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https://www.readbyqxmd.com/read/29334664/methyl-dehydroabietate-counters-high-fat-diet-induced-insulin-resistance-and-hepatic-steatosis-by-modulating-peroxisome-proliferator-activated-receptor-signaling-in-mice
#1
Hiroki Yoshioka, Yuki Mizuno, Tomohiro Yamaguchi, Yoshimi Ichimaru, Koichi Takeya, Yukio Hitotsuyanagi, Tsunemasa Nonogaki, Yutaka Aoyagi
The aim of this study was to investigate the therapeutic effects of methyl dehydroabietate (mDA) on adipocyte differentiation in 3T3-L1 preadipocytes and obesity characteristics induced by high-fat diet (HFD) in mice. Adipocyte differentiation in 3T3-L1 cells was evaluated after 14 days of incubation with mDA. mDA enhanced adipocyte differentiation in 3T3-L1 cells. For the in vivo evaluation, five-week-old male C57BL/6J mice were fed HFD or normal CE-2 diet (control) for eight weeks. During the experimental period, mice were administered mDA (50 mg/kg, p...
January 12, 2018: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/29334584/in-vitro-and-in-vivo-metabolite-identification-of-a-novel-benzimidazole-compound-zln005-by-lc-ms-ms
#2
Wenchao Sun, Khoa Dinh Nguyen, William L Fitch, Samuel D Banister, Hongxiang Tang, Xiaolan Zhang, Lewis Yu, Edgar G Engleman, Jayakumar Rajadas
RATIONALE: A novel benzimidazole compound ZLN005 was previously identified as a transcriptional activator of peroxisome proliferator-activated receptor γ coactivator 1α (PGC-1α) in certain metabolic tissues. Upregulation of PGC-1α by ZLN005 has been shown to have beneficial effect in a diabetic mouse model and in a coronary artery disease model in vitro. ZLN005 could also have therapeutic potential in neurodegenerative diseases involving down-regulation of PGC-1α. Given the phenotypic efficacy of ZLN005 in several animal models of human disease, its metabolic profile was investigated to guide the development of novel therapeutics using ZLN005 as the lead compound...
January 15, 2018: Rapid Communications in Mass Spectrometry: RCM
https://www.readbyqxmd.com/read/29333383/inhibitory-effects-of-butein-on-adipogenesis-through-upregulation-of-the-nrf2-ho-1-pathway-in-3t3-l1-adipocytes
#3
Jinwoo Yang, Jeehye Sung, Younghwa Kim, Heon Sang Jeong, Junsoo Lee
Butein is reported to have many biological effects, including anti-fibrogenic, anti-cancer, and anti-inflammatory activities. This study investigated the effects of butein on adipocyte differentiation and the Nrf2/heme oxygenase-1 (HO-1) pathway's involvement in its anti adipogenic mechanism. Butein treatment reduced protein expression of key adipogenic transcription factors such as CCAAT-enhancer-binding protein α (C/EBPα) and peroxisome proliferator-activated receptor γ (PPARγ). At a concentration of 5, 10, and 25 μM butein, PPARγ was decreased by 78...
December 2017: Preventive Nutrition and Food Science
https://www.readbyqxmd.com/read/29331649/friend-or-foe-reactive-oxygen-species-production-scavenging-and-signaling-in-plant-response-to-environmental-stresses
#4
Weronika Czarnocka, Stanisław Karpiński
In the natural environment, plants are exposed to a variety of biotic and abiotic stress conditions that trigger rapid changes in the production and scavenging of reactive oxygen species (ROS). The production and scavenging of ROS is compartmentalized, which means that, depending on stimuli type, they can be generated and eliminated in different cellular compartments such as the apoplast, plasma membrane, chloroplasts, mitochondria, peroxisomes, and endoplasmic reticulum. Although the accumulation of ROS is generally harmful to cells, ROS play an important role in signaling pathways that regulate acclimatory and defense responses in plants, such as systemic acquired acclimation (SAA) and systemic acquired resistance (SAR)...
January 10, 2018: Free Radical Biology & Medicine
https://www.readbyqxmd.com/read/29331639/identification-of-the-disinfection-byproducts-of-bisphenol-s-and-the-disrupting-effect-on-peroxisome-proliferator-activated-receptor-gamma-ppar%C3%AE-induced-by-chlorination
#5
Sai Zheng, Jiachen Shi, Jing Zhang, Yi Yang, Jianying Hu, Bing Shao
Bisphenol S (BPS), an alternative product to bisphenol A (BPA), has been the focus of increasing public concern due to its potential endocrine disrupting effect and its adverse effects related to metabolic disorders such as obesity. The detection of its residue in drinking water supply systems suggests that BPS can be chlorinated; however, whether its endocrine disrupting effect can be disrupted by this chlorination remains unclear. In the present study, we identified the byproducts of the reaction of BPS with chlorine and assessed the effect of the main byproducts on peroxisome proliferator-activated receptor gamma (PPARγ)...
January 5, 2018: Water Research
https://www.readbyqxmd.com/read/29331565/saroglitazar-reduces-obesity-and-associated-inflammatory-consequences-in-murine-adipose-tissue
#6
Durgesh Kumar, Umesh Kumar Goand, Sanchita Gupta, Kripa Shankar, Salil Varshney, Sujith Rajan, Ankita Srivastava, Abhishek Gupta, Achchhe Lal Vishwakarma, Anurag Kumar Srivastava, Anil N Gaikwad
Prevailing knowledge links chronic low-grade inflammation in the adipose tissue to obesity and its associated metabolic complications. In this study, we evaluated immunometabolic effects of a recently launched dual peroxisome proliferator-activated receptor (PPAR) α & γ agonist 'Saroglitazar' in a mouse model of diet-induced obesity (DIO). Body composition analysis revealed that saroglitazar treatment promoted hepatic weight gain, while attenuated epididymal white adipose tissue (eWAT) mass in DIO. In the eWAT of saroglitazar treated mice, histological analysis showed reduced adipocyte hypertrophy and matrix deposition (picrosirius red staining)...
January 10, 2018: European Journal of Pharmacology
https://www.readbyqxmd.com/read/29331469/peroxisome-proliferator-activated-receptor-delta-regulates-lipid-droplet-formation-and-transport-in-goat-mammary-epithelial-cells
#7
H B Shi, C H Zhang, Z A Xu, G G Lou, J X Liu, J Luo, J J Loor
Even though recent evidence in goat mammary epithelial cells (GMEC) suggest a role of peroxisome proliferator-activated receptor delta (PPARD) in regulating lipid homeostasis, its role is not fully understood. Our hypothesis was that PPARD regulates lipid transport processes in GMEC and, thus, plays a crucial role in regulating fat formation. The PPARD was overexpressed using an adenovirus system (Ad-PPARD) with recombinant green fluorescent protein (Ad-GFP) as the control. Results revealed that overexpression of PPARD markedly upregulated the mRNA abundance of PPARD...
January 10, 2018: Journal of Dairy Science
https://www.readbyqxmd.com/read/29331412/anti-leukemic-effects-of-ppar%C3%AE-ligands
#8
Somi Ryu, Dae Seong Kim, Myoung Woo Lee, Ji Won Lee, Ki Woong Sung, Hong Hoe Koo, Keon Hee Yoo
The peroxisome proliferator-activated receptor (PPAR) γ, a subtype of PPARs, is a member of the nuclear receptor family. PPARγ and its ligands contribute to various types of diseases including cancer. Given that currently developed therapies against leukemia are not very effective or safe, PPARγ ligands have been shown to be a new class of compounds with the potential to treat hematologic malignancies, particularly leukemia. The capability of PPARγ ligands to induce apoptosis, inhibit proliferation, and promote differentiation of leukemia cells suggests it has significant potential as a drug against leukemia...
January 10, 2018: Cancer Letters
https://www.readbyqxmd.com/read/29331071/hepatic-ppar%C3%AE-function-is-controlled-by-polyubiquitination-and-proteasome-mediated-degradation-via-the-coordinated-actions-of-paqr3-and-huwe1
#9
Zilong Zhao, Daqian Xu, Zheng Wang, Lin Wang, Ruomei Han, Zhenzhen Wang, Lujian Liao, Yan Chen
Peroxisome proliferator-activated receptor α (PPARα) is a key transcriptional factor that regulates hepatic lipid catabolism by stimulating fatty acid oxidation and ketogenesis in an adaptive response to nutrient starvation. However, how PPARα is regulated by post-translational modification is poorly understood. Here, we identified that PAQR3 promotes PPARα ubiquitination through the E3 ubiquitin ligase HUWE1, thereby negatively modulating PPARα functions both in vitro and in vivo. Adenovirus-mediated Paqr3 knockdown and liver-specific deletion of the Paqr3 gene reduced hepatic triglyceride levels while increasing fatty acid oxidation and ketogenesis upon fasting...
January 13, 2018: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
https://www.readbyqxmd.com/read/29331024/combination-therapy-of-lovastatin-and-ampk-activator-improves-mitochondrial-and-peroxisomal-functions-and-clinical-disease-in-eae-model
#10
Inderjit Singh, Devadoss J Samuvel, Seungho Choi, Nishant Saxena, Avtar K Singh, Jeseong Won
Recent studies report that loss and dysfunction of mitochondria and peroxisomes contribute to the myelin and axonal damage in multiple sclerosis (MS). In this study, we investigated the efficacy of lovastatin and AMPK activator (AICAR) combination on the loss and dysfunction of mitochondria and peroxisomes and myelin and axonal damage in the spinal cords, relative to the clinical disease symptoms, using a mouse model of experimental autoimmune encephalomyelitis (EAE, a model for MS). We observed that lovastatin and AICAR treatments individually provided partial protection of mitochondria/peroxisomes, myelin/axons, and thus partial attenuation of clinical disease in EAE mice...
January 13, 2018: Immunology
https://www.readbyqxmd.com/read/29330340/the-adiponectin-receptor-agonist-adiporon-ameliorates-diabetic-nephropathy-in-a-model-of-type-2-diabetes
#11
Yaeni Kim, Ji Hee Lim, Min Young Kim, Eun Nim Kim, Hye Eun Yoon, Seok Joon Shin, Bum Soon Choi, Yong-Soo Kim, Yoon Sik Chang, Cheol Whee Park
Adiponectin exerts renoprotective effects against diabetic nephropathy (DN) by activating the AMP-activated protein kinase (AMPK)/peroxisome proliferative-activated receptor-α (PPARα) pathway through adiponectin receptors (AdipoRs). AdipoRon is an orally active synthetic adiponectin receptor agonist. We investigated the expression of AdipoRs and the associated intracellular pathways in 27 patients with type 2 diabetes and examined the effects of AdipoRon on DN development in male C57BLKS/J db/db mice, glomerular endothelial cells (GECs), and podocytes...
January 12, 2018: Journal of the American Society of Nephrology: JASN
https://www.readbyqxmd.com/read/29330220/regulation-of-drug-metabolism-by-the-interplay-of-inflammatory-signaling-steatosis-and-xeno-sensing-receptors-in-heparg-cells
#12
Norman Tanner, Lisa Kubik, Claudia Luckert, Maria Thomas, Ute Hofmann, Ulrich M Zanger, Linda Bohmert, Alfonso Lampen, Albert Braeuning
Non-alcoholic fatty liver disease (NAFLD), characterized by triglyceride deposition in hepatocytes due to imbalanced lipid homeostasis, is of increasing concern in Western countries, with progression to non-alcoholic steatohepatitis (NASH), liver fibrosis, and cirrhosis. Previous studies suggest a complex, mutual influence of hepatic fat accumulation, NASH-related inflammatory mediators, and drug-sensing receptors regulating xenobiotic metabolism. Here, we investigated the suitability of human HepaRG hepatocarcinoma cells as a model for NAFLD and NASH...
January 12, 2018: Drug Metabolism and Disposition: the Biological Fate of Chemicals
https://www.readbyqxmd.com/read/29329928/cloning-and-characterization-of-%C3%A2-6-%C3%A2-5-fatty-acyl-desaturase-fad-gene-promoter-in-the-marine-teleost-siganus-canaliculatus
#13
Yewei Dong, Jianhong Zhao, Junliang Chen, Shuqi Wang, Yang Liu, Qinghao Zhang, Cuihong You, Óscar Monroig, Douglas R Tocher, Yuanyou Li
The rabbitfish Siganus canaliculatus was the first marine teleost demonstrated to have the ability of biosynthesizing long-chain polyunsaturated fatty acids (LC-PUFA) from C18 PUFA precursors, and all genes encoding the key enzymes for LC-PUFA biosynthesis have been cloned and functionally characterized, which provides us a potential model to study the regulatory mechanisms of LC-PUFA biosynthesis in teleosts. As the primary step to clarify such mechanisms, present research focused on promoter analysis of gene encoding ∆6/∆5 fatty acyl desaturase (Fad), a rate-limiting enzyme catalyzing the first step in the conversion of C18 PUFA to LC-PUFA...
January 9, 2018: Gene
https://www.readbyqxmd.com/read/29329611/early-intervention-with-didang-decoction-delays-macrovascular-lesions-in-diabetic-rats-through-regulating-amp-activated-protein-kinase-signaling-pathway
#14
Dan-Dan Ren, Jing Li, Bai Chang, Chun-Shen Li, Ju-Hong Yang
The study aimed to investigate the intervening role of Didang decoction (DDD) at different times in macrovascular endothelial defense function, focusing on its effects on the AMP-activated protein kinase (AMPK) signaling pathway. The effects of DDD on mitochondrial energy metabolism were also investigated in rat aortic endothelial cells (RAECs). Type 2 diabetes were induced in rats by streptozotocin (STZ) combined with high fat diet. Rats were randomly divided into non-intervention group, metformin group, simvastatin group, and early-, middle-, late-stage DDD groups...
November 2017: Chinese Journal of Natural Medicines
https://www.readbyqxmd.com/read/29329013/antiobesity-effect-of-lactobacillus-reuteri-263-associated-with-energy-metabolism-remodeling-of-white-adipose-tissue-in-high-energy-diet-fed-rats
#15
Li-Han Chen, Yi-Hsing Chen, Kuan-Chen Cheng, Ting-Yi Chien, Ching-Hung Chan, Shu-Ping Tsao, Hui-Yu Huang
Obesity is a serious and costly issue to the medical welfare worldwide. Probiotics have been suggested as one of the candidates to resolve the obesity-associated problems, but how they combat obesity is not fully understood. Herein, we investigated the effects of Lactobacillus reuteri 263 (L. reuteri 263) on antiobesity using four groups of Sprague-Dawley rats (n=10/group), namely, C (normal diet with vehicle treatment), HE [high-energy diet (HED) with vehicle treatment], 1X (HED with 2.1×109 CFU/kg/day of L...
November 16, 2017: Journal of Nutritional Biochemistry
https://www.readbyqxmd.com/read/29325970/the-role-of-adjuvant-immunomodulatory-agents-for-treatment-of-severe-influenza
#16
REVIEW
David S Hui, Nelson Lee, Paul K Chan, John H Beigel
A severe inflammatory immune response with hypercytokinemia occurs in patients hospitalized with severe influenza, such as avian influenza A(H5N1), A(H7N9), and seasonal A(H1N1)pdm09 virus infections. The role of immunomodulatory therapy is unclear as there have been limited published data based on randomized controlled trials (RCTs). Passive immunotherapy such as convalescent plasma and hyperimmune globulin have some studies demonstrating benefit when administered as an adjunctive therapy for severe influenza...
January 8, 2018: Antiviral Research
https://www.readbyqxmd.com/read/29323335/tanshinol-alleviates-impaired-bone-formation-by-inhibiting-adipogenesis-via-klf15-ppar%C3%AE-2-signaling-in-gio-rats
#17
Ya-Jun Yang, Zhu Zhu, Dong-Tao Wang, Xin-le Zhang, Yu-Yu Liu, Wen-Xiu Lai, Yu-Lin Mo, Jin Li, Yan-Long Liang, Zhuo-Qing Hu, Yong-Jie Yu, Liao Cui
Glucocorticoid (GC)-induced osteoporosis (GIO) is characterized by impaired bone formation, which can be alleviated by tanshinol, an aqueous polyphenol isolated from Salvia miltiorrhiza Bunge. In this study we investigated the molecular mechanisms underlying GC-induced modulation of osteogenesis as well as the possibility of using tanshinol to interfere with GIO. Female SD rats aged 4 months were orally administered distilled water (Con), prednisone (GC, 5 mg·kg-1·d-1), GC plus tanshinol (Tan, 16 mg·kg-1·d-1) or GC plus resveratrol (Res, 5 mg·kg-1·d-1) for 14 weeks...
January 11, 2018: Acta Pharmacologica Sinica
https://www.readbyqxmd.com/read/29323298/a-metabolic-function-of-fgfr3-tacc3-gene-fusions-in-cancer
#18
Véronique Frattini, Stefano M Pagnotta, Tala, Jerry J Fan, Marco V Russo, Sang Bae Lee, Luciano Garofano, Jing Zhang, Peiguo Shi, Genevieve Lewis, Heloise Sanson, Vanessa Frederick, Angelica M Castano, Luigi Cerulo, Delphine C M Rolland, Raghvendra Mall, Karima Mokhtari, Kojo S J Elenitoba-Johnson, Marc Sanson, Xi Huang, Michele Ceccarelli, Anna Lasorella, Antonio Iavarone
Chromosomal translocations that generate in-frame oncogenic gene fusions are notable examples of the success of targeted cancer therapies. We have previously described gene fusions of FGFR3-TACC3 (F3-T3) in 3% of human glioblastoma cases. Subsequent studies have reported similar frequencies of F3-T3 in many other cancers, indicating that F3-T3 is a commonly occuring fusion across all tumour types. F3-T3 fusions are potent oncogenes that confer sensitivity to FGFR inhibitors, but the downstream oncogenic signalling pathways remain unknown...
January 11, 2018: Nature
https://www.readbyqxmd.com/read/29323103/oridonin-exerts-anticancer-effect-on-osteosarcoma-by-activating-ppar-%C3%AE-and-inhibiting-nrf2-pathway
#19
Ying Lu, Yang Sun, Jianwei Zhu, Lisha Yu, Xiubo Jiang, Jie Zhang, Xiaochen Dong, Bo Ma, Qi Zhang
Osteosarcoma is the most common high-grade human primary malignant bone sarcoma with lower survival in the past decades. Oridonin, a bioactive diterpenoid isolated from Rabdosia rubescens, has been proved to possess potent anti-cancer effects. However, its potential mechanism still remains not fully clear nowadays. In this study, we investigated the anticancer effect of oridonin on human osteosarcoma and illuminated the underlying mechanisms. In vitro, oridonin inhibited the cell viability of various osteosarcoma cells...
January 11, 2018: Cell Death & Disease
https://www.readbyqxmd.com/read/29321595/microrna-7-mediates-cross-talk-between-metabolic-signaling-pathways-in-the-liver
#20
Ragunath Singaravelu, Curtis Quan, Megan H Powdrill, Tyler A Shaw, Prashanth Srinivasan, Rodney K Lyn, Rhea C Alonzi, Daniel M Jones, Roxana Filip, Rodney S Russell, John P Pezacki
MicroRNAs (miRNAs) have emerged as critical regulators of cellular metabolism. To characterise miRNAs crucial to the maintenance of hepatic lipid homeostasis, we examined the overlap between the miRNA signature associated with inhibition of peroxisome proliferator activated receptor-α (PPAR-α) signaling, a pathway regulating fatty acid metabolism, and the miRNA profile associated with 25-hydroxycholesterol treatment, an oxysterol regulator of sterol regulatory element binding protein (SREBP) and liver X receptor (LXR) signaling...
January 10, 2018: Scientific Reports
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