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Phenolic Compounds potential health Benefits and toxicity
Published in Quan V. Vuong, Utilisation of Bioactive Compounds from Agricultural and Food Waste, 2017
Deep Jyoti Bhuyan, Amrita Basu
Peroxisome proliferator-activated receptor gamma (PPAR-γ) has a vital role in glucose and fat metabolism. Thus, PPAR-γ agonists are widely used in the treatment of hyperglycemia, dyslipidaemia and their complications (Li et al. 2008). Phenolics with PPAR-γ ligand-binding activity have been obtained from licorice (Glycyrrhiza uralensis roots) which may help in the treatment of diabetes (Kuroda et al. 2003). Chronic sub-acute inflammation has also been accepted as an important factor in the development of insulin resistance and diabetes in animals and humans. Various nonflavonoid polyphenols have been shown to reduce the production of inflammatory mediators, such as IL-1β, IL-8, MCP-1, COX-2 or iNOS in these animal models of diabetes (Miranda et al. 2015).
Diabetes Mellitus/Anti-DM Pharmacological Management
Published in Mihai V. Putz, New Frontiers in Nanochemistry, 2020
Bogdan Bumbăcilă, Corina Duda-Seiman, Daniel Duda-Seiman, Mihai V. Putz
These molecules bind to receptor PPARγ, a regulatory protein that regulates the transcription of some genes involved in glucose and fat metabolisms. These PPARγ receptors act on some gene sequences named peroxisome proliferator hormone responsive elements (PPRE) which will influence further some insulin-sensitive genes. This process will enhance the production of mRNAs corresponding to insulin-dependent enzymes which translates to a better use of glucose by the cells (Michalik et al., 2006).
Nanoparticles for Cardiovascular Medicine: Trends in Myocardial Infarction Therapy
Published in Harishkumar Madhyastha, Durgesh Nandini Chauhan, Nanopharmaceuticals in Regenerative Medicine, 2022
Fujiwara et al. also targeted the inflammatory response in MI injury using PLGA nanoparticles (Fujiwara et al. 2019). The researchers loaded PLGA with TAK-242, a toll-like receptor 4 (TLR4) inhibitor. TAK-242-loaded PLGA nanoparticles attenuated MI through targeting monocytes/macrophages present within the spleen, blood, and heart. The nanoparticles inhibited Ly-6Chigh monocytes recruitment to infarcts but did not affect infarct size in TLR4/CCR2-deficient mice, indicating a TLR4-specific mechanism and monocyte/macrophage-mediated inflammation were primary therapeutic targets of TAK-242-PLGA nanoparticles in regulating MI in mice. Tokutome et al. focused on peroxisome proliferator-activated receptor-γ (PPARγ) (Tokutome et al. 2019). Binding of pioglitazone to PPARγ induces receptor heterodimerisation with retinoid X receptor (RXR). The PPARγ/RXR heterodimer complex binds PPAR response elements to regulate gene expression associated with adipogenesis, lipid/glucose metabolism (Ahmadian et al. 2013; Libby and Plutzky 2007), chemokine expression, and macrophage infiltration (Ricote and Glass 2007). In monocytes/macrophages, PPARγ activation drives pro-healing M2 polarisation of macrophages (Odegaard et al. 2007). Pioglitazone administered orally before I/R reduced infarct size in mouse and rat MI models (Ye et al. 2008); however, intraperitoneal injection of pioglitazone at the time of reperfusion resulted in lost effect (Honda et al. 2008). Cardioprotective agents are typically administered during reperfusion. Tokutome et al. determined that it was essential to use a carrier to facilitate pioglitazone delivery to effector cells in I/R injury (Tokutome et al. 2019). In lieu of reports that PLGA nanoparticles accumulate in I/R myocardium and were taken up by circulating macrophages (Nagaoka et al. 2015; Gustafson et al. 2015), researchers developed PLGA nanoparticles as carriers for pioglitazone and showed that they exerted an antiinflammatory effect, which in turn limited the infarct size in I/R mouse and porcine models. The rationale to target PPARγ was supported by the work of Nakano et al., which employed irbesartan as a therapeutic agent for MI (Nakano et al. 2016). Irbesartan blocks angiotensin II type 1 receptor and conveys a partial agonistic effect on PPARγ, and an irbesartan derivative was shown to reduce myocardial inflammation by reducing proinflammatory cytokine expression by cardiomyocytes after MI and conveyed an antihypertensive effect (Ugdutt et al. 2010). Thus, Nakano et al. developed PLGA nanoparticle-mediated delivery of irbesartan, which accumulated at the MI site when administered intravenously at the time of reperfusion, where the enhanced permeability and retention effect improved vascular permeability (Acharya and Sahoo 2011) and subsequently allowed nanoparticles to be rapidly taken up by mononuclear and phagocytic cells that had infiltrated the MI site. The mechanism of action was shown to be through irbesartan antagonising the additional recruitment of Ly6ChighCCR2+ inflammatory monocytes into the MI site.
Implications of peroxisome proliferator-activated receptor gamma (PPARY) with the intersection of organophosphate flame retardants and diet-induced obesity in adult mice
Published in Journal of Toxicology and Environmental Health, Part A, 2022
Gwyndolin M. Vail, Sabrina N. Walley, Ali Yasrebi, Angela Maeng, Thomas J. Degroat, Kristie M. Conde, Troy A. Roepke
Neuronal knockout of PPARγ has previously been noted to limit the rise in weight gain seen in mice fed HFD (Lu et al. 2011), and our findings reported similar trends of an approximate 10% less weight gain in HFD-fed PPARγKO mice than their WT counterparts (Vail et al. 2020). PPARγKO males were not directly affected by OPFR exposure with respect to weight gain or adiposity. However, in WT mice, OPFR-treated males experienced greater weight gain and fat mass than controls when fed HFD (Vail et al. 2020). Therefore, it is conceivable that OPFR-induced adiposity and weight gain in males might be attributed, in part, to interaction with PPARγ. PPARγ is well known for its endogenous regulation of adipose tissue and lipid metabolism (Janani and Ranjitha Kumari 2015; Wang 2010). Therefore, it follows that the OPFR disruption of PPARγ might manifest as dysregulated fat accumulation.
Biochanin A prevents 2,3,7,8-tetrachlorodibenzo-p-dioxin-induced adipocyte dysfunction in cultured 3T3-L1 cells
Published in Journal of Environmental Science and Health, Part A, 2019
Eun Mi Choi, Kwang Sik Suh, So Young Park, Sang Ouk Chin, Sang Youl Rhee, Suk Chon
As PPARγ plays an important role in adipocyte differentiation, it is recognized as the master regulator of adipogenesis. Activation of PPARγ triggers the expression of various genes that are closely related to lipogenesis, fatty acid synthesis, and energy metabolism.[19] Adiponectin, an adipocyte-derived hormone that is expressed in differentiated adipocytes, stimulates lipid accumulation and insulin-responsive transporters.[20] Adiponectin plays an important role in the regulation of glucose and lipid metabolism. In differentiated adipocytes, adiponectin over-expressing cells exhibit greater fat accumulation, and stimulate glucose uptake by activating GLUT4. Because adiponectin is induced by PPAR-γ activity, adiponectin is used as a marker of PPAR-γ efficacy.[21] Thus, an increase in adiponectin secretion has more favorable effects against insulin resistance.[22] Here, we found that biochanin A partially reverses the TCDD-induced decrease in PPARγ and adiponectin levels during differentiation of 3T3-L1 adipocytes, suggesting that biochanin A affects adipogenesis and lipid accumulation by modulating PPAR-γ signaling and adiponectin production.
Genetic polymorphisms of PPAR genes and human cancers: evidence for gene–environment interactions
Published in Journal of Environmental Science and Health, Part C, 2019
Previous studies have suggested that PPAR-γ may be playing a protective role in many malignancies and that PPAR-γ interaction with ligands would have an antitumor effect through decreasing cell growth and promoting apoptosis.103 Similar roles for PPAR-β/δ in tumor suppressing and anti-apoptotic pathways were suggested, including regulation of growth promoting genes, such as c-Myc and Cyclin-D1.104 Therefore, it is possible to postulate that certain functional mutations in the PPAR gene may be disrupting protective mechanisms, hence indirectly promoting tumorigenesis in cases of carcinogenic exposures, and directly triggering a wide range of metabolic alterations.9 More studies are needed to examine the mechanistic nature of these PPAR-xenobiotic interactions and how they vary in their contribution to cancer risk for carriers of the different genetic variants.