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Hormone and Metabolic Research =... May 2023The relationships of the PPARα Leu162Val and PPARδ+294 T>C polymorphisms with metabolic indexes have been reported to be inconsistent and even contradictory. The... (Meta-Analysis)
Meta-Analysis
The relationships of the PPARα Leu162Val and PPARδ+294 T>C polymorphisms with metabolic indexes have been reported to be inconsistent and even contradictory. The meta-analysis was conducted to clarify the relationships between the two variants and the indexes of obesity, insulin resistance, and blood lipids. PubMed, Google Scholar, Embase, and Cochrane Library were searched for eligible studies. Standardized mean difference with 95% confidence interval was calculated to estimate the differences in the metabolic indexes between the genotypes of the Leu162Val and+294 T>C polymorphisms. Heterogeneity among studies was assessed by Cochran's x2-based Q-statistic test. Publication bias was identified by using Begg's test. Forty-one studies (44 585 subjects) and 33 studies (23 018 subjects) were identified in the analyses for the Leu162Val and+294 T>C polymorphisms, respectively. C allele carriers of the+294 T>C polymorphism had significantly higher levels of total cholesterol and low-density lipoprotein cholesterol than TT homozygotes in the whole population. Notably, C allele carriers of the+294 T>C polymorphism had significantly higher levels of triglycerides and total cholesterol in East Asians, but lower levels of triglycerides in West Asians than TT homozygotes. Regarding the Leu162Val polymorphism, it was found that Val allele carriers had significantly higher levels of blood glucose than Leu/Leu homozygotes only in European Caucasians. The meta-analysis demonstrates that C allele of the+294 T>C polymorphism in PPARδ gene confers a higher risk of hypercholesterolemia, which may partly explain the relationship between this variant and coronary artery disease.
Topics: Humans; PPAR delta; Hypercholesterolemia; Insulin Resistance; Alleles; Triglycerides; Obesity; Cholesterol, LDL; Polymorphism, Single Nucleotide
PubMed: 37011890
DOI: 10.1055/a-2043-7707 -
Clinical Journal of Gastroenterology Dec 2021Dyslipidemia is a very common medical disorder affecting nearly 33.5% of US adults over 20 years of age. It represents the major risk factor for non-alcoholic fatty... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Dyslipidemia is a very common medical disorder affecting nearly 33.5% of US adults over 20 years of age. It represents the major risk factor for non-alcoholic fatty liver (NAFLD) and cardiovascular diseases, which is the most common cause of death worldwide. Elafibranor is a peroxisome proliferator-activated receptor (PPAR) alpha and delta dual agonist. A novel dual peroxisome proliferator-activated receptor alpha/delta (PPAR-α/δ), elafibranor, the agonist is an emerging therapy with promising hepatoprotective results.
OBJECTIVES
To estimate the efficacy of elafibranor in patients with liver abnormalities especially non-alcoholic steatohepatitis (NASH).
METHODS
We searched the following databases: PubMed, SCOPUS, Web of Science, and Cochrane Library for relevant clinical trials assessing the use of silymarin in patients with NAFLD. Risk of bias assessment was performed using Cochrane's risk of bias tool. We included the following outcomes: alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), gamma-glutamyl transferase (GGT), HOMA-IR, total cholesterol (TC), triglyceride (TG), HDL-cholesterol (HDL-C), and LDL-cholesterol (LDL-C).
RESULTS
We included four clinical trials. We found that elafibranor significantly reduced the levels of ALT {MD = - 4.60 [- 8.17, - 1.04], (P = 0.01)}, GGT {MD = - 16.57 [- 26.59, - 6.56], (P < 0.01)}, TC {MD = - 0.37 [- 0.66, - 0.08], (P = 0.01)}, TG {MD = - 0.37 [- 0.51, - 0.24], (P < 0.01)}, ALP {(MD = - 14.45 [- 18.99, - 9.91], (P < 0.01)}, and LDL {MD = - 0.20 [- 0.33, - 0.07], (P = 0.003)}. There was no significant difference regarding HOMA-IR {MD = - 0.32 [- 0.88, 0.24], (P = 0.26) and AST (P = 0.53).
CONCLUSION
PPAR-alpha/delta dual agonist, elafibranor, is a promising drug that improves most metabolic parameters in dyslipidemic patients.
Topics: Adult; Chalcones; Humans; Non-alcoholic Fatty Liver Disease; Propionates
PubMed: 34370218
DOI: 10.1007/s12328-021-01491-7 -
British Journal of Pharmacology Oct 2020Embase and PubMed were systematically searched for articles addressing the neuroprotective properties of phytocannabinoids, apart from cannabidiol and Δ... (Review)
Review
Embase and PubMed were systematically searched for articles addressing the neuroprotective properties of phytocannabinoids, apart from cannabidiol and Δ -tetrahydrocannabinol, including Δ -tetrahydrocannabinolic acid, Δ -tetrahydrocannabivarin, cannabidiolic acid, cannabidivarin, cannabichromene, cannabichromenic acid, cannabichromevarin, cannabigerol, cannabigerolic acid, cannabigerivarin, cannabigerovarinic acid, cannabichromevarinic acid, cannabidivarinic acid, and cannabinol. Out of 2,341 studies, 31 articles met inclusion criteria. Cannabigerol (range 5 to 20 mg·kg ) and cannabidivarin (range 0.2 to 400 mg·kg ) displayed efficacy in models of Huntington's disease and epilepsy. Cannabichromene (10-75 mg·kg ), Δ -tetrahydrocannabinolic acid (20 mg·kg ), and tetrahydrocannabivarin (range 0.025-2.5 mg·kg ) showed promise in models of seizure and hypomobility, Huntington's and Parkinson's disease. Limited mechanistic data showed cannabigerol, its derivatives VCE.003 and VCE.003.2, and Δ -tetrahydrocannabinolic acid mediated some of their effects through PPAR-γ, but no other receptors were probed. Further studies with these phytocannabinoids, and their combinations, are warranted across a range of neurodegenerative disorders.
Topics: Cannabidiol; Dronabinol; Humans; Huntington Disease; Seizures
PubMed: 32608035
DOI: 10.1111/bph.15185 -
PPAR Research 2013Pregnancy is a state of immunotolerance, and pregnancy outcome is strongly linked to the correct activation and balancing of the maternal immune system. Besides abortion...
Pregnancy is a state of immunotolerance, and pregnancy outcome is strongly linked to the correct activation and balancing of the maternal immune system. Besides abortion as possible result of improper early pregnancy development, other pregnancy associated conditions like preeclampsia (PE), intrauterine growth retardation (IUGR), preterm labour, or gestational diabetes mellitus (GDM) are linked to immunologic overactivation and dysregulation. Both the innate and the adaptive immune system, and therefore B and T lymphocytes, natural killer cells (NK), macrophages and dendritic cells (DCs) are all involved in trophoblast invasion, pregnancy maintenance, and development of pregnancy disorders. Peroxisome proliferator activated receptors (PPARs) are nuclear transcription factors with three known isotypes: PPARα, PPAR β / δ , and PPAR γ . They are expressed in most human organs and their function extends from regulating metabolism, homeostasis, and carcinogenesis to immune response. In the recent years, PPARs have been identified in most reproductive tissues and in all lines of immune cells. Only in few cases, the role of PPARs in reproductive immunology has been elucidated though the role of PPARs in immune answer and immunotolerance is evident. Within this paper we would like to give an update on today's knowledge about PPARs and immune cells in reproduction and highlight interesting interferences in regard of future therapeutic targets.
PubMed: 23554810
DOI: 10.1155/2013/970276 -
Clinical Endocrinology Mar 2010To study the association of polymorphisms in the genes encoding peroxisome proliferator-activated receptors (PPARs) with the polycystic ovary syndrome (PCOS). (Meta-Analysis)
Meta-Analysis Review
The role of genetic variation in peroxisome proliferator-activated receptors in the polycystic ovary syndrome (PCOS): an original case-control study followed by systematic review and meta-analysis of existing evidence.
OBJECTIVE
To study the association of polymorphisms in the genes encoding peroxisome proliferator-activated receptors (PPARs) with the polycystic ovary syndrome (PCOS).
DESIGN
Case-control study and meta-analysis of published evidence.
PATIENTS
One hundred and sixty-one polycystic ovary syndrome patients and 113 non-hyperandrogenic women.
MEASUREMENTS
Genotyping for PPAR-gamma coactivator-1 gene (PPARGC1A) Gly482Ser, PPAR-alpha Leu162Val, PPAR-delta rs2267668A/G, PPAR-delta-87T/C, PPAR-gamma2 Pro12Ala and PPAR-gamma2 -681C/G variants and systematic review of the literature using the Entrez-PubMed search engine, followed by meta-analysis whenever possible.
RESULTS
Polycystic ovary syndrome patients carried the Gly482Ser variant in PPARGC1A more frequently than controls (72%vs. 58%, chi(2 )=( )5.54 P = 0.019), whereas carriers of the PPAR-alpha Leu162Val, PPAR-delta rs2267668A/G, PPAR-delta-87T/C, PPAR-gamma2 Pro12Ala and PPAR-gamma2 -681C/G variants were distributed similarly among both groups. The interaction between the PPARGC1A Gly482Ser and PPAR-delta-87T/C variants was also associated with PCOS (OR = 1.24, 95% CI 1.05-1.50, P = 0.008). The systematic review identified 31 studies addressing associations between PPARs variants and PCOS; meta-analysis was possible for nine studies focusing on the PPAR-gamma2 Pro12Ala variant. Although the individual studies did not reveal any statistically significant association, meta-analysis uncovered that carrying the PPAR-gamma2 Pro12Ala variant was associated with a reduced probability of having PCOS (OR = 0.77, 95% CI 0.61-0.96, P = 0.025), and that this association may be mediated by an effect on insulin sensitivity.
CONCLUSIONS
Common polymorphisms in the PPARGC1A, PPAR-delta and PPAR-gamma2 loci are associated with PCOS.
Topics: Adult; Case-Control Studies; Female; Genetic Variation; Humans; Insulin Resistance; Peroxisome Proliferator-Activated Receptors; Phenotype; Polycystic Ovary Syndrome; Spain; Young Adult
PubMed: 19681917
DOI: 10.1111/j.1365-2265.2009.03679.x