scholarly journals Energy Balance, Myostatin, and GILZ: Factors Regulating Adipocyte Differentiation in Belly and Bone

PPAR Research ◽  
2007 ◽  
Vol 2007 ◽  
pp. 1-12 ◽  
Author(s):  
Xingming Shi ◽  
Mark Hamrick ◽  
Carlos M. Isales
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Energy Balance ◽  
Therapeutic Strategy ◽  
Adipocyte Differentiation ◽  
Bone Development ◽  
Nuclear Hormone Receptor ◽  
Liver Fat ◽  
Peroxisome Proliferator ◽  
Peroxisome Proliferator Activated Receptor

Peroxisome proliferator-activated receptor gamma (PPAR-γ) belongs to the nuclear hormone receptor subfamily of transcription factors. PPARs are expressed in key target tissues such as liver, fat, and muscle and thus they play a major role in the regulation of energy balance. Because of PPAR-γ's role in energy balance, signals originating from the gut (e.g., GIP), fat (e.g., leptin), muscle (e.g., myostatin), or bone (e.g., GILZ) can in turn modulate PPAR expression and/or function. Of the two PPAR-γisoforms, PPAR-γ2 is the key regulator of adipogenesis and also plays a role in bone development. Activation of this receptor favors adipocyte differentiation of mesenchymal stem cells, while inhibition of PPAR-γ2 expression shifts the commitment towards the osteoblastogenic pathway. Clinically, activation of this receptor by antidiabetic agents of the thiazolidinedione class results in lower bone mass and increased fracture rates. We propose that inhibition of PPAR-γ2 expression in mesenchymal stem cells by use of some of the hormones/factors mentioned above may be a useful therapeutic strategy to favor bone formation.

Regulation of adipocyte differentiation of 3T3-L1 cells by PDZRN3

2013 ◽  
Vol 304 (11) ◽  
pp. C1091-C1097 ◽  
Author(s):  
Takeshi Honda ◽  
Aiko Ishii ◽  
Makoto Inui
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Adipocyte Differentiation ◽  
Early Stage ◽  
Adipogenic Differentiation ◽  
Peroxisome Proliferator ◽  
Peroxisome Proliferator Activated Receptor ◽  
Protein Levels ◽  
Upstream Regulator ◽  
Pparγ Expression

PDZRN3, a member of the PDZRN (or LNX) family of proteins, is essential for the differentiation of mesenchymal stem cells into myotubes, but it plays an inhibitory role in the differentiation of these cells into osteoblasts. Given that mesenchymal stem cells also differentiate into adipocytes, we examined the possible role of PDZRN3 in adipogenesis in mouse 3T3-L1 preadipocytes. The expression of PDZRN3 decreased at both the mRNA and protein levels during adipogenic differentiation. RNAi-mediated depletion of PDZRN3 enhanced the differentiation of 3T3-L1 cells into adipocytes as assessed on the basis of lipid accumulation. The upregulation of aP2 and CCAAT/enhancer-binding protein (C/EBP)-β during adipocyte differentiation was also enhanced in the PDZRN3-depleted cells, as was the induction of peroxisome proliferator-activated receptor-γ (PPARγ), an upstream regulator of aP2 and C/EBPα, at both the mRNA and protein levels. Among transcription factors that control the expression of PPARγ, we found that STAT5b, but not STAT5a, was upregulated in PDZRN3-depleted cells at both mRNA and protein levels. Tyrosine phosphorylation of STAT5b, but not that of STAT5a, was also enhanced at an early stage of differentiation by PDZRN3 depletion. In addition, the expression of C/EBPβ during the induction of differentiation was enhanced at the mRNA and protein levels in PDZRN3-depleted cells. Our results thus suggest that PDZRN3 negatively regulates adipogenesis in 3T3-L1 cells through downregulation of STAT5b and C/EBPβ and consequent suppression of PPARγ expression.

scholarly journals PPAR-γSignaling Crosstalk in Mesenchymal Stem Cells

PPAR Research ◽  
2010 ◽  
Vol 2010 ◽  
pp. 1-6 ◽  
Author(s):  
Ichiro Takada ◽  
Alexander P. Kouzmenko ◽  
Shigeaki Kato
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Target Gene ◽  
Adipocyte Differentiation ◽  
Protein Complexes ◽  
Regulatory Function ◽  
Target Cells ◽  
Peroxisome Proliferator ◽  
Gene Promoters ◽  
Peroxisome Proliferator Activated Receptor

Peroxisome proliferator-activated receptor-gamma (PPAR-γ) is a member of the nuclear receptor (NR) superfamily of ligand-activated transcriptional factors. Among other functions, PPAR-γacts as a key regulator of the adipogenesis. Since several cytokines (IL-1, TNF-α, TGF-β) had been known to inhibit adipocyte differentiation in mesenchymal stem cells (MSCs), we examined the effect of these cytokines on the transactivation function of PPAR-γ. We found that the TNF-α/IL-1-activated TAK1/TAB1/NIK (NFκB-inducible kinase) signaling cascade inhibited both the adipogenesis and Tro-induced transactivation by PPAR-γby blocking the receptor binding to the cognate DNA response elements. Furthermore, it has been shown that the noncanonical Wnts are expressed in MSCs and that Wnt-5a was capable to inhibit transactivation by PPAR-γ. Treatment with Wnt5a-activated NLK (nemo-like kinase) induced physical association of the endogenous NLK and H3K9 histone methyltransferase (SETDB1) protein complexes with PPAR-γ. This resulted in histoneH3K9 tri-methylation at PPAR-γtarget gene promoters. Overall, our data show that cytokines and noncanonical Wnts play a crucial role in modulation of PPAR-γregulatory function in its target cells and tissues.

scholarly journals Simulated Microgravity Suppresses Osteogenic Differentiation of Mesenchymal Stem Cells by Inhibiting Oxidative Phosphorylation

2020 ◽  
Vol 21 (24) ◽  
pp. 9747
Author(s):  
Lin Liu ◽  
Yansiwei Cheng ◽  
Jie Wang ◽  
Zhongjie Ding ◽  
Alexander Halim ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Energy Metabolism ◽  
Oxidative Phosphorylation ◽  
Osteogenic Differentiation ◽  
Simulated Microgravity ◽  
Sirtuin 1 ◽  
Peroxisome Proliferator ◽  
Mtdna Copy Number ◽  
Peroxisome Proliferator Activated Receptor

Studies showed that energy metabolism plays a pivotal role in the differentiation of stem cells. Previous studies revealed that simulated microgravity (SMG) inhibits osteogenic differentiation of mesenchymal stem cells (MSCs). However, the underlying relationship between osteogenesis and energy metabolism under SMG conditions is not fully understood. In the present study, we investigated mitochondrial oxidative phosphorylation (OXPHOS) by assessing the level of peroxisome proliferator activated receptor γ coactivator 1α (PGC-1α), mitochondrial DNA (mtDNA) copy number, mitochondrial mass and oxygen consumption rate (OCR) during osteogenesis of MSCs under SMG conditions. We found that SMG inhibited osteogenic differentiation and OXPHOS of MSCs. Moreover, the expression of sirtuin 1 (Sirt1), an important energy sensor, significantly decreased. After upregulating the expression of Sirt1 using resveratrol, an activator of Sirt1, SMG-inhibited OXPHOS and osteogenic differentiation of MSCs were recovered. Taken together, our results suggest that SMG suppresses osteogenic differentiation of MSCs by inhibiting OXPHOS, indicating that OXPHOS might serve as a potential therapeutic target for repairing bone loss under microgravity conditions.

scholarly journals Mechanical Strain Inhibits Adipogenesis in Mesenchymal Stem Cells by Stimulating a Durable β-Catenin Signal

Endocrinology ◽  
2008 ◽  
Vol 149 (12) ◽  
pp. 6065-6075 ◽  
Author(s):  
Buer Sen ◽  
Zhihui Xie ◽  
Natasha Case ◽  
Meiyun Ma ◽  
Clinton Rubin ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Glycogen Synthase ◽  
Mechanical Strain ◽  
Bone Morphogenetic Protein 2 ◽  
Peroxisome Proliferator ◽  
Glycogen Synthase Kinase 3Β ◽  
Peroxisome Proliferator Activated Receptor ◽  
Morphogenetic Protein ◽  
Adiponectin Mrna

The ability of exercise to decrease fat mass and increase bone mass may occur through mechanical biasing of mesenchymal stem cells (MSCs) away from adipogenesis and toward osteoblastogenesis. C3H10T1/2 MSCs cultured in highly adipogenic medium express peroxisome proliferator-activated receptor γ and adiponectin mRNA and protein, and accumulate intracellular lipid. Mechanical strain applied for 6 h daily inhibited expression of peroxisome proliferator-activated receptor γ and adiponectin mRNA by up to 35 and 50%, respectively, after 5 d. A decrease in active and total β-catenin levels during adipogenic differentiation was entirely prevented by daily application of mechanical strain; furthermore, strain induced β-catenin nuclear translocation. Inhibition of glycogen synthase kinase-3β by lithium chloride or SB415286 also prevented adipogenesis, suggesting that preservation of β-catenin levels was important to strain inhibition of adipogenesis. Indeed, mechanical strain inactivated glycogen synthase kinase-3β, which was preceded by Akt activation, indicating that strain transmits antiadipogenic signals through this pathway. Cells grown under adipogenic conditions showed no increase in osteogenic markers runt-related transcription factor (Runx) 2 and osterix (Osx); subsequent addition of bone morphogenetic protein 2 for 2 d increased Runx2 but not Osx expression in unstrained cultures. When cultures were strained for 5 d before bone morphogenetic protein 2 addition, Runx2 mRNA increased more than in unstrained cultures, and Osx expression more than doubled. As such, mechanical strain enhanced MSC potential to enter the osteoblast lineage despite exposure to adipogenic conditions. Our results indicate that MSC commitment to adipogenesis can be suppressed by mechanical signals, allowing other signals to promote osteoblastogenesis. These data suggest that positive effects of exercise on both fat and bone may occur during mesenchymal lineage selection.

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