mRNA Levels Of Peroxisome Proliferator-activated Receptor Research Articles

PPAR mRNA Levels Are Modified by Dietary n–3 Fatty Acid Restriction and Energy Restriction in the Brain and Liver of Growing Rats

BackgroundWithout dietary sources of n–3 (ω-3) long-chain polyunsaturated fatty acids (LCPUFAs), α-linolenic acid (ALA; 18:3n–3) is the precursor for docosahexaenoic acid (DHA; 22:6n–3). It is not known how energy restriction (ER) affects ALA conversion to DHA. ObjectiveWe tested the hypothesis that ER reduces n–3 LCPUFA concentrations in tissues of growing rats fed diets replete with and deficient in ALA. MethodsMale Sprague-Dawley rats (23 d old) were provided AIN93G diets (4 wk) made with soybean oil (SO; ALA sufficient) or corn oil (CO; ALA deficient) providing 16% of energy as fat. For each dietary oil, ER rats were individually pair-fed 75% of another rat's ad libitum (AL) intake. Fatty acid (FA) concentrations in brain regions, liver, and plasma were analyzed. Expression of peroxisome proliferator–activated receptors (PPARs), uncoupling proteins (UCPs), and mitochondrial DNA was analyzed in the brain and liver. ResultsAL rats consuming CO had a 65% lower concentration of n–3 docosapentaenoic acid (22:5n–3) and a 10% lower DHA concentration in the cerebral cortex and cerebellum than did the SO-AL group. ER did not alter cerebral n–3 LCPUFA status. Liver n–3 LCPUFA concentrations were reduced in rats fed CO compared with SO. ER reduced hepatic linoleic acid (18:2n–6), ALA, and arachidonic acid (20:4n–6) regardless of oil. ER and n–3 FA deficiency had independent effects on the mRNA levels of Pparα, Pparβ/δ, and Pparγ in the liver, cerebral cortex, and cerebellum. ER reduced Ucp3 mRNA by nearly 50% in the cerebral cortex, cerebellum, and liver, and Ucp5 mRNA was 30% lower in the cerebellum of rats receiving the CO diet. ConclusionsSmall perturbations in PUFA concentration and ER modify the mRNA levels of Ppar and Ucp in the juvenile rat brain. More research is needed to identify the long-term physiologic and behavioral impacts of ER and PUFA restriction in the juvenile brain.

Effects of Gami-Cheongpyesagan-Tang on Body Fat in High Fat Diet-Fed Obese Mice

Objectives: This study was designed to investigate the effect of Gami-cheongpyesagan-tang extract (GCST) on high fat diet-induced obesity in rats. Methods: The mice were divided into six groups; normal diet control, high fat diet control (HFD), HFD＋GCST administrated group (100, 200, and 400 mg/kg) and olistat-admistrated group. Obesity was induced by high fat diet (45%) for 7 weeks in mice, and GCST was administrated orally every day for 7 weeks. The body weight, food intake, and serological markers such as total cholesterol, triglyceride, lipid contents, leptin, adiponectin and glutamic oxaloacetic transaminase/glutamic pyruvic transaminase were measured in mice. The mRNA expression of obese-associating genes such as sterol regulatory element-binding protein (SREBP)-1c, fatty acid synthase (FAS), stearoyl-CaP desaturase (SCD-1), peroxisome proliferator-activated receptor (PPAR)-, COA oxidase (ACO), and carnitine palmitoyltransferase (CPT-1) was analyzed by reverse transcription polymerase chain reaction. Results: The administration of GCST at 400 mg/kg, significantly reduced the increase of body weight and food intake as well as food efficiency compared to HFD group. GCST decreased the serum levels of triglyceride, total cholesterol, low-density lipoprotein-cholesterol, leptin in HFD control group and inhibited lipid accumulation in liver and adipose tissues, but did not increase high-density lipoprotein-cholesterol. In the liver tissues of GCST administrated HFD group, the mRNA levels of SREBP-1c, FAS and SCD-1 were decreased and the mRNA levels of PPAR-, ACO, and CPT-1 were increased. Conclusions: These results indicate that GCST could improve high fat diet induced obesity through inhibiting the hyperlipidemia in fatty Liver. It suggest that GCST may be used clinically for declining the accumultion of body fat with hyperlipidemia.

Effects of Diisodecyl Phthalate on PPAR:RXR-Dependent Gene Expression Pathways in Sea Bream Hepatocytes.

Evidence that endocrine-disrupting chemicals (EDCs) may target metabolic disturbances, beyond interference with the functions of the endocrine systems has recently accumulated. Among EDCs, phthalate plasticizers like the diisodecyl phthalate (DiDP) are commonly found contaminants of aquatic environments and have been suggested to function as obesogens by activating peroxisome proliferator activated receptors (PPARs), a subset of nuclear receptors (NRs) that act as metabolic sensors, playing pivotal roles in lipid homeostasis. However, little is known about the modulation of PPAR signaling pathways by DiDP in fish. In this study, we have first investigated the ligand binding efficiency of DiDP to the ligand binding domains of PPARs and retinoid-X-receptor-α (RXRα) proteins in fish using a molecular docking approach. Furthermore, in silico predictions were integrated by in vitro experiments to show possible dose-relationship effects of DiDP on PPAR:RXR-dependent gene expression pathways using sea bream hepatocytes. We observed that DiDP shows high binding efficiency with piscine PPARs demonstrating a greater preference for RXRα. Our studies also demonstrated the coordinate increased expression of PPARs and RXRα, as well as their downstream target genes in vitro. Principal component analysis (PCA) showed the strength of relationship between transcription of most genes involved in fatty acid metabolism and PPAR mRNA levels. In particular, fatty acid binding protein (FABP) was highly correlated to all PPARs. The results of this study suggest that DiDP can be considered an environmental stressor that activates PPAR:RXR signaling to promote long-term changes in lipid homeostasis leading to potential deleterious physiological consequences in teleost fish.

Plum polyphenolics prevent adipogenesis, inflammation and obesity‐induced metabolic disorders in obese Zucker rats

Obesity is a risk factor leading to inflammation and chronic diseases. We investigated how peach and plum polyphenolics can prevent metabolic disorders in obese Zucker rats. Experimental groups were feed with peach or plum juice ad libitum, the placebo and lean Zucker groups received same amount of sugars as peach and plum juices in drinking water. Body weights were weekly recorded and serum and fat tissue analyzed after 11 weeks. Results showed that body weight gain on the plum group was lower (p<0.05) than the peach and placebo groups, and this was correlated with increased leptin levels in serum (3‐fold of placebo); accordingly, peach and plum groups had lower levels of glucose (0.77‐fold), triglycerides (0.79‐and 0.75‐fold), and HDL cholesterol (0.47‐ and 0.40‐fold) than placebo group. Plum polyphenolics also exerted the highest antiadipogenic and antiinflammatory effects in fat tissue as demonstrated by decreased mRNA levels of PPAR (peroxisome proliferator‐activated receptor) γ2 (0.46‐fold), IL‐6 (0.52‐fold) and VCAM‐1 (0.58‐fold) and induced the expression of secretory leucocyte protease inhibitor (SLPI) (1.35‐fold), a protein involved in decreasing IL‐6 and inflammation in fat tissue. Overall, plum juice protected against inflammation and metabolic disorders at higher extent than peach juice and this was due to the higher content of polyphenolics (1270 vs 430 mg gallic acid equiv./mL).Grant Funding Source : ASN

Expression of Peroxisome Proliferator Activator Receptor β/δ (PPARβ/δ) in acne vulgaris

Sebum production is the key factor in the pathophysiology of acne. Studies in sebocyte and human sebaceous gland biology indicate that agonists of peroxisome proliferator-activated receptors (PPARs) alter sebaceous lipid production. Our objective was to detect the expression of PPARβ/δ in acne lesions and find its contribution to disease pathogenesis. Twenty five acne vulgaris patients (14 males, 11 females) were included. In addition, 12 healthy volunteers (6 males, 6 females) served as controls. Punch biopsies (3mm) were taken from lesional skin of all patients, non-lesional skin in 12 patients, and from the healthy controls. The biopsies were estimated quantitatively for the level of PPARβ/δ mRNA using reverse transcriptase-polymerase chain (RT-PCR) technique. PPARβ/δ mRNA levels were significantly higher in patients than controls (p=0.00) and in patients' lesional than non-lesional skin (p=0.00). No significant difference however, was found between inflammatory and non-inflammatory lesions. Age and disease duration had no influence on mean PPAR mRNA levels in lesional skin. PPARβ/δ is over expressed-in inflammatory and non-inflammatory acne vulgaris and may well be considered as a candidate target in future acne therapy. However, elucidation of its functional role is recommended.

Transcriptional activities of medaka Oryzias latipes peroxisome proliferator-activated receptors and their gene expression profiles at different temperatures

Medaka Oryzias latipes peroxisome proliferator-activated receptors (PPARs) α1, α2, β, and γ were characterized for their sequence structures and transcriptional activities. While the genes encoding PPARα2, β, and γ were determined for their full length, the PPARα1 gene remained undetermined for its 5′-end region, which encodes the DNA-binding domain and a part of ligand-binding domain. Transcriptional activities of medaka PPARα2, β, and γ were also examined by reporter assay using reporter plasmids containing three copies of acyl-coenzyme A (CoA) oxidase PPAR response element. The activity of PPARα2 was 1.5- to 2.0-fold upregulated by 5,8,11,14-eicosatetraynoic, arachidonic, eicosapentaenoic, and oleic acids. The transcripts of medaka PPARs were expressed in brain, gut, heart, kidney, and liver. The messenger RNA (mRNA) levels of PPARs in brain from medaka acclimated to 10°C were higher than those from fish acclimated to 30°C. The mRNA levels of PPAR target genes encoding carnitine palmitoyltransferase-I, carnitine acylcarnitine translocase, and medium-chain acyl-CoA dehydrogenase, which are involved in β-oxidation of fatty acids in other vertebrates, were also higher in various tissues from fish acclimated to 10°C than at 30°C.

Gender and genetic differences in bladder smooth muscle PPAR mRNA in a porcine model of the metabolic syndrome

The metabolic syndrome and diabetes are associated with bladder dysfunction in many people. Peroxisome proliferator-activated receptors (PPARs) may play a role in the effects of the metabolic syndrome on bladder smooth muscle (BSM). The purpose of this study was to determine if there are gender and genetic differences in PPAR levels in BSM. We measured PPAR levels using quantitative PCR in BSM from male Yucatan swine and male and female Ossabaw Island swine, which is a model for the metabolic syndrome. Male Ossabaw swine had 0.732 +/- 0.111 the amount of PPAR-alpha mRNA as male Yucatan swine (P < 0.05), suggesting a genetic difference in PPAR-alpha levels. This difference may possibly contribute to the incidence of metabolic syndrome in the Ossabaw model compared to the Yucatan model. PPAR-delta mRNA was 2-fold higher in male Ossabaw swine than in female Ossabaw swine, with no significant differences in PPAR-alpha levels. However, PPAR-gamma mRNA was 4.067 +/- 0.134 times higher in female Ossabaw swine than in their male counterparts (P < 0.001). Changing the percentage of calories derived from fat did not alter any PPAR mRNA levels. Thus, PPAR-delta and PPAR-gamma mRNA levels in male and female Ossabaw swine BSM are not only different, but may also result in gender differences in lipid metabolism in bladder smooth muscle. We conclude that PPAR profiles in BSM may contribute to the susceptibility of BSM to lipotoxicity in the metabolic syndrome.

Peroxisome proliferator‐activated receptor‐α and ‐γ mRNA levels are reduced in chronic hepatitis C with steatosis and genotype 3 infection

Steatosis in chronic hepatitis C is associated with inflammation and accelerated fibrogenesis. To assess the contribution of peroxisome proliferator-activated receptor-alpha and -gamma to the pathogenesis of hepatitis C virus associated steatosis is unknown. We measured peroxisome proliferator-activated receptor (PPAR)-alpha and -gamma mRNA by quantitative polymerase chain reaction in liver biopsies of 35 genotype 1 and 22 genotype 3 infected patients and in Huh7 cells expressing hepatitis C virus 1b or 3a core protein. PPAR-alpha mRNA was significantly reduced in livers of patients with genotype 3 compared with genotype 1. Steatosis was associated to a decreased expression of PPAR-alpha in genotype 1, but not in genotype 3. PPAR-gamma expression was significantly lower in genotype 3 compared with genotype 1 and steatosis was associated to decreased levels of PPAR-gamma, but only in genotype 1. There was no significant relationship between PPARs mRNA levels and liver activity or fibrosis. Expression of the hepatitis C virus 3a core protein was associated with an increase in triglyceride accumulation and with a significant reduction of PPAR-gamma mRNA compared with hepatitis C virus 1b. The presence of steatosis and hepatitis C virus genotype 3 are both associated with a significant down-regulation of PPARs. These receptors, and also additional factors, seem to play a role in the pathogenesis of hepatitis C virus-associated steatosis.

Peroxisome proliferator-activated receptor (PPAR) expression in cultured bovine endometrial cells and response to omega-3 fatty acid, growth hormone and agonist stimulation in relation to series 2 prostaglandin production

The peroxisome proliferator-activated receptors (PPARs) are a family of nuclear transcription factors thought to act as receptors for polyunsaturated fatty acids and to reduce production of series 2 prostaglandins (PG). The objectives of the current study were to characterize PPAR expression and the prostaglandin synthetic activity of cultured bovine endometrial cells in response to known PPAR ligands, as well as to key stimulators and inhibitors of series 2 prostaglandin secretion. PPARα and PPARδ, but not PPARγ, mRNAs are expressed in the BEND cell line regardless of treatment. Under resting conditions, PPARα mRNA levels increase in response to growth hormone ( P < 0.05). In cells stimulated with PdBu, growth hormone depresses PPARα mRNA levels, regardless of whether cells also are treated with IFNτ. In contrast, PPARδ mRNA levels are increased by exposure to PdBu, eicosapentanoic acid and IFNτ, and these effects are additive. PPAR mRNA levels are not predictive of prostaglandin accumulation. Agonist activation of PPARα, PPARδ or PPARγ augments PdBu-induced increases in prostaglandin H synthase-2 mRNA and media accumulation of prostaglandins F 2α and E 2. Treatment with the PPARα/δ agonist carbaprostacyclin, but not the PPARα agonist Wy14643 or PPARγ agonist ciglitazone, completely reverses the IFNτ suppression of prostaglandin synthesis. In conclusion, PPARα and PPARδ function in the response of bovine endometrium to growth hormone and long chain omega-3 polyunsaturated fatty acids.

Regulation of β-amyloid stimulated proinflammatory responses by peroxisome proliferator-activated receptor α

Amyloid deposition within the brains of Alzheimer's Disease patients results in the activation of microglial cells and the induction of a local inflammatory response. The interaction of microglia or monocytes with β-amyloid (Aβ) fibrils elicits the activation a complex tyrosine kinase-based signal transduction cascade leading to stimulation of multiple independent signaling pathways and ultimately to changes in proinflammatory gene expression. The Aβ -stimulated expression of proinflammatory genes in myeloid lineage cells is antagonized by the action of a family of ligand-activated nuclear hormone receptors, the peroxisome proliferator-activated receptors (PPARs). We report that THP-1 monocytes express predominantly PPARγ isoform and lower levels of PPARα and PPARδ isoforms. PPAR mRNA levels are not affected by differentiation of the cells into a macrophage phenotype, nor are they altered following exposure to the classical immune stimulus, lipopolysaccharide. Previous studies have found that PPARγ agonists act broadly to inhibit inflammatory responses. The present study explored the action of the PPARα isoform and found that PPARα agonists inhibited the Aβ-stimulated expression of TNFα and IL-6 reporter genes in a dose-dependent manner. Moreover, the PPARα agonist WY14643 inhibited macrophage differentiation and COX-2 gene expression. However, the PPARα agonists failed to inhibit Aβ-stimulated elaboration of neurotoxic factors by THP-1 cells. These findings demonstrate that PPARα acts to suppress a diverse array of inflammatory responses in monocytes.