WHAT IS THE PROCESS OF ADIPOGENESIS?

Adipogenesis is the complex mechanism responsible for the formation of completely developed fat cells, also known as adipocytes. This intricate process involves the transformation of pre-adipocytes, which are cells that serve as adipocyte precursor cells. Normally, mesenchymal stem cells play a role in the progression of adipocyte precursor differentiation, ultimately resulting in the formation of mature adipocytes. These versatile cells have the ability to transform into various cell types.
This cell differentiation process also involves changes in cell morphology, induction of insulin sensitivity and changes in secretory capacity of cells.

REGULATION OF 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 ^(1,4).

TYPE OF ADIPOSE TISSUE

There are two primary types of adipose tissue based on their biological functions:

White adipose tissue is in various parts of the body. It is under the skin (subcutaneous adipose tissue), around organs, and in female breasts (called mammary adipose tissue). This type of tissue is the most abundant and serves as a crucial energy storage in the form of triglycerides. Additionally, it functions as an important endocrine organ, primarily involved in weight regulation.
White adipocytes secrete leptin and adiponectin as well as common growth factors, hormones, cytokines, and chemokines...
Brown adipose tissue, characterized by energy expenditure, located in the regions near the neck, specifically the para-cervical and supra-clavicular areas. It plays a significant role in regulating heat production in response to food intake and cold temperatures. Among the genes expressed in brown adipose tissue, sterol regulatory element-binding protein 1 (SREBP1) ^(1,4).

THE PROCESS OF ADIPOGENESIS AND ITS CONNECTION TO VARIOUS DISEASES

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 ⁽²⁾.
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 ^(4,5).

Role of adipocyte as an active facilitator in breast cancer initiation, progression and metastasi ⁽⁵⁾ .

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 ⁽⁵⁾.
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 ⁽³⁾.

Adipose tissue effects in the tumour microenvironment ⁽³⁾

(1) Moseti D & al. Molecular Regulation of Adipogenesis and Potential Anti-Adipogenic Bioactive Molecules. Int J Mol Sci. (2016) 19;17(1).

(2) Han J & al. Regulation of Adipogenesis Through Differential Modulation of ROS and Kinase Signaling Pathways by 3,4'-Dihydroxyflavone Treatment. J Cell Biochem. (2017);118(5):1065-1077.

(3) Zhang Z1 & Scherer PE. Adipose tissue: The dysfunctional adipocyte - a cancer cell's best friend. Nat Rev Endocrinol. (2018);14(3):132-134.

(4) Duong MN & al. The fat and the bad: Mature adipocytes, key actors in tumor progression and resistance. Oncotarget. (2017).

(5) Choi J & al. Adipocyte biology in breast cancer: From silent bystander to active facilitator. Prog Lipid Res. (2018);(69):11-20.

ADIPOGENESIS SIGNALING PATHWAY BIOMARKER LIST

You can custom your own SignArrays® with the genes of interest of your choice, according to your project, you just have to download and complete our Personalized SignArrays® information file and send it at [email protected]

You can check the biomarker list included in this pathway, see below:

Species : Homo sapiens (human)

Human Adipogenesis

Signaling Pathways	Product ref	Informations
Adipogenesis	ADI1H1	List infos

Species : Mus musculus (mouse)

Mouse Adipogenesis

Signaling Pathways	Product ref	Informations
Adipogenesis	ADI1M1	List infos

Species : Rattus norvegicus (rat)

Rat Adipogenesis

Signaling Pathways	Product ref	Informations
Adipogenesis	*******	List In progress...

Species : Sus Scrofa (Pig)

Pig Adipogenesis

Signaling Pathways	Product ref	Informations
Adipogenesis	*******	List In progress...

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