Adipogenesis

Adipogenesis is the process of cell differentiation by which preadipocytes become adipocytes. Adipogenesis has been one of the most intensively studied models of cellular differentiation.

Differentiated Adipocyte stained with Oil Red O

Introduction

Adipocytes play a vital role in energy homeostasis and process the largest energy reserve as triglycerol in the body of animals.[1] Adipocytes stay in a dynamic state, they start expanding when the energy intake is higher than the expenditure and undergo mobilization when the energy expenditure exceeds the intake. This process is highly regulated by counter regulatory hormones to which these cells are very sensitive. The hormone insulin promotes expansion whereas the counter hormones epinephrine, glucagon,and ACTH promote mobilization. Adipogenesis is a tightly regulated cellular differentiation process, in which the preadipocytes are transformed into differentiated adipocyte cells. Comparing with cells from other lineage, the in vitro differentiation of fat cells is authentic and recapitulates most of the characteristic feature of in vivo adipogenesis. The key features of differentiated adipocytes are morphological change, growth arrest, high expression of lipogenic genes and production of hormones like leptin, resistin (in the mouse, not in humans) and TNF-alpha.

Models of differentiation

In vitro

The transition of the fibroblast cells to mature adipocytes is one of the best characterized processes of cellular differentiation.[2] Primary preadipose cells can be isolated from the stromal vascular fraction of adipose tissue; and when treated in cell culture with a combination of adipogenic effectors, they can differentiate into adipocytes.[3]

Cell Line Origin Differentiation Protocol
Committed Pre-adipocytes
3T3-L1 Sub-clone of Swiss 3T3[4] FBS+ I+ D+ M
3T3-F442A Sub-clone of Swiss 3T3[5] FBS + I
Ob17 Differentiated adipocyte from epididymal fat pad of C57BL/6J ob/ob mice[6] FBS+ I+ T3
TA1 Subclone of C3H10T1/2 [7] FBS + D + I
30A5 Subclone of C3H10T1/2[8] FBS + D + M + I
1246 Adipogenic Subclone of CH3 mouse teratocarcinoma cell line T984[9] D + M + I
Non-committed with adipogenic potential
NIH3T3 NIH Swiss mouse embryo cells[10] Ectopic expression of PPAR-gamma, C/EBP-alpha or C/EBP-beta + D+ M+ I
Swiss 3T3 Swiss mouse embryo cells[11] Ectopic expression of C/EBP-alpha
Balb/3T3 Balb/c mouse embryo cells[12] Ectopic expression of C/EBP-alpha
C3H 10T1/2 C3H mouse embryo cells[13] PPAR-gamma ligand
Kusa 4b10 mouse bone marrow stromal cell line[14] FBS + I + D + M
C2C12 Thigh muscles of C3H mice[15] Thiazolidinediones
G8 Hind limb muscles of fetal Swiss webster mouse[16] Ectopic expression of PPAR-gamma + CEBP/alpha +D + I
FBS = Fetal Bovine Serum, D = Dexamethasone, I = Insulin, M = Methylisobutylxanthine T3 = Triidothyronine

In vivo

An approach of studying adipose tissue development and regulation of adipose specific gene expression in an in vivo context was developed by Mandrup and co-workers.[17] 3T3-F4424 cells when implanted into an athymic (nude) mice gave rise to fat pads that were similar to endogenous white adipose tissue.[18]

Another approach, developed by Scherer and his colleagues is the AdipoChaser system.[19] This mouse uses and inducible, adipose specific LacZ transgene, where one can label all the currently existing adipocytes as LacZ positive (blue stained) and evaluate the new (white, unlabelled) adipocytes in vivo.

Hormonal regulation

Endocrine factors

Products of endocrine system such as insulin, IGF-1, cAMP, glucocorticoid,and triiodothyronine effectively induce adipogenesis in preadipocytes.[20][21][22]

References

  1. ↑ Cornelius, P; MacDougald, OA, Lane, MD (1994). "Regulation of adipocyte development.". Annual Review of Nutrition 14: 99–129. doi:10.1146/annurev.nu.14.070194.000531. PMID 7946535.
  2. ↑ MacDougald, OA; Lane, MD (1995). "Transcriptional regulation of gene expression during adipocyte differentiation.". Annual Review of Biochemistry 64: 345–73. doi:10.1146/annurev.bi.64.070195.002021. PMID 7574486.
  3. ↑ Kirkland, JL; Hollenberg, CH, Gillon, WS (Feb 1990). "Age, anatomic site, and the replication and differentiation of adipocyte precursors.". The American journal of physiology 258 (2 Pt 1): C206–10. PMID 2305864.
  4. ↑ Green, Howard; Kehinde, Olaniyi (28 February 1974). "Sublines of mouse 3T3 cells that accumulate lipid". Cell 1 (3): 113–116. doi:10.1016/0092-8674(74)90126-3.
  5. ↑ Green, H; Kehinde, O (Jan 1976). "Spontaneous heritable changes leading to increased adipose conversion in 3T3 cells.". Cell 7 (1): 105–13. doi:10.1016/0092-8674(76)90260-9. PMID 949738.
  6. ↑ R, Negrel; Grimaldi P; Ajlhaud G (December 1978). "Establishment of preadipocyte clonal line from epididymal fat pad of ob/ob mouse that responds to insulin and to lipolytic hormones" (PDF). Proc. Natl. Acad. Sci. USA 75 (12): 6054–6058. doi:10.1073/pnas.75.12.6054.
  7. ↑ Chapman, AB; Knight, DM, Dieckmann, BS, Ringold, GM (Dec 25, 1984). "Analysis of gene expression during differentiation of adipogenic cells in culture and hormonal control of the developmental program.". The Journal of Biological Chemistry 259 (24): 15548–55. PMID 6392298.
  8. ↑ Pape, ME; Kim, KH (May 1988). "Effect of tumor necrosis factor on acetyl-coenzyme A carboxylase gene expression and preadipocyte differentiation.". Molecular endocrinology (Baltimore, Md.) 2 (5): 395–403. doi:10.1210/mend-2-5-395. PMID 2901666.
  9. ↑ Darmon, M; Serrero, G; Rizzino, A; Sato, G (Apr 1981). "Isolation of myoblastic, fibro-adipogenic, and fibroblastic clonal cell lines from a common precursor and study of their requirements for growth and differentiation.". Experimental Cell Research 132 (2): 313–27. doi:10.1016/0014-4827(81)90107-5. PMID 7215448.
  10. ↑ Jainchill, JL; Aaronson, SA, Todaro, GJ (Nov 1969). "Murine sarcoma and leukemia viruses: assay using clonal lines of contact-inhibited mouse cells.". Journal of Virology 4 (5): 549–53. PMC 375908. PMID 4311790.
  11. ↑ TODARO, GJ; GREEN, H (May 1963). "Quantitative studies of the growth of mouse embryo cells in culture and their development into established lines.". The Journal of Cell Biology 17: 299–313. doi:10.1083/jcb.17.2.299. PMC 2106200. PMID 13985244.
  12. ↑ Aaronson, SA; Todaro, GJ (Oct 1968). "Development of 3T3-like lines from Balb-c mouse embryo cultures: transformation susceptibility to SV40.". Journal of cellular physiology 72 (2): 141–8. doi:10.1002/jcp.1040720208. PMID 4301006.
  13. ↑ Reznikoff, CA; Brankow, DW, Heidelberger, C (Dec 1973). "Establishment and characterization of a cloned line of C3H mouse embryo cells sensitive to postconfluence inhibition of division.". Cancer Research 33 (12): 3231–8. PMID 4357355.
  14. ↑ Allan, EH; Häusler KD,Wei T, Gooi JH, Quinn JM, Crimeen-Irwin B, Pompolo S, Sims NA, Gillespie MT, Onyia JE, Martin TJ C (Aug 2008). "EphrinB2 regulation by PTH and PTHrP revealed by molecular profiling in differentiating osteoblasts.". J Bone Miner Res 23 (8): 1170–81. doi:10.1359/jbmr.080324. PMID 18627264.
  15. ↑ Yaffe, D; Saxel, O (Dec 22–29, 1977). "Serial passaging and differentiation of myogenic cells isolated from dystrophic mouse muscle.". Nature 270 (5639): 725–7. doi:10.1038/270725a0. PMID 563524.
  16. ↑ Christian, CN; Nelson, PG, Peacock, J, Nirenberg, M (May 27, 1977). "Synapse formation between two clonal cell lines.". Science 196 (4293): 995–8. doi:10.1126/science.193191. PMID 193191.
  17. ↑ Mandrup, S; Loftus, TM, MacDougald, OA, Kuhajda, FP, Lane, MD (Apr 29, 1997). "Obese gene expression at in vivo levels by fat pads derived from s.c. implanted 3T3-F442A preadipocytes.". Proceedings of the National Academy of Sciences of the United States of America 94 (9): 4300–5. doi:10.1073/pnas.94.9.4300. PMC 20717. PMID 9113984.
  18. ↑ Green, H; Kehinde, O (Oct 1979). "Formation of normally differentiated subcutaneous fat pads by an established preadipose cell line.". Journal of cellular physiology 101 (1): 169–71. doi:10.1002/jcp.1041010119. PMID 541350.
  19. ↑ Wang, Qiong A; Tao, Caroline; Gupta, Rana K; Scherer, Philipp E (2013). "Tracking adipogenesis during white adipose tissue development, expansion and regeneration". Nature Medicine 19 (10): 1338–1344. doi:10.1038/nm.3324. ISSN 1078-8956.
  20. ↑ Student, AK; Hsu, RY, Lane, MD (May 25, 1980). "Induction of fatty acid synthetase synthesis in differentiating 3T3-L1 preadipocytes.". The Journal of Biological Chemistry 255 (10): 4745–50. PMID 7372608.
  21. ↑ Spiegelman, BM; Green, H (Sep 25, 1980). "Control of specific protein biosynthesis during the adipose conversion of 3T3 cells.". The Journal of Biological Chemistry 255 (18): 8811–18. PMID 6773950.
  22. ↑ Amri, EZ; Dani, C; Doglio, A; Etienne, J; Grimaldi, P; Ailhaud, G (Aug 15, 1986). "Adipose cell differentiation: evidence for a two-step process in the polyamine-dependent Ob1754 clonal line.". The Biochemical Journal 238 (1): 115–22. doi:10.1042/bj2380115. PMC 1147104. PMID 3800927.
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