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The utrophin–beta 2 syntrophin complex regulates adipocyte lipid droplet size independent of adipogenesis

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Abstract

Utrophin is a widely expressed cytoskeleton protein and is associated with lipid droplets (LDs) in adipocytes. The scaffold protein beta 2 syntrophin (SNTB2) controls signaling events by recruiting distinct membrane and cytoskeletal proteins, and binds to utrophin. Here we show that SNTB2 forms a complex with utrophin in adipocytes. SNTB2 protein is strongly diminished when utrophin is low. Of note, knock-down of utrophin or SNTB2 enhances LD growth during adipogenesis. SNTB2 reduction has no effect on basal and induced lipolysis, and insulin-stimulated phosphorylation of Akt is normal. The antilipolytic activity of insulin is enhanced in adipocytes with low SNTB2, while knock-down of utrophin has no effect. Uptake of exogenously supplied oleate and linoleate is comparable in scrambled and SNTB2 siRNA-treated cells. In the fibroblasts, diminished SNTB2 is associated with lower proliferation. CCAAT/enhancer-binding protein alpha and sterol regulatory element-binding proteins which are critical transcription factors for adipogenesis are normally expressed. Consequently, maturation of cells with SNTB2 knock-down is not grossly impaired. In fibroblasts, SNTB2 is localized to filamentous and vesicular structures which are distinct from beta actin, alpha tubulin, endoplasmic reticulum, early endosomes, lysosomes and mitochondria. Collectively, our data provide evidence that the utrophin–SNTB2 complex regulates LD size without affecting adipogenesis.

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Acknowledgements

The authors thank Prof. Marvin Adams for providing syntrophin-specific antibodies. The study was supported by a Grant from the German Research Foundation (BU 1141/8-1).

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  1. Department of Internal Medicine I, University Hospital of Regensburg, 93042, Regensburg, Germany

    Sabrina Krautbauer, Markus Neumeier, Elisabeth M. Haberl, Rebekka Pohl, Susanne Feder, Kristina Eisinger, Lisa Rein-Fischboeck & Christa Buechler

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  1. Sabrina Krautbauer
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Krautbauer, S., Neumeier, M., Haberl, E.M. et al. The utrophin–beta 2 syntrophin complex regulates adipocyte lipid droplet size independent of adipogenesis. Mol Cell Biochem 452, 29–39 (2019). https://doi.org/10.1007/s11010-018-3409-6

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