Oxysterol-binding protein-like 2 contributes to the developmental progression of preadipocytes by binding to β-catenin

Abstract

Oxysterol-binding protein-like 2 (OSBPL2), also known as oxysterol-binding protein-related protein (ORP) 2, is a member of lipid transfer protein well-known for its role in regulating cholesterol homeostasis. A recent study reported that OSBPL2/ORP2 localizes to lipid droplets (LDs) and is associated with energy metabolism and obesity. However, the function of OSBPL2/ORP2 in adipocyte differentiation is poorly understood. Here, we report that OSBPL2/ORP2 contributes to the developmental progression of preadipocytes. We found that OSBPL2/ORP2 binds to β-catenin, a key effector in the Wnt signaling pathway that inhibits adipogenesis. This complex plays a role in regulating the protein level of β-catenin only in preadipocytes, not in mature adipocytes. Our data further indicated that OSBPL2/ORP2 mediates the transport of β-catenin into the nucleus and thus regulates target genes related to adipocyte differentiation. Deletion of OSBPL2/ORP2 markedly reduces β-catenin both in the cytoplasm and in the nucleus, promotes preadipocytes maturation, and ultimately leads to obesity-related characteristics. Altogether, we provide novel insight into the function of OSBPL2/ORP2 in the developmental progression of preadipocytes and suggest OSBPL2/ORP2 may be a potential therapeutic target for the treatment of obesity-related diseases.

Comparative proximity biotinylation implicates the small GTPase RAB18 in sterol mobilization and biosynthesis

“…In contrast, HEK293 cells in which the exon 2 splice-donor site is probably excised show evidence for cholesterol insufficiency, including reduced DH4-accessible plasma membrane cholesterol, sensitivity to lipoprotein depletion in media, and impaired proliferation improved by cholesterol supplementation ( 48 ). Broadly, the findings of increased cholesterol are consistent with one set of models ( 47 , 56 , 57 , 58 ), whilst the findings of reduced accessible cholesterol are consistent with another ( 45 , 59 ).…”

“…This article contains supporting information ( 9 , 13 , 17 , 18 , 27 , 39 , 40 , 41 , 44 , 45 , 47 , 48 , 49 , 53 , 54 , 55 , 56 , 57 , 58 , 59 , 91 , 92 , 93 , 94 , 95 , 96 ).…”

Signaling pathways in obesity: mechanisms and therapeutic interventions

“… 244 , 245 Knockout of oxysterol-binding protein-like 2 (OSBPL2), a transport protein mediating the function of β-catenin, promoted the maturation of preadipocytes and caused an obese phenotype. 246 When Wnt signaling was activated within adipose progenitor cells, mice showed significantly reduced visceral fat and a higher degree of fibrosis in subcutaneous WAT due to alternation of the adipocyte into a fibroblastic lineage. 247 However, the stimulation of Wnt signaling within mature adipocytes did not yield the same result.…”

Stem cell differentiation with consistent lineage commitment induced by a flash of ultrafast-laser activation in vitro and in vivo

“…In our experiments, we found a series of proteins related to adipogenic differentiation that were also upregulated 24 h after photoactivation. By proteomic measurement of photoactivated ADSCs, the adipogenic differentiation factors (Abella et al, 2005;Hsieh et al, 2012;Donati et al, 2014;Park and Kim, 2020;Wang et al, 2021;Zhao et al, 2016), including cysteine dioxygenase type 1 (3.86-fold, p = 1.14 3 10 À7 ), glutamine synthetase (5.66-fold, p = 1.10 3 10 À16 ), caveolae-associated proteins (2.48-fold, p = 1.25 3 10 À7 ), oxysterol-binding protein (19.29fold, p = 1.10 3 10 À16 ), cyclin-dependent kinase 4 (1.87-fold, p = 3.24 3 10 À2 ), and keratins (1.88-fold, p = 7.3 3 10 À8 ) were all significantly higher than those of the control 24 h after photoactivation. Therefore, it is theoretically possible that some specific photoactivation may drive ADSCs to adipogenic differentiation by upregulating those factors.…”