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Metformin Decreases Caveolin‐1 Expression in Differentiated Human Preadipocytes
Author(s) -
Pfeifer Michaela A,
Zhang Yuebo,
Singh Prachi
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.1292.7
Subject(s) - leptin , metformin , caveolin 1 , endocrinology , medicine , glimepiride , insulin , signal transduction , adiponectin , caveolin , chemistry , biology , caveolae , microbiology and biotechnology , insulin resistance , obesity
Background We have previously shown that increased caveolin‐1 expression impairs leptin‐dependent activation of cellular signaling pathways and may be responsible for attenuating leptin‐mediated increases in adiponectin expression in obesity. Further, insulin and leptin cellular signaling mechanisms are closely related such that molecules known to impair insulin signaling also alter leptin signaling. Conversely, known insulin‐sensitizing drugs may improve leptin‐signaling via reducing caveolin‐1 expression. We therefore tested the hypothesis that insulin‐sensitizing drugs decrease caveolin‐1 expression. Methods We used an in‐vitro approach to examine the effects of different insulin‐sensitizing drugs on caveolin‐1 expression. Human white preadipocytes were cultured to confluence and differentiated for 15 days. After differentiation, cells were then treated with increasing concentrations of pioglitazone (5–30 μM), troglitazone (10–30 μM), metformin (1–5 mM), or glimepiride (20–100 μM) for 24 hours. Caveolin‐1 protein expression was determined by Western blot analysis. Results Among the insulin‐sensitizers used in our experiment, only treatment with increasing concentrations of metformin resulted in a dose‐dependent decease in caveolin‐1 expression (P =0.007). Treatment with increasing concentration of troglitazone upregulated caveolin‐1 expression (p=0.005), while pioglitazone (p=0.5020) and glimepiride (p=0.0965) had no effect of caveolin‐1 protein expression. Conclusions Metformin reduces caveolin‐1 expression in differentiated human white preadipocytes. In obesity, caveolin‐1 expression is increased which may contribute to impaired leptin signaling. Therefore, metformin may be used to decrease caveolin‐1 expression and consequently improve leptin signaling and leptin‐dependent increases in adiponectin expression in obese individuals. Support or Funding Information Michaela Pfeifer was supported by the American Physiological Society Stride Summer Undergraduate Research Fellowship NHLBI 1 R25 HL115473‐01; Prachi Singh was supported by the American Heart Association Scientist Development Grant 11SDG7260046.