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The mysterious birth of fat cells: Why do our bodies need them?
The formation of adipocytes, or adipogenesis, is the process of transforming stem cells into adipocytes. This process is divided into two stages: fate determination and terminal differentiation. During the fate determination stage, mesenchymal stem cells transform into preadipocytes, also known as lipoblasts or preadipocytes, which lose their potential to differentiate into other cell types, such as Chondrocytes, myocytes and osteoblasts. Subsequently, during the terminal differentiation stage, preadipocytes further transform into mature adipocytes.
Adipocytes store the largest energy reserves in the animal body in the form of triglycerides.
This process is regulated by a variety of hormones. When energy intake exceeds energy consumption, fat cells will expand, and when energy consumption exceeds intake, energy release occurs. Insulin is the hormone that promotes expansion, while epinephrine, glucagon, and adrenocorticotropic hormone promote the release of energy.
The development process of adipocytes
Adipogenesis is a tightly regulated process of cell differentiation from mesenchymal stem cells to preadipocytes and then to mature adipocytes. This process involves changes in gene expression patterns, with a shift from pluripotency gene expression to cell type-specific gene expression. Therefore, transcription factors are critical for adipogenesis.
The transcription factors PPARγ and C/EBPs are the main regulators of adipogenesis.
These transcription factors promote the expression of genes characteristic of mature adipocytes, and compared with cells from other sources, the in vitro differentiation process of adipocytes actually reproduces the characteristics of in vivo differentiation. Mature adipocytes have growth arrest, morphological changes, high expression of lipid synthesis genes, and the production of adipokines, such as adiponectin, leptin, and TNF-alpha.
Cell differentiation and its transcriptional regulation
In in vitro studies, adipogenesis is studied by using already committed preadipocyte cell lines, such as the 3T3-L1 or 3T3-F442A cell lines, or preadipocytes isolated from white adipose tissue. This process usually accompanies growth and is accompanied by early events such as morphological changes and induction of the transcription factors C/EBPβ and C/EBPδ.
PPARγ is a major regulator of adipogenesis and is necessary for the differentiation of embryonic stem cells into adipocytes.
During the second stage of growth cessation, two key transcription factors, PPARγ and C/EBPα, are expressed. These factors promote the expression of mature adipocyte characteristic genes, including insulin receptors and fatty acid synthase. This process leads to the accumulation of lipid vesicles, signaling cell maturation.
The synergistic effect of transcription factors
Although PPARγ and C/EBPα are the master regulators of adipogenesis, there are other transcription factors that play a role in the differentiation process. Adipocyte determination and differentiation factor 1 (ADD1) and steroid regulatory element binding protein 1 (SREBP1) can activate PPARγ by generating endogenous PPARγ ligands or directly promoting PPARγ expression.
The Wnt/β-catenin signaling pathway inhibits adipogenesis and promotes the differentiation of mesenchymal stem cells into muscle cells and bone cells.
Moreover, reduced adipogenesis in obese people is due to an increase in senescent cells in adipose tissue rather than a decrease in the number of stem cells or precursor cells. This fact demonstrates the potential influence of senescent cells in regulating adipogenesis.
Influence on the endocrine system
Products in the endocrine system such as insulin, IGF-1, cAMP, glucocorticoids, and triiodothyronine effectively induce lipogenesis in preadipocytes. Insulin regulates this process through the insulin-like growth factor 1 (IGF1) receptor signaling pathway, thereby promoting the induction of transcription factors related to terminal differentiation.
Bone morphogenetic proteins (BMPs) can also promote the differentiation of preadipocytes, showing the impact of multiple signaling pathways on adipogenesis.
However, BMP2 can stimulate pluripotent cell fate decisions and even promote bone formation through different receptor isoforms. This shows the intricate interactions between various factors, further emphasizing the multifaceted nature of regulating adipogenesis.
Thinking Summary
The formation of adipocytes is an important part of our understanding of energy balance and metabolism. However, with changes in social lifestyles, obesity has become an increasingly common problem. How do we balance the relationship between fat cell formation and health?
