scholarly journals Two Polymorphisms in the Peroxisome Proliferator-Activated Receptor-γ Gene Are Associated with Severe Overweight among Obese Women*

1999 ◽  
Vol 84 (10) ◽  
pp. 3708-3712 ◽  
Author(s):  
R. Valve ◽  
K. Sivenius ◽  
R. Miettinen ◽  
J. Pihlajamäki ◽  
A. Rissanen ◽  
...  
Keyword(s):  
Body Mass Index ◽  
Fat Mass ◽  
Adipocyte Differentiation ◽  
Population Based ◽  
Peroxisome Proliferator ◽  
Obese Women ◽  
Pro12ala Polymorphism ◽  
Peroxisome Proliferator Activated Receptor ◽  
Obese Subjects ◽  
Pparγ Gene

Abstract Peroxisome proliferator-activated receptor-γ (PPARγ) is a nuclear receptor that regulates adipocyte differentiation. Variations in the PPARγ gene may affect the function of the PPARγ and, therefore, body adipocity. We investigated the frequencies of the Pro12Ala polymorphism in exon B and the silent CAC478CAT polymorphism in exon 6 of the PPARγ gene and their effects on body weight, body composition, and energy expenditure in obese Finns. One hundred and seventy obese subjects [29 men and 141 women; body mass index (BMI), 35.7 ± 3.8 kg/m2; age, 43 ± 8 yr; mean ± sd) participated in the study. The frequencies of the Ala12 allele in exon B and CAT478 allele in exon 6 were not significantly different between the obese and population-based control subjects (0.14 vs. 0.13 and 0.19 vs. 0.21, respectively). The polymorphisms were associated with increased BMI [Pro12Pro, 34.5 ± 3.8; Pro12Ala, 34.8 ± 3.1; Ala12Ala, 39.2± 4.6 kg/m2 (P = 0.011); CAC478CAC, 34.5 ± 3.8; CAC478CAT, 34.5 ± 3.3; CAT478CAT, 37.7 ± 4.1 kg/m2 (P = 0.046)]. In addition, the women with both Ala12Ala and CAT478CAT genotypes (n = 5) were significantly more obese compared with the women having both Pro12Pro and CAC478CAC genotypes (n = 85; BMI, 40.6 ± 3.3 vs. 34.4 ± 3.9 kg/m2; P = 0.001), and they had increased fat mass (46.8 ± 9.1 vs. 36.8 ± 7.5 kg; P = 0.005). In conclusion, the Pro12Ala and CAC478CAT polymorphisms in the PPARγ gene are associated with severe overweight and increased fat mass among obese women.

scholarly journals Effect of the Pro12Ala polymorphism of the peroxisome proliferator-activated receptor γ2 gene on lipid profile and adipokines levels in obese subjects

2017 ◽  
Vol 20 (1) ◽  
pp. 71-80 ◽  
Author(s):  
E Becer ◽  
A Çırakoğlu
Keyword(s):  
Serum Lipid ◽  
Peroxisome Proliferator ◽  
Model Assessment ◽  
Pro12ala Polymorphism ◽  
Peroxisome Proliferator Activated Receptor ◽  
Pcr Rflp ◽  
Obese Subjects ◽  
Polymerase Chain ◽  
Lipid Parameters ◽  
Γ2 Gene

Abstract Peroxisome proliferator-activated receptor γ (PPARγ) is a key regulator of metabolism, adipokines production and secretion. The aim of this study was to investigate the association between the PPARγ2 gene Pro12Ala polymorphism in obesity in terms of body mass index (BMI), lipid parameters, homeostasis model assessment of insulin resistance (HOMA-IR), serum lipid, leptin, adiponectin, resistin and chemerin levels. The study included 160 obese and 140 non obese subjects. The Pro12Ala polymorphism was determined by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). Serum lipid, leptin, adiponectin, resistin and chemerin levels were measured. No association was found between the Pro12Ala polymorphism and BMI. Strikingly, in the study group, obese subjects with the AA genotype had significantly higher triglycerides (p = 0.046) and resistin (p <0.001) levels than those with the wild-type PP and heterozygous PA genotypes. Serum leptin and chemerin levels were significantly associated with Pro-12Ala poymorphism in the obese and non obese groups (p <0.01). In the obese group, subjects with the homozygous AA genotype had significantly lower adiponectin (p = 0.010) activity than the PP genotype. Our results suggest that the PPARγ2 gene Pro12Ala polymorphism has no direct association with obesity but does have significant influences on lipid profiles and adipokines levels.

scholarly journals Homozygosity for the Ala Allele of the PPARγ2 Pro12Ala Polymorphism Is Associated with Reduced Risk of Coronary Artery Disease

2010 ◽  
Vol 29 (5) ◽  
pp. 259-264 ◽  
Author(s):  
Andrea Galgani ◽  
AnaMaria Valdes ◽  
Henry A. Erlich ◽  
Calvin Mano ◽  
Suzanne Cheng ◽  
...  
Keyword(s):  
Coronary Artery Disease ◽  
Coronary Artery ◽  
Population Based ◽  
Peroxisome Proliferator ◽  
Italian Population ◽  
Pro12ala Polymorphism ◽  
Gene Encoding ◽  
Peroxisome Proliferator Activated Receptor ◽  
Artery Disease ◽  
Reduced Risk

Several studies suggest that the peroxisome proliferator-activated receptor gamma (PPARγ) is involved in atherogenesis. The Pro12Ala polymorphism in the gene encoding PPARγ (PPARγ2 gene) influences the risk for type 2 diabetes. Two population-based studies have shown that the Ala allele is associated with reduced carotid intimal-medial thickness (IMT). However, studies focusing on acute clinical events have yielded conflicting results. Our aim was to evaluate the role of the Pro12AlaPPARγ2 polymorphism on the risk of coronary artery disease (CAD) in an Italian population with a case-controlled genetic association study in which 478 CAD patients and 218 controls were genotyped for the Pro12Ala polymorphism. CAD was diagnosed by angiography. We found that homozygotes for the Ala12 allele had a significantly reduced risk of CAD after adjusting for diabetes, sex, age, body mass index (BMI), smoking, lipids and hypertension (OR = 0.007; 95% C.I. = 0.00–0.32p< 0.011). In this casecontrol study, homozygosity for the Ala allele at codon 12 of thePPAR2 gene resulted in reduced risk of CAD. This is consistent with reports from previous studies focusing on atherosclerosis and myocardial infarction.

scholarly journals Effect of the Pro12Ala polymorphism of the peroxisome proliferator-activated receptor gamma-2 gene on adiposity, insulin sensitivity and lipid profile in the Spanish population

2002 ◽  
pp. 495-501 ◽  
Author(s):  
JL Gonzalez Sanchez ◽  
M Serrano Rios ◽  
C Fernandez Perez ◽  
M Laakso ◽  
MT Martinez Larrad
Keyword(s):  
Insulin Resistance ◽  
Adipose Tissue ◽  
Insulin Sensitivity ◽  
Ppar Gamma ◽  
Population Based ◽  
Peroxisome Proliferator ◽  
Model Assessment ◽  
Pro12ala Polymorphism ◽  
Peroxisome Proliferator Activated Receptor ◽  
Sagittal Abdominal Diameter

OBJECTIVE: To investigate the role of the Pro12Ala peroxisome proliferator-activated receptor (PPAR) gamma-2 polymorphism in the susceptibility to the insulin resistance syndrome and its metabolic complications in a population-based nationwide multicenter study in Spain. DESIGN: 464 unrelated adults (45.3% men and 54.7% women) aged between 35 and 64 years were randomly chosen from a nationwide population-based survey of obesity and related conditions including insulin resistance and cardiovascular risk factors. METHODS: Anthropometric determinations included: body mass index (BMI), waist-to-hip ratio, sagittal abdominal diameter; biochemical determinations included: fasting plasma glucose concentration and concentration 2 h after an oral glucose tolerance test (OGTT), total cholesterol, high and low density lipoprotein-cholesterol, triglycerides, leptin and insulin. Systolic and diastolic blood pressure were also measured. Genotyping of the PPARgamma-2 Pro12Ala polymorphism was determined by polymerase chain reaction and single strand conformation polymorphism analysis. RESULTS: The Ala12 allele frequency was higher in obese men than in lean men (0.15 vs 0.08, P=0.03). Men carriers of the Ala12 allele had a higher BMI than non-carriers (38.9% vs 21.3%; adjusted odds ratio 2.36, 95% confidence interval 1.10-5.05, P=0.03). However, despite higher BMI obese men carriers of the Ala12 allele had lower sagittal abdominal diameter than Pro12 homozygotes (24.1+/-3.2 vs 26.3+/-2.5 cm, P=0.01). The Ala12 allele was associated with lower total triglycerides levels in the overall population and it was also associated with lower fasting insulin levels and a higher insulin sensitivity by homeostasis model assessment (HOMA) in women. CONCLUSIONS: Our results suggest that the Pro12Ala polymorphism of the PPARgamma-2 gene promotes peripheral deposition of adipose tissue and increased insulin sensitivity for a given BMI. The results in women might be due to their different adipose tissue distribution.

scholarly journals Effect of Salusin-ß on Peroxisome Proliferator-Activated Receptor Gamma Gene Expression in Vascular Smooth Muscle Cells and its Possible Mechanism

2015 ◽  
Vol 36 (6) ◽  
pp. 2466-2479 ◽  
Author(s):  
XiaoLe Xu ◽  
Mengzi He ◽  
Tingting Liu ◽  
Yi Zeng ◽  
Wei Zhang
Keyword(s):  
Gene Expression ◽  
Smooth Muscle ◽  
Vascular Smooth Muscle ◽  
Smooth Muscle Cells ◽  
Vascular Smooth Muscle Cells ◽  
Nuclear Translocation ◽  
Muscle Cells ◽  
Peroxisome Proliferator ◽  
Peroxisome Proliferator Activated Receptor ◽  
Pparγ Gene

Background/Aims: salusin-ß is considered to be a potential pro-atherosclerotic factor. Regulation and function of vascular smooth muscle cells (VSMCs) are important in the progression of atherosclerosis. Peroxisome proliferator-activated receptor gamma (PPARγ) exerts a vascular protective role beyond its metabolic effects. Salusin-ß has direct effects on VSMCs. The aim of the present study was to assess the effect of salusin-ß on PPARγ gene expression in primary cultured rat VSMCs. Methods: Western blotting analysis, real-time PCR and transient transfection approach were used to determine expression of target proteins. Specific protein knockdown was performed with siRNA transfection. Cell proliferation was determined by 5-bromo-2'-deoxyuridine incorporation. The levels of inflammation indicators interleukin-6 (IL-6) and tumor necrosis factor-a (TNF-a) were determined using enzyme-linked immunosorbent assay. Results: Salusin-ß negatively regulated PPARγ gene expression at protein, mRNA and gene promoter level in VSMCs. The inhibitory effect of salusin-ß on PPARγ gene expression contributed to salusin-ß-induced VSMCs proliferation and inflammation in vitro. IγBa-NF-γB activation, but not NF-γB p50 or p65, mediated the salusin-ß-induced inhibition of PPARγ gene expression. Salusin-ß induced nuclear translocation of histone deacetylase 3 (HDAC3). HDAC3 siRNA prevented salusin-ß-induced PPARγ reduction. Nuclear translocation of HDAC3 in response to salusin-ß was significantly reversed by an IγBa inhibitor BAY 11-7085. Furthermore, IγBa-HDAC3 complex was present in the cytosol of VSMCs but interrupted after salusin-ß treatment. Conclusion: IγBa-HDAC3 pathway may contribute to salusin-ß-induced inhibition of PPARγ gene expression in VSMCs.

Adipocyte differentiation of 3T3-L1 preadipocytes is dependent on lipoxygenase activity during the initial stages of the differentiation process

2003 ◽  
Vol 375 (3) ◽  
pp. 539-549 ◽  
Author(s):  
Lise MADSEN ◽  
Rasmus K. PETERSEN ◽  
Morten B. SØRENSEN ◽  
Claus JØRGENSEN ◽  
Philip HALLENBORG ◽  
...  
Keyword(s):  
Adipocyte Differentiation ◽  
Critical Evaluation ◽  
Nordihydroguaiaretic Acid ◽  
Whole Body ◽  
Transcriptional Networks ◽  
Peroxisome Proliferator ◽  
The Novel ◽  
Differentiation Process ◽  
Peroxisome Proliferator Activated Receptor ◽  
Brown Adipose

Adipocytes play a central role in whole-body energy homoeostasis. Complex regulatory transcriptional networks control adipogensis, with ligand-dependent activation of PPARγ (peroxisome proliferator-activated receptor γ) being a decisive factor. Yet the identity of endogenous ligands promoting adipocyte differentiation has not been established. Here we present a critical evaluation of the role of LOXs (lipoxygenases) during adipocyte differentiation of 3T3-L1 cells. We show that adipocyte differentiation of 3T3-L1 preadipocytes is inhibited by the general LOX inhibitor NDGA (nordihydroguaiaretic acid) and the 12/15-LOX selective inhibitor baicalein. Baicalein-mediated inhibition of adipocyte differentiation was rescued by administration of rosiglitazone. Treatment with baicalein during the first 4 days of the differentiation process prevented adipocyte differentiation; supplementation with rosiglitazone during the same period was sufficient to rescue adipogenesis. Accordingly, we demonstrate that adipogenic conversion of 3T3-L1 cells requires PPARγ ligands only during the first 4 days of the differentiation process. We show that the baicalein-sensitive synthesis of endogenous PPARγ ligand(s) increases rapidly upon induction of differentiation and reaches a maximum on days 3–4 of the adipocyte differentiation programme. The conventional platelet- and leucocyte-type 12(S)-LOXs and the novel eLOX-3 (epidermis-type LOX-3) are expressed in white and brown adipose tissue, whereas only eLOX-3 is clearly expressed in 3T3-L1 cells. We suggest that endogenous PPARγ ligand(s) promoting adipocyte differentiation are generated via a baicalein-sensitive pathway involving the novel eLOX-3.

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