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Updated: Sep 20, 2025
Isolation and Differentiation of Adipose-Derived Stem Cells from Porcine Subcutaneous Adipose Tissues
Published on: March 31, 2016
The fatty acid synthase inhibitor C75 differentially affects the adipogenic differentiation of multipotent cells and
Kuo-Yun Tseng1, Ko-Hung Liu2, Hung-Ming Wu2,3,4,5
1Institute of Infectious Diseases and Vaccinology, National Health Research Institutes, Zhunan, Taiwan.
Abstract:
Previously, we revealed the dual enhancing effect of netoglitazone, an agonist of the peroxisome proliferator-activated receptor γ, on adipogenesis and osteoblastogenesis, and reported that fatty acid synthase (FASN) knockdown selectively repressed its pro-adipogenic effect. Here, we examined if a FASN inhibitor, C75, could selectively repress the pro-adipogenic effect of netoglitazone. Surprisingly, C75 promoted the adipogenic differentiation of multipotent C3H10T1/2 cells but inhibited 3T3-L1 preadipocytes. By identifying glycogen synthase kinase-3β and intracellular cAMP levels as regulatory targets of C75, we ultimately found the differential expression of adenosine receptor 3 (AR3) and AR2a on these cells. Inhibition of AR3 on C3H10T1/2 and AR2a on 3T3-L1 inhibited the effects of C75 on the differentiation of these cells. Our findings imply that cell-type-specific AR expression might account for the differential adipogenic effects of C75.
Insights
Fatty acid synthase inhibitor C75 showed opposing effects on adipogenesis in different cell types. Cell-specific adenosine receptor expression (AR3 and AR2a) explains these differential effects on cell differentiation.
Area of Science:
- Biochemistry
- Cell Biology
- Molecular Pharmacology
Background:
- Netoglitazone, a PPARγ agonist, enhances adipogenesis and osteoblastogenesis.
- Fatty acid synthase (FASN) knockdown selectively inhibits netoglitazone's pro-adipogenic effect.
Purpose of the Study:
- To investigate if the FASN inhibitor C75 selectively represses netoglitazone's pro-adipogenic effect.
- To elucidate the mechanisms underlying C75's differential effects on adipogenesis.
Main Methods:
- Utilized multipotent C3H10T1/2 cells and 3T3-L1 preadipocytes.
- Investigated the roles of glycogen synthase kinase-3β, intracellular cAMP, and adenosine receptors (AR3 and AR2a).
- Assessed adipogenic differentiation and cellular responses to C75 and receptor modulators.
Main Results:
- C75 promoted adipogenic differentiation in C3H10T1/2 cells but inhibited it in 3T3-L1 cells.
- Identified glycogen synthase kinase-3β and cAMP levels as C75 regulatory targets.
- Demonstrated that cell-specific expression of AR3 (on C3H10T1/2) and AR2a (on 3T3-L1) mediates C75's differential effects.
Conclusions:
- C75 exhibits cell-type-specific regulation of adipogenesis.
- Differential expression of adenosine receptors (AR3 and AR2a) is responsible for C75's opposing effects on adipogenic differentiation.
- Findings highlight the importance of cell-specific receptor expression in drug response.
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