Activated Receptor Gamma Research Articles

Hepatic oxidative stress in ovariectomized transgenic mice expressing the hepatitis C virus polyprotein is augmented through suppression of adenosine monophosphate‐activated protein kinase/proliferator‐activated receptor gamma co‐activator 1 alpha signaling

Oxidative stress plays an important role in hepatocarcinogenesis of hepatitis C virus (HCV)-related chronic liver diseases. Despite the evidence of an increased proportion of females among elderly patients with HCV-related hepatocellular carcinoma (HCC), it remains unknown whether HCV augments hepatic oxidative stress in postmenopausal women. The aim of this study was to determine whether oxidative stress was augmented in ovariectomized (OVX) transgenic mice expressing the HCV polyprotein and to investigate its underlying mechanisms. OVX and sham-operated female transgenic mice expressing the HCV polyprotein and non-transgenic littermates were assessed for the production of reactive oxygen species (ROS), expression of inflammatory cytokines and antioxidant potential in the liver. Compared with OVX non-transgenic mice, OVX transgenic mice showed marked hepatic steatosis and ROS production without increased induction of inflammatory cytokines, but there was no increase in ROS-detoxifying enzymes such as superoxide dismutase 2 and glutathione peroxidase 1. In accordance with these results, OVX transgenic mice showed less activation of peroxisome proliferator-activated receptor-γ co-activator-1α (PGC-1α), which is required for the induction of ROS-detoxifying enzymes, and no activation of adenosine monophosphate-activated protein kinase-α (AMPKα), which regulates the activity of PGC-1α. Our study demonstrated that hepatic oxidative stress was augmented in OVX transgenic mice expressing the HCV polyprotein by attenuation of antioxidant potential through inhibition of AMPK/PGC-1α signaling. These results may account in part for the mechanisms by which HCV-infected women are at high risk for HCC development when some period has passed after menopause.

Association of Genetic Polymorphism of Peroxisome Proliferator‐Activated Receptor‐Gamma Gene and Polycystic Ovary Syndrome

BackgroundPeroxisome proliferative‐ activated receptor gamma (PPARs) is a nuclear receptor which controls transcription of genes involved in free fatty acid uptake and lipogenesis, and is essential for differention and survival of adipocytes.AimTo investigate the association of Pro12Ala polymorphism in PPAR gamma gene with polycystic ovary syndrome (PCOS) and its related metabolic disorders.Material and MethodThe study consisted of 50 women diagnosed with PCOS and 96 healthy women as a control group. Individuals were genotyped for Pro12Ala genetic polymorphism of PPAR gamma by using polymerase chain reaction‐ restriction fragment length polymorphism. Statistical analysis was done by SPSS program.ResultsFrequency of Pro12/Pro12 and Pro12/Ala12 genotypes were 86% and 14% in PCOS group compared to 77.1% and 22.9% in control group. The carriers of Pro12/Pro12 genotype exhibited a significant greater risk for PCOS compared to carriers of Pro12/Ala12 genotype (OR= 1.8, 95%CI= 0.7–4.6). Furthermore they were at higher risk of different metabolic disorders such as obesity, insulin resistance and diabetes mellitus.ConclusionPro12/Pro12 genotype is a risk factor for PCOS and its related metabolic disorders.Source of Fund: Dubai Medical College for girls.

Peroxisome proliferator-activated receptor gamma inhibits liver cancer proliferation and metastasis in vitro

Objective To investigate the inhibitory effect of peroxisome proliferator- activated receptor gamma( PPARγ) on the development,progression,invasion,and metastasis of liver cancer cells. Methods Hepatocellular carcinoma( HCC) MHCC97L cells were randomly assigned to be transfected with Ad- PPARγ or Ad- LacZ( control). The cells were also exposed to PPARγ agonist rosiglitazone. Cell proliferation,apoptosis,migration,and invasive ability were evaluated using MTS assay,flow cytometry,wound healing test,and transwell invasion assay. Multiple comparisons of means between groups were conducted using one- way analysis of variance with Bonferroni correction; the means of two groups were compared using the t test. Results Ad- PPARγ transfection resulted in higher expression of PPARγprotein in HCC cells compared with control cells,which suppressed cell proliferation( P 0. 01),induced cell apoptosis( P 0. 01),and suppressed cell migration and invasion. Moreover,the invasiveness of HCC cells transfected with Ad- PPARγ was reduced by 20% ~ 60%.Rosiglitazone enhanced the inhibitory effect of Ad- PPARγ on the growth and migration of HCC cells. Conclusion PPARγ exerts an inhibitory effect on the proliferative,invasive,and metastatic potential of HCC cells in vitro. This study sheds new light on the search for potential markers and gene therapies for liver cancer.

Pioglitazone protects against cisplatin induced nephrotoxicity in rats and potentiates its anticancer activity against human renal adenocarcinoma cell lines

Cisplatin-induced nephrotoxicity is a serious problem that limits its use in cancer treatment. The present study aimed to investigate the renal protective capacity of pioglitazone to reduce the cisplatin- induced nephrotoxicity. The underlying suggested mechanism(s) and whether this nephroprotective effect (if any) interferes with the cytotoxic effect of cisplatin on cancer cells were also investigated.Pioglitazone, Bisphenol A diglycidyl ether, BADGE, IP injected (Peroxisome proliferator- activated receptor gamma (PPAR-γ) antagonist), or their combination were administered to rats one hour before cisplatin injection. Moreover, their effects on the cell viability of human renal adenocarcinoma cell models (ACHN) were studied. The obtained results showed that pioglitazone improved the renal function, structural changes, renal malondialdehyde (MDA), tumor necrosis factor alpha (TNF-α), nuclear factor kappa B (NF-κB) genes expression in cisplatin injected rats. It increased both renal reduced glutathione (GSH) content and PPAR-γ gene expression. In contrast to the data obtained by prior administration of BADGE. Pioglitazone also potentiated the cytotoxic effect of cisplatin on human renal adenocarcinoma cells and this effect was abolished by BADGE co administration. In conclusion, these results suggested that pioglitazone protected against cisplatin- induced nephrotoxicity through its interaction with PPAR-γ receptors and antioxidant effects. Furthermore, pioglitazone did not interfere but rather potentiated the cytotoxic effects of cisplatin on human renal adenocarcinoma cells.

Ascorbic acid‐induced reduction in adiponectin is not improved by alpha tocopherol and is accompanied by a small reduction in protein levels of Peroxisome Proliferator‐ Activated Receptor Gamma in 3T3‐L1 adipocytes

Adipocytes play a role in metabolism and regulation of homeostasis through the release of cytokines such as adiponectin. Adiponectin is an anti‐inflammatory adipokine and has been shown to improve insulin sensitivity and enhance beta‐oxidation of fatty acids. A reduction in adiponectin has been associated with increased inflammation, metabolic syndrome and chronic diseases. Since oxidative stress has been known to regulate metabolic disease, we previously investigated the role of ascorbic acid and found that it abolished adiponectin expression in adipocytes. We hypothesized that treatment with ascorbic acid may cause a reduction in PPARgamma protein levels and that alpha tocopherol may mitigate the effect of ascorbic acid on adiponectin synthesis. We used 3T3‐L1 cells to monitor adiponectin protein levels. Differentiated 3T3‐L1 (Day 8), cells were treated with ascorbic acid, with and without alpha tocopherol. We found that the reduction of adiponectin in cell lysates was not overcome with the addition of alpha tocopherol. Further, we also observed a small reduction in PPARgamma in adipocytes treated with ascorbic acid. These results suggest that adipocyte metabolism may be influenced by dietary antioxidants. This research was funded by Florida International University.

Association of serum uric acid with Pro12Ala polymorphism in PPAR-γ2 among Chinese nonagenarians/centenarians.

In previous studies, Pro12Ala polymorphism in peroxisome proliferator- activated receptors gamma 2 (PPAR-γ2) was shown to be associated with both longevity and metabolic syndrome, which was closely related with hyperuricemia. We examined long-lived subjects (≥90 years), to ascertain whether the polymorphism is associated with the level of serum uric acid (SUA). The present study analysed data from a survey conducted in 2005 on all residents aged 90 years or more in a district with 2,311,709 inhabitants. The sample comprised 669 unrelated Chinese participants (aged 90-108 years, mean: 93.54±3.53 years; 67.2% women). The genotype frequencies of the Pro12Ala polymorphism were 0% Ala12Ala and 9.0% Pro12Ala, 91.0% Pro12Pro. Between men or women, and between subjects who were or were not 12Ala carriers, neither in SUA levels nor the prevalence of hyperuricemia were significant. Between subjects with and without hyperuricemia, the difference in prevalence of 12Ala carriers was also non-significant. Unadjusted and adjusted multiple logistic regressions showed that the odds ratios (OR) for hyperuricemia were not associated with Pro12Ala polymorphism in PPAR-γ2. In Chinese nonagenarians and centenarians, SUA levels are not associated with polymorphism in PPAR-γ2.

Abstract LB-121: Polymorphic variants in PPARGC1A and PCMTD1 associate with earlier age of onset in ER-negative breast cancer

Abstract Background: Breast cancer is the most frequent cancer and leading cause of cancer death among women worldwide. As <10% of breast cancers are due to mutations in BRCA1 and BRCA2, other perturbations such as single nucleotide polymorphisms (SNPs) may be genetic contributors. Peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PPARGC1A) enhances estrogen receptor (ER) and estrogen related receptor gamma (ERRγ) activity by acting as a coactivator. ERRγ has been demonstrated to regulate vascular endothelial growth factor mRNA expression in both ER-positive and ER-negative breast cancer cell lines, indicating that it may accelerate angiogenesis and metastasis. PCMTD1 encodes protein-L-isoaspartate O-methyltransferase domain-containing protein 1, a S-adenosylmethionine-dependent methyltransferase whose biological relevance is largely unknown to present. SNPs in PPARGC1A have been correlated with metabolic diseases, but within the three studies evaluating cancer phenotypes for this gene, only Thr612Met (76873 C→T) revealed a significant association with familial breast cancers. Experimental Procedure: SNPs in PPARGC1A and PCMTD1 were selected using a bioinformatics approach based on SNP associations with drug response in NCI-60 cell lines and evidence of selection bias for haplotype frequencies. Allelic discrimination assays were performed on genomic DNA isolated from whole blood from over 900 Caucasian breast cancer patients with ductal carcinomas. Clinical information was linked to genotypes to search for genotype-phenotype correlations, and statistical analyses were carried out. Results: Analysis of PPARGC1A rs4619879 revealed a mean age of diagnosis of ER-negative cases for CC and AA carriers at 50.1 and 43.8 years, respectively (p=0.019). The difference was less striking in ER-positive ductal carcinomas, with only a 2.7year earlier onset for AA carriers (p=0.013). For PCMTD1 rs9298462, the mean age at diagnosis of ER-negative cases for CC carriers was 41.2, compared to 48.8 for the TT carriers (p=0.004). No significant difference was seen in ER-positive ductal carcinomas (p=0.15). Conclusions: Our results indicate that polymorphisms in PPARGC1A and PCMTD1, two transcriptional regulators, may play a role in age at diagnosis in breast cancer, particularly ER-negative ductal carcinomas. We are performing functional studies to further evaluate these findings and to elucidate the molecular mechanisms underlying these observations. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr LB-121. doi:10.1158/1538-7445.AM2011-LB-121

Association of PPARγ2 (Pro12Ala) and neuropeptide Y (Leu7Pro) gene polymorphisms with obstructive sleep apnea in obese Asian Indians.

Background: Obstructive sleep apnea (OSA) is prevalent in 7.5% in urban Asian Indians. Peroxisome proliferator activated receptor gamma2 (PPARγ2) has been implicated in adipocyte differentiation. Neuropeptide Y (NPY) is also considered as a candidate gene for excess body fat accumulation. The association of PPARγ2 (Pro12Ala) and NPY (Leu7Pro) gene polymorphisms with OSA has not been studied in Asian Indians. Objective: To study the distribution of PPARγ2 (Pro12Ala) and NPY (Leu7Pro) polymorphism in Asian Indians with and without OSA. Methods and results: This study was carried out in 252 obese subjects [(body mass index (BMI > 25 kg/m2)]; 142 with OSA and 110 without OSA. Measurements included anthropometric and biochemical parameters (fasting blood glucose, lipid profile, various circumferences and skin-fold thicknesses). PPARγ2 (Pro12Ala) and NPY (Leu7Pro) gene polymorphisms were studied in all subjects. The frequency of the variant allele (Ala12) of PPARγ2 gene was significantly higher in subjects with OSA (14.4%) when compared with subjects without OSA (5.5%; χ2 = 9.7; p = 0.001). The distribution of the variant allele (Pro7) of NPY gene was comparable in subjects with OSA (3.5%) and without OSA (3.6%; χ 2 = 0.001, p = 0.94). Conclusion: This study reveals a significantly higher frequency of PPARγ2 (Ala12) allele in obese Asian Indians with OSA when compared to obese Asian Indians without OSA.

Association of PPARγ2(Pro12Ala) and Neuropeptide Y (Leu7Pro) Gene Polymorphisms with Obstructive Sleep Apnea in Obese Asian Indians

Background:Obstructive sleep apnea (OSA) is prevalent in 7.5% in urban Asian Indians.Peroxisome proliferator activated receptor gamma2 (PPARγ2)has been implicated in adipocyte differentiation.Neuropeptide Y (NPY)is also considered as a candidate gene for excess body fat accumulation. The association ofPPARγ2 (Pro12Ala)andNPY (Leu7Pro)gene polymorphisms with OSA has not been studied in Asian Indians.Objective:To study the distribution ofPPARγ2 (Pro12Ala)andNPY (Leu7Pro)polymorphism in Asian Indians with and without OSA.Methods and results:This study was carried out in 252 obese subjects [(body mass index (BMI > 25 kg/m2)]; 142 with OSA and 110 without OSA. Measurements included anthropometric and biochemical parameters (fasting blood glucose, lipid profile, various circumferences and skin-fold thicknesses).PPARγ2 (Pro12Ala) and NPY (Leu7Pro) genepolymorphisms were studied in all subjects. The frequency of the variantallele (Ala12) of PPARγ2 genewas significantly higher in subjects with OSA (14.4%) when compared with subjects without OSA (5.5%; χ2= 9.7;p= 0.001). The distribution of the variantallele (Pro7)ofNPY genewas comparable in subjects with OSA (3.5%) and without OSA (3.6%; χ2= 0.001,p= 0.94).Conclusion:This study reveals a significantly higher frequency ofPPARγ2 (Ala12) allelein obese Asian Indians with OSA when compared to obese Asian Indians without OSA.

PGC‐1 (Peroxissome‐proliferator activated receptor gamma co activator 1) α/β and melanoma growth: a possible energy‐mediated relation.

The uncontrolled cell proliferation is a remarkable feature of cancer and it is known to require a large amount of energy. PGC‐1α/β were described as co activators capable of promoting mitochondria biogenesis and increase its respiratory function. Our hypothesis is that PGC‐1α/β may be over expressed in melanoma cells, increasing its capability of proliferation. We cultured normal melanocytes (Ma) and two cancer lineages (Tm1 and Tm5) and mRNA expression of PGC‐1α/β and TFAM (Mitochondrial Transcription Factor A) were analyzed by RT‐PCR. Cell growth was determined by counting in Neubawer's chamber at every 24 hours, within 5 days, using Tripan Blue exclusion to check cell viability. PGC1α mRNA was increased in Tm1 and Tm5 compared to Ma (Ma=1,23±0,24 vs Tm1=2,67±0,23 vs Tm5=3,05±0,43, p<0,01). PGC‐1β (Ma=0,47±0,02 and Tm1=0,67±0,02 vs. Tm5=0,81±0,03, p<0,05) and TFAM (Ma=0,91±0,07 e Tm1=0,89±0,03 vs. Tm5=1,17±0,06, p<0,05) expression were increased only in Tm5. Cancer cells duplication time was 24 hours whereas Ma was duplicated at 72 hours and all lineages presented 95% to 100% viability during the experiment. In conclusion, exponential growth in cancer lineages may be related to increasing energy availability mediated by PGC‐1 α/β expression. Financial support: FAPESP and DIREX‐LIM.

Selective effects of PPARγ agonists and antagonists on human pre‐adipocyte differentiation

The insulin sensitizer rosiglitazone (RTZ) acts by activating peroxisome proliferator and activated receptor gamma (PPAR gamma), an effect accompanied in vivo in humans by an increase in fat storage. We hypothesized that this effect concerns PPARgamma(1) and PPARgamma(2) differently and is dependant on the origin of the adipose cells (subcutaneous or visceral). To this aim, the effect of RTZ, the PPARgamma antagonist GW9662 and lentiviral vectors expressing interfering RNA were evaluated on human pre-adipocyte models. Two models were investigated: the human pre-adipose cell line Chub-S7 and primary pre-adipocytes derived from subcutaneous and visceral biopsies of adipose tissue (AT) obtained from obese patients. Cells were used to perform oil-red O staining, gene expression measurements and lentiviral infections. In both models, RTZ was found to stimulate the differentiation of pre-adipocytes into mature cells. This was accompanied by significant increases in both the PPARgamma(1) and PPARgamma(2) gene expression, with a relatively stronger stimulation of PPARgamma(2). In contrast, RTZ failed to stimulate differentiation processes when cells were incubated in the presence of GW9662. This effect was similar to the effect observed using interfering RNA against PPARgamma(2). It was accompanied by an abrogation of the RTZ-induced PPARgamma(2) gene expression, whereas the level of PPARgamma(1) was not affected. Both the GW9662 treatment and interfering RNA against PPARgamma(2) are able to abrogate RTZ-induced differentiation without a significant change of PPARgamma(1) gene expression. These results are consistent with previous results obtained in animal models and suggest that in humans PPARgamma(2) may also be the key isoform involved in fat storage.

Initiation of the expression of peroxisome proliferator - activated receptor gamma (PPAR gamma) in the rat ovary and the role of FSH

PPARgamma is highly expressed in granulosa cells by 23 days post-partum (pp) and is down-regulated in response to the LH surge. We tested the hypothesis that high levels of FSH during the neonatal period trigger the expression of PPARgamma. To determine when PPARgamma expression is initiated, ovaries were collected from neonatal rats. Messenger RNA for PPARgamma was undetectable on day 1, low from days 5-14, and increased by day 19 pp (p < 0.05). PPARgamma was detected in select granulosa cells in primary/early secondary follicles. Messenger RNA for the FSH receptor was detected as early as day 1 and remained steady throughout day 19 pp. The FSH receptor was detected by immunoblot analysis in ovaries collected 1, 2, and 5-9 days pp. In a subsequent experiment, neonatal rats were treated with acyline (GnRH antagonist) which significantly reduced FSH (p < 0.05) but not levels of mRNA for PPARgamma. The role of FSH in the induction of PPARgamma expression was further assessed in ovarian tissue from FORKO mice. Both mRNA and protein for PPARgamma were identified in ovarian tissue from FORKO mice. In summary, the FSH/FSH receptor system is present in granulosa cells prior to the onset of expression of PPARgamma. Reducing FSH during the neonatal period, or the ability to respond to FSH, did not decrease expression of mRNA for PPARgamma. These data indicate that FSH is not a primary factor initiating the expression of PPARgamma and that other agents play a role in activating its expression in the ovary.

The expression of PPAR-gamma in patients of pulmonary hypertension by chronic obstructive pulmonary disease

Objective To investigate the relationship among peroxisome proliferators - activated receptor gamma (PPAR-γ), pul-monary arterial systolic pressure(PASP) ,and insulin resistance in Chronic Obstructive Pulmonary Disease (COPD) patients. Methods A-mong 63 COPD patients, 30 patients with level of PASP above 40mmHg were enrolled in PAH group and other 33 patients were enrolled in COPD group. Twenty healthy medical examination subjects were enrolled in control group. The expression of PPAR-γ, mRNA was detected by real time fluorescent quantitative RT- PCR. Radioimmunoassay was used to measure the level of fasting plasma insulin (FIN). Fasting plas-ma glucose (FPG) was detected by glucose oxidase method. Results The expression of PPAR-γ mRNA was significantly decreased in PAH and COPD group, while FPG, FIN and IRI increased significantly. PAH group had more increased PASP, decreased expression of PPAR-γ and higher IRI than COPD group. Expression of PPAR-γ was negatively related to PASP and IRI. Conclusions The significantly down reg-ulated expression of PPAR-γ maybe explain the higher FPG and PASP. Key words: PPAR gamma/ME; Pulmonary disease; chronic obstructive/CO; Hypertension; pulmonary/CO/ME; Insulin resistance

Role of Peroxisome Proliferator-Activated Receptor gamma 2 (PPAR-γ2) Gene Polymorphism in Type 2 Diabetes Mellitus

Objective: To find out the relation between Pro 12 Ala polymorphism of peroxisome proliferator- activated receptor gamma2 (PPAR-g2) gene with type 2 diabetes mellitus and the possible role of this gene polymorphism as a link between obesity and type 2 diabetes mellitus. Subjects and Methods: Subjects of this study were classified into 3 groups: (15) Apparently healthy lean individuals (Group I), (15) obese non diabetic individuals (group II) and (24) patients with type 2 diabetes mellitus (group III). This group divided into: Diabetic non obese patients (12 patients) (Group IIIa) and: Diabetic obese patients (12 patients) (Group IIIb). The subjects were subjected to clinical examination, serum insulin level and estimation of PPAR-g2 gene polymorphism by Restriction fragment length polymorphism (RFLP) polymerase chain reaction (PCR). Results: Frequency of Pro allele was significant increase in diabetic non obese patients& diabetic non obese patients when compared to control group (P= 0.048 and 0.003, respectively). However, there was no difference between obese non diabetic group and control group as regard the allelic frequencies (p= 0.462). While diabetic non obese patients had higher Pro allele frequency (p= 0.003) than in diabetic obese patients (p= 0.048). Insulin resistance by homeostasis model assessment (HOMA-IR) was significantly increased in Pro/Pro carriers in group II and group III when compared to that of Pro/Ala plus Ala/Ala carriers (p= 0.004 and 0.023; respectively). Conclusion: Pro12 allele of PPAR-g2 gene could be a genetic risk factor for insulin resistance and type 2 diabetes mellitus.

Embryonic Germ Cells Are Capable of Adipogenic DifferentiationIn VitroandIn Vivo

There is an extensive clinical need for soft tissue filler materials, such as adipose tissue, for plastic and reconstructive surgery. Due to limitations with autologous adipose transplantation, engineered adipose tissue provides a potential alternative therapy. Embryonic germ cells form embryoid bodies and subsequent embryoid body-derived (EBD) cells have the ability to differentiate toward multiple tissue types. The objective of this study was to demonstrate that EBD cells were capable of adipogenic differentiation in vitro and in vivo using a poly(ethylene glycol)-based hydrogel scaffold. EBD cells underwent adipogenic differentiation in vitro and in vivo. Results were directly compared to adipogenic differentiation of adult bone marrow-derived mesenchymal stem cells (MSCs). Differentiated EBD cells in both monolayer and three-dimensional in vitro culture demonstrated fat granules by light microscopy, stained positive for lipids with oil red-O, and expressed adipocyte-specific genes (lipoprotein lipase [LPL], peroxisome proliferator activated receptor gamma2, and adipocyte-specific fatty acid binding protein [alphaP2]). In vivo constructs demonstrated adipogenic differentiation by alphaP2 and LPL gene expression and oil red-O staining of lipid granules. In conclusion, EBD cells are capable of differentiating toward an adipogenic lineage in vitro and in vivo. EBD cells' adipogenic differentiation is comparable to that of MSCs and demonstrate therapeutic potential for soft tissue augmentation and reconstruction.

P303 - Peroxisome proliferator-activated receptor gamma (PPARγ) expression and activation in colonic epithelial cells from patients with ulcerative colitis: a randomized, controlled pilot study of the effect of topical treatment with rosiglitazone enemas

P303 - Peroxisome proliferator-activated receptor gamma (PPARγ) expression and activation in colonic epithelial cells from patients with ulcerative colitis: a randomized, controlled pilot study of the effect of topical treatment with rosiglitazone enemas

P300 - Correlation of age and serum dipeptidyl peptidase IV (DPP IV/CD26) activity in patients with inflammatory bowel diseases

P300 - Correlation of age and serum dipeptidyl peptidase IV (DPP IV/CD26) activity in patients with inflammatory bowel diseases

Diabetes and Osteoporosis

Increased life expectancy and increased obesity have contributed to an increasing incidence of osteoporosis and diabetes mellitus. Recent meta-analyses and cohort studies confirm that diabetes is associated with a higher risk of fracture. Patients with type 2 diabetes exhibit increased fracture risks despite a higher bone mass, which are mainly attributable to non-skeletal risk factors. Patients with type 1 diabetes may have impaired bone formation because of absence of the anabolic effects of insulin and insulin-like growth factor I (IGF-I) system. Several clinical studies have reported adverse skeletal actions of peroxisome proliferator -activated receptor gamma (PPARγ) agonist in humans. Obesity regulates bone metabolism not only by increasing weight loading but also by modulating adipokines tha t are known to affect bone remodeling. (Korean Diabetes J 33:169-177, 2009)

Interaction among abnormal fatty acid oxidation, endothelial function disorder, and oxidative stress in the onset of severe preeclampsia

To investigate the association of abnormal fatty acid oxidation (FAO), endothelial function activation, and oxidative stress in pathogenesis of severe preeclampsia ( S-PE). Placenta tissues were obtained from 70 S-PE patients with onset in different gestational weeks with or without liver damage. The protein expression of long chain 3-hydroxyacyl-CoA dehydrogenase (LCHAD), tumor necrosis factor (TNF)-alpha, vascular cell adhesion molecule (VCAM)-1, and peroxisome proliferator activated receptor (PPAR) gamma were analyzed using immunohistochemistry. 54 samples from normal pregnancy in first, second and third trimester were collected as controls. Protein expression of LCHAD, TNF-alpha, VCAM-1, and PPARgamma could be seen in both placenta of normal pregnancy and S-PE. The protein expression on level of LCHAD of the cases of S-PE that came down of the disease before 32 gestational weeks, especially of the cases complicated with liver damage, was significantly lower than that of the controls (P < 0.05). However, no differences in the LCHAD protein expression were found between the S-PE patients with the onset after and 32 gestational weeks and the controls. The TNF-alpha protein expression levels of the S-PE patients with different onset weeks were all significantly higher than those of the controls (all P < 0.05). The VCAM-1 protein expression levels of the S-PE patients with the onset after 34 gestational weeks was significantly higher than that of the controls (P < 0.05). There was no significant difference in the PPARgamma protein expression between the S-PE patients and the controls. The placental LCHAD protein expression of the S-PE patients with the onset before 32 gestational weeks, especially of the cases with liver function damage, was dramatically decreased in comparison with the controls, and the placental TNF-alpha protein expression was dramatically increased, however, there was no linear correlation between LCHAD and TNF-alpha expression. There was no significant difference in expression of PPARgamma and VCAM-1 between the S-PE patients and the controls. There was no linear correlation among the expression levels of LCHAD, TNF-alpha, VCAM-1, and PPARgamma between the S-PE patients with the onset before and after 32 gestation weeks. Abnormal FAO may be one of the factors related to some cases of PE with the onset before 32 gestational-weeks, especially those with liver damage. The correlation among LCHAD, TNF-alpha, VCAM-1, and PPARgamma are complicated.

Adiponectin and peroxisome proliferator‐activated receptor γ expression in subcutaneous and omental adipose tissue in children

To compare the expression levels of the adiponectin and peroxisome proliferator -activated receptor gamma (PPARgamma) genes in subcutaneous adipose tissue (SC) and omental adipose tissue (OM) in children with relation to age and anthropometric variables. Paired biopsies (SC and OM) were obtained from 53 children (age 0.2-14 years, BMI 12.5-25.8 kg/m(2)). Adiponectin and PPARgamma mRNA levels in adipose tissue were measured by real-time PCR. In overweight, but not in normal weight children, the median adiponectin mRNA level was significantly lower in OM [0.51 (0.1-2.17)] compared to SC [1.29 (0.16-5.08)], (p = 0.03). Adiponectin mRNA levels were strongly associated with PPARgamma mRNA levels in both SC (r = 0.73, p < 0.001) and OM (r = 0.78, p < 0.001). The lower adiponectin expression in OM relative to SC in overweight children indicates that metabolic-endocrine alterations begin already in childhood. The close association between adiponectin and PPARgamma expression supports the hypothesis this transcription factor is involved in adiponectin gene regulation.