Silk peptides inhibit adipocyte differentiation through modulation of the Notch pathway in C3H10T1/2 cells.
Silk protein is a biocompatible material that has been used in many biotechnological applications and exhibits body fat-lowering effects. Recent studies have shown that silk peptides increase expression of osteogenic markers in osteoblast-like cells. Because osteogenic and adipogenic differentiation from common mesenchymal progenitor cells are inverse processes and often regulated reciprocally, we hypothesized that silk peptides might suppress adipocyte differentiation. We therefore endeavored to evaluate the effects of silk peptides on adipocyte differentiation in C3H10T1/2 cells. We find that silk peptides inhibit lipid accumulation and morphological differentiation in these cells. Molecular studies show that silk peptides block expression of adipocyte-specific genes such as peroxisome proliferator-activated receptor γ and its targets, including aP2, Cd36, CCAAT enhancer binding proteinα. Silk peptides appear to inhibit adipogenesis by suppression of the Notch pathway, repressing the Notch target genes Hes-1 and Hey-1. In addition, these peptides inhibit endogenous Notch activation, as shown by a reduction in generation of Notch intracellular domain. N-[N-(3.5-difluorophenacetyl)-L-alanyl]-S-phenylglycine t-butylester, compound E, and WPE-III-31C, which are all known Notch signaling inhibitors, block adipocyte differentiation to an extent similar to silk peptides. Together, our data demonstrate that silk peptides can modulate adipocyte differentiation through inhibition of the Notch signaling and further suggest potential future strategies for treating obesity and its related metabolic diseases.
Department of Food Science and Biotechnology, Sungkyunkwan University, Suwon 440-746, Korea.
So-Ra
SR
Jung
No-Joon
NJ
Song
Hyun Sook
HS
Hwang
Jae Jin
JJ
An
Yong-Jun
YJ
Cho
Hae Young
HY
Kweon
Seok-Woo
SW
Kang
Kwang Gill
KG
Lee
Keejung
K
Yoon
Byung-Joon
BJ
Kim
Chu Won
CW
Nho
Soo Young
SY
Choi
Kye Won
KW
Park
D041721:3T3-L1 Cells; D017667:Adipocytes / Q000166:cytology / Q000187:drug effects*; D050156:Adipogenesis / Q000187:drug effects; D000273:Adipose Tissue / Q000166:cytology / Q000378:metabolism; D000818:Animals; D051792:Basic Helix-Loop-Helix Proteins / Q000235:genetics / Q000378:metabolism; D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism; D002454:Cell Differentiation / Q000187:drug effects*; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000187:drug effects; D051379:Mice; D047495:PPAR gamma / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D010455:Peptides / Q000737:chemistry*; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D047011:Silk / Q000737:chemistry*; D000072056:Transcription Factor HES-1
D051792:Basic Helix-Loop-Helix Proteins; D018797:Cell Cycle Proteins; D018398:Homeodomain Proteins; D047495:PPAR gamma; D010455:Peptides; D012097:Repressor Proteins; D047011:Silk; D000072056:Transcription Factor HES-1; C489734:Hes1 protein, mouse; C120420:Hey1 protein, mouse