scholarly journals PPAR: The Portrait of a Target Ally to Cancer Chemopreventive Agents

PPAR Research ◽  
2008 ◽  
Vol 2008 ◽  
pp. 1-10 ◽  
Author(s):  
Ioannis Sainis ◽  
Katerina Vareli ◽  
Vasilios Karavasilis ◽  
Evangelos Briasoulis
Keyword(s):  
Cell Differentiation ◽  
Adipocyte Differentiation ◽  
Peroxisome Proliferator ◽  
Biological Processes ◽  
Peroxisome Proliferator Activated Receptor ◽  
Chemopreventive Agents ◽  
Bioactive Natural Products ◽  
Great Relevance ◽  
Ppar Ligands ◽  
Tumor Types

Peroxisome proliferator-activated receptor-gamma (PPAR), one of three ligand-activated transcription factors named PPAR, has been identified as a molecular target for cancer chemopreventive agents. PPAR was initially understood as a regulator of adipocyte differentiation and glucose homeostasis while later on, it became evident that it is also involved in cell differentiation, apoptosis, and angiogenesis, biological processes which are deregulated in cancer. It is now established that PPAR ligands can induce cell differentiation and yield early antineoplastic effects in several tumor types. Moreover, several bioactive natural products with cancer protecting potential are shown to operate through activation of PPAR. Overall, PPAR appears to be a prevalent target ally to cancer chemopreventive agents and therefore pursuing research in this area is of great relevance.

scholarly journals Functions of Peroxisome Proliferator-Activated Receptor Gamma (PPARγ) in Gynecologic Disorders

2015 ◽  
Vol 9 ◽  
pp. CMO.S23527 ◽  
Author(s):  
Ping Ren ◽  
Yuquan Zhang ◽  
Yan Huang ◽  
Yingli Yang ◽  
Ming Jiang
Keyword(s):  
Cell Differentiation ◽  
Energy Metabolism ◽  
Hormone Receptors ◽  
Adipocyte Differentiation ◽  
Peroxisome Proliferator ◽  
Regulation Of Expression ◽  
Peroxisome Proliferator Activated Receptor ◽  
Gynecological Disorders ◽  
Apoptosis And Inflammation ◽  
Regulate Energy Metabolism

Peroxisome proliferator-activated receptor gamma (PPARγ) is a member of a class of nuclear hormone receptors intimately involved in the regulation of expression of myriad genes that regulate energy metabolism, cell differentiation, apoptosis, and inflammation. Although originally discovered as a pivotal regulator of adipocyte differentiation, the roles that PPARγ plays in gynecological disorders are still unknown. There are a number of studies on the functions of PPARγ and its agonists in gynecological disorders. In this mini-review, we provide a brief summary of the advances in recent years.

scholarly journals The Multiple Endocrine Neoplasia Type 1 (MEN1) Tumor Suppressor Regulates Peroxisome Proliferator-Activated Receptor γ-Dependent Adipocyte Differentiation

2009 ◽  
Vol 29 (18) ◽  
pp. 5060-5069 ◽  
Author(s):  
Koen M. A. Dreijerink ◽  
Radhika A. Varier ◽  
Olivier van Beekum ◽  
Ellen H. Jeninga ◽  
Jo W. M. Höppener ◽  
...  
Keyword(s):  
Tumor Suppressor ◽  
Adipocyte Differentiation ◽  
Activation Function ◽  
Suppressor Gene ◽  
Peroxisome Proliferator ◽  
Methyltransferase Activity ◽  
Peroxisome Proliferator Activated Receptor ◽  
Lxxll Motif ◽  
Helix 12 ◽  
Tumor Types

ABSTRACT Menin, the product of the MEN1 (multiple endocrine neoplasia type 1) tumor suppressor gene, is involved in activation of gene transcription as part of an MLL1 (mixed-lineage leukemia 1)/MLL2 (KMT2A/B)-containing protein complex which harbors methyltransferase activity for lysine 4 of histone H3 (H3K4). As MEN1 patients frequently develop lipomas and peroxisome proliferator-activated receptor γ (PPARγ) is expressed in several MEN1-related tumor types, we investigated regulation of PPARγ activity by menin. We found that menin is required for adipocyte differentiation of murine 3T3-L1 cells and PPARγ-expressing mouse embryonic fibroblasts. Menin augments PPARγ target gene expression through recruitment of H3K4 methyltransferase activity. Menin interacts directly with the activation function 2 transcription activation domain of PPARγ in a ligand-independent fashion. Ligand-dependent coactivation, however, is dependent on the LXXLL motif of menin and the intact helix 12 of PPARγ. We propose that menin is an important factor in PPARγ-mediated adipogenesis and that loss of PPARγ function may contribute to lipoma development in MEN1 patients.

Adipocyte differentiation of 3T3-L1 preadipocytes is dependent on lipoxygenase activity during the initial stages of the differentiation process

2003 ◽  
Vol 375 (3) ◽  
pp. 539-549 ◽  
Author(s):  
Lise MADSEN ◽  
Rasmus K. PETERSEN ◽  
Morten B. SØRENSEN ◽  
Claus JØRGENSEN ◽  
Philip HALLENBORG ◽  
...  
Keyword(s):  
Adipocyte Differentiation ◽  
Critical Evaluation ◽  
Nordihydroguaiaretic Acid ◽  
Whole Body ◽  
Transcriptional Networks ◽  
Peroxisome Proliferator ◽  
The Novel ◽  
Differentiation Process ◽  
Peroxisome Proliferator Activated Receptor ◽  
Brown Adipose

Adipocytes play a central role in whole-body energy homoeostasis. Complex regulatory transcriptional networks control adipogensis, with ligand-dependent activation of PPARγ (peroxisome proliferator-activated receptor γ) being a decisive factor. Yet the identity of endogenous ligands promoting adipocyte differentiation has not been established. Here we present a critical evaluation of the role of LOXs (lipoxygenases) during adipocyte differentiation of 3T3-L1 cells. We show that adipocyte differentiation of 3T3-L1 preadipocytes is inhibited by the general LOX inhibitor NDGA (nordihydroguaiaretic acid) and the 12/15-LOX selective inhibitor baicalein. Baicalein-mediated inhibition of adipocyte differentiation was rescued by administration of rosiglitazone. Treatment with baicalein during the first 4 days of the differentiation process prevented adipocyte differentiation; supplementation with rosiglitazone during the same period was sufficient to rescue adipogenesis. Accordingly, we demonstrate that adipogenic conversion of 3T3-L1 cells requires PPARγ ligands only during the first 4 days of the differentiation process. We show that the baicalein-sensitive synthesis of endogenous PPARγ ligand(s) increases rapidly upon induction of differentiation and reaches a maximum on days 3–4 of the adipocyte differentiation programme. The conventional platelet- and leucocyte-type 12(S)-LOXs and the novel eLOX-3 (epidermis-type LOX-3) are expressed in white and brown adipose tissue, whereas only eLOX-3 is clearly expressed in 3T3-L1 cells. We suggest that endogenous PPARγ ligand(s) promoting adipocyte differentiation are generated via a baicalein-sensitive pathway involving the novel eLOX-3.

scholarly journals Evidence for the Regulatory Role of Lipocalin 2 in High-Fat Diet-Induced Adipose Tissue Remodeling in Male Mice

Endocrinology ◽  
2013 ◽  
Vol 154 (10) ◽  
pp. 3525-3538 ◽  
Author(s):  
Hong Guo ◽  
Merlijn Bazuine ◽  
Daozhong Jin ◽  
Merry M. Huang ◽  
Samuel W. Cushman ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
High Fat Diet ◽  
Adipocyte Differentiation ◽  
Tissue Remodeling ◽  
Peroxisome Proliferator ◽  
Lipocalin 2 ◽  
Peroxisome Proliferator Activated Receptor ◽  
Adipose Tissue Remodeling ◽  
Fat Depot

Lipocalin 2 (Lcn2) has previously been characterized as an adipokine/cytokine playing a role in glucose and lipid homeostasis. In this study, we investigate the role of Lcn2 in adipose tissue remodeling during high-fat diet (HFD)-induced obesity. We find that Lcn2 protein is highly abundant selectively in inguinal adipose tissue. During 16 weeks of HFD feeding, the inguinal fat depot expanded continuously, whereas the expansion of the epididymal fat depot was reduced in both wild-type (WT) and Lcn2−/− mice. Interestingly, the depot-specific effect of HFD on fat mass was exacerbated and appeared more pronounced and faster in Lcn2−/− mice than in WT mice. In Lcn2−/− mice, adipocyte hypertrophy in both inguinal and epididymal adipose tissue was more profoundly induced by age and HFD when compared with WT mice. The expression of peroxisome proliferator-activated receptor-γ protein was significantly down-regulated, whereas the gene expression of extracellular matrix proteins was up-regulated selectively in epididymal adipocytes of Lcn2−/− mice. Consistent with these observations, collagen deposition was selectively higher in the epididymal, but not in the inguinal adipose depot of Lcn2−/− mice. Administration of the peroxisome proliferator-activated receptor-γ agonist rosiglitazone (Rosi) restored adipogenic gene expression. However, Lcn2 deficiency did not alter the responsiveness of adipose tissue to Rosi effects on the extracellular matrix expression. Rosi treatment led to the further enlargement of adipocytes with improved metabolic activity in Lcn2−/− mice, which may be associated with a more pronounced effect of Rosi treatment in reducing TGF-β in Lcn2−/− adipose tissue. Consistent with these in vivo observations, Lcn2 deficiency reduces the adipocyte differentiation capacity of stromal-vascular cells isolated from HFD-fed mice in these cells. Herein Rosi treatment was again able to stimulate adipocyte differentiation to a similar extent in WT and Lcn2−/− inguinal and epididymal stromal-vascular cells. Thus, combined, our data indicate that Lcn2 has a depot-specific role in HFD-induced adipose tissue remodeling.

scholarly journals Flubendiamide Enhances Adipogenesis and Inhibits AMPKα in 3T3-L1 Adipocytes

Molecules ◽  
2018 ◽  
Vol 23 (11) ◽  
pp. 2950 ◽  
Author(s):  
Quancai Sun ◽  
Jie Lin ◽  
Yukui Peng ◽  
Ruichang Gao ◽  
Ye Peng
Keyword(s):  
Adipocyte Differentiation ◽  
Peroxisome Proliferator ◽  
Potential Influence ◽  
Peroxisome Proliferator Activated Receptor ◽  
Acetyl Coenzyme A ◽  
Enhancer Binding Protein ◽  
Triglyceride Content ◽  
Important Regulator ◽  
Amp Activated Protein Kinase ◽  
Acetyl Coenzyme A Carboxylase

Flubendiamide, a ryanoid class insecticide, is widely used in agriculture. Several insecticides have been reported to promote adipogenesis. However, the potential influence of flubendiamide on adipogenesis is largely unknown. The current study was therefore to determine the effects of flubendiamide on adipogenesis utilizing the 3T3-L1 adipocytes model. Flubendiamide treatment not only enhanced triglyceride content in 3T3-L1 adipocytes, but also increased the expression of cytosine-cytosine-adenosine-adenosine-thymidine (CCAAT)/enhancer-binding protein α and peroxisome proliferator-activated receptor gamma-γ, two important regulators of adipocyte differentiation. Moreover, the expression of the most important regulator of lipogenesis, acetyl coenzyme A carboxylase, was also increased after flubendiamide treatment. Further study revealed that 5-aminoimidazole-4-carboxamide ribonucleotide (AICAR) or A769662, two Adenosine 5′-monophosphate (AMP)-activated protein kinase α activators, subverted effects of flubendiamide on enhanced adipogenesis. Together, these results suggest that flubendiamide promotes adipogenesis via an AMPKα-mediated pathway.

Methanol Extract of Mongolian Iris bungei Maxim. Stimulates 3T3-L1 Adipocyte Differentiation

2021 ◽  
Vol 21 (7) ◽  
pp. 3943-3949
Author(s):  
Jaegoo Yeon ◽  
Sung-Suk Suh ◽  
Ui-Joung Youn ◽  
Badamtsetseg Bazarragchaa ◽  
Ganbold Enebish ◽  
...  
Keyword(s):  
Bacterial Infections ◽  
Fatty Acid Synthase ◽  
Molecular Mechanisms ◽  
Adipocyte Differentiation ◽  
Methanol Extract ◽  
Regulatory Element ◽  
Peroxisome Proliferator ◽  
Dependent Manner ◽  
Concentration Dependent Manner ◽  
Peroxisome Proliferator Activated Receptor

Iris bungei Maxim. (IB), which is native to China and Mongolia, is used as a traditional medicine for conditions such as inflammation, cancer, and bacterial infections. However, the effects of Iris bungei Maxim. on adipocyte differentiation have not been studied. In the present study, we first demonstrated the molecular mechanisms underlying the adipogenic activity of the methanol extract of Mongolian I. bungei Maxim. (IB). IB significantly enhanced intracellular lipid accumulation and adipocyte differentiation in 3T3-L1 preadipocytes in a concentration-dependent manner. Moreover, IB markedly stimulated the expression of genes related to adipogenesis such as peroxisome proliferator-activated receptor γ, adiponectin, and aP2. In addition, we also observed that IB induces lipogenic genes such as fatty acid synthase, sterol regulatory element binding protein 1c, stearoyl-CoA desaturase, and acetyl-CoA carboxylase. Interestingly IB regulated adipocyte differentiation in both the early and middle stages. Taken together, these adipogenic and lipogenic effects of IB suggest its efficacy for the prevention and/or treatment of type 2 diabetes.

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