WHAT IS ADIPOGENESIS?

In mammalian cells, the transcription factors associated with adipogenesis control the differentiation of adipocytes. This includes the CCAAT/enhancer binding proteins (C/EBPs)(C/EBPα, β, and δ) and peroxisome proliferator-activated receptor γ (PPARγ). Fatty acid synthase (FAS), adiponectin, and fatty acid binding protein 4 (FABP4) combine to form mature adipocytes.
In addition to PPARγ and C/EBPα, other transcription factors positively regulate adipocyte differentiation. The Kruppel-like factors (KLFs) are among them. Activation of the KLF transcription factors KLF4, KLF5, KLF9, and KLF15 accompanies adipocyte differentiation in 3T3-L1 cell lines.

Researchers have shown that ectopic expression of KLF15 in NIH 3T3 cells induces lipid accumulation and expression of PPARγ. This suggests that KLF15 plays an important role in adipogenesis.

Expression of the active form of CREB in 3T3-L1 pre-adipocytes is sufficient to induce adipogenesis. CREB induces accumulation of Triglyceride and expression of two adipocyte marker genes, PPARγ and fatty acid binding protein.

In vitro studies show that transforming growth factor β (TGF-β) target the transcription factors linked to adipogenesis. PPAR, C/EBPβ, and C/EBPδ factors, followed by TGF-β-mediated adipogenesis inhibition. TGF-β inhibits adipocyte differentiation by interacting with C/EBP and repressing its transcriptional activity.

Adipocyte differentiation studies are important for controlling obesity in humans and animals. Obesity can lead to complications like type II diabetes, hypertension, and heart disease.
The adipose tissue spreads into different organs. This brings adipocytes into close contact with cancer cells in many solid tumors. During tumor growth, local invasion or bone metastases as well as in blood cancers.
Produced molecules like leptin and HGF can cause cancer cells to secrete various MMPs, thereby indirectly promoting tumor invasion. In breast cancer, adipocytes (stromal cells), play a critical role in the growth, survival and invasion.

During postsurgical autologous fat grafting, adipocytes can pose challenges to therapy by resisting different breast cancer treatments. Additionally, they may serve as a reservoir for dormant tumor cells.
Sheng and colleagues recently reported an additional and potentially important mechanism by which adipocytes contribute to drug resistance. They reported that adipocytes not only sequester the chemotherapeutic drug daunorubicin, but also efficiently metabolize it to a metabolite with reduced therapeutic efficacy, daunorubicinol.