CCAAT/enhancer-binding protein beta, delta ($C/EBP{\beta}$, ${\delta}$)는 지방세포분화 과정의 초기에 필수적으로 요구되며 지방생성 주요 조절인자인 proliferator-activated receptorgamma ($PPAR{\gamma}$) and CCAAT/enhancer-binding protein-alpha ($C/EBP{\alpha}$)의 발현을 유도한다. 본 연구에서는 silibinin의 지방세포 분화 억제 효과 및 이러한 효과가 지방세포 분화초기에 $C/EBP{\beta}$ 및 $C/EBP{\delta}$의 발현 조절을 통해 일어난 다는 것을 확인하였다. Silibinin은 지방세포 내 지질축적을 억제하고 세포분화 과정 동안 관여하는 다양한 유전자의 mRNA 발현을 억제하였다. 또한 lipoprotein lipase (LPL), fatty acid binding protein 4 (AP2) 및 adiponectin과 같은 지방세포 분화 관련 유전자의 발현을 억제시켰다. 따라서, Silibinin의 지방세포 분화 억제효과는 $C/EBP{\beta}$ 및 $C/EBP{\delta}$의 발현억제에 의한 것으로 보인다. 더불어, Silibinin은 capspase-3 활성을 통해 분화하는 세포에 특이적으로 세포사멸을 유도하는 것을 확인하였다.
CCAAT/enhancer-binding protein beta, delta ($C/EBP{\beta}$, ${\delta}$)는 지방세포분화 과정의 초기에 필수적으로 요구되며 지방생성 주요 조절인자인 proliferator-activated receptor gamma ($PPAR{\gamma}$) and CCAAT/enhancer-binding protein-alpha ($C/EBP{\alpha}$)의 발현을 유도한다. 본 연구에서는 silibinin의 지방세포 분화 억제 효과 및 이러한 효과가 지방세포 분화초기에 $C/EBP{\beta}$ 및 $C/EBP{\delta}$의 발현 조절을 통해 일어난 다는 것을 확인하였다. Silibinin은 지방세포 내 지질축적을 억제하고 세포분화 과정 동안 관여하는 다양한 유전자의 mRNA 발현을 억제하였다. 또한 lipoprotein lipase (LPL), fatty acid binding protein 4 (AP2) 및 adiponectin과 같은 지방세포 분화 관련 유전자의 발현을 억제시켰다. 따라서, Silibinin의 지방세포 분화 억제효과는 $C/EBP{\beta}$ 및 $C/EBP{\delta}$의 발현억제에 의한 것으로 보인다. 더불어, Silibinin은 capspase-3 활성을 통해 분화하는 세포에 특이적으로 세포사멸을 유도하는 것을 확인하였다.
$C/EBP{\beta}$ and $C/EBP{\delta}$ are required for the initiation of adipogenesis and induce the expression of key adipogenic regulators, such as $PPAR{\gamma}$ and $C/EBP{\alpha}$. In the present study, we have examined the effects of silibinin and its p...
$C/EBP{\beta}$ and $C/EBP{\delta}$ are required for the initiation of adipogenesis and induce the expression of key adipogenic regulators, such as $PPAR{\gamma}$ and $C/EBP{\alpha}$. In the present study, we have examined the effects of silibinin and its possible molecular mechanisms in regulating adipocyte differentiation and expression of $C/EBP{\beta}$ and $C/EBP{\delta}$ in the early stage of adipogenesis. Silibinin statistically significantly inhibits intracellular lipid accumulation and the mRNA expression of various genes involved at different stages during adipogenesis. Silibinin also suppresses expression of lipoprotein lipase (LPL), fatty acid binding protein 4 (AP2), and adiponectin in 3T3-L1 adipocytes. Thus, the anti-adipogenic effect of silibinin seems to originate from the ability to inhibit the expression of $C/EBP{\beta}$ and $C/EBP{\delta}$. Furthermore, silibinin decreases cell viability for differentiation period and induces apoptotic cell death through capspase-3 activation.
$C/EBP{\beta}$ and $C/EBP{\delta}$ are required for the initiation of adipogenesis and induce the expression of key adipogenic regulators, such as $PPAR{\gamma}$ and $C/EBP{\alpha}$. In the present study, we have examined the effects of silibinin and its possible molecular mechanisms in regulating adipocyte differentiation and expression of $C/EBP{\beta}$ and $C/EBP{\delta}$ in the early stage of adipogenesis. Silibinin statistically significantly inhibits intracellular lipid accumulation and the mRNA expression of various genes involved at different stages during adipogenesis. Silibinin also suppresses expression of lipoprotein lipase (LPL), fatty acid binding protein 4 (AP2), and adiponectin in 3T3-L1 adipocytes. Thus, the anti-adipogenic effect of silibinin seems to originate from the ability to inhibit the expression of $C/EBP{\beta}$ and $C/EBP{\delta}$. Furthermore, silibinin decreases cell viability for differentiation period and induces apoptotic cell death through capspase-3 activation.
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가설 설정
We hypothesized that cytotoxic effects of silibinin was predominantly due to apoptosis in differentiating adipocytes. To test this hypothesis, we examined the protein expression of apoptotic makers after the treatment of silibinin with MDI solution for 24 h.
제안 방법
25 μM DEX, 167 nM insulin, and 100 μM indomethacin) in DMEM and 10% FBS for 2 days (from day 0 to day 2). The culture medium was then replaced with DMEM supplemented with 10% FBS and insulin (from day 2 to day 9), which was changed every 2 days. To examine the effect of silibinin on adipogenesis, the cells were cultured with the differentiation medium in the presence or absence of silibinin (7.
To investigate the effects of silibinin on the differentiation of 3T3-L1 preadipocytes into mature adipocytes, we treated the cells with silibinin at concentrations of 7.5 or 75 μM for 8 days and performed ORO staining and a TG colorimetric assay.
Adipocyte differentiation is accompanied by alterations in the expression of various transcriptional factors and adipogenesis-specific genes [14]. To investigate the mechanisms underlying the action of silibinin to suppress differentiation of 3T3-L1 cells, we treated cells that were in the process of differentiation with silibinin for 8 days and performed RT-PCR. Treatment with silibinin at concentrations of either 7.
대상 데이터
Silibinin, Dulbecco’s Modified Eagle’s Medium (DMEM), antibiotics (100,000 unit/l penicillin, 100 mg/l streptomycin), fetal bovine serum (FBS), and bovine calf serum (BCS) were purchased from Gibco (USA). Insulin, 3- isobutyl-1-methylxanthine (IBMX), dexamethasone (DEX), indomethacin, and Oil Red O (ORO) reagent were purchased from Sigma-Aldrich (USA) and 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide (MTT) was purchased from Amresco (USA). A triglyceride quantification kit (#K622-100) was supplied by Biovision Inc.
Silibinin, Dulbecco’s Modified Eagle’s Medium (DMEM), antibiotics (100,000 unit/l penicillin, 100 mg/l streptomycin), fetal bovine serum (FBS), and bovine calf serum (BCS) were purchased from Gibco (USA).
The 3T3-L1 mouse cell line was purchased from the Korean Cell Line Bank (Korea) and maintained in DMEM with 10% BCS at 37℃ in a humidified 5% CO2 incubator. The 3T3-L1 cells were seeded into six-well plates and differentiated into mature adipocytes.
데이터처리
0 (IBM Corporation, USA). Statistical comparisons between groups were performed using 1-way ANOVA. Values of p< 0.
성능/효과
Treatment with silibinin at concentrations of either 7.5 or 75 μM significantly reduced mRNA expression of transcription factors PPAR, C/EBPα, and C/EBPδ and also decreased the expression of adipocyte-specific genes, fatty acid-binding protein 4 (aP2), lipoprotein lipase (LPL), and adiponectin.
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