Regulation of Peroxisome Proliferator–Activated Receptor-γ Activity by Mammalian Target of Rapamycin and Amino Acids in Adipogenesis

Kim, Jae Eun; Chen, Jiawen

doi:10.2337/diabetes.53.11.2748

Cited by 419 publications

(355 citation statements)

References 59 publications

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“…At this time point of differentiation, the S6 protein becomes phosphorylated. Both phosphorylation events argue for an increase of the mTOR kinase activity during the adipogenesis (43), which is in agreement with reports in 3T3-L1 cells (44). Down-regulation of the mTORC1 occurs on day 6 through expression changes of the adaptor protein Raptor.…”

Section: Discussionsupporting

confidence: 80%

In situ characterization of the mTORC1 during adipogenesis of human adult stem cells on chip

Schneider

Platen

et al. 2016

Proc. Natl. Acad. Sci. U.S.A.

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Mammalian target of rapamycin (mTOR) is a central kinase integrating nutrient, energy, and metabolite signals. The kinase forms two distinct complexes: mTORC1 and mTORC2. mTORC1 plays an essential but undefined regulatory function for regeneration of adipose tissue. Analysis of mTOR in general is hampered by the complexity of regulatory mechanisms, including protein interactions and/or phosphorylation, in an ever-changing cellular microenvironment. Here, we developed a microfluidic large-scale integration chip platform for culturing and differentiating human adiposederived stem cells (hASCs) in 128 separated microchambers under standardized nutrient conditions over 3 wk. The progression of the stem cell differentiation was measured by determining the lipid accumulation rates in hASC cultures. For in situ protein analytics, we developed a multiplex in situ proximity ligation assay (mPLA) that can detect mTOR in its two complexes selectively in single cells and implemented it on the same chip. With this combined technology, it was possible to reveal that the mTORC1 is regulated in its abundance, phosphorylation state, and localization in coordination with lysosomes during adipogenesis. High-content image analysis and parameterization of the in situ PLA signals in over 1 million cells cultured on four individual chips showed that mTORC1 and lysosomes are temporally and spatially coordinated but not in its composition during adipogenesis.microfluidics | stem cell differentiation | adipogenesis | mTORC1 regulation | multiplexed PLA

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Section: Discussionsupporting

confidence: 80%

In situ characterization of the mTORC1 during adipogenesis of human adult stem cells on chip

Schneider

Platen

et al. 2016

Proc. Natl. Acad. Sci. U.S.A.

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“…[41][42][43] However, in this study, we did not observe frequent activation of mTOR in tumors of smooth muscle cell, adipocyte, or chondrocyte origin in contrast to rhabdomyosarcoma. Probably, the functional involvement of mTOR is different in tumor vs normal tissue, or the involvement of mTOR in those tumors may be transient in the specific stage during oncogenesis.…”

Section: Discussioncontrasting

confidence: 75%

EGFR-dependent and independent activation of Akt/mTOR cascade in bone and soft tissue tumors

et al. 2009

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“…3, June 2014 adipocytes, suggested that rapamycin affected the maintenance of adipogenic characteristics in mature adipocytes. Their study also showed that C/EBPβ and C/EBPδ levels would highly increased one day after induction, and after day 4 it was gradually decreased until day 8 in control group [17]. It is similar with the result of this study.…”

Section: Expression Of C/ebpδsupporting

confidence: 81%

The Role of Creb in Adipogenesis through Mammalian Target of Rapamycin of Complex 1 (mTORC1) Pathyway

Triawanti¹,

Indra²,

Tjokroprawiro³

et al. 2014

IJCEA

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Abstract-One of the tissues taking the biggest part in the pathogenesis of obesity is adipose tissue mainly formed by white fat cells. Recently, the processes adipogenesis become a treatment target for obesity. One of the pathway that allegedly participated in the process of adipogenesis is activated via CREB. The upstream pathway is by means of protein of mammalian targets of rapamycin (mTOR). This study was aimed to determine the role of CREB in adipogenesis through the activation of p70S6K1 by mTORC1.This was an experimental study. Subjects were primary cultured preadipocytes taken from visceral fat of white rats (Rattus norvegicus). Cell cultures were classified into 4 groups: (K) Control of adipogenesis: without rapamycin and RNAi CREB, (A): was given rapamycin 10 nM, (B): was given RNAi CREB 100 nM, (C): was given rapamycin 10 nM and RNAi CREB 100 nM. p70S6K1, CREB activation, and expression of C/EBPδ measured on day 2, 4, and 6, and the morphology of adipocytes on day 6. Data were analyzed with Anova test, LSD test, and Pearson correlation test with 95% confidence level.The data showed that rapamycin activated p70S6K1 and caused lower CREB compared with control group during adipogenesis. These results indicated that adipogenesis was blocked, which resulted from the inhibition of p70S6K1 and CREB activation by rapamycin and RNAi CREB. The inhibition was stronger in rapamycin + RNAi CREB group. Statistically, there was significant correlation between p70S6K1 and CREB; and between CREB and C/EBPδ.It was concluded that the role of CREB in adipogenesis was mediated by the activation of p706K1 by mTORC1.Index Terms-Obesity, adipogenesis, mTORC1, p70S6K1, CREB, C/EBPδ.

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Regulation of Peroxisome Proliferator–Activated Receptor-γ Activity by Mammalian Target of Rapamycin and Amino Acids in Adipogenesis

Cited by 419 publications

References 59 publications

In situ characterization of the mTORC1 during adipogenesis of human adult stem cells on chip

In situ characterization of the mTORC1 during adipogenesis of human adult stem cells on chip

EGFR-dependent and independent activation of Akt/mTOR cascade in bone and soft tissue tumors

The Role of Creb in Adipogenesis through Mammalian Target of Rapamycin of Complex 1 (mTORC1) Pathyway

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