scholarly journals Peroxisome Proliferator-Activated Receptor Targets for the Treatment of Metabolic Diseases

2013 ◽  
Vol 2013 ◽  
pp. 1-18 ◽  
Author(s):  
Francisco A. Monsalve ◽  
Radha D. Pyarasani ◽  
Fernando Delgado-Lopez ◽  
Rodrigo Moore-Carrasco
Keyword(s):  
Risk Factors ◽  
Metabolic Syndrome ◽  
Lipid Metabolism ◽  
Glucose Homeostasis ◽  
Metabolic Diseases ◽  
Therapeutic Potential ◽  
Atherogenic Dyslipidemia ◽  
Acid Oxidation ◽  
Peroxisome Proliferator ◽  
The Metabolic Syndrome

Metabolic syndrome is estimated to affect more than one in five adults, and its prevalence is growing in the adult and pediatric populations. The most widely recognized metabolic risk factors are atherogenic dyslipidemia, elevated blood pressure, and elevated plasma glucose. Individuals with these characteristics commonly manifest a prothrombotic state and a proinflammatory state as well. Peroxisome proliferator-activated receptors (PPARs) may serve as potential therapeutic targets for treating the metabolic syndrome and its related risk factors. The PPARs are transcriptional factors belonging to the ligand-activated nuclear receptor superfamily. So far, three isoforms of PPARs have been identified, namely, PPAR-α, PPAR-β/δ, and PPAR-γ. Various endogenous and exogenous ligands of PPARs have been identified. PPAR-αand PPAR-γare mainly involved in regulating lipid metabolism, insulin sensitivity, and glucose homeostasis, and their agonists are used in the treatment of hyperlipidemia and T2DM. Whereas PPAR-β/δfunction is to regulate lipid metabolism, glucose homeostasis, anti-inflammation, and fatty acid oxidation and its agonists are used in the treatment of metabolic syndrome and cardiovascular diseases. This review mainly focuses on the biological role of PPARs in gene regulation and metabolic diseases, with particular focus on the therapeutic potential of PPAR modulators in the treatment of thrombosis.

scholarly journals Sex Differences in Rest-Activity Circadian Rhythm in Patients With Metabolic Syndrome

2021 ◽  
Vol 12 ◽  
Author(s):  
Antonino Mulè ◽  
Eleonora Bruno ◽  
Patrizia Pasanisi ◽  
Letizia Galasso ◽  
Lucia Castelli ◽  
...  
Keyword(s):  
Risk Factors ◽  
Metabolic Syndrome ◽  
Circadian Rhythm ◽  
Metabolic Diseases ◽  
Activity Level ◽  
Activity Count ◽  
Cross Sectional ◽  
The Metabolic Syndrome ◽  
Parametric Analyses ◽  
Rest Activity

Rest-Activity circadian Rhythm (RAR) can be used as a marker of the circadian timing system. Recent studies investigated the relationship between irregular circadian rhythms and cardiovascular risk factors such as hypertension, obesity, and dyslipidemia. These factors are related to the Metabolic Syndrome (MS), a clustering of metabolic risk factors that increases the risk of several cardiovascular and metabolic diseases. This cross-sectional analysis aimed to explore the RAR characteristics by actigraphy in subjects with MS, particularly in relation to sex and MS parameters, using parametric and non-parametric analyses. Distinguishing the characteristics of RAR based on sex could prove useful as a tool to improve the daily level of activity and set up customized activity programs based on each person’s circadian activity profile. This study showed that female participants exhibited higher values than male participants in the Midline Estimating Statistic of Rhythm (MESOR) (243.3 ± 20.0 vs 197.6 ± 17.9 activity count), Amplitude (184.5 ± 18.5 vs 144.2 ± 17.2 activity count), which measures half of the extent of the rhythmic variation in a cycle, and the most active 10-h period (M10) (379.08 ± 16.43 vs 295.13 ± 12.88 activity count). All these parameters are indicative of a higher daily activity level in women. Female participants also had lower Intradaily Variability (IV) than male participants (0.75 ± 0.03 vs 0.85 ± 0.03 activity count), which indicates a more stable and less fragmented RAR. These preliminary data provide the first experimental evidence of a difference in RAR parameters between male and female people with MS.

scholarly journals Peroxisome Proliferator–Activated Receptors and The Metabolic Syndrome

2009 ◽  
Vol 1 (1) ◽  
pp. 4 ◽  
Author(s):  
Anna Meiliana ◽  
Andi Wijaya
Keyword(s):  
Insulin Resistance ◽  
Metabolic Syndrome ◽  
Energy Balance ◽  
Glucose Homeostasis ◽  
Gene Activation ◽  
Sugar Metabolism ◽  
Endocrine Function ◽  
Peroxisome Proliferator ◽  
Peroxisome Proliferator Activated Receptor ◽  
The Metabolic Syndrome

BACKGROUND: Obesity is a growing threat to global health by virtue of its association with insulin resistance, inflammation, hypertension, and dyslipidemia, collectively known as the metabolic syndrome (MetS). The nuclear receptors PPARα and PPARγ are therapeutic targets for hypertriglyceridemia and insulin resistance, respectively, and drugs that modulate these receptors are currently in clinical use. More recent work on the PPARδ has uncovered a dual benefit for both hypertriglyceridemia and insulin resistance, highlighting the broad potential of PPARs in the treatment of metabolic disease.CONTENT: We have learned much about PPARs, the metabolic fat sensors, and the molecular pathways they regulate. Through their distinct tissue distribution and specific target gene activation, the three PPARs together control diverse aspects of fatty acid metabolism, energy balance, insulin sensitivity glucose homeostasis, inflammation, hypertension and atherosclerosis. These studies have advanced our understanding of the etiology for the MetS. Mechanisms revealed by these studies highlight the importance of emerging concepts, such as the endocrine function of adipose tissue, tissue-tissue cross-talk and lipotoxicity, in the pathogenesis of type 2 diabetes mellitus and CVD.SUMMARY: The elucidation of key regulators of energy balance and insulin signaling have revolutionized our understanding of fat and sugar metabolism and their intimate link. The three ‘lipidsensing’ (PPARα, PPARγ and PPARδ) exemplify this connection, regulating diverse aspects of lipid and glucose homeostasis, and serving as bonafide therapeutic targets.KEYWORDS: Peroxisome Proliferator, Activated Receptor, Metabolic Syndrome

scholarly journals Sirt1-PPARS Cross-Talk in Complex Metabolic Diseases and Inherited Disorders of the One Carbon Metabolism

Cells ◽  
2020 ◽  
Vol 9 (8) ◽  
pp. 1882 ◽  
Author(s):  
Viola J. Kosgei ◽  
David Coelho ◽  
Rosa-Maria Guéant-Rodriguez ◽  
Jean-Louis Guéant
Keyword(s):  
Metabolic Syndrome ◽  
Vitamin B12 ◽  
Metabolic Diseases ◽  
Preclinical Study ◽  
Peroxisome Proliferator ◽  
Inherited Disorders ◽  
Peroxisome Proliferator Activated Receptor ◽  
Altered Expression ◽  
The Metabolic Syndrome ◽  
Pregnancy And Lactation

Sirtuin1 (Sirt1) has a NAD (+) binding domain and modulates the acetylation status of peroxisome proliferator-activated receptor-γ coactivator-1α (PGC1α) and Fork Head Box O1 transcription factor (Foxo1) according to the nutritional status. Sirt1 is decreased in obese patients and increased in weight loss. Its decreased expression explains part of the pathomechanisms of the metabolic syndrome, diabetes mellitus type 2 (DT2), cardiovascular diseases and nonalcoholic liver disease. Sirt1 plays an important role in the differentiation of adipocytes and in insulin signaling regulated by Foxo1 and phosphatidylinositol 3′-kinase (PI3K) signaling. Its overexpression attenuates inflammation and macrophage infiltration induced by a high fat diet. Its decreased expression plays a prominent role in the heart, liver and brain of rat as manifestations of fetal programming produced by deficit in vitamin B12 and folate during pregnancy and lactation through imbalanced methylation/acetylation of PGC1α and altered expression and methylation of nuclear receptors. The decreased expression of Sirt1 produced by impaired cellular availability of vitamin B12 results from endoplasmic reticulum stress through subcellular mislocalization of ELAVL1/HuR protein that shuttles Sirt1 mRNA between the nucleus and cytoplasm. Preclinical and clinical studies of Sirt1 agonists have produced contrasted results in the treatment of the metabolic syndrome. A preclinical study has produced promising results in the treatment of inherited disorders of vitamin B12 metabolism.

MicroRNA regulation of mitochondrial and ER stress signaling pathways: implications for lipoprotein metabolism in metabolic syndrome

2014 ◽  
Vol 307 (9) ◽  
pp. E729-E737 ◽  
Author(s):  
Patricia Christian ◽  
Qiaozhu Su
Keyword(s):  
Metabolic Syndrome ◽  
Er Stress ◽  
Molecular Mechanisms ◽  
Metabolic Diseases ◽  
Lipoprotein Metabolism ◽  
Density Lipoprotein ◽  
Acid Oxidation ◽  
Aberrant Expression ◽  
The Metabolic Syndrome ◽  
Mitochondrial Fatty Acid

The development of metabolic syndrome is closely associated with the deregulation of lipid metabolism. Emerging evidence has demonstrated that microRNAs (miRNAs) are intensively engaged in lipid and lipoprotein metabolism by regulating genes involved in control of intracellular lipid synthesis, mitochondrial fatty acid oxidation, and lipoprotein assembly. Mitochondrial dysfunction induced by altered miRNA expression has been proposed to be a contributing factor in the onset of metabolic diseases, while at the same time, aberrant expression of certain miRNAs is associated with the induction of endoplasmic reticulum (ER) stress induced by nutrient-surplus. These studies position miRNAs as a link between oxidative stress and ER stress, two cellular stress pathways that are deregulated in metabolic disease and are associated with very-low-density lipoprotein (VLDL) overproduction. Dyslipoproteinemia frequently accompanied with metabolic syndrome is initiated largely by the overproduction of VLDL and altered biogenesis of high-density lipoprotein (HDL). In this review, we highlight recent findings on the regulatory impact of miRNAs on the metabolic homeostasis of mitochondria and ER as well as their contribution to the aberrant biogenesis of both VLDL and HDL in the context of metabolic disorders, in an attempt to gain further insights into the molecular mechanisms of dyslipidemia in the metabolic syndrome.

scholarly journals Overnutrition, ectopic lipid and the metabolic syndrome

2016 ◽  
Vol 64 (6) ◽  
pp. 1082-1086 ◽  
Author(s):  
Scott M Grundy
Keyword(s):  
Risk Factors ◽  
Metabolic Syndrome ◽  
Elevated Serum ◽  
Density Lipoprotein ◽  
Metabolic Risk Factors ◽  
Atherogenic Dyslipidemia ◽  
Current View ◽  
Metabolic Risk ◽  
Serum Triglycerides ◽  
The Metabolic Syndrome

The metabolic syndrome is a constellation of metabolic risk factors including atherogenic dyslipidemia (elevated serum triglycerides, reduced high-density lipoprotein (HDL) cholesterol), elevated blood pressure, dysglycemia (insulin resistance and elevated serum glucose), a pro-inflammatory state, and a prothrombotic state. Most persons with metabolic syndrome are obese, and usually have abdominal obesity. Generally, obesity is a reflection of overnutrition. A current view is that when adipose tissue fails to store all excess nutrients as triglyceride, lipid begins to accumulate in various tissues (eg, muscle, liver, pancreas, and heart). This accumulation is called ectopic lipid. Various mechanisms have been proposed whereby ectopic lipid is detrimental in different tissues; these derangements induce metabolic risk factors. The foundation of the metabolic syndrome thus appears to be overnutrition, that is, more nutrient intake than can be safely disposed by lipid oxidation. Excess dietary carbohydrate also induces ectopic lipid. Of interest, less than half of obese individuals develop metabolic syndrome. Through various mechanisms they adapt to overnutrition so as to minimize lipid overload in tissues, and consequently, prevent the syndrome.

scholarly journals Peroxisome Proliferator-Activated Receptors - Alpha in Chronic Inflammation - Mini-Review

2019 ◽  
Vol 12 ◽  
pp. 1-11
Author(s):  
Elena Popa ◽  
Florin Zugun-Eloae ◽  
Mihaela Zlei ◽  
Maria Traian ◽  
Agnes Bacusca ◽  
...  
Keyword(s):  
Metabolic Syndrome ◽  
Transcription Factors ◽  
Lipid Metabolism ◽  
Visceral Obesity ◽  
Peroxisome Proliferator ◽  
Proinflammatory Response ◽  
The Metabolic Syndrome ◽  
Metabolic Complication ◽  
Peroxisome Proliferator Activated Receptors ◽  
Proinflammatory Factors

The pathogeny of the metabolic syndrome (MetS ) is not fully elucidated, but a link between visceral obesity and the increase of the proinflammatory response was proven. Atherosclerosis, perceived as a metabolic complication, draws attention to the peroxisome proliferator-activated receptors- alpha (PPARα). PPARα receptors are transcription factors involved in lipid metabolism, inflammation and atheromatosis. Hence, it interferes in the pathogeny of cardiovascular diseases and other chronic diseases too (neurological, psychical, neoplasical). The study of the expression of PPARα and its modulation on different level may be beneficial in the treatment of metabolic syndrome, intervening in the modulation of another proinflammatory factors.

scholarly journals Preventing type 2 diabetes and cardiovascular disease in metabolic syndrome: the role of PPARα

2007 ◽  
Vol 4 (3_suppl) ◽  
pp. S12-S14 ◽  
Author(s):  
Jorge Plutzky
Keyword(s):  
Type 2 Diabetes ◽  
Metabolic Syndrome ◽  
Lipid Metabolism ◽  
Drug Target ◽  
Peroxisome Proliferator ◽  
Peroxisome Proliferator Activated Receptor ◽  
Central Target ◽  
The Metabolic Syndrome

The clustering of cardiovascular risk factors associated with the metabolic syndrome and type 2 diabetes suggests central mechanisms may exist that account for the presence of these abnormalities. Likewise, this clustering also suggests that key therapeutic targets may exist that could allow improvements in many of these parameters. Extensive data implicate peroxisome proliferator-activated receptor-alpha (PPARα) as an important transcriptional regulator of lipid metabolism, energy balance and inflammation. PPARα is also an established drug target. Experimental data show that activation of PPARα by agonists such as fenofibrate improves dyslipidaemia, increases cholesterol efflux and limits inflammation. All of these effects would also be predicted to decrease atherosclerotic risk. Evidence from surrogate markers in humans is also supportive of the concept that PPARα may act as a central target capable of influencing a variety of different pathways involved in lipid metabolism. Thus, fenofibrate offers the potential for inducing a co-ordinated PPARα response that may improve dyslipidaemia, repress inflammation and limit atherosclerosis in patients with the metabolic syndrome or type 2 diabetes.

scholarly journals COVID-19 Comorbidity and Metabolic Syndrome: Is There a Molecular Basis?

2020 ◽  
Author(s):  
Madhurima Basu ◽  
Chinmay Saha ◽  
Kamalika Roy Choudhury ◽  
Susmita Dutta ◽  
Sujoy Ghosh ◽  
...  
Keyword(s):  
Risk Factors ◽  
Metabolic Syndrome ◽  
Molecular Basis ◽  
Metabolic Diseases ◽  
Viral Proteins ◽  
Host Protein ◽  
Acid Oxidation ◽  
Biological Processes ◽  
Host Proteins ◽  
Alcoholic Fatty Liver

The risk factors associated with COVID-19 related severity, morbidity, and mortality, i.e., obesity (often associated with NAFLD), hyperglycemia, hypertension and dyslipidemia all cluster together as metabolic syndrome (MetS). Instead of studying association of these risk factors with COVID-19, it makes sense studying the association between MetS on one hand and COVID-19 on the other. This study explores a molecular basis underpinning the above association. Severity of COVID-19 patients with MetS could be due to functional alterations of host proteins due to their interactions with viral proteins. We collected data from Enrichr (https://amp.pharm.mssm.edu/Enrichr/), DisGeNET (https://www.disgenet.org/) and others and carried out enrichment analysis using Enrichr. Various biological processes and pathways associated with viral protein interacting partners are known to involve in metabolic diseases. The molecular pathways underlying insulin resistance, insulin signaling and insulin secretion are not only involved in diabetes but also in CVD and obesity (associated with non-alcoholic fatty liver disease; NAFLD). Lipid metabolism/lipogenesis, fatty acid oxidation and inflammation are associated with MetS. Viral interacting host proteins are associated and enriched with terms like hyperglycemia, coronary artery disease, hypertensive disease related to CVD and liver diseases in DisGeNET. Association of viral interacting proteins with disease-relevant biological processes, pathways and disease-related terms suggests that altered host protein function following interaction with viral proteins might contribute to frequent occurrence and/or severity of COVID-19 in subjects with MetS. Such analysis not only provides a molecular basis of comorbidity but also incriminates host proteins in viral replication, growth and identifies possible drug targets for intervention.

scholarly journals FEATURES OF CARDIOVASCULAR ADAPTATION IN NEWBORNS BORN FROM MOTHERS WITH METABOLIC SYNDROME

2021 ◽  
Vol 11 (4(42)) ◽  
pp. 9-14
Author(s):  
V. Pokhylko ◽  
O. Kovalova ◽  
Y. Cherniavska ◽  
Y. Klymchuk ◽  
O. Yakovenko
Keyword(s):  
Risk Factors ◽  
Blood Pressure ◽  
Metabolic Syndrome ◽  
Lipid Metabolism ◽  
High Blood Pressure ◽  
Premature Infants ◽  
Negative Relationship ◽  
Main Group ◽  
Overweight And Obesity ◽  
The Metabolic Syndrome

Introduction. Overweight and obesity, the manifestations of metabolic syndrome during pregnancy, and their consequences are huge public health challenges. The effect of a mother`s metabolic syndrome on the condition of a newborn is insufficiently studied. The aim is to establish the features of cardiovascular adaptation of premature infants born from mothers with metabolic syndrome, and to identify metabolic maternal and infant risk factors that are mostly associated with high blood pressure and cardiopathy. Material and methods. A cohort prospective study was conducted, which included 97 premature newborns who were treated in the intensive care unit. Two groups were formed: the main group included premature infants born from mothers with metabolic syndrome (n = 40), and the comparison group included premature infants born from mothers without metabolic syndrome (n = 57). Results. Infants born from mothers with metabolic syndrome had significantly higher blood pressure than normal according to the gestational age of a child (45.5 ± 0.13 vs. 42.56 ± 0.13 mm Hg, p <0.001). High blood pressure in infants was significantly associated with maternal lipid metabolism disorders (OR 30.9) and hypertension (OR 4.8). The study found a significant positive relationship between blood pressure and overweight in an infant (Coef. 0.168), and a significant negative relationship with glucose level in blood serum (Coef. -0.037). It was found that cardiomyopathy is significantly more common in children of the main group (p = 0.010), its development is associated with the presence of diabetes in a mother (OR 7.57). The more components of the metabolic syndrome a woman has, the more likely a child is to have cardiomyopathy. The risk of developing cardiomyopathy is significantly influenced by a number of risk factors on the part of a newborn. Conclusions: High blood pressure in premature infants is significantly associated with a complex of components of the metabolic syndrome in mothers (hypertension and / or preeclampsia, obesity, diabetes and disorders of lipid metabolism in a mother (OR 14.71, p <0.001)). The role of carbohydrate metabolism disorders in a child in the development of high blood pressure has been demonstrated. It is proved that the development of cardiopathy in newborns is associated with risk factors from both a child and a mother, which indicates a complex effect of metabolic factors on the adaptation of the cardiovascular system.

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