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Adipose‐Derived Exosomes From Severely Obese Individuals Regulate Skeletal Muscle Metabolism
Author(s) -
Park Sanghee,
Zheng Donghai,
Barberio Matt,
Hubal Monica,
Houmard Joseph
Publication year - 2016
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.30.1_supplement.1245.32
Subject(s) - microvesicles , insulin resistance , adipose tissue , skeletal muscle , endocrinology , medicine , glucose uptake , biology , exosome , insulin , microrna , biochemistry , gene
Accumulation of subcutaneous and visceral fat mass with severe obesity (BMI > 40 kg/m 2 ) is closely associated with various metabolic derangements, including insulin resistance, type 2 diabetes and cardiovascular disease. The mechanism in which expanded visceral tissue promotes insulin resistance in peripheral tissues (i.e. skeletal muscle) is unclear. Exosomes, extracellular nano‐vesicles secreted from almost all types of organs in the body, are known to regulate cellular signaling through endocrine mechanism suggesting that exosomes released from visceral fat can be one of important mediators to communicate with skeletal muscle. In addition, a previous study has shown that certain mature miRNAs from visceral exosomes, which target many confirmed or putative mRNAs, are differentially expressed in adipose‐derived exosomes from obese vs. lean individuals, indicating that adipose‐derived exosomal miRNAs in obesity may play an important role in developing metabolic dysfunction in human skeletal muscle. We, therefore, hypothesize that adipose‐derived exosomes may induce insulin resistance in skeletal muscle. Exosomes were isolated from visceral adipose tissues from severely obese individuals (BMI > 40kg/m 2 ) using ExoQuick‐TC (System Biosciences). Skeletal muscle cells were obtained from lean and several obese individuals (N=8: BMI < 25kg/m 2 and BMI > 40kg/m 2 , respectively). Following proliferation and differentiation, fully mature myotubes were incubated with adipose‐derived exosomes (0.3ug/ml) for 24 hours and stimulated by insulin (100nM) for the last10 minutes. Then, cells were harvested to measure protein expressions in glucose metabolism using immunoblotting techniques. To measure the functional importance of exosome treatment, we examined insulin‐stimulated glycogen synthesis and glucose oxidation. While adipose‐derived exosomes significantly suppressed phosphorylation of Akt Ser 473 in skeletal muscle cells from both lean and obese individuals, we could not observe any changes in insulin‐stimulated glycogen synthesis and glucose oxidation. The main finding from this study is that adipose‐derived exosomes significantly suppressed Akt phosphorylation; however, there were no changes in glucose metabolism. This would suggest that, though it impairs intracellular signaling, exosomes may not be responsible for impaired glucose metabolism with severe obesity. Support or Funding Information This study was supported by the National Institute of Health (DK 56112).