Evaluation of the Regulatory Effect of the Pan-PPAR Agonist Chiglitazar on the Dawn Phenomenon

Diabetes Therapy, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 28, 2025

The dawn phenomenon (DP), characterized by early morning hyperglycemia, poses a significant challenge in diabetes management and is associated with increased glycemic variability long-term complications. Despite its clinical impact, effective therapeutic strategies remain limited. Chiglitazar, novel pan-PPAR agonist, has demonstrated benefits improving lipid metabolism insulin sensitivity, but potential role mitigating DP remains unexplored. This study evaluates the regulatory effect of chiglitazar on investigates possible mechanisms beyond modulation. retrospective observational included 22 hospitalized diabetic patients who received (20 mg). Blood glucose levels at 3:00 a.m. fasting over three consecutive days were measured pre- post-treatment, intensity was calculated. Lipid profiles assessed to explore correlations changes. Following administration, reductions observed LDL-C (43.82 ± 18.27 vs. 36.97 16.90, p < 0.05), FFA (6.00 2.38 5.06 1.77, mean blood (Z = – 2.03, 2.96, 0.05). also significantly improved 3.48, 0.01). However, no correlation found between improvements profile changes (p > suggesting an alternative mechanism action. Chiglitazar effectively reduces improves control, independent effects metabolism. These findings suggest link chiglitazar's circadian rhythm regulation, possibly through modulation REV-ERB nuclear receptors. Further research needed confirm this hypothesis evaluate management.

Language: Английский

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Pharmacological (or Synthetic) and Nutritional Agonists of PPAR-γ as Candidates for Cytokine Storm Modulation in COVID-19 Disease

Molecules, Journal Year: 2020, Volume and Issue: 25(9), P. 2076 - 2076

Published: April 29, 2020

The cytokine storm is an abnormal production of inflammatory cytokines, due to the over-activation innate immune response. This mechanism has been recognized as a critical mediator influenza-induced lung disease, and it could be pivotal for COVID-19 infections. Thus, immunomodulatory approach targeting over-production cytokines proposed viral aggressive pulmonary disease treatment. In this regard, peroxisome proliferator-activated receptor (PPAR)-γ, member PPAR transcription factor family, represent potential target. Beside well-known regulatory role on lipid glucose metabolism, PPAR-γ also represses process. Similarly, agonist thiazolidinediones (TZDs), like pioglitazone, are anti-inflammatory drugs with ameliorating effects severe pneumonia. addition pharmacological agonists, nutritional ligands PPAR-γ, curcuma, lemongrass, pomegranate, possess properties through activation. Here, we review main synthetic ligands, proposing dual based strengthening system using dietary strategies attempt prevent/treat in case coronavirus infection.

Language: Английский

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PPAR Beta/Delta and the Hallmarks of Cancer

Cells, Journal Year: 2020, Volume and Issue: 9(5), P. 1133 - 1133

Published: May 4, 2020

Peroxisome proliferator-activated receptors (PPARs) belong to the nuclear hormone receptor family. Three different isoforms, PPAR alpha, beta/delta and gamma have been identified. They all form heterodimers with retinoic X activate or repress downstream target genes dependent on presence/absence of ligands coactivators corepressors. PPARs differ in their tissue expression profile, specific agonists antagonists. attract attention as potential therapeutic targets for a variety diseases. alpha are clinical use treatment dyslipidemias diabetes. For both receptors, several trials cancer ongoing. In contrast, has suggested metabolic syndrome. However, risks settings less clear. A studies investigated activation/inhibition cell models vitro, but relevance growth vivo is well documented controversial. this review, we summarize critically knowledge functions hallmarks biological capabilities, which interplay determine growth.

Language: Английский

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PPAR-γ Modulators as Current and Potential Cancer Treatments

Frontiers in Oncology, Journal Year: 2021, Volume and Issue: 11

Published: Sept. 23, 2021

Worldwide, cancer has become one of the leading causes mortality. Peroxisome Proliferator-Activated Receptors (PPARs) is a family critical sensors lipids as well regulators diverse metabolic pathways. They are also equipped with capability to promote eNOS activation, regulate immunity and inflammation response. Aside from established properties, emerging discoveries made in PPAR's functions field. All considerations given, there exists great potential PPAR modulators which may hold management cancers. In particular, PPAR-γ, most expressed subtype adipose tissues two isoforms different tissue distribution, been proven be able inhibit cell proliferation, induce cycle termination apoptosis multiple cells, intercellular adhesion, cripple inflamed state tumor microenvironment, both on transcriptional protein level. However, despite multi-functionalities, safety PPAR-γ still clinical concern terms dosage, drug interactions, types stages, etc. This review aims consolidate current applications modulators, challenges applying treatment, laboratory settings. We sincerely hope provide comprehensive perspective prospect applicability field treatment.

Language: Английский

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PPARs and Microbiota in Skeletal Muscle Health and Wasting

International Journal of Molecular Sciences, Journal Year: 2020, Volume and Issue: 21(21), P. 8056 - 8056

Published: Oct. 29, 2020

Skeletal muscle is a major metabolic organ that uses mostly glucose and lipids for energy production has the capacity to remodel itself in response exercise fasting. wasting occurs many diseases during aging. Muscle often accompanied by chronic low-grade inflammation associated inter- intra-muscular fat deposition. During aging, advanced due increased movement disorders, as result of restricted physical exercise, frailty, pain with arthritis. atrophy characterized protein degradation, where ubiquitin-proteasomal autophagy-lysosomal pathways, atrogenes, growth factor signaling all play an important role. Peroxisome proliferator-activated receptors (PPARs) are members nuclear receptor family transcription factors, which activated fatty acids their derivatives. PPARs regulate genes involved development, metabolism, inflammation, cellular processes different organs. also expressed exert pleiotropic specialized responses upon activation ligands. There three PPAR isotypes, viz., PPARα, -β/δ, -γ. The expression PPARα high tissues effective acid catabolism, including skeletal muscle. PPARβ/δ more ubiquitously predominant isotype It mitochondrial biogenesis, fiber-type switching. PPARγ adipocytes, but it implicated lipid deposition other Collectively, isotypes have impact on homeostasis either directly or indirectly. Furthermore, reciprocal interactions been found between gut microbiota along gut–muscle axis both health disease. Herein, we review functions interaction context wasting.

Language: Английский

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Perspective: The Saturated Fat–Unsaturated Oil Dilemma: Relations of Dietary Fatty Acids and Serum Cholesterol, Atherosclerosis, Inflammation, Cancer, and All-Cause Mortality

Advances in Nutrition, Journal Year: 2021, Volume and Issue: 12(3), P. 647 - 656

Published: Jan. 23, 2021

PUFAs are known to regulate cholesterol synthesis and cellular uptake by multiple mechanisms that do not involve SFAs. Polymorphisms in any of the numerous proteins involved homeostasis, as a result genetic variation, could lead higher or lower serum cholesterol. susceptible lipid peroxidation, which can oxidative stress, inflammation, atherosclerosis, cancer, disorders associated with such insulin resistance, arthritis, inflammatory syndromes. Eicosanoids from arachidonic acid among most powerful mediators initiate an immune response, wide range PUFA metabolites physiological processes. There is misconception dietary SFAs cause although endogenous palmitic converted ceramides other cell constituents response after it initiated derived PUFAs. This article will discuss many misconceptions regarding how lipids cholesterol, fact all-cause death rate humans low compared normal moderately elevated total adverse effects increasing carbohydrate relative SFAs, well metabolic conversion MUFAs protective mechanism. Consequently, saturated fats seem be less harmful than proposed alternatives.

Language: Английский

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The circadian clock and metabolic homeostasis: entangled networks

Cellular and Molecular Life Sciences, Journal Year: 2021, Volume and Issue: 78(10), P. 4563 - 4587

Published: March 8, 2021

Abstract The circadian clock exerts an important role in systemic homeostasis as it acts a keeper of time for the organism. synchrony between daily challenges imposed by environment needs to be aligned with biological processes and internal clock. In this review, is provided in-depth view molecular functioning clock, how system organized, central peripheral clocks communicate each other. sense, we provide overview neuro-hormonal factors controlled they affect tissues. We also evaluate signals released organs their effects other brain areas. Additionally, possible communication tissues novel layer organization reviewing recent studies literature. last section, analyze can modulate intracellular tissue-dependent metabolic organs. Taken altogether, goal review integrative function emphasis

Language: Английский

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Prenatal and postnatal exposure to PFAS and cardiometabolic factors and inflammation status in children from six European cohorts

Environment International, Journal Year: 2021, Volume and Issue: 157, P. 106853 - 106853

Published: Sept. 6, 2021

Developing children are particularly vulnerable to the effects of exposure per- and polyfluoroalkyl substances (PFAS), a group endocrine disrupting chemicals. We hypothesized that early life PFASs is associated with poor metabolic health in children. studied association between prenatal postnatal mixture cardiometabolic children, role inflammatory proteins. In 1,101 mothers-child pairs from Human Early Life Exposome project, we measured concentrations PFAS blood collected pregnancy at 8 years (range = 6-12 years). applied Bayesian Kernel Machine regression (BKMR) estimate associations factors as age sex- specific z-scores waist circumference (WC), systolic diastolic pressures (BP), triglycerides (TG), high-density lipoprotein (HDL-C) low-density (LDL-C) cholesterol. thirty six biomarkers child plasma examined underlying status for exposure-outcome by integrating three panels into network. Exposure was positively HDL-C BP, negatively WC, LDL-C TG. When independent individual chemicals mixture, PFHxS PFNA WC these were opposing directions overall mixture. Further, network consisted five distinct communities connected positive negative correlations. The selected positively, while related included factors, only PFOA pro-inflammatory cytokine IL-1beta WC. Our study supports prenatal, rather than postnatal, might contribute an unfavorable lipidemic profile adiposity childhood.

Language: Английский

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Thiazole derivatives in medicinal chemistry: Recent advancements in synthetic strategies, structure activity relationship and pharmacological outcomes

Journal of Molecular Structure, Journal Year: 2022, Volume and Issue: 1266, P. 133479 - 133479

Published: June 8, 2022

Language: Английский

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New Drugs for Hepatic Fibrosis

Frontiers in Pharmacology, Journal Year: 2022, Volume and Issue: 13

Published: June 13, 2022

The morbidity and mortality of hepatic fibrosis caused by various etiologies are high worldwide, the trend is increasing annually. At present, there no effective method to cure except liver transplantation, its serious complications threaten health patients cause medical burdens. Additionally, specific drug for treatment fibrosis, many drugs with anti-hepatic effects in research development stage. Recently, remarkable progress has been made targeting different targets. We searched websites such as PubMed, ScienceDirect, Home-ClinicalTrials.gov found approximately 120 anti-fibrosis properties, some which phase Ⅱ or Ⅲ clinical trials. although these against animal models, most trials have shown poor results, mainly because models do not capture complexity human fibrosis. Besides, effect natural products on widely recognized at home abroad. Furthermore, a single target prone adverse reactions. Therefore, currently, requires combination that multiple Ten new potential were selected highlighted this mini-review, provides reference use.

Language: Английский

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