Selenium as a predictor of metabolic syndrome in middle age women.

BACKGROUND: Selenium plays an important role in metabolic homeostasis. It has been suggested that it may also affect the expression and activity of PPAR-γ. The aim of study was to analyze the relationships between these variables in the context of the health of women, for whom the risk of MetS increases with age. MATERIAL AND METHODS: The study involved 390 women in middle age. The stages of study: a survey-based part; anthropometric measurements; analysis of biological material (blood) in terms of glycemia, triglyceride, HDL, and selenium levels, as well as genetic analysis of the PPAR-γ polymorphisms. RESULTS: It was found that selenium may moderate the effect of the G allele of the PPAR-γ gene on the occurrence of elevated waist circumference (OR=1.030, 95%CI 1.005-1.057, p=0.020); and the effect of the C (OR=1.077, 95%CI 1.009-1.149, p=0.026) and the G alleles (OR=1.052, 95%CI 1.025-1.080, p<0.000) on the odds of elevated blood pressure. Women in whom HDL levels were not significantly reduced, had higher selenium levels (p=0.007). CONCLUSIONS: 1. The effect of selenium on MetS and its components has not been demonstrated. 2. The effect of individual alleles of the PPAR-γ gene on MetS and its components was not demonstrated. 3. The concentration of selenium may affect waist circumference in carriers of the G allele, and arterial hypertension in carriers of the C and G alleles by affecting the expression of PPAR-γ. 4. Higher selenium concentrations increased the odds of higher HDL levels in the group of subjects meeting the MetS criteria.

Transcriptome analysis of the response of four immune related organs of tilapia (Oreochromis niloticus) to the addition of resveratrol in feed.

Resveratrol (RES) has been found to have immunological enhancement effects on Oreochromis niloticus. In O. nilocticus, the liver, spleen and kidney act as immune target tissues, while intestine works for nutrition sensing organ. In the present study, we determined RES administration on these immune tissues transcriptomic response in genetically improved farmed tilapia (GIFT), and further analyzed the relationship between transcriptomic response and intestinal microbiota. As results, hepatic hemosiderin and intestinal goblet cells significantly increased with RES addition. Kyoto encyclopedia of genes and genomes (KEGG) pathways associated with herpes simplex virus 1 infection, calcium signaling pathway, cell adhesion molecules, apoptosis, and mitogen-activated protein kinase (MAPK)/peroxisome proliferators-activated receptors (PPAR) signaling pathways were enriched. In particular, the differentially enriched genes (DEGs) associated pathways were present in different sampling tissues, times, and comparisons, interestingly, the PPAR signaling pathway was enriched with increasing time of RES addition. The assembled DEGs presented verified expression in the kidney, liver, spleen, and intestine tissues, and fabp6 was highly expressed in the intestine. Serial DEGs of fatty acid-binding proteins (fabp7, fabp7a, fabp10a) decreased in the liver and kidney, and fabp6 significantly increased in the spleen. With time, the pathways of energy metabolism, glycan biosynthesis, and metabolism decreased and increased in the intestinal metagenome. Some Candidatus branches significantly increased (C. cerribacteria and C. harrisonbacteria) and while others decreased (C. glodbacteria, etc.), whereas C. verstraetearchaeota fluctuated with RES addition. slc27a6 and dbi were negatively correlated with bacteria involved in the lipid, energy, and carbohydrate metabolism pathways. The present study suggests that RES supplementation affected lipid metabolism in immune-related organs may be related to the PPAR signaling pathway.

Transcriptomic and biochemical analyses revealed the improved growth, lipid metabolism, and flesh quality of grass carp (Ctenopharyngodon idellus) by dietary Eucommia ulmoides bark and leaf supplementation.

The objective of this study was to investigate the dietary effects of Eucommia ulmoides bark and leaf (EB, EL) supplementation on the growth, lipid metabolism, flesh quality, and transcriptome of grass carp (Ctenopharyngodon idellus). EB and EL were individually added to the basal diet (control) at concentrations of 20 g/kg and 40 g/kg, respectively, and then the three diets were fed to grass carp (59.7 ±â€…0.3 g) for 60 d. The results showed that the weight gain was improved, and the feed conversion ratio was decreased by supplementation with EB and EL (P < 0.05). Compared to the control, the EB and EL groups showed higher flesh hardness; water-holding capacity; and collagen, docosahexaenoic acid (DHA), and n-3 polyunsaturated fatty acids (n-3PUFAs) contents and lower mesenteric lipid and muscle crude lipid contents (P < 0.05). Moreover, dietary EB and EL supplementation increased the activities of superoxide dismutase and glutathione peroxidase and decreased the contents of malondialdehyde and protein carbonyl in flesh (P < 0.05). In muscle transcriptome profiling, a total of 979, 1980 differentially expressed genes (DEGs) were identified, and 29, 199 Gene Ontology (GO) terms and 13, 39 Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways were significantly enriched in the EB and EL groups, respectively. Some key pathways and genes involved in promoting growth, lipid metabolism and flesh quality were obtained, including mTOR and PPAR signaling pathways, muscle cytoskeleton- and extracellular matrix-related genes (myosin and collagen), etc. Overall, dietary EB and EL supplementation improved the growth, lipid metabolism, and flesh quality of grass carp, and several potential pathways and genes were identified behind the improvement mechanism of EB and EL supplementation.

As a traditional herb, Eucommia ulmoides (E. ulmoides) has been utilized in East Asia for at least 2 000 years. In recent years, E. ulmoides has been applied in the culture of fish for its functions of promoting growth, lipid metabolism, and flesh quality. However, the underlying molecular mechanism of improving growth, lipid metabolism, and flesh quality is not well understood. Our study showed that the improvement of flesh quality is the combined effect of antioxidant capacity, muscle texture, water-holding capacity, and nutritional composition. Additionally, several potential pathways and differentially expressed genes were identified through RNA sequencing to further study the improvement mechanism of dietary E. ulmoides bark and leaf supplementation on growth, lipid metabolism, and flesh quality in fish.

When Two plus Two Is More than Four: Evidence for a Synergistic Effect of Fatty Acids on Peroxisome Proliferator-Activated Receptor Activity in a Bovine Hepatic Model.

The inclusion of fat in livestock diets represents a valuable and cost-effective way to increase the animal's caloric intake. Beyond their caloric value, fatty acids can be understood in terms of their bioactivity, via the modulation of the ligand-dependent nuclear peroxisome proliferator-activated receptors (PPAR). Isotypes of PPAR regulate important metabolic processes in both monogastric and ruminant animals, including the metabolism of fatty acids (FA), the production of milk fat, and the immune response; however, information on the modulation of bovine PPAR by fatty acids is limited. The objective of this study was to expand our understanding on modulation of bovine PPAR by FA, both when used individually and in combination, in an immortalized cell culture model of bovine liver. Of the 10 FA included in the study, the greatest activation of the PPAR reporter was detected with saturated FA C12:0, C16:0, and C18:0, as well as phytanic acid, and the unsaturated FA C16:1 and C18:1. When supplemented in mixtures of 2 FA, the most effective combination was C12:0 + C16:0, while in mixtures of 3 FA, the greatest activation was caused by combinations of C12:0 with C16:0 and either C18:0, C16:1, or C18:1. Some mixtures display a synergistic effect that leads to PPAR activation greater than the sum of their parts, which may be explained by structural dynamics within the PPAR ligand-binding pocket. Our results provide fundamental information for the development of tailored dietary plans that focus on the use of FA mixtures for nutrigenomic purposes.

Compound Danshen Dripping Pill ameliorates post ischemic myocardial inflammation through synergistically regulating MAPK, PI3K/AKT and PPAR signaling pathways.

ETHNOPHARMACOLOGICAL RELEVANCE: Compound Danshen Dripping Pill (CDDP), composed of Salvia miltiorrhiza Bunge, Panax notoginseng (Burkill) F.H. Chen and Borneol, is a famous traditional Chinese medicine formula which has made great achievements in the treatment of ischemic heart disease, but the profound mechanism of CDDP improving post ischemic myocardial inflammation hasn't been clearly discussed. AIM OF THE STUDY: The aim of this study was to explore the biological mechanism of constituents in CDDP synergistically improving post ischemic myocardial inflammation. MATERIALS AND METHODS: The pharmacologic studies were applied to assess the cardio protection effect of CDDP in acute myocardial ischemic rats. To identify the anti-inflammatory ingredients in CDDP, an ultra-performance liquid chromatography/quadrupole time-of-flight mass spectrometry combined with a dual-luciferase reporter assay for NF-κB inhibition were used. The network pharmacology and molecular docking assay were adopted to predict targets of anti-inflammatory ingredients and then the regulation effects of these active components on their targets were also verified. RESULTS: Our results indicated that CDDP exerted an excellent cardio protection effect by reversing echocardiographic abnormalities, attenuating histopathological lesion, ameliorating circulating myocardial markers and inflammation cytokines. Tanshinol, salvianolic acid B (Sal B), tanshinone IIA (Tan IIA) and notoginsenoside R1 (NGR1) were the pivotal anti-inflammatory ingredients in CDDP. The anti-inflammatory mechanism is that tanshinol and Sal B respectively targeted on PPARγ and JNK, while Tan IIA worked on AKT1 and NGR1 bound to PI3K. CONCLUSIONS: Our results firstly demonstrated that CDDP effectively ameliorated post ischemic myocardial inflammation through simultaneously modulating MAPK, PI3K/AKT and PPAR pathways in a multi-components synergetic manner.

Comparative evaluation for phytochemical composition and regulation of blood glucose, hepatic oxidative stress and insulin resistance in mice and HepG2 models of four typical Chinese dark teas.

BACKGROUND: Dark tea, comprising one of the six major teas, has many biological activities, which originate from their active substrates, such as polyphenols, polysaccharides, and so on. The hypoglycemic effect is one of its most prominent activities, although less is known about their evaluation and potential role in the hypoglycemic mechanism. RESULTS: In the present study, we separately analyzed the phytochemical composition, glycosidase inhibition and free radical scavenging activities, and hypoglycemic activity in type 2 diabetes mellitus mice, as well as the alleviation of insulin resistance in HepG2 cells of four dark tea aqueous extracts. The results showed that the phytochemical composition of dark tea aqueous extracts was significantly different, and they all had good glycosidase inhibition and free radical scavenging activities, in vivo hypoglycemic activity and alleviation of insulin resistance, and could also activate the phosphatidylinositol 3-kinase-Akt-perixisome proliferation-activated receptor cascade signaling pathway to regulate glucose and lipid metabolism, change the key enzyme activities related to glucose metabolism and antioxidant activity, and reduce oxidative stress and inflammatory factor levels. Among them, Liubao brick tea (LBT) and Pu-erh tea (PET) possessed better glycosidase inhibitory activity, in vivo hypoglycemic activity and improved insulin resistance activity, whereas Qingzhuan brick tea and Fuzhuan brick tea had better free radical scavenging activity, which may be explained by their distinct phytochemical compositions, such as tea proteins, polysaccharides, polyphenols, catechins, and tea pigments and some elements. CONCLUSION: Dark tea is a highly attractive candidate for developing antidiabetic food, LBT and PET may be good natural sources of agricultural products with anti-diabetic effects. © 2021 Society of Chemical Industry.

Paternal trans-fatty acid and vitamin E diet affects rat offspring's semen quality and PPARs expression.

Trans-fatty acids (TFAs) consumption has created concerns regarding male/female reproductive system. However, the effects of TFA in paternal diet on offspring's reproduction have not been addressed. The purpose of this study is to investigate the effects of rat paternal TFAs and vitamin E consumption on offspring's sperm quality and expression pattern of peroxisome proliferator-activated receptors (PPARs) in testis tissues. Forty adult male rats were randomly divided into four groups: Control diet (C); Control diet plus TFA (CTH); diet supplemented with vitamin E (E) and a diet containing vitamin E and TFA (ETH). Mother rats had normal diet during gestation period. Three offspring from each group were chosen randomly and their testicular samples were collected, and sperm parameters were measured by CASA. Our results indicate that feeding fathers with TFA can negatively affect offspring's sperm concentration and motility, while consumption of vitamin E can improve these parameters (p < .05). The paternal diet containing TFA down-regulated the expression of PPARß and PPARγ genes, whereas vitamin E-containing diet up-regulated the transcription of PPAR genes. In conclusion, TFA intake in paternal diet may have negative effects on reproductive system of the offspring while vitamin E may not diminish these effects.

Bezafibrate activation of PPAR drives disturbances in mitochondrial redox bioenergetics and decreases the viability of cells from patients with VLCAD deficiency.

Very long-chain acyl-CoA dehydrogenase (VLCAD) deficiency is the most common inborn long-chain fatty acid oxidation (FAO) disorder. VLCAD deficiency is characterized by distinct phenotypes. The severe phenotypes are potentially life-threatening and affect the heart or liver, with a comparatively milder phenotype characterized by myopathic symptoms. There is an unmet clinical need for effective treatment options for the myopathic phenotype. The molecular mechanisms driving the gradual decrease in mitochondrial function and associated alterations of muscle fibers are unclear. The peroxisome proliferator-activated receptor (PPAR) pan-agonist bezafibrate is a potent modulator of FAO and multiple other mitochondrial functions and has been proposed as a potential medication for myopathic cases of long-chain FAO disorders. In vitro experiments have demonstrated the ability of bezafibrate to increase VLCAD expression and activity. However, the outcome of small-scale clinical trials has been controversial. We found VLCAD deficient patient fibroblasts to have an increased oxidative stress burden and deranged mitochondrial bioenergetic capacity, compared to controls. Applying heat stress under fasting conditions to bezafibrate pretreated patient cells, caused a marked further increase of mitochondrial superoxide levels. Patient cells failed to maintain levels of the essential thiol peptide antioxidant glutathione and experienced a decrease in cellular viability. Our findings indicate that chronic PPAR activation is a plausible initiator of long-term pathogenesis in VLCAD deficiency. Our findings further implicate disruption of redox homeostasis as a key pathogenic mechanism in VLCAD deficiency and support the notion that a deranged thiol metabolism might be an important pathogenic factor in VLCAD deficiency.

Network modeling and inference of peroxisome proliferator-activated receptor pathway in high fat diet-linked obesity.

Systems biology aims to understand how holistic systems theory can be used to explain the observable living system characteristics, and mathematical modeling tools have been successful in understanding the intricate relationships underlying cellular functions. Lately, researchers have been interested in understanding molecular mechanisms underlying obesity, which is a major health concern worldwide and has been linked to several diseases. Various mechanisms such as peroxisome proliferator-activated receptors (PPARs) are known to modulate obesity-induced inflammation and its consequences. In this study, we have modeled the PPAR pathway using a Bayesian model and inferred the sub-pathways that are potentially responsible for the activation of the output processes that are associated with high fat diet (HFD)-induced obesity. We examined a previously published dataset from a study that compared gene expression profiles of 40 mice maintained on HFD against 40 mice fed with chow diet (CD). Our simulations have highlighted that GPCR and FATCD36 sub-pathways were aberrantly active in HFD mice and are therefore favorable targets for anti-obesity strategies. We further cross-validated our observations with experimental results from the literature. We believe that mathematical models such as those presented in the present study can help in inferring other pathways and deducing significant biological relationships.

Species-specific metabolic responses of songbird, shorebird, and murine cultured myotubes to n-3 polyunsaturated fatty acids.

Migratory birds may benefit from diets rich in polyunsaturated fatty acids (PUFAs) that could improve exercise performance. Previous investigations suggest that different types of birds may respond differently to PUFA. We established muscle myocyte cell culture models from muscle satellite cells of a migratory passerine songbird (yellow-rumped warbler, Setophaga coronata coronata) and a nonpasserine shorebird (sanderling, Calidris alba). We differentiated and treated avian myotubes and immortalized murine C2C12 myotubes with n-3 PUFA docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA), and with monounsaturated oleic acid (OA) to compare effects on aerobic performance, metabolic enzyme activities, key fatty acid (FA) transporters, and expression of peroxisome proliferator-activated receptors (PPARs). Sanderling and C2C12 myotubes increased expression of PPARs with n-3 PUFA treatments, whereas expression was unchanged in yellow-rumped warblers. Both sanderlings and yellow-rumped warblers increased expression of fatty acid transporters, whereas C2C12 cells decreased expression following n-3 PUFA treatments. Only yellow-rumped warbler myotubes increased expression of some metabolic enzymes, whereas the sanderling and C2C12 cells were unchanged. PUFA supplementation in C2C12 myotubes increased mitochondrial respiratory chain efficiency, whereas sanderlings increased proton leak-associated respiration and maximal respiration (measurements were not made in warblers). This research indicates that songbirds and shorebirds respond differently to n-3 PUFA and provides support for the hypothesis that n-3 PUFA increase the aerobic capacity of migrant shorebird muscle, which may improve overall endurance flight performance.

Network Pharmacology-Based Strategy Reveals the Effects of Hedysarum multijugum Maxim.-Radix Salviae Compound on Oxidative Capacity and Cardiomyocyte Apoptosis in Rats with Diabetic Cardiomyopathy.

OBJECTIVE: To explore the effects of the Hedysarum multijugum Maxim.-Radix Salviae compound (Huangqi-Danshen Compound (HDC)) on oxidative capacity and cardiomyocyte apoptosis in rats with diabetic cardiomyopathy by a network pharmacology-based strategy. METHODS: Traditional Chinese Medicine (TCM)@Taiwan, TCM Systems Pharmacology Database and Analysis Platform (TCMSP), TCM Integrated Database (TCMID), and High-Performance Liquid Chromatography (HPLC) technology were used to obtain and screen HDC's active components, and the PharmMapper database was used to predict HDC human target protein targets. The DCM genes were collected from the GeneCards and OMIM databases, and the network was constructed and analyzed by Cytoscape 3.7.1 and the Database for Annotation, Visualization, and Integrated Discovery (DAVID). Finally, HDC was used to intervene in diabetic cardiomyopathy (DCM) model rats, and important biological processes and signaling pathways were verified using techniques such as immunohistochemistry. RESULTS: A total of 176 of HDC's active components and 442 potential targets were obtained. The results of network analysis show that HDC can regulate DCM-related biological processes (such as negative regulation of the apoptotic process, response to hypoxia, the steroid hormone-mediated signaling pathway, cellular iron ion homeostasis, and positive regulation of phosphatidylinositol 3-kinase signaling) and signaling pathways (such as the HIF-1 signaling pathway, the estrogen signaling pathway, insulin resistance, the PPAR signaling pathway, the VEGF signaling pathway, and the PI3K-Akt signaling pathway). Animal experiments show that HDC can reduce fasting plasma glucose (FPG), HbA1c, and malondialdehyde (MDA) and increase superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) (P < 0.05). The results of immunohistochemistry showed that HDC can regulate the protein expression of apoptosis-related signaling pathways in DCM rats (P < 0.05). CONCLUSION: It was initially revealed that HDC improves DCM through its antiapoptotic and anti-inflammatory effects. HDC may play a therapeutic role by improving cardiomyocyte apoptosis in DCM rats.

Peroxisome proliferator-activated receptors (PPARs) as a mediator of dietary fatty acids affects reproductive performance in broiler breeder roosters.

This study analyzed the effects of dietary sources of omega-3 and omega-6 fatty acids on semen parameters and fertility potential in broiler breeder roosters. The mRNA and protein profiles of peroxisome proliferator-activated receptors-γ (PPAR-γ) expression in sperm as potential mediator of FAs were considered. Roosters were categorized into three groups and received their diets for 24 weeks as follows: 1) control diet received a basal diet (CTRL); 2) Fish oil based diet (FO) received the basal diet supplemented with 15 g/kg of diet fish oil; and 3) sunflower oil based diet (SO) received the basal diet supplemented with 15 g/kg of diet sunflower oil. While the different diets had significant effects on semen parameters, the effect of sampling time was not significant. The effect of the diets on sperm parameters were significantly higher in the SO and FO groups in total motility, progressive motility, amplitude of lateral head displacement, linearity, straightness, wobble and viability (P ≤ 0.05). Fertility rate was significantly improved in the FO and SO groups (P = 0001). The highest value for PPAR-γ mRNA was observed in the SO group compared to other groups (P ≤ 0.05). Moreover, supplementation of the roosters' diets with FO and SO increased PPAR-γ protein expression compared to the control. It seems that PPAR-γ could be a strong potential mediator of the underlying mechanism of improvement in semen parameters and reproductive performance of roosters under the effects of both dietary omega-3 and omega-6 polyunsaturated fatty acids.

A dietary anthocyanin cyanidin-3-O-glucoside binds to PPARs to regulate glucose metabolism and insulin sensitivity in mice.

We demonstrate the mechanism by which C3G, a major dietary anthocyanin, regulates energy metabolism and insulin sensitivity. Oral administration of C3G reduced hepatic and plasma triglyceride levels, adiposity, and improved glucose tolerance in mice fed high-fat diet. Hepatic metabolomic analysis revealed that C3G shifted metabolite profiles towards fatty acid oxidation and ketogenesis. C3G increased glucose uptake in HepG2 cells and C2C12 myotubes and induced the rate of hepatic fatty acid oxidation. C3G directly interacted with and activated PPARs, with the highest affinity for PPARα. The ability of C3G to reduce plasma and hepatic triglycerides, glucose tolerance, and adiposity and to induce oxygen consumption and energy expenditure was abrogated in PPARα-deficient mice, suggesting that PPARα is the major target for C3G. These findings demonstrate that the dietary anthocyanin C3G activates PPARs, a master regulators of energy metabolism. C3G is an agonistic ligand of PPARs and stimulates fuel preference to fat.

Identification of the active compounds and drug targets of Chinese medicine in heart failure based on the PPARs-RXRα pathway.

ETHNOPHARMACOLOGICAL RELEVANCE: Danqi Pill (DQP), commonly known as a routinely prescribed traditional Chinese medicine (TCM), is composed of Salviae Miltiorrhizae Radix et Rhizoma and Notoginseng Radix et Rhizoma and effective in treating heart failure (HF) clinically due to their multicompound and multitarget properties. However, the exact active compounds and corresponding targets of DQP are still unknown. AIM OF THE STUDY: This study aimed to investigate active compounds and drug targets of DQP in heart failure based on the PPARs-RXRα pathway. MATERIALS AND METHODS: Network pharmacology was used to predict the compound-target interactions of DQP. Left anterior descending (LAD)-induced HF mouse model and oxygen-glucose deprivation/recovery (OGD/R)-induced H9C2 model were constructed to screen the active compounds of DQP. RESULTS: According to BATMAN-TCM (a bioinformatics analysis tool for molecular mechanism of traditional Chinese medicine we previously developed), 24 compounds in DQP were significantly enriched in the peroxisome proliferator activated receptors-retinoid X receptor α (PPARs-RXRα) pathway. Among them, Ginsenoside Rb3 (G-Rb3) had the best pharmacodynamics against OGD/R-induced loss of cell viability, and it was selected to verify the compound-target interaction. In HF mice, G-Rb3 protected cardiac functions and activated the PPARs-RXRα pathway. In vitro, G-Rb3 protected against OGD/R-induced reactive oxygen species (ROS) production, promoted the expressions of RXRα and sirtuin 3 (SIRT3), thereafter improved the intracellular adenosine triphosphate (ATP) level. Immunofluorescent staining demonstrated that G-Rb3 could activate RXRα, and facilitate RXRα shifting to the nucleus. HX531, the specific inhibitor of RXRα, could abolish the protective effects of G-Rb3 on RXRα translocation. Consistently, the effect was also confirmed on RXRα siRNA cardiomyocytes model. Moreover, surface plasmon resonance (SPR) assays identified that G-Rb3 bound directly to RXRα with the affinity of KD = 10 × 10-5 M. CONCLUSION: By integrating network pharmacology and experimental validation, we identified that as the major active compound of DQP, G-Rb3 could ameliorate ROS-induced energetic metabolism dysfunction, maintain mitochondrial function and facilitate energy metabolism via directly targeting on RXRα. This study provides a promising strategy to dissect the effective patterns for TCM and finally promote the modernization of TCM.

First evidence on the role of palmitoylethanolamide in energy homeostasis in fish.

The objective of this study was to investigate the role of palmitoylethanolamide (PEA) in the regulation of energy homeostasis in goldfish (Carassius auratus). We examined the effects of acute or chronic intraperitoneal treatment with PEA (20 µg·g-1 body weight) on parameters related to food intake and its regulatory mechanisms, locomotor activity, glucose and lipid metabolism, and the possible involvement of transcription factors and clock genes on metabolic changes in the liver. Acute PEA treatment induced a decrease in food intake at 6 and 8 h post-injection, comparable to that observed in mammals. This PEA anorectic effect in goldfish could be mediated through interactions with leptin and NPY, as PEA increased hepatic expression of leptin aI and reduced hypothalamic expression of npy. The PEA chronic treatment reduced weight gain, growth rate, and locomotor activity. The rise in glycolytic potential together with the increased potential of glucose to be transported into liver suggests an enhanced use of glucose in the liver after PEA treatment. In addition, part of glucose may be exported to be used in other tissues. The activity of fatty acid synthase (FAS) increased after chronic PEA treatment, suggesting an increase in the hepatic lipogenic capacity, in contrast with the mammalian model. Such lipogenic increment could be linked with the PEA-induction of REV-ERBα and BMAL1 found after the chronic treatment. As a whole, the present study shows the actions of PEA in several compartments related to energy homeostasis and feeding behavior, supporting a regulatory role for this N-acylethanolamine in fish.

Regulation of calcific vascular and valvular disease by nuclear receptors.

PURPOSE OF REVIEW: This review addresses recent developments in studies of lipid regulation of calcific disease of arteries and cardiac valves, including the role of nuclear receptors. The role of lipid-soluble signals and their receptors is timely given the recent evidence and concerns that lipid-lowering treatment may increase the rate of progression of coronary artery calcification, which has been long associated with increased cardiovascular risk. Understanding the mechanisms will be important for interpreting such clinical information. RECENT FINDINGS: New findings support regulation of calcific vascular and valvular disease by nuclear receptors, including the vitamin D receptor, glucocorticoid receptor, nutrient-sensing nuclear receptors (liver X receptor, farnesoid X receptor, and peroxisome proliferator-activated receptors), and sex hormone (estrogen and androgen) receptors. There were two major unexpected findings: first, vitamin D supplementation, which was previously believed to prevent or reduce vascular calcification, showed no cardiovascular benefit in large randomized, controlled trials. Second, both epidemiological studies and coronary intravascular ultrasound studies suggest that treatment with HMG-CoA reductase inhibitors increases progression of coronary artery calcification, raising a question of whether there are mechanically stable and unstable forms of coronary calcification. SUMMARY: For clinical practice and research, these new findings offer new fundamental mechanisms for vascular calcification and provide new cautionary insights for therapeutic avenues.

Anti-obesity effects of Spirulina platensis protein hydrolysate by modulating brain-liver axis in high-fat diet fed mice.

Spirulina platensis is a blue-green algae with potential anti-obesity effects. In this study, the anti-obesity effects of whole Spirulina platensis (WSP), Spirulina platensis protein (SPP) and Spirulina platensis protein hydrolysate (SPPH) were compared in high-fat diet fed mice, and the potential acting mechanism of SPPH was also investigated. Totally, SPPH exhibited good anti-obesity effects (reducing 39.8%±9.7% of body weight), lowering 23.8%±1.6% of serum glucose, decreasing 20.8%±1.4% of total cholesterol, while positive drug Simvastatin had the corresponding values: 8.3%±4.6%, 24.8%±1.9% and -2.1%±0.2%, respectively. Subsequently, PCR array was used to conduct gene expression analysis in brain and liver tissues of SPPH-treated mice, which displayed distinctly different expression pattern. The most markedly changed genes included: Acadm (-34.7 fold), Gcg (2.5 fold), Adra2b (2 fold) and Ghsr (2 fold) in brain; Retn (39 fold), Fabp4 (15.5 fold), Ppard (6 fold) and Slc27a1 (5.4 fold) in liver. Further network analysis demonstrated that the significantly expressed genes in brain and liver tissues were mapped into an interacting network, suggesting a modulatory effect on brain-liver axis, major pathways were involved in the axis: PPAR, adipocytokine, AMPK, non-alcoholic fatty liver disease and MAPK. This study showed that Spirulina platensis protein hydrolysate possessed anti-obesity effect in mice.

Development of a Ligand Screening Tool Using Full-Length Human Peroxisome Proliferator-Activated Receptor-Expressing Cell Lines to Ameliorate Metabolic Syndrome.

Peroxisome proliferator-activated receptors (PPARs) belong to the nuclear hormone receptor superfamily and include three subtypes (PPARα, PPARδ, and PPARγ). They regulate gene expression in a ligand-dependent manner. PPARα plays an important role in lipid metabolism. PPARγ is involved in glucose metabolism and is a potential therapeutic target in Type 2 diabetes. PPARδ ligands are candidates for the treatment of metabolic disorders. Thus, the detection of PPAR ligands may facilitate the treatment of various diseases. In this study, to identify PPAR ligands, we engineered reporter cell lines that can be used to quantify PPARγ and PPARδ activity. We evaluated several known ligands using these reporter cell lines and confirmed that they are useful for PPAR ligand detection. Furthermore, we evaluated extracts of approximately 200 natural resources and found various extracts that enhance reporter gene activity. Finally, we identified a main alkaloid of the Evodia fruit, evodiamine, as a PPARγ activator using this screening tool. These results suggest that the established reporter cell lines may serve as a useful cell-based screening tool for finding PPAR ligands to ameliorate metabolic syndromes.

Weight loss effect of sweet orange essential oil microcapsules on obese SD rats induced by high-fat diet.

Obesity is one of the most common and major health concerns worldwide. Weight management through dietary supplements with natural plant extracts has become the focus of current research. Sweet orange essential oil (SOEO) is a natural plant extract, with many bioactivities. In order to evaluate the weight loss effect of SOEO microcapsules and investigate the underlying mechanism, we fed high-fat diet-induced obese SD rats with SOEO microcapsules for 15 days and found that SOEO microcapsules reduced body weight gain by 41.4%, decreased total cholesterol level, alleviated liver and adipose tissue pathological alteration. The results of fluorescence quantitative PCR revealed that decreasing the expression of peroxisome proliferators-activated receptor-γ, upregulating of uncoupling protein 2, hormone sensitive lipase and carnitine palmitoyltransferase I, inhibiting the expression of acetyl-CoA carboxylase appear to be the mechanism of SOEO microcapsules to lose weight. This study suggests that SOEO microcapsule is a potential dietary supplement for weight loss. Abbreviations: SOEO: sweet orange essential oil; TC: total cholesterol; TG: triglyceride; LDL-c: low-density lipoprotein cholesterol; HDL-c: high-density lipoprotein cholesterol; PPARα: peroxisome proliferators-activated receptor-α; PPARγ: peroxisome proliferators-activated receptor-γ; UCP2: uncoupling protein 2; HSL: hormone sensitive lipase; CPT1: carnitine palmitoyltransferase I; ACC: acetyl-CoA carboxylase; NPY: neuropeptide Y; LEP: leptin; INS: insulin; ALT: alanine aminotransferase; AST: aspartate aminotransferase.

PPARs and pain.

Chronic pain is a common cause of disability worldwide and remains a global health and socio-economic challenge. Current analgesics are either ineffective in a significant proportion of patients with chronic pain or associated with significant adverse side effects. The PPARs, a family of nuclear hormone transcription factors, have emerged as important modulators of pain in preclinical studies and therefore a potential therapeutic target for the treatment of pain. Modulation of nociceptive processing by PPARs is likely to involve both transcription-dependent and transcription-independent mechanisms. This review presents a comprehensive overview of preclinical studies investigating the contribution of PPAR signalling to nociceptive processing in animal models of inflammatory and neuropathic pain. We examine current evidence from anatomical, molecular and pharmacological studies demonstrating a role for PPARs in pain control. We also discuss the limited evidence available from relevant clinical studies and identify areas that warrant further research. LINKED ARTICLES: This article is part of a themed section on 8th European Workshop on Cannabinoid Research. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v176.10/issuetoc.