Type I collagen inhibits adipogenic differentiation via YAP activation in vitro

Abstract

Extracellular matrix (ECM) has a marked influence on adipose tissue development.Adipose tissue formation is initiated with proliferation of preadipocytes and migration before undergoing further differentiation into mature adipocytes. Previous studies showed that collagen I (col I) provides a good substratum for 3T3-L1 preadipocytes to grow and migrate. However, it remains unclear whether and how col I regulates adipogenic differentiation of preadipocytes. This study reports that lipid accumulation, representing in vitro adipogenesis of the 3T3-L1 preadipocytes or the mouse primary adipocyte precursor cells derived from subcutaneous adipose tissue in the inguinal region is inhibited by the culture on col I, owing to downregulation of adipogenic factors. Previous study shows that col I enhances 3T3-L1 cell migration via stimulating the nuclear translocation of yes-associated protein (YAP). In this study, we report that downregulation of YAP is associated with in vitro adipogenesis of preadipocytes as well as with in vivo adipose tissue of high-fat diet fed mice. Increased expression of YAP in the cells cultured on col I-coated dishes is correlated with repression of adipogenic differentiation processes. The inactivation of YAP using YAP inhibitor, verteporfin, or YAP small-interfering RNA enhanced adipogenic differentiation and reversed the inhibitory effect of col I. Activation of YAP either by the transfection of YAP plasmid or the silence of large tumor suppressor 1 (LATS1), an inhibitory kinase of YAP, inhibited adipogenic differentiation. The results indicate that col I inhibits adipogenic differentiation via YAP activation in vitro. K E Y W O R D S adipogenic differentiation, collage I, preadipocyte, YAP

Cancer-associated adipocytes: emerging supporters in breast cancer

“…In addition, YAP is activated in CAFs in response to mechanical stress, perturbation of the actin cytoskeleton and ECM stiffness [86,87]. Besides, the increased expression of YAP in preadipocytes is correlated with the repression of adipogenic differentiation processes [89]. Wang et al conducted a transcriptomic analysis to find that mesenchymal stromal/stem cell (MSC)-differentiated adipocyte exosomes activated the Hippo signaling pathway involved in two key downstream Hippo proteins YAP and TAZ in MCF-7 cells, while the Hippo pathway blockade could lead to reduced tumor growth [90].…”

Caveolin-1 mediates soft scaffold-enhanced adipogenesis of human mesenchymal stem cells

“…On 2D culture, increasing YAP activity suppresses adipogenic differentiation [ 39 ]. In contrast, inactivation of YAP using small molecule or siRNA promotes adipogenic differentiation [ 40 ]. In a study using gelatin scaffolds with stiffness gradients from 8 kPa to 30 kPa, activation of YAP was found in the cells encapsulated in low-stiffness regions [ 36 ], similar to our findings here.…”

Developments for Collagen Hydrolysate in Biological, Biochemical, and Biomedical Domains: A Comprehensive Review

“…The research proposes the SB fibrils for scaffolds due to the diverse morphologies and good thermal characteristics [ 61 ]. Another recent work by Liu et al presents the lipid accumulation to proliferate the preadipocytes (3T3-L1) for development of adipose tissues [ 62 ]. The proliferation of preadipocytes is increased with the downregulation of Yes associated proteins (YAP) found in a cultured Type 1 collagen assay [ 62 ].…”

“…Another recent work by Liu et al presents the lipid accumulation to proliferate the preadipocytes (3T3-L1) for development of adipose tissues [ 62 ]. The proliferation of preadipocytes is increased with the downregulation of Yes associated proteins (YAP) found in a cultured Type 1 collagen assay [ 62 ]. A similar nature of research is reported by the same author, but with a different research group [ 63 ], about the effects of collagen Type I on cell migration and differentiation through the culturing of mouse C2C12 myoblasts for skeletal muscle regeneration.…”