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Why is the birth of fat cells so miraculous? Explore the two key stages of lipogenesis!
Adipogenesis, the process by which fat cells are born from stem cells, is actually very complex and fascinating. This process can be divided into two key stages: determination and terminal differentiation. The defined phase is when mesenchymal stem cells commit to transforming into adipocyte precursor cells, known as lipoblasts or preadipocytes, and lose the potential to transform into other cell types such as chondrocytes, muscle cells, and bone cells. Terminal differentiation is the transformation of preadipocytes into mature adipocytes.
"Adipocytes play a key role in energy homeostasis in animals and are dedicated to handling maximum energy reserves."
Mature adipocytes have the function of storing energy and can expand when energy intake exceeds consumption and mobilize when energy expenditure exceeds intake. This process is highly regulated by a variety of hormones, and these cells are very sensitive to these hormones. For example, insulin promotes dilation, while corresponding hormones such as epinephrine, glucagon, and adrenocorticotropic hormone (ACTH) promote mobilization.
Differentiation process
Adipogenesis is a tightly regulated cell differentiation process. Precommitted preadipocytes, such as the 3T3-L1 and 3T3-F442A cell lines, or preadipocytes isolated from the stromal vascular fraction of white adipose tissue are prime candidates for in vitro studies. During the process of differentiation in vitro, first, proliferating preadipocytes stop growing due to contact inhibition. Subsequently, the cessation of this growth prompts the cells to enter an early stage of change, exhibiting a morphological change from a fibroblastic to a rounded appearance and concomitant induction of expression of the transcription factors C/EBPβ and C/EBPδ.
"The differentiation process of adipocytes in vitro is highly orderly, and the expression of key transcription factors at different stages is crucial."
Next, during the second phase of growth arrest, the expression of two key transcription factors, PPARγ and C/EBPα, increases, which promote the expression of genes that are characteristic of mature adipocytes. These genes include adipocyte protein (aP2), insulin receptor, glycerophosphate dehydrogenase, fatty acid synthase, acetyl-CoA carboxylase, and glucose transporter GLUT4. Through this process, lipid droplets gradually accumulate within fat cells.
Transcriptional regulation
PPARγ (peroxisome proliferator-activated receptor gamma) is a major regulator of adipogenesis and belongs to the nuclear receptor superfamily. This transcription factor heterodimerizes with the retinoic acid X receptor (RXR) and binds to DNA, thereby initiating the expression of downstream genes. Activation of PPARγ affects multiple characteristics of mature adipocytes, such as morphological changes, lipid accumulation, and sensitivity to insulin.
"PPARγ expression alone is sufficient to promote the conversion of fibroblasts into adipocytes in vitro."
In addition, other factors that promote adipogenesis also induce the expression of PPARγ. For example, the C/EBP family and Krupel-like factors (KLFs) have been found to activate the promoter of PPARγ. However, C/EBPγ inhibits differentiation, possibly due to inactivation by C/EBPβ.
Other regulatory factors
Products of the endocrine system such as insulin, IGF-1, cAMP, glucocorticoids, and triiodothyronine can effectively induce lipogenesis in preadipocytes. These signals are closely related to the process of adipocyte differentiation. In particular, insulin regulates adipogenesis through IGF-1 receptor signaling and promotes the expression of transcription factors for terminal differentiation.
"The Wnt/sigmoid (β-catenin) signaling pathway has an inhibitory effect during adipogenesis and can guide mesenchymal stem cells to differentiate into muscle cells and bone cells."
In physiological anatomy, senescence of adipogenic precursor cells suppresses adipogenesis with age, suggesting that an increase in the number of aged cells, rather than stem cells, in the adipose tissue of obese patients is the primary cause of reduced adipogenesis. or a decrease in the number of precursor cells.
The storage and consumption of energy seems to be an eternal theme in the survival of living organisms. So, have you ever thought about how to effectively manage our lipogenesis process?
