PPARα Expression Research Articles

Electroacupuncture reduces oxidative stress response and improves secondary injury of intracerebral hemorrhage in rats by activating the peroxisome proliferator-activated receptor-γ/nuclear factor erythroid2-related factor 2/γ-glutamylcysteine synthetase pathway.

Intracerebral hemorrhage (ICH) is a severe stroke subtype. Secondary injury is a key factor leading to neurological deficits after ICH. Electroacupuncture (EA) can improve the neurological function after ICH, however, its internal mechanism is still unclear. The aim of this study is to investigate whether EA could ameliorate secondary injury after ICH through antioxidative stress and its potential regulatory mechanism. A rat model of ICH was established by injecting autologous blood into striatum. After the intervention of EA and EA combined with peroxisome proliferator-activated receptor-γ (PPARγ) blocker, Zea-longa scores, modified neurological severity scores and open field tests were used to evaluate the neurological function of the rats. Flow cytometry detected tissue reactive oxygen species (ROS) levels. Tissue tumor necrosis factor-α (TNF-α) levels were analyzed by enzyme-linked immunosorbent assays. The protein expressions of PPAR γ, nuclear factor erythroid2-related factor 2 (Nrf2) and γ-glutamylcysteine synthetase (γ-GCS) were detected by Western blot. Immunohistochemistry was used to observe the activation of microglia. The demyelination degree of axon myelin was observed by transmission electron microscope. Compared with the model group, EA intervention improved neurological function, decreased ROS and TNF-α levels, increased the protein expression of PPARγ, Nrf2 and γ-GCS, and reduced the activation of microglia, it also alleviated axonal myelin sheath damage. In addition, the neuroprotective effect of EA was partially attenuated by PPARγ blocker. EA ameliorated the neurological function of secondary injury after ICH in rats, possibly by activating the PPARγ/Nrf2/γ-GCS signaling pathway, reducing microglia activation, and inhibiting oxidative stress, thus alleviating the extent of axonal demyelination plays a role.

Effect of valine on expression of fatty acid metabolism-regulated genes PPARα and FASN in porcine primary hepatocytes

Effect of valine on expression of fatty acid metabolism-regulated genes PPARα and FASN in porcine primary hepatocytes

Effects of fermented cottonseed meal inclusions on growth performance, serum biochemical parameters and hepatic lipid metabolism of geese during 28–70 d of age

The aim of this study was to investigate the effects of solid-state fermented cottonseed meal (FCSM) inclusion levels on the growth performance, serum biochemical parameters and hepatic lipid metabolism in geese from 28 to 70 d of age. A total of 288 28‐d‐old male geese were randomly divided into 4 treatments with FCSM levels of 0, 5, 15 and 25% including 0, 22.74, 67.33, 111.27 mg FG/kg diet, respectively. Each treatment contained 6 replicates and 12 birds per replicate. Treatments of FCSM inclusions from 0 to 25% had no effect on growth rate and feed intake in geese during d 28-70. The F/G ratio was increased (P < 0.05) in geese fed the diet with 25% FCSM compared with birds fed the diet with 0% FCSM. Treatment with 25% FCSM levels had no effect on the contents of TC, TG, HDL-C, LDL-C, but increased (P < 0.05) AST and ALT activities in serum of geese at d 70. Treatment with 25% FCSM increased the contents of FG, HDL-C, TC, C18:2n6, C20:4n6 and PUFA and decreased (P < 0.05) the contents of NEFA, SFA, MUFA in liver compared with treatment of 0% FCSM inclusion. Additionally, treatment with 25% FCSM decreased (P < 0.05) the PPARα, AMPK and LXR mRNA expression related to lipid deposition, and increased (P < 0.05) PPARγ and ACC mRNA expression related to lipolysis in liver compared with birds fed the diet with 0% FCSM. Overall, treatment with 0-15% FCSM (<=67.33 mg FG/kg diet) had no adverse effects on the growth performance and lipid metabolism of geese. However, treatment fed 25% FCSM (111.27 mg FG/kg diet) decreased feed efficiency and promoted hepatic lipid deposition associated with the alteration of related gene expression in geese at 28-70 d of age.

Tempol maintained the cellular integrity of the cerebellar cortex by preserving neuron survival, autophagy, glial cells, and synapses after cisplatin exposure

Backgroundtempol is a free radical scavenger that passes through the blood-brain barrier. This study aimed to assess its ameliorative role in the cerebellar cortex after cisplatin injection. Methodsthe examined forty-eight adult male wistar albino rats were divided into four groups. The saline group received 0.5 ml of normal saline, the tempol group was injected with 0.5 ml of tempol (100 mg/kg/day), the cisplatin group was injected with cisplatin single dose (7 mg/kg) on the 8th day, and cisplatin + tempol group received combined treatment. All groups were dosed through intraperitoneal injections. Resultshistological examination revealed meningeal congestion and thickening with excess collagen, discrete vacuolated cortical cells, with pyknotic nuclei, and tissue loss after cisplatin. Immunohistochemical expression of NF-kβ and GFAP were enhanced, while LC3-II and synaptophysin expression decreased with cisplatin. Cisplatin treatment reduced mRNA expression of NGF, GLP-1, BDNF, PGC1-α, and PPAR-α while it boosted Caspase-3 expression. Moreover, it tripled the level of MDA and lowered levels of SOD, CAT, and GSH in cerebellar tissue homogenate. Tempol supplementation restored the meningeal and the normal histological structure of the cerebellar cortex. The immunohistochemical as well as mRNA expressions of different genes were highly normalized but still showed variable significant differences when compared to the control except for NGF, PGC1-α, and Caspase-3 genes. Great restoration of biochemical markers was evident with tempol, especially for CAT that showed no significant difference in comparison with the saline group. Conclusiontempol cisplatin combination can enhance neuronal survival, promote autophagy, decrease astrogliosis, and preserve synapses.

Inhibitory Effect of Prickly Ash (Zanthoxylum bungeanum) Seed Kernel Oil on Lipid Metabolism of Grass Carp (Ctenopharyngodon idellus) in High-Fat Diet

To investigate the effect of prickly ash (Zanthoxylum bungeanum) seed kernel oil (PASO) on the lipid metabolism of grass carp (Ctenopharyngodon idellus) under a high-fat diet, PASO were added into two lipid-level (4 g/kg and 8 g/kg) diets to form four isonitrogenous diets: soybean oil (SO), PASO, high-fat soybean oil (HSO), and high-fat prickly ash seed oil (HPASO). A total of 216 healthy grass carp (9.43 ± 0.82 g) were randomly divided into four groups and fed with the four diets, respectively, for 56 days. The result showed that the viscerosomatic index (VSI) and the content of the crude lipid in the hepatopancreas and muscle was significantly higher by oil levels (p &lt; 0.05). The linolenic acid content in the body of the fish significantly increased in PASO and HPASO compared to that in SO and HSO (p &lt; 0.05). The fatty acid composition of the hepatopancreas, intraperitoneal fat, and muscle in four dietary groups was significantly similar to the fatty acid composition in the diets (p &lt; 0.05). More significant fat infiltration and nuclear translocation in the hepatopancreas of fish was found in the HSO group but was decreased in the HPASO group. The adipocyte size in the intraperitoneal fat tissue in the PASO group was significantly lower than that in the SO group (p &lt; 0.05). The relative mRNA expression of the lipogenesis-related genes ppar-γ, cebp-α, and srebp-1c was significantly down-regulated in the PASO group compared with the SO group (p &lt; 0.05), and the mRNA expression of lipolysis-related genes ppar-α and cpt-1 were significantly up-regulated in the PASO group (p &lt; 0.05). In conclusion, dietary PASO showed the function of reducing lipid accumulation in the fish. This reduction might be attributed to the inhibition of the lipogenesis-related genes and the stimulation of the lipolysis-related genes, which were probably modulated by the high content of linolenic acid in PASO.

Regulation of lipid metabolism by the major components of orange essential oil in high-fat diet mice

Orange essential oil (OEO) is an important citrus by-product that has been utilized as a nutritional modulator. In the study, we investigated the effects of limonene, linalool, and decanal (the major components of OEO) on hepatic lipid composition and metabolism in high-fat diet (HFD) mice. The results showed that limonene, linalool and decanal treatments alleviated weight gain and dyslipidemia induced by HFD. In addition, compared to the HFD group, hepatic lipids were significantly altered in the treated groups, PIs, PEs and PGs screened as marker metabolites. Furthermore, we found that limonene, linalool and decanal accelerated the oxidation of fatty acids by stimulating of PPAR-α and CPT-1 expression. Therefore, our study can provide theoretical support for aromatics as nutritional regulators.

A study on the treatment effects of Crataegus pinnatifida polysaccharide on non-alcoholic fatty liver in mice by modulating gut microbiota.

The objective of this study was to investigate the protective effect of Crataegus pinnatifida polysaccharide (CPP) on non-alcoholic fatty liver disease (NAFLD) induced by a high-fat diet (HFD) in mice. The findings demonstrated that CPP improved free fatty acid (FFA)-induced lipid accumulation in HepG2 cells and effectively reduced liver steatosis and epididymal fat weight in NAFLD mice, as well as decreased serum levels of TG, TC, AST, ALT, and LDL-C. Furthermore, CPP exhibited inhibitory effects on the expression of fatty acid synthesis genes FASN and ACC while activating the expression of fatty acid oxidation genes CPT1A and PPARα. Additionally, CPP reversed disturbances in intestinal microbiota composition caused by HFD consumption. CPP decreased the firmicutes/Bacteroidetes ratio, increased Akkermansia abundance, and elevated levels of total short-chain fatty acid (SCFA) content specifically butyric acid and acetic acid. Our results concluded that CPP may intervene in the development of NAFLD by regulating of intes-tinal microbiota imbalance and SCFAs production. Our study highlights that CPP has a potential to modulate lipid-related pathways via alterations to gut microbiome composition thereby ex-erting inhibitory effects on obesity and NAFLD development.

Genetic analysis of impaired healing responses after periodontal therapy in type 2 diabetes: Clinical and invivo studies.

This study aims to investigate the mechanisms underlying the impaired healing response by diabetes after periodontal therapy. Outcomes of periodontal therapy in patients with diabetes are impaired compared with those in patients without diabetes. However, the mechanisms underlying impaired healing response to periodontal therapy have not been sufficiently investigated. Zucker diabetic fatty (ZDF) and lean (ZL) rats underwent experimental periodontitis by ligating the mandibular molars for one week. The gingiva at the ligated sites was harvested one day after ligature removal, and gene expression was comprehensively analyzed using RNA-Seq. In patients with and without type 2 diabetes (T2D), the corresponding gene expression was quantified in the gingiva of the shallow sulcus and residual periodontal pocket after non-surgical periodontal therapy. Ligation-induced bone resorption and its recovery after ligature removal were significantly impaired in the ZDF group than in the ZL group. The RNA-Seq analysis revealed 252 differentially expressed genes. Pathway analysis demonstrated the enrichment of downregulated genes involved in the peroxisome proliferator-activated receptor (PPAR) signaling pathway. PPARα and PPARγ were decreased in mRNA level and immunohistochemistry in the ZDF group than in the ZL group. In clinical, probing depth reduction was significantly less in the T2D group than control. Significantly downregulated expression of PPARα and PPARγ were detected in the residual periodontal pocket of the T2D group compared with those of the control group, but not in the shallow sulcus between the groups. Downregulated PPAR subtypes expression may involve the impaired healing of periodontal tissues by diabetes.

Single-cell transcriptome reveals a novel mechanism of C-Kit+-liver sinusoidal endothelial cells in NASH

AimTo understand how liver sinusoidal endothelial cells (LSECs) respond to nonalcoholic steatohepatitis (NASH).MethodsWe profiled single-LSEC from livers of control and MCD-fed mice. The functions of C-Kit+-LSECs were determined using coculture and bone marrow transplantation (BMT) methods.ResultsThree special clusters of single-LSEC were differentiated. C-Kit+-LSECs of cluster 0, Msr1+-LSECs of cluster 1 and Bmp4+Selp+-VECs of cluster 2 were revealed, and these cells with diverse ectopic expressions of genes participated in regulation of endothelial, fibrosis and lipid metabolism in NASH. The number of C-Kit+-primary LSECs isolated from MCD mice was lower than control mice. Immunofluorescence co-staining of CD31 and C-KIT showed C-Kit+-LSECs located in hepatic sinusoid were also reduced in NASH patients and MCD mice, compared to AIH patients and control mice respectively. Interestingly, lipotoxic hepatocytes/HSCs cocultured with C-Kit+-LSECs or the livers of MCD mice receipting of C-Kit+-BMCs (bone marrow cells) showed less steatosis, inflammation and fibrosis, higher expression of prolipolytic FXR and PPAR-α, lower expression of TNF-α and α-SMA. Furthermore, coculturing or BMT of C-Kit+-endothelial derived cells could increase the levels of hepatic mitochondrial LC3B, decrease the degree of mitochondrial damage and ROS production through activating Pink1-mediated mitophagy pathway in NASH.ConclusionsHence, a novel transcriptomic view of LSECs was revealed to have heterogeneity and complexity in NASH. Importantly, a cluster of C-Kit+-LSECs was confirmed to recovery Pink1-related mitophagy and NASH progression.

Potential Benefits of Ethanol extract of Anredera cordifolia for Antiobesity of High Fat diet-Induced Obesity in White Male Rat Wistar

تستمر الوفيات المرتبطة بالسمنة في الارتفاع ، لذلك من الضروري إنقاص الوزن لتجنب المضاعفات ، نريديرا كورديفوليا هو نوع من النباتات النضرة من الجنس، باسيللسيا يستخدم على نطاق واسع في طب الأعشاب لتقليل وزن الجسم. تهدف الدراسة الحالية إلى تقييم الفوائد المحتملة لمستخلص الإيثانول من نريديرا كورديفوليا لنماذج الفئران السمنة لتقليل الوزن الناجم عن نظام غذائي عالي الدهون. من خلال تجريب مع اختبارات ما بعد فقد تم تصميم مجموعة ضابطة مع نموذج سمنة 36 جرذًا ، مقسمة إلى مجموعتين: ثلاث مجموعات تحكم (K1 ، K2 ، K3) وثلاث مجموعات معالجة (K1 ، K3 ، K4) (P1 ، P2 ، P3) ، أعطيت جميع مجموعات تحتوي على نسبة عالية من الدهون باستثناء K1 نظام غذائي قياسي ، K2 بدون علاج ، و K3 مع أورليستات. تلقت مجموعة العلاج من مستخلص الإيثانول نريديرا كورديفوليا بجرعات مختلفة ، P1 50 مجم / كجم من وزن الجسم ، P2 100 مجم / كجم من وزن الجسم، و P3 150 مجم / كجم من وزن الجسم. بعد 4 أسابيع من العلاج، قُتلت جميع مجموعات الفئران ، وتم قياس مستويات ERK و PPARγ في الأنسجة الدهنية الحشوية في البطن باستخدام ELISA والكيمياء المناعية. يتم قياس وزن الجسم ومحيط البطن أثناء فحص القياسات، وقد لوحظ فقدان الوزن عند تناول مستخلص الإيثانول نريديرا كورديفوليا بجرعات 100 و 150 مجم / كجم من وزن الجسم، مع انخفاض مستويات ERK و PPAR . يستخدم مستخلص الإيثانول من نريديرا كورديفوليا كمضاد للسمنة. تقلل آلية فقدان الوزن هذه من عامل نسخ PPARγ وتقلل من مستويات ERK بحيث تقل عملية تكوين الدهون.

The ameliorative effect of turmeric (Curcuma longa Linn) extract and its major constituent, curcumin, and its analogs on ethanol toxicity.

Ethanol toxicity is a major public health problem that can cause damage to various organs in the body by several mechanisms inducing oxidative stress, inflammation, and apoptosis. Recently, there has been a growing interest in the potential of herbal medicines as therapeutic agents for the prevention and treatment of various disorders. Turmeric (Curcuma longa) extracts and its main components including curcumin have antioxidant, anti-inflammatory, and anti-apoptotic properties. This review aims to evaluate the literature on the ameliorative effects of turmeric extracts and their main components on ethanol toxicity. The relevant studies were identified through searches of Google Scholar, PubMed, and Scopus without any time limitation. The underlying mechanisms of turmeric and curcumin were also discussed. The findings suggest that turmeric and curcumin ameliorate ethanol-induced organ damage by suppressing oxidative stress, inflammation, apoptosis, MAPK activation, TGF-β/Smad signaling pathway, hyperlipidemia, regulating hepatic enzymes, expression of SREBP-1c and PPAR-α. However, the limited clinical evidence suggests that further research is needed to determine the efficacy and safety of turmeric and curcumin in human subjects. In conclusion, the available evidence supports the potential use of turmeric and curcumin as alternative treatments for ethanol toxicity, but further high-quality studies are needed to firmly establish the clinical efficacy of the plant.

Black pepper (Piper nigrum L.) essential oil counteracts dexamethasone-induced hepatic injury via modulating PGC-1α/ PPAR-α pathway in rats

We previously characterized the volatile compounds of black pepper (Piper nigrum) essential oil (BPEO) and demonstrated its mitigating effect against dexamethasone-induced pancreatic damage. Herein, we investigated the protective effect of the oil against dexamethasone-induced hepatotoxicity in rats and pinned the possible underlying mechanisms. In the in vivo experiment, male Wistar rats were divided into five groups. The first group served as the normal control receiving a saline solution (Control). The second group was subjected to hepatic damage through dexamethasone exposure (Dexa) at 10 mg/kg. The third group received both dexamethasone and metformin (Met) at a dose of 50 mg/kg. The remaining two groups were exposed to dexamethasone along with black pepper oil administration at low and high doses (BPEO, 0.5 mL/kg and 1 mL/kg). We showed that BPEO offset toxicity manifestations, as indicated by reducing monocyte infiltration, hepatocyte degeneration and vacuolation, and reduction of ALT and AST levels. Moreover, relative to the dexamethasone-treated rats, BPEO declined the number of PGC-1α positive hepatocytes and activated the expression of PPAR-α in the liver. BPEO showed comparable hepatoprotective potency to the standard drug, metformin, especially at the higher dose tested (1 mL/kg). This study showcases the promising potential of BPEO in thwarting dexamethasone-induced adverse effects on the liver by alleviating hepatic biomarkers hikes and preventing histopathological changes and fibrosis. Finally, it opens a new avenue on the potential role of BPEO in modulating steroid-induced hepatic injury through the PGC-1α/ PPAR-α pathway.

Genistein and Sex Hormone Supplementation Modulated Hepatic PPARα, δ, and γ Subtypes and STAT1 Expressions in a NASH Rat Model with Bilateral Orchidectomy.

Nonalcoholic steatohepatitis (NASH) is a progressive form of nonalcoholic fatty liver disease (NAFLD) that is characterized by hepatic inflammation and steatosis. Currently, limited data exist regarding the risk of NASH in transgender women and the treatment options for this particular population. The use of testosterone supplementation is unfavorable for transgender women, and estrogen supplementation is linked to an increased risk of breast cancer; thus, an isoflavone derivative compound known as "genistein" could serve as a viable substitute for a hormone supplement in this context. The purpose of this study was to investigate the treatment effects and mechanisms of actions of genistein and sex hormones in orchidectomized (ORX) rats with nonalcoholic steatohepatitis induced via a high-fat high-fructose diet (HFHF) model. Male Sprague-Dawley rats (n = 42) were randomly assigned into seven groups; control, ORX + standard diet, HFHF, ORX + HFHF, ORX + HFHF diet + testosterone (50 mg/kg body weight (BW) once weekly), ORX + HFHF diet + estradiol (1.6 mg/kg BW daily), and ORX + HFHF diet + genistein (16 mg/kg BW daily). The duration of the study was 6 weeks. Some parts of liver tissue were used for histological examination by H&E staining. The determination of fat accumulation was performed using Oil Red O staining. SREBP1c and FAS gene expression were quantified using real-time PCR technique. The levels of all types of peroxisome proliferator-activated receptors (PPARs; α, δ, γ), proteins, and signal transducer and activator of transcription 1 (STAT1) signaling pathway were determined by both immunoblotting and immunohistochemistry. Rats in the ORX + HFHF group had the highest degree of hepatic steatosis, lobular inflammation, and hepatocyte ballooning, and showed higher levels of genes related to de novo lipogenesis, including SREBP1c and FAS. The expression of PPARγ and STAT1 were upregulated, while the expression of PPARα and PPARδ were downregulated in the ORX + HFHF group. Testosterone, estradiol and genistein treatments improved NASH histopathology together with the reversal of all types of PPAR protein expressions. Interestingly, genistein decreased the levels of STAT1 protein expression more than those of testosterone and estradiol treatment. Genistein and sex hormone treatment could ameliorate NASH through the upregulation of PPARα, and PPARδ, and the suppression of PPARγ and STAT1 expression.

PPARα/δ dual agonist H11 alleviates diabetic kidney injury by improving the metabolic disorders of tubular epithelial cells

Diabetic kidney disease (DKD) is responsible for nearly half of all end-stage kidney disease and kidney failure is a major driver of mortality among patients with diabetes. To date, few safe and effective drugs are available to reverse the decline of kidney function. Kidney tubules producing energy by fatty acid metabolism are pivotal in development and deterioration of DKD. Peroxisome proliferator-activated receptors (PPARs), comprising PPARα, PPARδ and PPARγ play a senior role in the pathogenesis of DKD for their functions in glycemic control and lipid metabolism; whereas systemic activation of PPARγ causes serious side-effects in clinical settings. Compound H11 was a potent PPARα and PPARδ (PPARα/δ) dual agonist with potent and well-balanced PPARα/δ agonistic activity and a high selectivity over PPARγ. In this study, the potential therapeutic effects of compound H11 were determined in a db/db mouse model of diabetes. Expressions of PPARα and PPARδ in nuclei of tubules were markedly reduced in diabetes. Transcriptional changes of tubular cells showed that H11 was an effective PPARα/δ dual agonist taking effects both in vivo and in vitro. Systemic administration of H11 showed glucose tolerance and lipid metabolic benefits in db/db mice. Moreover, H11 treatment exerted protective effects on diabetic kidney injury. In addition to fatty acid metabolism, H11 also regulated diabetes-induced metabolic alternations of branch chain amino acid degradation and glycolysis. The present study demonstrated a crucial role of H11 in regulation of energy homeostasis and metabolism in glucose-treated tubular cells. Overall, compound H11 holds therapeutic promise for DKD.

Evaluation of the hepatotoxicity of Psoralea corylifolia L. based on a zebrafish model.

Objective: Psoralea corylifolia L. (FP) has received increasing attention due to its potential hepatotoxicity. Methods: In this study, zebrafish were treated with different concentrations of an aqueous extract of FP (AEFP; 40, 50, or 60μg/mL), and the hepatotoxic effects of tonicity were determined by the mortality rate, liver morphology, fluorescence area and intensity of the liver, biochemical indices, and pathological tissue staining. The mRNA expression of target genes in the bile acid metabolic signaling pathway and lipid metabolic pathway was detected by qPCR, and the mechanism of toxicity was initially investigated. AEFP (50μg/mL) was administered in combination with FXR or a peroxisome proliferator-activated receptor α (PPARα) agonist/inhibitor to further define the target of toxicity. Results: Experiments on toxic effects showed that, compared with no treatment, AEFP administration resulted in liver atrophy, a smaller fluorescence area in the liver, and a lower fluorescence intensity (p < 0.05); alanine transaminase (ALT), aspartate transaminase (AST), and γ-GT levels were significantly elevated in zebrafish (p < 0.01), and TBA, TBIL, total cholesterol (TC), TG, low-density lipoprotein cholesterol (LDL-C), and high-density lipoprotein cholesterol (HDL-C) levels were elevated to different degrees (p < 0.05); and increased lipid droplets in the liver appeared as fatty deposits. Molecular biological validation revealed that AEFP inhibited the expression of the FXR gene, causing an increase in the expression of the downstream genes SHP, CYP7A1, CYP8B1, BSEP, MRP2, NTCP, peroxisome proliferator-activated receptor γ (PPARγ), ME-1, SCD-1, lipoprotein lipase (LPL), CPT-1, and CPT-2 and a decrease in the expression of PPARα (p < 0.05). Conclusion: This study demonstrated that tonic acid extracts are hepatotoxic to zebrafish through the inhibition of FXR and PPARα expression, thereby causing bile acid and lipid metabolism disorders.

Adiponectin improves endometrial receptivity in rats with polycystic ovary syndrome by upregulating the PPARα/HOXA10 pathway

To explore the role of the PPARα/HOXA10 signaling pathway in mediating the effect of adiponectin (APN) for improving endometrial receptivity in a rat model of polycystic ovary syndrome (PCOS). Forty female SD rat models with letrozole-induced PCOS were randomized, with 10 normal rats as the control, into 4 equal groups for treatment with APN alone, APN combined with GW6471 (a specific PPARα inhibitor) or the vehicle for 20 days, or no further treatment (PCOS model group). GW6471 treatment (daily dose of 1 mg/kg) and vehicle treatment were initiated on the 11th day following the start of APN treatment, all administered via intraperitoneal injection. The rats were observed for changes in estrous cycle, body weight, ovarian index and morphology, uterine index and morphology, serum hormone levels and lipid metabolism parameters. Endometrial expressions of PPARα and HOXA10 were detected with immunohistochemistry and Western blotting. The development of endometrial pinopodes was observed under electron microscope, and pregnancies of the rats were recorded. The rat models of PCOS exhibited obvious estrous cycle disorders with significantly prolonged estrous interval, increased body weight and ovarian index, decreased uterine index, disordered serum hormones and lipid metabolism (P < 0.05), and polycystic ovarian changes, and these changes were significantly improved by APN treatment. Endometrial expressions of PPARα and HOXA10 were significantly lowered in PCOS rats and effectively up-regulated after APN treatment, but GW6471 treatment obviously blocked the effect of APN (P < 0.05). APN showed strong protective effect against PCOS-induced impairment of endometrial pinopode development, and this effect was obviously attenuated by GW6471. APN also significantly increased the pregnancy rate and embryo number in PCOS rats, while GW6471 obviously reduced the embryo number and caused developmental retardation of the embryos. APN can improve endometrial receptivity in PCOS rats by upregulating the PARα/HOXA10 pathway.

Amelioration of obesity induction by a high-fat diet and related inflammation by Phasa fish (Setipinna phasa) oil in BALB/c mice.

We have extracted and characterized Phasa fish (Setipinna phasa) oil for the first time to evaluate the anti-obesity and related anti-inflammatory effects on obese mice. Inbred male albino BALB/c mice were segregated into three categories: control (C), Obese control group (OC), and Phasa fish oil treated group (TX). To establish the potentiality of Setipinna phasa oil for its anti-obesity and anti-inflammatory properties, it was extracted and characterized using GC-MS method. To evaluate the anti-obesity effect, different parameters were considered, such as body weight, lipid composition, obesity, and obesity associated inflammation. The physicochemical characteristics of Phasa fish oil revealed that the oil quality was good because acid value, peroxide value, p-anisidine value, Totox value, refractive index, and saponification value were within the standard value range. The GC-MS study explored the presence of fatty acids beneficial to health such as Hexadec-9-enoic acid; Octadec-11-enoic acid; EPA, DHA, Methyl Linolenate, etc. The application of Setipinna phasa oil on the treated mice group acutely lowered body weight and serum lipid profile compared to the obese group. In connection with this, leptin, FAS, and pro-inflammatory cytokines TNF-α genes expression were downregulated in the treated group compared to the obese group. The Phasa oil treated group had an elevated expression of PPAR-α, adiponectin, LPL gene, and anti-inflammatory markers IL-10 and IL-1Ra compared to the obese group. This study suggests that Phasa fish oil, enriched with essential fatty acid, might be used as an anti-obesity and anti-inflammatory supplement.

Shen-Shuai-II-Recipe inhibits tubular inflammation by PPARα-mediated fatty acid oxidation to attenuate fibroblast activation in fibrotic kidneys

BackgroundShen Shuai Ⅱ Recipe (SSR) is clinically used to treat chronic kidney diseases (CKDs) with remarkable efficacy and safety. In earlier research, we found the anti-inflammatory, antioxidant, and mitochondrial protective properties of SSR in hypoxic kidney injury model, which is closely related to its renal protection. Further work is needed to understand the underlying molecular mechanisms. PurposeFurther investigation of the mechanisms of action of SSR against renal interstitial fibrosis (RIF) building on previous research leads. MethodsRats receiving CKD model surgery were given with Fenofibrate or SSR once a day for eight weeks. In vitro, the NRK-52E cells were treated with SSR in the presence or absence of 10 μM Sc75741, 0.5 μM PMA, or 1 μM fenofibrate under 1% O2. The effects of SSR on NF-κB/NLRP3 inflammatory cascade, secretion of pro-inflammatory cytokines, fatty acid oxidation (FAO), and renal tubular injury were determined by immunoblotting, luminex liquid suspension chip assay, transmission electron microscopy, and Oil red O staining. Next, we delivered PPARα-interfering sequences to kidney tissue and NRK-52E cells by adeno-associated virus (AAV) injection and siRNA transfection methods. Finally, we evaluated the effect of renal tubular cells on fibroblast activation by co-culture method. ResultsSSR attenuated the release of IL-18, VEGF, and MCP1 cytokines, inhibited the activation of NF-κB/NLRP3 cascade, increased the PPARα, CPT-1α, CPT-2, ACADL, and MCAD protein expression, and improved the lipid accumulation. Further studies have demonstrated that one of the ways in which SSR suppresses the inflammatory response to protect renal tubular cells is through the restoration of PPARα-mediated FAO. In addition, by means of co-culture ways, the results demonstrated that SSR attenuated secretion of inflammatory mediators in NRK-52E cells by PPARα/NF-κB/NLRP3 pathway, thereby inhibiting renal fibroblast activation. ConclusionSSR inhibits RIF by suppressing inflammatory response of hypoxia-exposed RTECs through PPARα-mediated FAO.

Uxi (Endopleura uchi (Huber) Cuatrec) bark extract mitigates HFD-induced adiposity in rats via targeting oxidative stress, and lipogenic genes expression

Here, we compared the modulatory effects of different dose levels of Uxi (Endopleura uchi aqueous bark extract, EUAE) vs simvastatin (SIM) on hyperlipidemia, metabolic stress, and liver dysfunction in HFD-induced obese rats. HFD significantly increased BMI, lee index, body adipose index, atherogenic indices, cellular toxicity markers, blood glucose level, adipokines, pro-inflammatory mediators, lipid peroxidation and promoted lipid accumulation and HMGCR and ACC. Furthermore, it significantly decreased antioxidants, ghrelin, and AG/UAG ratio as well as hepatic glycogen content, while these changes were mitigated by either SIM or EUAE treatment. The expression of FASN & SREBP1c genes were elevated in the HFD group, with downregulation of PPARα expression. These alterations were ameliorated by SIM or EUAE treatment. The beneficial effects of EUAE may be attributed to its phenolic compounds and their derivatives. This study supports the hypothesis that Uxi may have antihyperlipidemic, antioxidant, hepatoprotective, and anti-inflammatory properties in rat model of obesity.

Effect of Supplementation with Omega-3 Polyunsaturated Fatty Acids on Metabolic Modulators in Skeletal Muscle of Rats with an Obesogenic High-Fat Diet.

Previous studies provided evidence of the benefits of omega-3 polyunsaturated fatty acids (ω-3 PUFA) on the cardiovascular system and inflammation. However, its possible effect on skeletal muscle is unknown. This study aimed to evaluate whether ω-3 PUFA reverses the dysregulation of metabolic modulators in the skeletal muscle of rats on a high-fat obesogenic diet. For this purpose, an animal model was developed using male Wistar rats with a high-fat diet (HFD) and subsequently supplemented with ω-3 PUFA. Insulin resistance was assessed, and gene and protein expression of metabolism modulators in skeletal muscle was also calculated using PCR-RT and Western blot. Our results confirmed that in HFD rats, zoometric parameters and insulin resistance were increased compared to SD rats. Furthermore, we demonstrate reduced gene and protein expression of peroxisome proliferator-activated receptors (PPARs) and insulin signaling molecules. After ω-3 PUFA supplementation, we observed that glucose (24.34%), triglycerides (35.78%), and HOMA-IR (40.10%) were reduced, and QUICKI (12.16%) increased compared to HFD rats. Furthermore, in skeletal muscle, we detected increased gene and protein expression of PPAR-α, PPAR-γ, insulin receptor (INSR), insulin receptor substrate 1 (ISR-1), phosphatidylinositol-3-kinase (PI3K), and glucose transporter 4 (GLUT-4). These findings suggest that ω-3 PUFAs decrease insulin resistance of obese skeletal muscle.