Early expression of p107 is associated with 3T3-L1 adipocyte differentiation

Liu, Kenian; Yu, Guoce; MacNicol, Melanie C.; MacNicol, Angus M.; McGehee, Robert E.

doi:10.1016/s0303-7207(02)00188-0

Cited by 19 publications

(17 citation statements)

References 22 publications

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“…In 3T3-L1 cells, the p130:p107 switch was originally thought to be involved in regulating the cell cycle re-entry leading to the clonal expansion phase [15]. However, it was subsequently reported using 3T3-L1 cells under pharmacological manipulation with the MEK inhibitors, PD98059, or U0126, that terminal adipocyte differentiation and clonal expansion could be uncoupled, resulting in complete adipocyte differentiation in the absence of clonal expansion [8]. These experiments also demonstrated that the transient increase in p107 protein expression was independent of clonal expansion, suggesting a role for p107 in terminal adipocyte differentiation, an observation consistent with another study that demonstrated antisense inhibition of p107 protein expression blocked differentiation in 3T3-L1 cells [16].…”

Section: Discussionmentioning

confidence: 99%

“…The cells where re-fed every 3 days with adipocyte medium [9,13]. Cells were stained with Oil Red O, harvested for RNA analysis, harvested for protein analysis, or counted via hemocytometer as previously described [8]. …”

Section: Methodsmentioning

confidence: 99%

Section: Nih-pa Author Manuscriptmentioning

confidence: 99%

“…Cells were grown as previously described [8] on 60 mm plates and stimulated to differentiate using the protocol outlined above. Cells were counted at the same time in daily intervals from day 0 to day 10 of differentiation.…”

Section: Cell Countingmentioning

confidence: 99%

“…By terminal differentiation on day 4, there is a resetting of the switch back to levels observed in quiescent day 0 cells [6]. Additional studies in which expression of these proteins were examined under conditions that uncoupled clonal expression from differentiation revealed that p107 is associated with terminal adipocyte differentiation and not the clonal expansion phase, while p130 was more associated with clonal expansion and not terminal differentiation [8].Several recent reports have demonstrated that human adipose-derived stem cells (hASC) isolated from human adipose tissue are multipotent and capable of undergoing in vitro differentiation into adipocytes as well as other mesenchymal lineages [9][10][11]. hASC therefore provide a unique cell model in which to investigate human adipogenesis.…”

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Expression of p107 and p130 during human adipose-derived stem cell adipogenesis

Ross

Tsang

Shewmake

et al. 2008

Biochemical and Biophysical Research Communications

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Within the first 24 h of hormonally stimulated adipocyte differentiation, murine 3T3-L1 preadipocytes undergo a mitotic expansion phase prior to terminal differentiation. During this time, the cell cycle regulatory proteins, p130 and p107 undergo dramatic differential expression and the transient increase in expression of p107 appears to be required for terminal differentiation. Recently, human adipose-derived human stem cells (hASC) of mesenchymal origin have been used as a model of human adipocyte differentiation and we sought to determine if differentiating hASC undergo clonal expansion and if the regulated expression of p130/p107 was similar to that observed during 3T3-L1 adipogenesis. Results indicate that differentiating hASC, unlike 3T3-L1 cells do not undergo clonal expansion and p130 expression gradually diminishes across differentiation. However, p107 expression is transiently increased during hASC differentiation in a manner analogous to 3T3-L1 cells suggesting a similar role for p107 in terminal differentiation in human adipocytes. Keywords3T3-L1 cells; hASC cells; Human adult stem cells; Adipocyte differentiation; p130; p107The past 20 years have seen a dramatic increase in obesity in the United States. To date, more than 17% of American children and adolescents are considered overweight, and almost one third of adults are classified as obese [1]. This is particularly alarming given that obesity represents a significant risk factor for many diseases and health conditions including hypertension, dyslipidemia, type 2 diabetes, coronary heart disease, stroke, gallbladder disease, osteoarthritis, sleep apnea, and endometrial, breast, and colon cancers [1]. Due to the increasing epidemic of obesity and the health risks associated with the condition, much research has focused on identifying the underlying causes of obesity. However, in order to develop better control strategies, a better understanding of the molecular mechanisms that initiate differentiation of preadipocytes and stem cell into adipocytes in humans is still needed.Significant portions of the current understanding of adipocyte differentiation have been obtained through the study of in vitro cellular models of adipocyte differentiation such as the murine 3T3-L1 preadipocyte cell line and the process of 3T3-L1 preadipocyte differentiation into mature adipocytes is well characterized [2,3]. Culturing 3T3-L1 cells in serumsupplemented medium results in growth to confluence, leading to contact inhibition and growth arrest [4]. Differentiation is induced by a 4 day hormonal treatment regimen consisting of insulin, dexamethasone, and 1-methyl-3-isobutylmethylxanthine [5]. Hormonal induction results in re-entry into the cell cycle, and the cells undergo one to two rounds of mitotic clonal NIH-PA Author ManuscriptNIH-PA Author Manuscript NIH-PA Author Manuscript expansion for about 24-36 h. They then permanently withdraw from the cell cycle and undergo terminal differentiation into mature adipocytes [6]. We have previously demonstrated that...

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Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Nih-pa Author Manuscriptmentioning

confidence: 99%

Section: Cell Countingmentioning

confidence: 99%

mentioning

confidence: 99%

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Expression of p107 and p130 during human adipose-derived stem cell adipogenesis

Ross

Tsang

Shewmake

et al. 2008

Biochemical and Biophysical Research Communications

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Luteolin inhibits adipogenic differentiation by regulating PPARγ activation

Park

Kim

et al. 2009

BioFactors

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Luteolin (3',4',5,7-tetrahydroxyflavone), a flavonoid, has been known to possess antimutagenic, antitumorigenic, antioxidant, and anti-inflammatory properties. In this study, we investigated the role of luteolin in the regulation of adipogenic differentiation in 3T3-L1 preadipocytes. Luteolin inhibited intracellular triglyceride accumulation in a dose-dependent manner without cytotoxicity. Western blot and reverse transcription-polymerase chain reaction analyses showed that this inhibition was accompanied by attenuated expression of the adipogenic transcription factors: peroxisome proliferator-activated receptor gamma (PPARgamma) and CCAAT/enhancer-binding protein alpha. Luteolin inhibited the PPARgamma transactivation stimulated by rosiglitazone, a synthetic agonist, in COS-7 cells and inhibited rosiglitazone-induced adipogenic differentiation in 3T3-L1 cells. These data suggest that luteolin exerts antiadipogenic effects by suppressing adipogenic transcription factors and by inhibiting the transactivation of PPARgamma.

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p107 Determines a Metabolic Checkpoint Required for Adipocyte Lineage Fates

et al. 2017

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We show that the transcriptional corepressor p107 orchestrates a metabolic checkpoint that determines adipocyte lineage fates for non-committed progenitors. p107 accomplishes this when stem cell commitment would normally occur in growth arrested cells. p107-deficient embryonic progenitors are characterized by a metabolic state resembling aerobic glycolysis that is necessary for their pro-thermogenic fate. Indeed, during growth arrest they have a reduced capacity for NADH partitioning between the cytoplasm and mitochondria. Intriguingly, this occurred despite an increase in the capacity for mitochondrial oxidation of non-glucose substrates. The significance of metabolic reprogramming is underscored by the disruption of glycolytic capacities in p107-depleted progenitors that reverted their fates from pro-thermogenic to white adipocytes. Moreover, the manipulation of glycolytic capacity on nonspecified embryonic and adult progenitors forced their beige fat commitment. These innovative findings introduce a new approach to increase pro-thermogenic adipocytes based on simply promoting aerobic glycolysis to manipulate nonspecified progenitor fate decisions. Stem Cells 2017;35:1378-1391.

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Early expression of p107 is associated with 3T3-L1 adipocyte differentiation

Cited by 19 publications

References 22 publications

Expression of p107 and p130 during human adipose-derived stem cell adipogenesis

Expression of p107 and p130 during human adipose-derived stem cell adipogenesis

Luteolin inhibits adipogenic differentiation by regulating PPARγ activation

p107 Determines a Metabolic Checkpoint Required for Adipocyte Lineage Fates

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