No abstract available.
Lipid Metabolism* ; Peroxisomes*

Peroxisomes are subcellular organells catalyzing a number of important functions in cellular metabolism. Their functions are mostly related to lipid metabolism. Genetic disorders of peroxisomes are divided into 2 categories: peroxisomal biogenesis disorders and single peroxisomal enzyme deficiencies. This paper describes an overview of the peroxisomal disorders, including metabolic basis, and clinical and laboratory findings.
Lipid Metabolism ; Metabolism ; Peroxisomal Disorders* ; Peroxisomes ; Organelle Biogenesis

To understand the etiology of metabolic disorders, including obesity and type II diabetes, it is essential to gain better insight into how stored and available energy sources are monitored by the central nervous system. In particular, a comprehension of the fine cellular interplay and intracellular mechanisms that enable appropriate hypothalamic and consequent endocrine and behavioral responses to both circulating hormonal and nutrient signals remains elusive. Recent data, including those from our laboratories, raised the notion that reactive oxygen species (ROS) generation is not merely a by-product of substrate oxidation, but it plays a crucial role in modulating cellular responses involved in the regulation of energy metabolism. These review summarizes the published recent data on the effect of ROS levels in the regulation of neuronal function, including that of hypothalamic melanocortin neurons, pro-opiomelanocortin and neuropeptide Y-/agouti related peptide-neurons, in the modulation of food intake.
Central Nervous System ; Comprehension ; Eating ; Energy Metabolism ; Hypothalamus ; Neurons ; Neuropeptides ; Obesity ; Peroxisomes ; Pro-Opiomelanocortin ; Reactive Oxygen Species

PURPOSE: To analyze the possible involvement of a change in the lipid metabolism and PPARgamma2 level in the occurrence of ON of the femoral head. MATERIAL AND METHODS: The lipid profiles (Cholesterol, Triglyceride, LDL, HDL and Free fatty acid) of 130 patients with ON of the femoral head and 30 control persons were evaluated. The level of PPARgamma2 mRNA expression was examined by performing, RT-PCR using the bone marrow stromal cells obtained from 17 patients during THA. RESULTS: Among the 130 patients, the free fatty acid level in the alcohol (676.9+/-264.7 mg/dl,) and steroid (666.0+/-163.4 mg/dl) induced ON groups was higher than the control (453.5+/-169.3 mg/dl) and idiopathic (468.5+/-194.1 mg/dl) groups. The triglyceride level in the alcohol (223.7+/-70.9 mg/dl) and steroid (183.6+/-58.4 mg/dl) induced groups was higher than the control (93.1+/-79.0 mg/dl) and idiopathic groups (130.9+/-63.1 mg/dl). The level of PPARgamma2 mRNA expression in the ON patients was significantly higher than the other groups (P <0.05). CONCLUSION: These results are significant and suggest hyperlipidemia as a risk factor for ON of the femoral head. Higher expression of PPARgamma2 mRNA was found in ON. However, functional studies of PPARgamma2 mRNA in vivo would be needed to reveal the pathogenesis of ON of the femoral head.
Head* ; Humans ; Hyperlipidemias ; Lipid Metabolism ; Mesenchymal Stromal Cells ; Osteonecrosis* ; Peroxisomes* ; PPAR gamma ; Risk Factors ; RNA, Messenger ; Triglycerides

Peroxisome proliferator-activated receptor (PPAR)-alpha belongs to the nuclear family of ligand-activated transcriptional factors. The main role of PPAR-alpha is to activate the expression of the genes that are involved in fatty acid oxidation to achieve energy homeostasis. Fibrates are a known class of PPAR-alpha agonists, and they been used clinically for their effects of lowering triglycerides and elevating high-density lipoprotein-cholesterol (HDL-C). Further, recent experimental studies have demonstrated the anti-inflammatory and anti-atherosclerotic actions of PPAR-alpha agonists directly on the vascular wall. PPAR agonists are currently emerging as a promising therapeutic option to control systemic and vascular atherogenic factors. Regardless of their strong anti-atherosclerotic properties, large clinical studies have demonstrated inconsistent results for the cardioprotective effect of PPAR-alpha agonists; moreover, it has been observed that they did not decrease the total mortality, which stands in contrast to the statin trials. This review summarizes the current knowledge regarding the PPAR biology and the mechanisms of the effects of PPAR-alpha on lipid metabolism, the vessel wall and the cardiac metabolism. We also describe the results and lessons learned from the important clinical trials of PPAR-alpha agonists and we discuss these drugs' efficacy and safety.
Biology ; Cardiovascular Diseases* ; Fibric Acids ; Homeostasis ; Hydroxymethylglutaryl-CoA Reductase Inhibitors ; Lipid Metabolism ; Metabolism ; Mortality ; Nuclear Family ; Peroxisome Proliferator-Activated Receptors ; Peroxisomes* ; Triglycerides

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

Resveratrol (3,4,5-trihydroxy-trans-stilbene), a phytoalexin found in grape skin, grape products, and peanuts as well as red wine, has been reported to have various biological and pharmacological properties. The purpose of this study was to investigate the anti-obesity effect of resveratrol-amplified grape skin extracts on adipocytes. The anti-obesity effects of grape skin extracts were investigated by measuring proliferation and differentiation in 3T3-L1 cells. The effect of grape skin ethanol extracts on cell proliferation was detected by the MTS assay. The morphological changes and degree of adipogenesis of preadipocyte 3T3-L1 cells were measured by Oil Red-O staining assay. Treatment with extracts of resveratrol-amplified grape skin decreased lipid accumulation and glycerol-3-phosphate dehydrogenase activity without affecting 3T3-L1 cell viability. Grape skin extract treatment resulted in significantly attenuated expression of key adipogenic transcription factors, including peroxisome proliferator-activated receptor, CCAAT/enhancer-binding proteins, and their target genes (FAS, aP2, SCD-1, and LPL). These results indicate that resveratrol-amplified grape skin extracts may be useful for preventing obesity by regulating lipid metabolism.
3T3-L1 Cells ; Adipocytes ; Adipogenesis ; Arachis ; Cell Proliferation ; Ethanol ; Glycerolphosphate Dehydrogenase ; Lipid Metabolism ; Obesity ; Peroxisomes ; Proteins ; Sesquiterpenes ; Skin ; Stilbenes ; Transcription Factors ; Vitis ; Wine

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

Protamine has been widely used as a pharmaceutical product and natural food preservative. However, few studies have been conducted to assess the beneficial function of dietary protamine. This study examined the effects of dietary salmon protamine on serum and liver lipid levels and the expression levels of genes encoding proteins involved in lipid homeostasis in the liver of rats. Groups of male Wistar rats were fed AIN93G diet containing 2% or 5% protamine. After 4 weeks of feeding these diets, markedly decreased serum and liver cholesterol (CHOL) and triacylglycerol levels were noted. Increased activity of liver carnitine palmitoyltransferase-2 and acyl-CoA oxidase, which are key enzymes of fatty acid beta-oxidation in the mitochondria and peroxisomes, was found in rats fed on protamine. Furthermore, rats fed protamine showed enhanced fecal excretion of CHOL and bile acid and increased liver mRNA expression levels of ATP-binding cassette (ABC) G5 and ABCG8, which form heterodimers and play a major role in the secretion of CHOL into bile. The decrease in triacylglycerol levels in protamine-fed rats was due to the enhancement of liver beta-oxidation. Furthermore, rats fed protamine exhibited decreased CHOL levels through the suppression of CHOL and bile acid absorption and the enhancement of CHOL secretion into bile. These results suggest that dietary protamine has beneficial effects that may aid in the prevention of lifestyle-related diseases such as hyperlipidemia and atherosclerosis.
Absorption ; Acyl-CoA Oxidase ; Animals ; Atherosclerosis ; Bile ; Carnitine ; Cholesterol ; Diet ; Homeostasis ; Humans ; Hyperlipidemias ; Lipid Metabolism ; Liver ; Male ; Mitochondria ; Peroxisomes ; Proteins ; Rats ; Rats, Wistar ; RNA, Messenger ; Salmon ; Triglycerides

High-fat diet up-regulates either insulin resistance or triglycerides, which is assumed to be related to the expression of peroxisome proliferator-activated receptor (PPAR)-alpha and PPAR-gamma. The beneficial effects of vitamin E on insulin resistance are well known; however, it is not clear if vitamin E with a high-fat diet alters the expression of PPAR-alpha and PPAR-gamma. We investigated the effects of d-alpha-tocopherol supplementation on insulin sensitivity, blood lipid profiles, lipid peroxidation, and the expression of PPAR-alpha and PPAR-gamma in a high-fat (HF) diet-fed male C57BL/6J model of insulin resistance. The animals were given a regular diet (CON; 10% fat), a HF diet containing 45% fat, or a HF diet plus d-alpha-tocopherol (HF-E) for a period of 20 weeks. The results showed that the HF diet induced insulin resistance and altered the lipid profile, specifically the triglyceride (TG) and total cholesterol (TC) levels (P < 0.05). In this animal model, supplementation with d-alpha-tocopherol improved insulin resistance as well as the serum levels of TG and very-low-density lipoprotein-cholesterol (VLDL-C) (P < 0.05). Moreover, the treatment decreased the levels of malondialdehyde (MDA) in the serum and liver while increasing hepatic PPAR-alpha expression and decreasing PPAR-gamma expression. In conclusion, the oral administration of d-alpha-tocopherol with a high-fat diet had positive effects on insulin resistance, lipid profiles, and oxidative stress through the expression of PPAR-alpha and PPAR-gamma in a high-fat diet-fed male mice.
Administration, Oral ; Animals* ; Cholesterol ; Diet ; Diet, High-Fat ; Humans ; Insulin Resistance ; Lipid Metabolism* ; Lipid Peroxidation ; Liver ; Male ; Malondialdehyde ; Mice ; Models, Animal* ; Oxidative Stress ; Peroxisomes ; Triglycerides ; Vitamin E ; Vitamins