Peroxisome proliferator-activated receptor-&amp;gamma; agonists and diabetes: Current evidence and future perspectives

Chiarelli, Francesco; Marzio, D. Di

doi:10.2147/vhrm.s993

Cited by 107 publications

(38 citation statements)

References 84 publications

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“…The yolk cells in zebrafish were shown to process lipids during development, and the exposure of zebrafish with a PPARγ antagonist changed the composition of the lipid profile of 5DPF larvae with increasing/decreasing effects on different lipid species, mainly phospholipids [50]. Studies in mice and clinical trials of PPARγ agonists as thiazolidinediones showed that PPARγ had a role on the distribution of body fat [51]. As a response to TZD (thiazolidinedione) treatment, the metabolically more harmful adipose tissue (the visceral adipose tissue) decreased, while subcutaneous adipose tissue increased, which in part explained the beneficial effects of TZD.…”

Section: Discussionmentioning

confidence: 99%

Chlorophyll Derivatives from Marine Cyanobacteria with Lipid-Reducing Activities

et al. 2019

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Marine organisms, particularly cyanobacteria, are important resources for the production of bioactive secondary metabolites for the treatment of human diseases. In this study, a bioassay-guided approach was used to discover metabolites with lipid-reducing activity. Two chlorophyll derivatives were successfully isolated, the previously described 132-hydroxy-pheophytin a (1) and the new compound 132-hydroxy-pheofarnesin a (2). The structure elucidation of the new compound 2 was established based on one- and two-dimensional (1D and 2D) NMR spectroscopy and mass spectrometry. Compounds 1 and 2 showed significant neutral lipid-reducing activity in the zebrafish Nile red fat metabolism assay after 48 h of exposure with a half maximal effective concentration (EC50) of 8.9 ± 0.4 µM for 1 and 15.5 ± 1.3 µM for 2. Both compounds additionally reduced neutral lipid accumulation in 3T3-L1 multicellular spheroids of murine preadipocytes. Molecular profiling of mRNA expression of some target genes was evaluated for the higher potent compound 1, which indicated altered peroxisome proliferator activated receptor gamma (PPARγ) mRNA expression. Lipolysis was not affected. Different food materials (Spirulina, Chlorella, spinach, and cabbage) were evaluated for the presence of 1, and the cyanobacterium Spirulina, with GRAS (generally regarded as safe) status for human consumption, contained high amounts of 1. In summary, known and novel chlorophyll derivatives were discovered from marine cyanobacteria with relevant lipid-reducing activities, which in the future may be developed into nutraceuticals.

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Section: Discussionmentioning

confidence: 99%

Chlorophyll Derivatives from Marine Cyanobacteria with Lipid-Reducing Activities

et al. 2019

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“…PPARγ agonists (e.g. pioglitazone) have been widely used in the treatment of diabetes mellitus [17] and the prevention of macrovascular events and the development of diabetes in patients with insulin resistance [18].…”

Section: Introductionmentioning

confidence: 99%

The PPARγ agonist pioglitazone prevents TGF-β induced renal fibrosis by repressing EGR-1 and STAT3

et al. 2019

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Background It has been proposed that peroxisome proliferator-activated receptor-γ (PPARγ) agonists might reduce renal fibrosis, however, several studies had contradictory results. Moreover, the possible interaction of TGF-β 1 , PPARγ, and transcription factors in renal fibrosis have not been investigated. We hypothesized that oral pioglitazone treatment would inhibit TGF-β–driven renal fibrosis and its progression, by modulating profibrotic transcription factors in TGF-β 1 transgenic mice. Methods Male C57Bl/6 J mice (control, CTL, n = 14) and TGF-β overexpressing transgenic mice (TGFβ, n = 14, having elevated plasma TGF-β 1 level) were divided in two sets at 10 weeks of age. Mice in the first set were fed with regular rodent chow (CTL and TGFβ, n = 7/group). Mice in the second set were fed with chow containing pioglitazone (at a dose of 20 mg/kg/day, CTL + Pio and TGFβ+Pio, n = 7/group). After 5 weeks of treatment, blood pressure was assessed and urine samples were collected, and the kidneys were analyzed for histology, mRNA and protein expression. Results TGF-β 1 induced glomerulosclerosis and tubulointerstitial damage were significantly reduced by pioglitazone. Pioglitazone inhibited renal mRNA expression of all the profibrotic effectors: type-III collagen, TGF-β 1 , CTGF and TIMP-1, and alike transcription factors cFos/cJun and protein expression of EGR-1, and STAT3 protein phosphorylation. Conclusions Oral administration of PPARγ agonist pioglitazone significantly reduces TGF-β 1 -driven renal fibrosis, via the attenuation of EGR-1, STAT3 and AP-1. This implies that PPARγ agonists might be effective in the treatment of chronic kidney disease patients. Electronic supplementary material The online version of this article (10.1186/s12882-019-1431-x) contains supplementary material, which is available to authorized users.

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“…PPARG plays a predominant role in adipogenesis and maintains the sensitivity to insulin. Due to this, TZD class of drugs that act as PPARG agonist has been widely used as insulin-sensitizing drugs in type-2 diabetes (Chiarelli and Di Marzio, 2008). PPAR can have a diverse role in physiology as evident from the fact that different isoforms have differential tissue expression and elicit different responses (Janani and Ranjitha Kumari, 2015).…”

Section: Introductionmentioning

confidence: 99%

Peroxisome Proliferator Activated Receptor Gamma Sensitizes Non-small Cell Lung Carcinoma to Gamma Irradiation Induced Apoptosis

et al. 2019

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The nuclear receptors known as peroxisome proliferator activated receptor gamma (PPARG) are lipid-activated transcription factors that have emerged as key regulators of inflammation. PPARG ligands have been shown to have an anti-proliferative effect on a variety of cancers. These ligands can induce apoptosis via TP53 (Tumor protein p53) or ERK1/2 (Extracellular signal-regulated kinases 1/2) (EPHB2) pathways. However, the exact mechanism is not known. PPAR, a type II nuclear hormone receptor deserves attention as a selective target for radiotherapy. Our study examines the potential of selective agonism of PPARG for radiation therapy in non-small cell lung carcinoma (NSCLC). We found that the overexpression of PPARG protein as well as its induction using the agonist, rosiglitazone was able to stimulate radiation-induced cell death in otherwise radio resistant NSCLC A549 cell line. This cell death was apoptotic and was found to be BAX (BCL2 associated X) mediated. The treatment also inhibited radiation-induced AKT (Protein Kinase B) phosphorylation. Interestingly, the ionising radiation (IR) induced apoptosis was found to be inversely related to TP53 levels. A relatively significant increase in the levels of radiation induced apoptosis was observed in H1299 cells (TP53 null) under PPARG overexpression condition further supporting the inverse relationship between apoptosis and TP53 levels. The combination of PPARG agonist and radiation was able to induce apoptosis at a radiation dose at which A549 and H1299 are radioresistant, thus confirming the potential of the combinatorial strategy. Taken together, PPARG agonism was found to invigorate the radiosensitising effect and hence its use in combination with radiotherapy is expected to enhance sensitivity in otherwise resistant cancer types.

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Peroxisome proliferator-activated receptor-γ agonists and diabetes: Current evidence and future perspectives

Cited by 107 publications

References 84 publications

Chlorophyll Derivatives from Marine Cyanobacteria with Lipid-Reducing Activities

Chlorophyll Derivatives from Marine Cyanobacteria with Lipid-Reducing Activities

The PPARγ agonist pioglitazone prevents TGF-β induced renal fibrosis by repressing EGR-1 and STAT3

Peroxisome Proliferator Activated Receptor Gamma Sensitizes Non-small Cell Lung Carcinoma to Gamma Irradiation Induced Apoptosis

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