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HIV protease inhibitors activate the adipocyte renin angiotensin system.

BACKGROUND: HIV-infected patients under antiretroviral therapy that includes HIV protease inhibitors (PIs) are prone to develop a complex metabolic syndrome including insulin resistance, lipodystrophy and hypertension. Whether hypertension and cardiovascular events could result from the adipocyte renin angiotensin system (RAS) overactivation has never been investigated. METHODS: Primary human adipocytes and 3T3-F442A murine adipocytes were incubated with lopinavir or atazanavir boosted with ritonavir, with or without the angiotensin II type-1 receptor (AT1R) blockers (ARBs), irbesartan or tel

PPARgamma agonists inhibit TGF-beta induced pulmonary myofibroblast differentiation and collagen production: implications for therapy of lung fibrosis.

Pulmonary fibrosis is a progressive life-threatening disease for which no effective therapy exists. Myofibroblasts are one of the key effector cells in pulmonary fibrosis and are the primary source of extracellular matrix production. Drugs that inhibit the differentiation of fibroblasts to myofibroblasts have potential as antifibrotic therapies. Peroxisome proliferator-activated receptor (PPAR)-gamma is a transcription factor that upon ligation with PPARgamma agonists activates target genes containing PPAR response elements. PPARgamma agonists have anti-inflammatory activities and may have pot

Telmisartan is a promising cardiometabolic sartan due to its unique PPAR-gamma-inducing property.

The metabolic syndrome is strongly associated with insulin resistance and consists of a constellation of factors such as hypertension and hyperlipidemia that raise the risk for cardiovascular diseases and diabetes mellitus. Indeed, hypertension occurs approximately twice as frequently in patients with diabetes compared with in non-diabetic controls. Conversely, hypertensive patients are more likely than normotensive persons to develop diabetes. In addition, up to 75% of CVD in diabetic patients can be attributed to hypertension. Therefore, the primary goals of treating hypertensive patients wi

Peroxisome proliferator-activated receptor gamma agonists for preventing recurrent stroke and other vascular events in patients with stroke or transient ischaemic attack.

BACKGROUND: Peroxisome proliferator-activated receptor gamma (PPAR-γ) agonists are insulin-sensitising drugs used for the treatment of insulin resistance. In addition to lowering glucose in diabetes, these drugs may also protect against hyperlipidaemia and arteriosclerosis, which are risk factors for stroke. OBJECTIVES: To assess the efficacy and safety of PPAR-γ agonists in the secondary prevention of stroke and related vascular events for people with stroke or transient ischaemic attack (TIA). SEARCH METHODS: We searched the Cochrane Stroke Group Trials Register (July 2015), the Cochrane C

Peroxisome proliferator-activated receptor gamma agonists for preventing recurrent stroke and other vascular events in patients with stroke or transient ischaemic attack.

BACKGROUND: Peroxisome proliferator-activated receptor gamma (PPAR-γ) agonists are insulin-sensitising drugs used for the treatment of insulin resistance. In addition to lowing glucose in diabetes, these drugs may also protect against hyperlipidaemia and arteriosclerosis, which are risk factors for stroke. OBJECTIVES: To assess the efficacy and safety of PPAR-γ agonists in the secondary prevention of stroke and related vascular events for people with stroke or transient ischaemic attack (TIA). SEARCH METHODS: We searched the Cochrane Stroke Group Trials Register (August 2013), the Cochrane C

Rosiglitazone promotes the differentiation of Langerhans cells and inhibits that of other dendritic cell types from CD133 positive hematopoietic precursors.

Dendritic cells and their precursors express PPAR-gamma, whose stimulation has inhibitory effects on the maturation and function of dendritic cells in vivo. Dendritic cells can differentiate in vitro from CD133+ progenitors; the influence of PPAR-gamma stimulation on this process is unknown. We have addressed the effect of PPAR-gamma agonist rosiglitazone, at a concentration as used in clinics, on the differentiation of dendritic cells from human CD133+ progenitors. Cells were harvested from cord blood by density gradient and immunomagnetic separation, and cultured for 18 days with fetal calf

Homocysteine inhibits adipogenesis in 3T3-L1 preadipocytes.

Hyperhomocysteinemia (HHcy) is a characteristic metabolic abnormality in several pathological conditions, including hypertension, diabetes and alcoholic liver disease. Emerging evidence indicates that adipose tissue contributes to HHcy and homocysteine (Hcy) conversely affects adipose tissue function. However, the specific effect of Hcyon adipogenesis is poorly understood. In the present study, we investigated the effects and mechanisms of Hcy on adipogenic process using 3T3-L1 preadipocytes, a well-established in vitro model for the study of adipogenesis. Confluent mouse embryo 3T3-L1 preadip

Virtual screening, pharmacokinetics & MD simulation study of active phytoconstituents of Ficus Carica Linn. against PPAR-γ in diabetes mellitus.

F. carica is a small tree and commonly used as a traditional medicine against several disorders. Diabetes is currently treated with insulin and oral hypoglycemic medicines such as sulphonyl urea derivatives, bigunides, thiazolidinediones and alpha-glucosidase inhibitors. Peroxisome proliferator-activated receptor gamma (PPAR-γ) agonists were found to be very much beneficial in the management of diabetes by inhibiting hepatic gluconeogenesis. The aim of this study is to evaluate the bioactive phytoconstituents from Ficus carica Linn. against the target PPAR-γ agonist by in silico docking approa

Citreoviridin induces myocardial apoptosis through PPAR-γ-mTORC2-mediated autophagic pathway and the protective effect of thiamine and selenium.

Citreoviridin (CIT), a mycotoxin and ATP synthase inhibitor, is regarded as one of aetiology factors of cardiac beriberi and Keshan disease. Thiamine (VB1) and selenium (Se) improve the recovery of these two diseases respectively. The underlying mechanisms of cardiotoxic effect of CIT and cardioprotective effect of VB1 and Se have not been fully elucidated. In this study, we found that ectopic ATP synthase was more sensitive to CIT treatment than mitochondrial ATP synthase in H9c2 cardiomyocytes. CIT inhibited the transcriptional activity of peroxisome proliferator activated receptor gamma (PP

Mitochondria, ciglitazone and liver: a neglected interaction in biochemical pharmacology.

Peroxisome proliferator activated receptors (PPARs) are a class of nuclear receptors now actively investigated for their involvement in lipid and glucidic metabolism, immune regulation and cell differentiation. Drugs binding and activating PPARs are therefore attracting attention for their potential therapeutic role in various diseases like type 2 diabetes, dyslipidemias, atherosclerosis, obesity (i.e., metabolic syndrome). Agonists of these receptors have been already used in therapeutic protocols: fibrates (PPAR-alpha ligands) are being used in hyperlipidemias, and thiazolidinediones (mainly

PPAR-γ in Melanoma and Immune Cells: Insights into Disease Pathogenesis and Therapeutic Implications.

Changes in skin pigmentation, like hyperpigmentation or moles, can affect appearance and social life. Unlike locally containable moles, malignant melanomas are aggressive and can spread rapidly, disproportionately affecting younger individuals with a high potential for metastasis. Research has shown that the peroxisome proliferator-activated receptor gamma (PPAR-γ) and its ligands exhibit protective effects against melanoma. As a transcription factor, PPAR-γ is crucial in functions like fatty acid storage and glucose metabolism. Activation of PPAR-γ promotes lipid uptake and enhances sensitivi

Совпадение в полном тексте источника
… PPAR-gamma agonists inhibit profibrotic phenotypes in human lung fibroblasts and bleomycin-induced pulmonary fibrosis Am. J. Physiol. Lung Cell. Mol. Physiol. 2008 294 L891 L901 10.1152/ajplung.00333.2007 18162602 PMC5926773 47. Mössner R. Schulz U. Krüger U. Middel P. Schinner S. Füzesi L. …

Reassessing the role of PPARgamma in vascular effects of cannabinoids: A critical appraisal.

This focused review provides a critical narrative appraisal of the mechanisms underlying cannabinoid-induced vascular effects, with particular emphasis on cannabinoid receptor- and PPARgamma-independent pathways, as well as on ion channel modulation. Priority was given to studies providing mechanistic insights into vascular signaling pathways mediating the vasodilator effects of cannabinoids and commonly used PPARgamma ligands. The available experimental evidence supporting a role for PPARgamma in the vascular actions of cannabinoids is critically evaluated. Given the partially overlapping pha

The role of nuclear receptor peroxisome proliferator-activated receptor gamma (PPAR-γ) and Nrf2 signalling in methanol-induced on brain, eye, and pancreas toxicity in rats.

Toxic methyl alcohol is widely employed in industry, and it is highly toxic. Only 15 cc ingestion can result in irreversible blindness. The mechanism of toxicity is still a matter of debate. This study was conducted to investigate the incorporation of nuclear receptor peroxisome proliferator-activated receptor gamma (PPAR-γ) and Nrf2 signaling pathways in the toxicity of the brain, eye, and pancreas following ingestion of methyl alcohol and the possible protective role of PPAR-γ modulators. Twenty-four adult Wister albino rats were divided into four groups of six rats each: a control group, a

Leveraging Advanced AI Frameworks for Dual PPAR α/γ Agonist Discovery in Alzheimer's Disease.

The dual activating potential of peroxisome proliferator-activated receptors (PPAR) α and γ offers a promising way to address metabolic issues, neuroinflammation, and protein balance in the development of Alzheimer's disease (AD). The current study intends to underscore the emerging importance of artificial intelligence (AI) in the accelerated discovery and optimization of dual PPAR α/γ modulators based on machine learning (ML), deep learning (DL), and generative modeling. The role of autonomous and agentic-AI systems in hypothesis generation, lead optimization, and closed-loop screening proce

In vitro characterization of N1- and N2-like neutrophil polarization and the putative regulatory role of Pparγ in common carp (Cyprinus carpio L.).

Neutrophils are key regulators of innate immunity and display substantial phenotypic plasticity shaped by the local cytokine and hormonal environment. In mammals, neutrophils can polarize into pro-inflammatory (N1) or anti-inflammatory (N2) phenotypes, but this process has not been comprehensively described in fish. This study investigated whether neutrophils of carp can acquire N1- and N2-like phenotypes and examined the role of peroxisome proliferator-activated receptor gamma (Pparγ) in their polarization. A neutrophil-enriched cell population was isolated from the head kidney of common carp

Dual PPAR-α/γ enhances beta cell identity, preserving islet structure in HF-fed mice.

The pancreas suffers from lipotoxicity, which threatens the survival of pancreatic islets. Dual peroxisome proliferator-activated receptor-alpha/gamma (PPAR-α/γ) agonism is a promising method for treating type 2 diabetes mellitus (T2DM). This study evaluated the effects of single PPAR-α and PPAR-γ or their combined activation on pancreatic islet remodelling, beta cell proliferation, identity and maintenance in an experimental obesity model. Fifty three-month-old mice, randomly divided to receive the control (C) or high-fat (HF) diet for ten weeks, were then redivided for a four-week treatment:

Role of peroxisome proliferator-activated receptor beta/delta in chicken adipogenesis.

The adipocyte differentiation process involves a cascade of transcriptional events that culminates in the expression of peroxisome proliferator-activated receptor (PPAR)gamma. The present study was undertaken to identify the role of PPARbeta/delta in chicken adipocyte differentiation, with experiments performed using a PPARgamma agonist, a PPARbeta/delta agonist, a PPARgamma antagonist and fatty acid (oleate). Preadipocyte cells cultured in a differentiation medium (DMEM containing 500nM dexamethasone, 0.5mM 3-isobutyl-1-methylxanthine, 20microg/mL bovine insulin and 10% fetal bovine serum) su

15-Deoxy-{delta}12,14-prostaglandin j2 inhibits interleukin-1{beta}-induced nuclear factor-{kappa}b in human amnion and myometrial cells: mechanisms and implications.

Proinflammatory cytokines and prostaglandins play key roles in term and preterm human labor. The expression of the prostaglandin synthetic enzyme cyclooxygenase (COX)-2 and cytokines IL-1beta and IL-8 increases within the uterus at the time of labor, and each is regulated by the transcription factor nuclear factor-kappaB (NF-kappaB). In addition to its role in driving inflammation, COX-2 may also synthesize 15-deoxy-Delta (12, 14)-prostaglandin J(2) (15d-PGJ(2)), an antiinflammatory cyclopentenone prostaglandin (cyPG), which acts in some cells as an agonist of peroxisome proliferator-activated

Therapeutic potential of PPARγ natural agonists in liver diseases.

Peroxisome proliferator-activated receptor gamma (PPARγ) is a vital subtype of the PPAR family. The biological functions are complex and diverse. PPARγ plays a significant role in protecting the liver from inflammation, oxidation, fibrosis, fatty liver and tumours. Natural products are a promising pool for drug discovery, and enormous research effort has been invested in exploring the PPARγ-activating potential of natural products. In this manuscript, we will review the research progress of PPARγ agonists from natural products in recent years and probe into the application potential and prospe

Hesperidin regresses cardiac hypertrophy by virtue of PPAR-γ agonistic, anti-inflammatory, antiapoptotic, and antioxidant properties.

Hesperidin (HES), a flavanone glycoside, predominant in citrus fruits, has an agonistic activity on peroxisome proliferator-activated receptor gamma (PPAR-γ). PPAR-γ is an inhibitor of cardiac hypertrophy (CH) signaling pathways. In this study, we investigated the cardioprotective effect of HES in isoproterenol (ISO)-induced CH through PPAR-γ agonistic activity. For this, male albino Wistar rats were divided into six groups (n = 6), that is, normal, ISO-control, HES treatment group (200 mg kg-1 ; p.o.), HES per se (200 mg kg-1 ; p.o.), enalapril treatment group (30 mg kg-1 ; p.o.), and combina