Adipocytes are now recognized as endocrine cells secreting adipocytokines, regulating multiple metabolic pathways. In this study, we addressed secretion of microvesicles by 3T3-L1 adipocytes. We found that MFG-E8, one of the exosomal proteins, was present in the microvesicles and was distributed in the sucrose density fractions with 1.13-1.20 g/ml, which has been reported for exosomes. Several integral, cytosolic, and nuclear proteins such as caveolin-1, c-Src kinase, and heat shock protein 70 were also found to be microvesicle components. Unexpectedly, adiponectin was also substantially distributed in the microvesicle fractions. Furthermore, proteomic analysis of the microvesicles revealed that many other proteins such as extracellular matrix-related proteins were also present. Microvesicles secreted by 3T3-L1 adipocytes exhibited heterogeneity in size and comprised both smaller exosome-like and larger membrane vesicles as revealed by electron microscopy. Milk fat globule-epidermal growth factor 8 (MFG-E8)-associated adiposomes exhibited binding activity toward phosphatidylserine and apoptotic cells. MFG-E8 in the microvesicles was reduced when cultured in the low-glucose medium or cultured in the high-glucose medium with antioxidant N-acetyl cysteine. Insulin and TNF-alpha also up-regulated MFG-E8 in the microvesicles. Moreover, MFG-E8 was strongly up-regulated in the hypertrophic adipose tissue, predominantly in adipocyte fractions, of diet-induced obese C57BL/6 mice, where increased oxidative stress is induced. Thus, it is suggested that microvesicles, especially MFG-E8-associated ones, modulate adipose functions under redox- and hormone-dependent regulation. Based on the above findings, the adipocyte-derived microvesicles were named adiposomes.
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http://dx.doi.org/10.1210/en.2006-1479 | DOI Listing |
Plant Foods Hum Nutr
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Department of Food Science and Nutrition, School of Food Science and Nutrition, Mukogawa Women's University, 6-46, Ikebiraki-Cho, Nishinomiya, Hyogo, 663-8558, Japan.
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Department of Human Nutrition and Dietetics, University of Agriculture, Balicka 122, 30-149 Kraków, Poland.
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Department of Mechanical and Materials Engineering, University of Nebraska-Lincoln, Lincoln, NE 68588, USA.
Adipose tissue in vivo is physiologically exposed to compound mechanical loading due to bodyweight bearing, posture, and motion. The capability of adipocytes to sense and respond to mechanical loading milieus to influence metabolic functions may provide a new insight into obesity and metabolic diseases such as type 2 diabetes (T2D). Here, we evidenced physiological mechanical loading control of adipocyte insulin signaling cascades.
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Department of Biochemistry, Microbiology and Physics, Faculty of Agriculture, Trakia University, 6000 Stara Zagora, Bulgaria.
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Institute of Biomedical Sciences, Federal University of Rio de Janeiro (UFRJ), Avenida Carlos Chagas Filho 373, bloco F, 3° floor, room 301, Cidade Universitária, Rio de Janeiro CEP 21941-902, RJ, Brazil.
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