Spermidine is indispensable in differentiation of 3T3-L1 fibroblasts to adipocytes

نویسندگان

  • Susanna Vuohelainen
  • Eija Pirinen
  • Marc Cerrada-Gimenez
  • Tuomo A Keinänen
  • Anne Uimari
  • Marko Pietilä
  • Alex R Khomutov
  • Juhani Jänne
  • Leena Alhonen
چکیده

Impaired adipogenesis has been shown to predispose to disturbed adipocyte function and development of metabolic abnormalities. Previous studies indicate that polyamines are essential in the adipogenesis in 3T3-L1 fibroblasts. However, the specific roles of individual polyamines during adipogenesis have remained ambiguous as the natural polyamines are readily interconvertible inside the cells. Here, we have defined the roles of spermidine and spermine in adipogenesis of 3T3-L1 cells by using (S')- and (R')- isomers of alpha-methylspermidine and (S,S')-, (R,S)- and (R,R')-diastereomers of alpha,omega-bismethylspermine. Polyamine depletion caused by alpha-difluoromethylornithine (DFMO), an irreversible inhibitor of ornithine decarboxylase, prevented adipocyte differentiation by suppressing the expression of its key regulators, peroxisome proliferator-activated receptor gamma and CCAAT/enhancer binding protein alpha. Adipogenesis was restored by supplementation of methylspermidine isomers but not of bismethylspermine diastereomers. Although both spermidine analogues supported adipocyte differentiation only (S)-methylspermidine was able to fully support cell growth after extended treatment with alpha-DFMO. The distinction between the spermidine analogues in maintaining growth was found to be in their different capability to maintain functional hypusine synthesis. However, the differential ability of spermidine analogues to support hypusine synthesis did not correlate with their ability to support differentiation. Our results show that spermidine, but not spermine, is essential for adipogenesis and that the requirement of spermidine for adipogenesis is not strictly associated with hypusine modification. The involvement of polyamines in the regulation of adipogenesis may offer a potential application for the treatment of dysfunctional adipocytes in patients with obesity and metabolic syndrome.

برای دانلود رایگان متن کامل این مقاله و بیش از 32 میلیون مقاله دیگر ابتدا ثبت نام کنید

ثبت نام

اگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید

منابع مشابه

Fifty Percent Ethanolic Extract of Momordica charantia Inhibits Adipogenesis and Promotes Adipolysis in 3T3-L1 Pre-Adipocyte Cells

Background: Natural products have gained importance recently for the treatment of obesity and its complications, partly because of the side effects of modern drugs.Hence, we aimed to study and compare the effect of varying concentrations of Momordicacharantiaon adipogenesis and adipolysis using 3T3-L1 pre-adipocyte cell lines. Methods: 3T3-L1 pre-adipocytes were procured from the National Ce...

متن کامل

Development of a Novel Anti-Obesity Compound with Inhibiting Properties on the Lipid Accumulation in 3T3-L1 Adipocytes

Background: Obesity as a developing global challenge can be characterized by increase in adipocyte number and size arising from adipogenesis. Control of adipogenesis, as a potential strategy, can prevent and manage obesity. So far, the effectiveness of herbal medicine and active ingredients therapies for obesity and metabolic syndrome treatment has been investigated. In this study, a novel comb...

متن کامل

Alteration of proteoglycan metabolism during the differentiation of 3T3- L1 fibroblasts into adipocytes

3T3-L1 fibroblasts were induced to differentiate to 3T3-L1 adipocytes by dexamethasone, isobutyl-methylxanthine, and insulin. To study how differentiation affects extracellular matrix production, the accumulation of proteoglycans was studied by labeling the 3T3-L1 cells with [35S]sulphate for 24 h. The labeled proteoglycans were isolated from the medium and cell layer extracts by anion-exchange...

متن کامل

Cyclic AMP effects on cell-to-cell junctional membrane permeability during adipocyte differentiation of 3T3-L1 fibroblasts

Mouse 3T3-L1 fibroblast cells, also know as preadipocytes, differentiate in vitro into adipocytes when treated with promoting agents and acquire numerous properties characteristic of mature fat cells. We studied junctional cell-to-cell communication by measuring the incidence of electrical coupling and transfer of carboxy-fluorescein among these cells. When 3T3-L1 cells were induced to differen...

متن کامل

A novel, multifuntional c-Cbl binding protein in insulin receptor signaling in 3T3-L1 adipocytes.

The protein product of the c-Cbl proto-oncogene is prominently tyrosine phosphorylated in response to insulin in 3T3-L1 adipocytes and not in 3T3-L1 fibroblasts. After insulin-dependent tyrosine phosphorylation, c-Cbl specifically associates with endogenous c-Crk and Fyn. These results suggest a role for tyrosine-phosphorylated c-Cbl in 3T3-L1 adipocyte activation by insulin. A yeast two-hybrid...

متن کامل

ذخیره در منابع من


  با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید

عنوان ژورنال:

دوره 14  شماره 

صفحات  -

تاریخ انتشار 2010