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

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.

Functional significance of gain-of-function H19 lncRNA in skeletal muscle differentiation and anti-obesity effects

“…The expression of utrophin exhibits low tissue specificity [ 66 ]. Utrophin has been previously shown to regulate adipocyte droplet size [ 67 ]. Hence, the effect of stabilized utrophin on adipose tissues and insulin resistance could be an interesting research direction for further investigation.…”

Adipocyte Hypertrophy and Improved Postprandial Lipid Response in Beta 2 Syntrophin Deficient Mice

“…Effects of SNTA and SNTB2 on lipid droplet size in 3T3-L1 cells are independent of adipogenesis and expression of proteins mostly upregulated in differentiated adipocytes is not changed [11,12]. Thus, 3T3-L1 adipocytes with low SNTB2 have normal insulin-induced Akt phosphorylation [12]. Basal and β-adrenergic lipolysis are similar to controls while insulin stimulated antilipolytic effect is enhanced [12].…”

“…The adaptor proteins of the syntrophin family have been mostly studied in skeletal muscle where they are part of the dystrophin associated protein complex [10]. Alpha syntrophin (SNTA) and beta 2 syntrophin (SNTB2) are also expressed in adipocytes [11][12][13]. Recent work from our group showed that small lipid droplets are formed upon the knock down of SNTA during 3T3-L1 adipogenesis [11].…”

“…SNTA null mice have small adipocytes, are less obese, and are protected from lipid accumulation in skeletal muscle and the liver in a high fat diet model [14]. Knock down of SNTB2 during 3T3-L1 cell adipogenesis enables the formation of large lipid droplets [12]. Effects of SNTA and SNTB2 on lipid droplet size in 3T3-L1 cells are independent of adipogenesis and expression of proteins mostly upregulated in differentiated adipocytes is not changed [11,12].…”

“…Knock down of SNTB2 during 3T3-L1 cell adipogenesis enables the formation of large lipid droplets [12]. Effects of SNTA and SNTB2 on lipid droplet size in 3T3-L1 cells are independent of adipogenesis and expression of proteins mostly upregulated in differentiated adipocytes is not changed [11,12]. Thus, 3T3-L1 adipocytes with low SNTB2 have normal insulin-induced Akt phosphorylation [12].…”