pp.61~68 (2008)
- Peirson, L., "Treatment for overweight and obesity in adult populations : a systematic review and meta-analysis", CMAJ Open, 2, pp.E306~E317 (2014)
- Han, T. S., "A clinical perspective of obesity, metabolic syndrome and cardiovascular disease", JRSM Cardiovasc. Dis, 5, pp.204800401663337~ (2016)
- Guilherme, A., "Adipocyte dysfunctions linking obesity to insulin resistance and type 2 diabetes", Nat. Rev. Mol. Cell Biol, 9, pp.367~377 (2008)
- Scherer, P. E., "Adipose Tissue", Diabetes, 55, pp.1537~1545 (2006)
- Shabalina, I. G., "UCP1 in Brite", Beige Adipose Tissue Mitochondria Is Functionally Thermogenic, 2013, pp.5, 1196~1203
- Wu, J., "Beige Adipocytes Are a Distinct Type of Thermogenic Fat Cell in Mouse and Human", Cell, 150, pp.366~376 (2012)
- Vaicik, M. K., "Laminin α4 Deficient Mice Exhibit Decreased Capacity for Adipose Tissue Expansion and Weight Gain", PLoS One, 9, pp.e109854~ (2014)
- Sun, K., "Adipose tissue remodeling and obesity", J. Clin. Invest, 121, pp.2094~2101 (2011)
- Lee, M. H., "ECM microenvironment unlocks brown adipogenic potential of adult human bone marrow-derived MSCs", Sci. Rep, 6, pp.21173~ (2016)
- Lee, S. G., "Endothelial angiogenic activity and adipose angiogenesis is controlled by extracellular matrix protein TGFBI", Sci. Rep, 11, pp.9644~ (2021)
- Gealekman, O., "Depot-Specific Differences and Insufficient Subcutaneous Adipose Tissue Angiogenesis in Human Obesity", Circulation, 123, pp.186~194 (2011)
- Zafar, M. I., "Association between the expression of vascular endothelial growth factors and metabolic syndrome or its components : a systematic review and meta-analysis", Diabetol. Metab. Syndr, 10, pp.62~ (2018)
- Nijhawans, P., "Angiogenesis in obesity", Biomed. Pharmacother, 126, pp.110103~ (2020)
- Yamaguchi, K., "Notch1 haploinsufficiency in mice accelerates adipogenesis", Sci. Rep, 11, pp.16761~ (2021)
- Garcés, C., "Notch-1 Controls the Expression of Fatty Acid-activated Transcription Factors and Is Required for Adipogenesis", J. Biol. Chem, 272, pp.29729~29734 (1997)
- Bae, J. -S., "Transforming Growth Factor β–induced Protein Promotes Severe Vascular Inflammatory Responses", Am. J. Respir. Crit. Care Med, 189, pp.779~786 (2014)
- Kim, J. -E., "A TGF-Beta-inducible cell adhesion molecule, Big-h3, is downregulated in melorheostosis and involved in osteogenesis", J. Cell. Biochem, 77, pp.169~178 (2000)
- Soleimani, M., "A protocol for isolation and culture of mesenchymal stem cells from mouse bone marrow", Nat. Protoc, 4, pp.102~106 (2009)
- Toda, G., "Preparation and culture of bone marrow-derived macrophages from mice for functional analysis", STAR Protoc, 2, pp.100246~ (2021)
- Kim, J. S., "Eupatilin inhibits adipogenesis through suppression of PPARγactivity in 3T3-L1 cells", Biomed. Pharmacother, 103, pp.135~139 (2018)
- Lee, S. G., "Hispidulin inhibits adipogenesis in 3T3-L1 adipocytes through PPARγ pathway", Chem. Biol. Interact, 293, pp.89~93 (2018)
- Williams, A. S., "Integrin α1-null Mice Exhibit Improved Fatty Liver When Fed a High Fat Diet Despite Severe Hepatic Insulin Resistance", J. Biol. Chem, 290, pp.6546~6557 (2015)
- Bonner, J. S., "Relaxin Treatment Reverses Insulin Resistance in Mice Fed a High-Fat Diet", Diabetes, 62, pp.3251~3260 (2013)
- Taylor, E. B., "The complex role of adipokines in obesity, inflammation, and autoimmunity", Clin. Sci, 135, pp.731~752 (2021)
- Lo, J. C., "Adipsin Is an Adipokine that Improves β", Cell Funct. Diabetes Cell, 158, pp.41~53 (2014)
- Li, Y., "Fat-Produced Adipsin Regulates Inflammatory Arthritis", Cell Rep, 27, pp.2809~2816 (2019)
- Searfoss, G. H., "Adipsin, a Biomarker of Gastrointestinal Toxicity Mediated by a Functional γ-Secretase Inhibitor", J. Biol. Chem, 278, pp.46107~46116 (2003)
- Bi, P., "Inhibition of Notch signaling promotes browning of white adipose tissue and ameliorates obesity", Nat. Med, 20, pp.911~918 (2014)
- Koh, K. H., "Nonimmune cell–derived ICOS ligand functions as a renoprotective αvβ3 integrin–selective antagonist", J. Clin. Invest, 129, pp.1713~1726 (2019)
- Spencer, M., "Adipose Tissue Extracellular Matrix and Vascular Abnormalities in Obesity and Insulin Resistance", J. Clin. Endocrinol. Metab, 96, pp.E1990~E1998 (2011)
- Ruiz-Ojeda, F. J., "Extracellular Matrix Remodeling of Adipose Tissue in Obesity and Metabolic Diseases", Int. J. Mol. Sci, 20, pp.4888~ (2019)
- Ozawa, D., "TGFBI Expression in Cancer Stromal Cells is Associated with Poor Prognosis and Hematogenous Recurrence in Esophageal Squamous Cell Carcinoma", Ann. Surg. Oncol, 23, pp.282~289 (2016)
- Betts-Obregon, B. S., "TGFβ induces BIGH3 expression and human retinal pericyte apoptosis : a novel pathway of diabetic retinopathy", Eye, 30, pp.1639~1647 (2016)
- Park, K. S., "Genetic polymorphisms in the transforming growth factor betainduced gene associated with BMI", Hum. Mutat, 25, pp.322~322 (2005)
- Yu, H., "Targeted Disruption of TGFBI in Mice Reveals Its Role in Regulating Bone Mass and Bone Size through Periosteal Bone Formation", Calcif. Tissue Int, 91, pp.81~87 (2012)
- Paulo, E., "Towards a Better Understanding of Beige Adipocyte Plasticity", Cells, 8, pp.1552~ (2019)
- Lecker, L. S. M., "TGFBI Production by Macrophages Contributes to an Immunosuppressive Microenvironment in Ovarian Cancer", Cancer Res, 81, pp.5706~5719 (2021)
- Steitz, A. M., "Tumor-associated macrophages promote ovarian cancer cell migration by secreting transforming growth factor beta induced(TGFBI)and tenascin C", Cell Death Dis, 11, pp.249~ (2020)
- Hirata, K., "Role of leukotriene B4 receptor signaling in human preadipocyte differentiation", Biochem. Biophys. Res. Commun, 429, pp.197~203 (2012)
- Fu, L. -Q., "The roles of tumor-associated macrophages in tumor angiogenesis and metastasis", Cell. Immunol, 353, pp.104119~ (2020)
- Dace, D. S., "Interleukin-10 Promotes Pathological Angiogenesis by Regulating Macrophage Response to Hypoxia during Development", PLoS One, 3, pp.e3381~ (2008)
- Seki, T., "Ablation of endothelial VEGFR1 improves metabolic dysfunction by inducing adipose tissue browning", J. Exp. Med, 215, pp.611~626 (2018)
- Omran, F., "Inflammatory Signaling and Brown Fat Activity", Front. Endocrinol, 11, pp.156~ (2020)
- Sung, H. -K., "Adipose Vascular Endothelial Growth Factor Regulates Metabolic Homeostasis through Angiogenesis", Cell Metab, 17, pp.61~72 (2013)
- Wolf, Y., "Brown-adipose-tissue macrophages control tissue innervation and homeostatic energy expenditure", Nat. Immunol, 18, pp.665~674 (2017)
- Kotzbeck, P., "Brown adipose tissue whitening leads to brown adipocyte death and adipose tissue inflammation", J. Lipid Res, 59, pp.784~794 (2018)
- Keuper, M., "On the role of macrophages in the control of adipocyte energy metabolism", Endocr. Connect, 8, pp.R105~R121 (2019)
- Li, D., "The Notch ligand Jagged1 as a target for anti-tumor therapy", Front. Oncol, 4, pp.254~ (2014)
- Shan, T., "Roles of Notch Signaling in Adipocyte Progenitor Cells and Mature Adipocytes", J. Cell. Physiol, 232, pp.1258~1261 (2017)
