Fatty Liver, Alcoholic ; metabolism ; Humans ; Lipid Metabolism ; Peroxisome Proliferator-Activated Receptors ; metabolism ; Signal Transduction

No abstract available.
Humans ; Peroxisome Proliferator-Activated Receptors/*metabolism ; Prostaglandin-Endoperoxide Synthase/*metabolism ; Stomach Neoplasms/*metabolism

Animals ; Fatty Liver ; metabolism ; Humans ; Liver Cirrhosis ; metabolism ; Liver Neoplasms ; metabolism ; Peroxisome Proliferator-Activated Receptors ; metabolism ; Peroxisome Proliferators ; metabolism ; Protein Isoforms ; metabolism

OBJECTIVETo study the expression pattern of peroxisome proliferator-activated receptor (PPAR) pathway molecules in rat lung tissue under hyperbaric oxygen exposure.

METHODSTwenty seven male SD rats were randomly divided into hyperbaric normoxia group (0.23 MPa air), hyperbaric oxygen treatment time series group (0.23 MPa oxygen, were exposed for 2 h, 4 h, 6 h or 8 h), continuous small flow of ventilation to maintain cabin O2 concentration > 99%. HE staining of lung tissue morphological changes and application oligo microarray to each time point lung were observed. Part of the PPAR pathway genes were validated by RT-PCR.

RESULTSCompared with hyperbaric normoxia group, the lung injury caused by hyperbaric oxygen treatment gradually deteriorated during the time series. Expression microarray analysis of gene ontology (Go) enrichment analysis results in a class of PPAR pathway class included multiple PPAR pathway molecule. RT-PCR results suggested that PPAR-8 and PPAR-Y were up-regulated in the lung tissue after a long time exposure to hyperbaric oxygen.

CONCLUSIONPro-longed hyperbaric oxygen exposure causing pulmonary oxygen toxicity can induce the activation of the PPAR pathway.

Animals ; Hyperbaric Oxygenation ; adverse effects ; Lung ; metabolism ; pathology ; Male ; Peroxisome Proliferator-Activated Receptors ; metabolism ; Rats ; Rats, Sprague-Dawley ; Signal Transduction

BACKGROUNDPrenatal hyperglycaemia may increase metabolic syndrome susceptibility of the offspring. An underlying component of the development of these morbidities is hepatic gluconeogenic molecular dysfunction. We hypothesized that maternal hyperglycaemia will influence her offsprings hepatic peroxisome proliferator-activated receptor coactivator-1α (PGC-1α) expression, a key regulator of glucose production in hepatocytes.

METHODWe established maternal hyperglycaemia by streptozotocin injection to induce the maternal hyperglycaemic Wistar rat model. Offspring from the severe hyperglycemia group (SDO) and control group (CO) were monitored until 180 days after birth. Blood pressure, lipid metabolism indicators and insulin resistance (IR) were measured. Hepatic PGC-1α expression was analyzed by reverse transcription polymerase chain reaction and Western blotting. mRNA expression of two key enzymes in gluconeogenesis, glucose-6-phosphatase (G-6-Pase) and phosphoenolpyruvate carboxykinase (PEPCK), were analyzed and compared.

RESULTSIn the SDO group, PGC-1α expression at protein and mRNA levels were increased, so were expression of G-6-Pase and PEPCK (P < 0.05). The above effects were seen prior to the onset of IR.

CONCLUSIONThe hepatic gluconeogenic molecular dysfunction may contribute to the metabolic morbidities experienced by this population.

Animals ; Female ; Hyperglycemia ; chemically induced ; physiopathology ; Insulin Resistance ; physiology ; Liver ; metabolism ; Male ; Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha ; Peroxisome Proliferator-Activated Receptors ; metabolism ; Pregnancy ; Prenatal Exposure Delayed Effects ; RNA-Binding Proteins ; Rats ; Rats, Wistar ; Streptozocin ; toxicity ; Transcription Factors

Bile is concentrated in the gallbladder, and is often supersaturated in terms of cholesterol concentration. Such high levels of cholesterol in gallbladder bile has clinical implications with respect to cholesterol gallstone formation. Gallbladder epithelial cells (GBEC) are exposed to high cholesterol concentrations on their apical surface. Therefore, GBEC are uniquely positioned to play an important role in modulating biliary cholesterol concentration. Recently, it has been documented that the key-transporter for polarized cholesterol and phospholipid efflux in GBEC is ATP-binding cassette transporter A1 (ABCA1) and liver X receptor alpha(LXR alpha)/retinoid X receptor (RXR) in the nucleus of GBEC which regulates ABCA1 expression. In addition, it also has been demonstrated that ligands of peroxisome proliferator-activated receptor alpha(PPARalpha) and PPARgamma modulate inflammation and affect ABCA1 expression in GBEC. This evidence proves that GBEC has a perfect system for cholesterol transport. We herein introduce the roles and mechanisms of ABCA1, ABCG5/ABCG8, scavenger receptor class B-I (SR-BI), LXRalpha/RXR, farnesoid X receptor (FXR), and PPARs related to cholesterol transport in GBEC with a review of our study experience and related literature.
Bile ; Cholesterol* ; Epithelial Cells* ; Gallbladder* ; Gallstones ; Inflammation ; Ligands ; Liver ; Metabolism* ; Peroxisome Proliferator-Activated Receptors ; Peroxisomes ; PPAR gamma ; Receptors, Cytoplasmic and Nuclear* ; Receptors, Scavenger

BACKGROUND/AIMS: Gastric cancer is still the most frequently diagnosed malignancy in Korea. It has been reported that COX-2 and PPAR are involved in multi-step gastric carcinogenesis. The aim of the present study was to examine the expression of COX-2 and PPAR in gastric cancer. METHODS: A total of 75 subjects including 45 patients with gastric cancer and 30 controls were enrolled. All subjects underwent upper gastrointestinal endoscopic examination with tissue collection. mRNA extraction from the tissues and real-time PCR for COX-2, PPAR-delta, and PPAR-gamma were performed. Gastric mucosal concentration of PGE2, which is a final product of COX-2, and 15d-PGJ2, which is a ligand of PPAR-gamma, were measured by the enzyme immunoassay method. RESULTS: COX-2 mRNA expression was significantly higher in both early gastric cancer tissues (EGC, 8.32 +/- 4.84 micro gram/micro L, p<0.005) and advanced gastric cancer tissues (AGC, 8.16 +/- 2.67 micro gram/micro L, p<0.001) than in non-cancerous tissues of controls (3.46 +/- 1.72 micro gram/micro L). There was no significant difference of PPAR-delta and PPAR-gamma mRNA expression between gastric cancer tissues and controls. Mucosal PGE2 concentration was significantly higher in both EGC tissues (5.31 +/- 0.49 micro gram/mg protein, p<0.001) and AGC tissues (5.46 +/- 0.54 micro gram/mg protein, p<0.001) than in non-cancerous tissues of controls (4.22 +/- 0.8 micro gram/mg protein). There was no significant difference of 15d-PGJ2 concentration between gastric cancer tissues and controls. CONCLUSIONS: COX-2 overexpression and increased PGE2 concentration in gastric tissues may play an important role in gastric carcinogenesis. However, the role of PPAR (delta and gamma) and 15d-PGJ2 in gastric carcinogenesis is uncertain. Further studies are needed.
Adult ; Aged ; English Abstract ; Female ; Gastric Mucosa/*metabolism ; Humans ; Male ; Middle Aged ; Peroxisome Proliferator-Activated Receptors/*metabolism ; Prostaglandin-Endoperoxide Synthase/*metabolism ; Stomach Neoplasms/*metabolism

BACKGROUND/AIMS: Both the farnesoid X receptor (FXR) and peroxisome proliferator-activated receptor (PPAR) play important roles in lipid metabolism and atherosclerosis. We investigated the interaction between FXR and PPARgamma. METHODS: Apolipoprotein E knockout (ApoE-/-) mice and FXR knockout (FXR-/-) mice were crossed to generate ApoE-/-FXR-/- mice. The mice were divided into ApoE-/-, ApoE-/-FXR-/-, and ApoE-/-FXR-/- + pioglitazone groups. All mice were fed a high-fat, high-cholesterol diet for 12 weeks. The ApoE-/-FXR-/- + pioglitazone group was also treated with pioglitazone, 20 mg/kg body weight. Body weight, blood glucose level, lipid profile, and liver enzyme levels were measured. To evaluate atherosclerotic lesions, the aorta was stained with Oil red O. RESULTS: There were no differences in body weight or blood glucose level among the three groups. The serum lipid concentration and liver enzyme levels increased in the ApoE-/-FXR-/- group compared with the ApoE-/- group (p < 0.01). The ApoE-/-FXR-/- + pioglitazone group had lower high-density lipoprotein (HDL) (55 +/- 4 vs. 28 +/- 2 mg/dL, p < 0.01) and low-density lipoprotein (LDL) (797 +/- 26 vs. 682 +/- 47 mg/dL, p = 0.04) cholesterol than the ApoE-/-FXR-/- group. The respective percentages of aortic atherosclerotic plaques in the ApoE-/-, ApoE-/-FXR-/-, and ApoE-/-FXR-/- + pioglitazone groups were 2.7 +/- 0.2%, 7.7 +/- 1.2%, and 18.6 +/- 1.0%. In ApoE-/-FXR-/- mice, the administration of pioglitazone significantly increased the number of atherosclerotic lesions (p = 0.02). CONCLUSIONS: Pioglitazone increased the number of atherosclerotic plaques in ApoE-/-FXR-/- mice. This suggests that when FXR is inhibited, the activation of PPARgamma can aggravate atherosclerosis.
Animals ; Aorta ; Apolipoproteins ; Atherosclerosis ; Blood Glucose ; Body Weight ; Cholesterol ; Diet ; Lipid Metabolism ; Lipoproteins ; Liver ; Mice ; Peroxisome Proliferator-Activated Receptors ; Peroxisomes ; Plaque, Atherosclerotic ; PPAR gamma ; Receptors, Cytoplasmic and Nuclear ; Thiazolidinediones

For the regulation of energy balance in various internal organs including gut, pancreas and liver, visceral adipose tissue and brain perform important sensing and signaling roles via neural and endocrine pathway. Among these, adipose tissue has been known as a simple energy-storing organ, which stores excess energy in triglyceride. However, it became apparent that adipocytes have various receptors related to energy homeostasis, and secrete adipocytokines by endocrine, paracrine and autocrine mechanisms. In this review, basic roles of adipocytes in energy homeostasis and the correlation between adipocyte signals and digestive diseases are discussed.
Adipocytes/*metabolism ; Adipokines/*physiology ; Adiponectin/physiology ; Digestive System Diseases/*metabolism ; *Energy Metabolism ; Homeostasis ; Humans ; Leptin/physiology ; Peroxisome Proliferator-Activated Receptors/physiology ; Resistin/physiology ; Signal Transduction

Animals ; Fatty Liver ; genetics ; metabolism ; Female ; Liver ; metabolism ; Liver Diseases, Alcoholic ; genetics ; metabolism ; Peroxisome Proliferator-Activated Receptors ; biosynthesis ; genetics ; Random Allocation ; Rats ; Rats, Wistar