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From stem cells to fat cells: Which genes are behind this transformation?
Fat cells (adipocytes) are important tissues for energy storage in the body. The process of their formation is called adipogenesis, a process full of secrets and challenges of gene regulation. Adipogenesis is divided into two stages, the first being the determination stage, followed by the terminal differentiation stage. During the determination phase, mesenchymal stem cells transform into fat precursor cells, often called lipoblasts or preadipocytes, during which they lose their potential to become other cell types (such as The potential for differentiation into chondrocytes, muscle cells and osteocytes.
In the terminal differentiation stage, preadipocytes will further change into mature adipocytes, and the cell differentiation in this process is strictly regulated by genes.
Energy storage and hormone regulation
Fat cells play a key role in energy homeostasis in animals and store energy in the form of triglycerides. These cells swell when energy intake exceeds expenditure and mobilize when energy expenditure exceeds intake. This process is influenced by a variety of counter-regulatory hormones, to which adipocytes are very sensitive. Insulin promotes cell expansion, while adrenaline, glucagon, and adrenocorticotropic hormone (ACTH) promote cell mobilization.
During adipogenesis, key transcription factors are responsible for regulating the transition of gene expression, which causes the pluripotent cell expression pattern to change to the adipocyte-specific gene expression pattern. Among them, peroxisome proliferator-activated receptor γ (PPARγ) and CCAAT enhancer binding proteins (C/EBPs) are regarded as the main regulators of adipogenesis. These transcription factors play crucial roles in the development of adipocytes.
PPARγ and C/EBPα are not only the master regulators of adipogenesis, but also affect the characteristics of adipocytes at all times, such as morphological changes, lipid accumulation and insulin sensitivity.
Cellular Models of Differentiation
Adipogenesis studies performed in vitro typically use pre-committed preadipocyte cell lines, such as the 3T3-L1 and 3T3-F442A cell lines, or preadipocytes isolated from the stromal vascular zone of white adipose tissue. . These differentiation processes show good orderliness.
First, proliferating preadipocytes stop growing due to contact inhibition, and then their shape changes from a fibroblastic state to a rounded state, a process accompanied by the induction of C/EBPβ and C/EBPδ transcription factors. Current studies have shown that the expression of these factors increases transiently in the early stage, and then the expression of PPARγ and C/EBPα will promote the expression of genes related to mature adipocyte characteristics, such as adipocyte protein (aP2), insulin receptor, glycerophosphodiesterase, and lipopolysaccharide. Dehydrogenase, etc.
However, it is often difficult to successfully differentiate preadipocytes from preadipocyte lines in vitro, demonstrating the complexity and challenge of this process.
Transcriptional regulatory mechanisms
Importance of PPARγ
PPARγ, as a master regulator of adipogenesis, forms a heterodimer with retinoic acid X receptor (RXR), then binds to DNA and activates the promoter of downstream genes. Activation of PPARγ enhances the expression of adipocyte-specific genes.
C/EBPs and their role
C/EBPs belong to the basic-leucine zipper class of transcription factors, which also play an important role in adipogenesis. As an inducing factor of adipogenesis, cAMP can promote the expression of C/EBPβ and C/EBPδ. The transient increase of these factors in the early stage of differentiation will activate adipogenesis-related transcription factors such as PPARγ and C/EBPα.
The influence of internal and external factors on fat production
Insulin and IGF-1
Insulin regulates adipogenesis through insulin-like growth factor 1 (IGF1) receptor signaling and promotes the induction of transcription factors that are critical for terminal differentiation.
Wnt signaling and BMPs
The Wnt/β-myelin signaling pathway can inhibit adipogenesis and promote the differentiation of mesenchymal stem cells into muscle cells or bone cells, while preventing the conversion to the adipogenesis pathway. The production of bone morphogenetic proteins (BMPs) can stimulate the differentiation of preadipocytes, demonstrating their active role in this process.
In addition, aging preadipocytes have been shown to inhibit the production of adipocytes, which is one of the important factors causing the reduction of fat production in obese people.
With a deeper understanding of the mechanisms of adipogenesis, we have a clearer understanding of the genetic regulation behind this process. These studies not only provide new targets for the treatment of obesity and related metabolic diseases, but also lead us to think about whether these molecular mechanisms, once fully understood in the future, can be successfully transformed into treatment options to combat obesity-related health challenges?
