Adipocytes play a vital role in energy homeostasis and process the largest energy reserve as triglycerol in the body of animals. 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
The transition of the fibroblast cells to mature adipocytes is one of the best characterized processes of cellular differentiation. 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.
|Cell Line||Origin||Differentiation Protocol|
|3T3-L1||Sub-clone of Swiss 3T3||FBS+ I+ D+ M|
|3T3-F442A||Sub-clone of Swiss 3T3||FBS + I|
|Ob17||Differentiated adipocyte from epididymal fat pad of C57BL/6J ob/ob mice||FBS+ I+ T3|
|TA1||Subclone of C3H10T1/2 ||FBS + D + I|
|30A5||Subclone of C3H10T1/2||FBS + D + M + I|
|1246||Adipogenic Subclone of CH3 mouse teratocarcinoma cell line T984||D + M + I|
|Non-committed with adipogenic potential|
|NIH3T3||NIH Swiss mouse embryo cells||Ectopic expression of PPAR-gamma, C/EBP-alpha or C/EBP-beta + D+ M+ I|
|Swiss 3T3||Swiss mouse embryo cells||Ectopic expression of C/EBP-alpha|
|Balb/3T3||Balb/c mouse embryo cells||Ectopic expression of C/EBP-alpha|
|C3H 10T1/2||C3H mouse embryo cells||PPAR-gamma ligand|
|Kusa 4b10||mouse bone marrow stromal cell line||FBS + I + D + M|
|C2C12||Thigh muscles of C3H mice||Thiazolidinediones|
|G8||Hind limb muscles of fetal Swiss webster mouse||Ectopic expression of PPAR-gamma + CEBP/alpha +D + I|
|FBS = Fetal Bovine Serum, D = Dexamethasone, I = Insulin, M = Methylisobutylxanthine T3 = Triidothyronine|
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. 3T3-F4424 cells when implanted into an athymic (nude) mice gave rise to fat pads that were similar to endogenous white adipose tissue.
Another approach, developed by Scherer and his colleagues is the AdipoChaser system. This mouse uses an 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.
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