Peroxisome proliferator‐activated receptor (PPAR) modulators: Diabetes and beyond*

Jones, A. Brian

doi:10.1002/med.1025

Cited by 65 publications

(37 citation statements)

References 64 publications

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“…Synthetic PPAR α agonists such as fenofibrate and clofibrate are clinically proven lipid-lowering drugs [9]. A class of PPAR γ ligands called thiazolidinediones (TZDs), such as rosiglitazone and pioglitazone, has been introduced in clinical practice for improving glycemic control via insulin sensitization in patients with type 2 diabetes [10]. Increasing evidence also points to a potential role of PPAR β / δ activators in improving insulin resistance and dyslipidemia [11].…”

Section: Introductionmentioning

confidence: 99%

PPARs Integrate the Mammalian Clock and Energy Metabolism

2014

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Peroxisome proliferator-activated receptors (PPARs) are a group of nuclear receptors that function as transcription factors regulating the expression of numerous target genes. PPARs play an essential role in various physiological and pathological processes, especially in energy metabolism. It has long been known that metabolism and circadian clocks are tightly intertwined. However, the mechanism of how they influence each other is not fully understood. Recently, all three PPAR isoforms were found to be rhythmically expressed in given mouse tissues. Among them, PPARα and PPARγ are direct regulators of core clock components, Bmal1 and Rev-erbα, and, conversely, PPARα is also a direct Bmal1 target gene. More importantly, recent studies using knockout mice revealed that all PPARs exert given functions in a circadian manner. These findings demonstrated a novel role of PPARs as regulators in correlating circadian rhythm and metabolism. In this review, we summarize advances in our understanding of PPARs in circadian regulation.

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Section: Introductionmentioning

confidence: 99%

PPARs Integrate the Mammalian Clock and Energy Metabolism

2014

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“…However, some studies show that carriers of the C allele for the IL-6 polymorphism rs1800795 have higher BMI, IL-6, CRP, insulin resistance and lipoprotein levels, identified in children, adolescents and adults (Eklund et al 2006, Goyenechea et al 2006, Jones et al 2001.…”

Section: Discussionmentioning

confidence: 99%

Association of IL-6 and CRP gene polymorphisms with obesity and metabolic disorders in children and adolescents

Todendi

Klinger

Ferreira

et al. 2015

An. Acad. Bras. Ciênc.

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Activation of adipose tissue inflammation is associated with obesity caused by lipid accumulation in adipocytes. Through this activation, proinflammatory cytokines, such as Interleukin-6 (IL-6) and C-reactive protein (CRP) seem to influence metabolic disorders. The present study evaluated whether polymorphisms in the CRP (rs1205) and IL-6 (rs1800795, rs2069845) genes are associated with the development of metabolic disorders in children and adolescents. A cross-sectional study was performed, consisting of 470 students from the municipality of Santa Cruz do Sul, Brazil, aged 7-17 years. Body mass index (BMI) was classified according to overweight and obesity. Genotyping was performed by real-time Polymerase Chain Reaction (PCR). Anthropometric characteristics, biochemical markers, immunological markers and blood pressure were assessed. Descriptive statistics, chi-square and logistic regression were used for the analyses. No association was detected between the rs1800795 polymorphism and the assessed variables. Individuals with the risk genotype in the rs1205 gene were associated with the risk of developing hypercholesterolemia (OR 2.79; CI 1.40, 5.57; p = 0.003). Carriers of the risk genotype in the rs2069845 gene are associated with the risk of developing obesity (OR 3.07; CI 1.08, 8.72; p = 0.03). The polymorphism rs2069845 was associated with obesity and rs1205 was associated with the risk of developing hypercholesterolemia in Brazilian schoolchildren.

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“…142,144 In clinical studies, fibrates such as fenofibrate and bezafibrate reduce plasma triglycerides, reduce VLDL and LDL cholesterol, increase HDL cholesterol through increases in apolipoprotein A1 production, and favorably affect atherosclerotic progression and cardiovascular outcomes. 142,144,[155][156][157][158][159][160] Similarly, in vervets, fenofibrate increases HDL cholesterol and decreases triglycerides, 161 and in obese rhesus monkeys, fenofibrate lowers plasma triglycerides and LDL cholesterol, increases HDL cholesterol, and ameliorates hyperinsulinemia. 143 Although fenofibrate is not specific for PPARα activation and shows similar PPARγ activation, 144,156 the ability of PPARα agonism to favorably affect glycemic control independent of associated PPARγ agonism was confirmed using a highly specific PPARα agonist, CP-900691.…”

Section: Pharmacologic Interventions In Nonhuman Primatesmentioning

confidence: 99%

“…142,144,[155][156][157][158][159][160] Similarly, in vervets, fenofibrate increases HDL cholesterol and decreases triglycerides, 161 and in obese rhesus monkeys, fenofibrate lowers plasma triglycerides and LDL cholesterol, increases HDL cholesterol, and ameliorates hyperinsulinemia. 143 Although fenofibrate is not specific for PPARα activation and shows similar PPARγ activation, 144,156 the ability of PPARα agonism to favorably affect glycemic control independent of associated PPARγ agonism was confirmed using a highly specific PPARα agonist, CP-900691. 162 In addition to reducing plasma triglycerides and triglyceride-rich lipoproteins and elevating HDL cholesterol in diabetic cynomolgus monkeys, CP-900691 also improved glycemic control and reduced exogenous insulin requirement.…”

Section: Pharmacologic Interventions In Nonhuman Primatesmentioning

confidence: 99%

Nonhuman Primates and other Animal Models in Diabetes Research

Harwood

Listrani

Wagner

2012

J Diabetes Sci Technol

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Abbreviations: (CB 1) cannabinoid 1, (CVD) cardiovascular disease, (GDM) gestational diabetes mellitus, (GLP-1) glucagon-like peptide-1, (HbA1c) hemoglobin A1c, (HDL) high-density lipoprotein, (IGT) impaired glucose tolerance, (IR) insulin resistance, (LDL) low-density lipoprotein, (NHP) nonhuman primate, (PPAR) peroxisome proliferator-activated receptor, (STZ) streptozotocin, (T1DM) type 1 diabetes mellitus, (T2DM) type 2 diabetes mellitus, (VLDL) very-low-density lipoprotein.

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Peroxisome proliferator‐activated receptor (PPAR) modulators: Diabetes and beyond*

Cited by 65 publications

References 64 publications

PPARs Integrate the Mammalian Clock and Energy Metabolism

PPARs Integrate the Mammalian Clock and Energy Metabolism

Association of IL-6 and CRP gene polymorphisms with obesity and metabolic disorders in children and adolescents

Nonhuman Primates and other Animal Models in Diabetes Research

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