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Research on the adipogenic differentiation of AMSCs and DFATs in pigs

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한국동물생명공학회(구 한국수정란이식학회) (Journal of Animal Reproduction & Biotechnology)
초록

Adipose tissue is the largest energy storage in the body, with the endocrine, paracrine and autocrine function, and they constitute a network regulatory signal, and participate in energy balance and metabolism regulation in adipose tissue. When adipose tissue is excessively accumulated or obesity, inflammatory signaling pathway is activated as the secretion increase of a variety of inflammatory cytokines, then, the body is under the state of chronic inflammation, causing insulin resistance and many metabolic diseases, such as type 2 diabetes, atherosclerosis, cancer and other chronic metabolic disease, and bringing a serious health crisis to humans. And, excessive fat deposition reduces the feed conversion rate, leading to the increase of livestock and poultry production cost and the reduction of meat food quality. Therefore, the regulation of adipogenic differentiation has become an important field in the study of human health and animal production.
1. The source of adipose tissue The formation of adipose tissue is due to the increase of adipose cell number caused by differentiation and the increase of adipose cell volume and adipose accumulation during development. This process is that adipose mescenchymal stem cells (AMSCs) are transformed to preadipocytes in adipogenic environment, and differentiation related specific transcription factors start to express and induce the specific expression of adipose cell genes and terminal differentiation, finally, mature adipose cells are formed after adipose accumulation. Recent studies have suggested that dedifferentiated fat cells (DFATs) may be an important source of adipose tissue. Mature adipose cells can be dedifferentiated to the sub cells (DFATs) with the dividing ability in vitro culture, and DFATs are pluripotent and can be redifferentiated to adipose cells or transdifferentiated to other cell types, such as cartilage cells, bone cells, muscle cells, etc. by induction. This suggests that DFATs are progenitor cells with the stem cell properties, showing the great potential in tissue engineering and regenerative medicine. Research on the mechanism of DFATs redifferentiation and transdifferentiation has an important significance for human health and animal production.
2. Regulation of adipocyte differentiation and transcription The adipocyte differentiation lies in the transcription level regulation, involving the cascade and cooperative effects of multiple transcription factors, among which, the core transcription factor is peroxisome proliferator activated receptors-γ (PPARγ), which specifically expresses in adipose tissue, combines the promoters of downstream genes promoter and induces their expression, such as lipoprotein lipase (LPL), insulin sensitive glucose transporter 4 (GLUT4), fatty acid synthase (FAS), adipose-specific fatty acid binding protein-2 (AP2) and adiponectin, and promotes the differentiation and maturation of adipose cells.
3. Transcription regulation of PPARγ by Kruppel like factors Kruppel like factors (KLFs) are a class of transcription factors with zinc finger structure, which is involved in the regulation of cell proliferation, cell apoptosis, cell differentiation and tumor formation in a variety of animal cell types. Since KLF15 is first proved to have the transcriptional regulation capability of adipose differentiation by Gray, et al. in 2002, other KLFs are also found to be involved in the adipose differentiation regulation. According to the recent studies of KLFs regulation of adipose differentiation, Christopher, et al. in 2009 summarized KLFs transcription regulation network in the PPARγ upstream. This network includes 8 types of KLFs, namely, KLF2-7, KLF11 and KLF15, among which, KLF2, KLF3 and KLF7 are involved in the negative regulation of adipose formation, while KLF4-6, KLF11 and KLF15 positively regulates adipose formation, and they express according to a certain time sequence during adipocyte differentiation.
4. Regulation of adipose differentiation by curcumin Curcumin is a kind of polyphenols extracted from Curcuma longa L.. Curcumin can reduce the mice obesity formation, directly interfere with the preadipocytes differentiation and decrease the adipocyte number and adipose accumulation. Moreover, curcumin plays a role in the early stage of adipocyte differentiation, and inhibit the mitotic proliferation process and the expression levels of PPARγ, C/EBPα, and certain downstream transcription factors.
5. Regulation of AMSCs and DFATs adipogenic differentiation in pigs It is generally believed that pigs are the most suitable animal models for the application of human clinical medicine. Also, pigs are the largest source of human meat food, and one of animals with the most fat content. Therefore, research on the regulation of porcine adipocyte differentiation has an important significance for the establishment of human disease model and the production of low fat and lean meat pigs. This report summarizes the expression patterns of different KLFs and the effect of curcumin on the KLFs and PPARγ expression during the adipogenic differentiation of porcine AMSCs and DFATs in recent years.

저자
  • Xuexiong Song(College of Animal Science and Technology, Qingdao Agricultural University, China)