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Xavier Palomer, Emma Barroso, Javier Pizarro-Delgado, Lucía Peña, Gaia Botteri, Mohammad Zarei, David Aguilar, Marta Montori-Grau, Manuel Vázquez-Carrera
Research in recent years on peroxisome proliferator-activated receptor (PPAR)β/δ indicates that it plays a key role in the maintenance of energy homeostasis, both at the cellular level and within the organism as a whole. PPARβ/δ activation might help prevent the development of metabolic disorders, including obesity, dyslipidaemia, type 2 diabetes mellitus and non-alcoholic fatty liver disease. This review highlights research findings on the PPARβ/δ regulation of energy metabolism and the development of diseases related to altered cellular and body metabolism...
March 20, 2018: International Journal of Molecular Sciences
Yan Wang, Shun Qiao, De-Wu Han, Xin-Ren Rong, Yi-Xiao Wang, Jing-Jing Xue, Jing Yang
BACKGROUND: Diabetes mellitus, metabolic syndrome, and other obesity-related diseases are characterized by insulin resistance (IR) as a common pathophysiological change and are closely related to cardiovascular disease, which seriously threaten human health. Telmisartan belongs to a group of drugs called angiotensin II receptor antagonists (ARBs) and it can partially activate peroxisome proliferator-activated receptors. Animal experiments have confirmed that telmisartan can regulate glucose and lipid metabolism, and improve IR...
March 16, 2018: American Journal of Therapeutics
A Ulate-Campos, J Petanas-Argemi, M Rebollo-Polo, C Jou, C Sierra, J Armstrong, M C Fons-Estupina
INTRODUCTION: X-linked adrenoleukodystrophy (X-ALD) is the most frequent peroxisomal disease. It is due to a mutation in the ABCD1 gene. The loss of functioning of ABCD1 triggers ineffective beta oxidation of very long-chain fatty acids, which gives rise to an accumulation of these fatty acids. The typical alteration revealed in neuroimaging scans in the cerebral form is symmetrical periventricular demyelination with posterior location. CASE REPORT: We report the case of a 10-year-old boy with right spastic hemiparesis and subacute cognitive impairment...
April 1, 2018: Revista de Neurologia
Tomohiro Kimura, Atsuko Kimura, Mindong Ren, Bob Berno, Yang Xu, Michael Schlame, Richard M Epand
Tafazzin is the mitochondrial enzyme that catalyzes transacylation between a phospholipid and a lysophospholipid in remodeling. Mutations in tafazzin cause Barth syndrome, a potentially life-threatening disease with the major symptom of cardiomyopathy. In the tafazzin-deficient heart, cardiolipin (CL) acyl chains become abnormally heterogeneous unlike those in the normal heart with a single dominant linoleoyl species; tetralinoleoyl CL. In addition, the amount of CL decreases and monolysocardiolipin (MLCL) accumulates...
March 20, 2018: Biochemistry
S M Plummer, J Wright, R A Currie
An increased incidence of liver tumours in the long term rodent bioassay is not an uncommon finding, invariably as a result of a non-genotoxic mode of action. Non-genotoxic liver carcinogenesis has been found to involve activation of certain nuclear hormone receptors (NHR) including the constitutive androstane receptor (CAR), peroxisome proliferator activated receptor alpha (PPARalpha) and arylhydrocarbon receptor (AHR) and more recently the induction of specific microRNAs (miRs), has also been demonstrated following CAR activation in studies up to 90 days (Koufaris et al...
2018: Toxicology Reports
Hui Cao, Senlin Li, Rui Xie, Na Xu, Ying Qian, Hongdan Chen, Qinyu Hu, Yihong Quan, Zhihong Yu, Junjun Liu, Ming Xiang
Dangguiliuhuang decoction (DGLHD) has been demonstrated to be effective in treating inflammatory, hepatic steatosis, and insulin resistance. In the study, we tried to elucidate the pharmacological efficacy and mechanism of DGLHD against liver fibrosis and predicate potential active ingredients and targets via network analysis and experimental validation. In the formula, we totally discovered 76 potential active ingredients like baicalein, berberine, and wogonin, and 286 corresponding targets including PTGS (prostaglandin-endoperoxide synthase) 2, PPAR (peroxisome proliferator-activated receptors) -γ, and NF-κB (nuclear factor-κB)...
2018: Frontiers in Pharmacology
Naiqian Zhao, Xiaoyan Li, Ying Feng, Jinxiang Han, Ziling Feng, Xifeng Li, Yanfang Wen
Excessive triglyceride accumulation in hepatocytes is the hallmark of obesity-associated nonalcoholic fatty liver disease (NAFLD). Elevated levels of the saturated free fatty acid palmitate in obesity are a major contributor to excessive hepatic lipid accumulation. The nuclear orphan receptor Nur77 is a transcriptional regulator and a lipotoxicity sensor. Using human HepG2 hepatoma cells, this study aimed to investigate the functional role of Nur77 in palmitate-induced hepatic steatosis. The results revealed that palmitate significantly induced lipid accumulation and suppressed lipolysis in hepatocytes...
March 19, 2018: Scientific Reports
Tatsuhiro Ayabe, Rena Ohya, Keiji Kondo, Yasuhisa Ano
Dementia and cognitive decline have become worldwide public health problems, and it was recently reported that life-style related diseases and obesity are key risk factors in dementia. Iso-α-acids, hop-derived bitter components of beer, have been reported to have various physiological functions via activation of peroxisome proliferator-activated receptor γ. In this report, we demonstrated that daily intake of iso-α-acids suppresses inflammations in the hippocampus and improves cognitive decline induced by high fat diet (HFD)...
March 19, 2018: Scientific Reports
Kim L Gonzalez, Sarah E Ratzel, Kendall H Burks, Charles H Danan, Jeanne M Wages, Bethany K Zolman, Bonnie Bartel
Peroxisomes are eukaryotic organelles critical for plant and human development because they house essential metabolic functions, such as fatty acid β-oxidation. The interacting ATPases PEX1 and PEX6 contribute to peroxisome function by recycling PEX5, a cytosolic receptor needed to import proteins targeted to the peroxisomal matrix. Arabidopsis pex6 mutants exhibit low PEX5 levels and defects in peroxisomal matrix protein import, oil body utilization, peroxisomal metabolism, and seedling growth. These defects are hypothesized to stem from impaired PEX5 retrotranslocation leading to PEX5 polyubiquitination and consequent degradation of PEX5 via the proteasome or of the entire organelle via autophagy...
March 19, 2018: Proceedings of the National Academy of Sciences of the United States of America
Ireen Vieweg, Eider Bilbao, James P Meador, Ibon Cancio, Morgan Lizabeth Bender, Miren P Cajaraville, Jasmine Nahrgang
Polar cod is an abundant Arctic key species, inhabiting an ecosystem that is subjected to rapid climate change and increased petroleum related activities. Few studies have investigated biological effects of crude oil on lipid metabolism in this species, despite lipids being a crucial compound for Arctic species to adapt to the high seasonality in food abundance in their habitat. This study examines the effects of dietary crude oil exposure on transcription levels of genes related to lipid metabolism (peroxisome proliferator-activated receptors [ppar-α, ppar-γ], retinoic X receptor [rxr-β], palmitoyl-CoA oxidase [aox1], cytochrome P4507A1 [cyp7α1]), reproduction (vitellogenin [vtg-β], gonad aromatase [cyp19a1]) and biotransformation (cytochrome P4501A1 [cyp1a1], aryl hydrocarbon receptor [ahr2])...
March 16, 2018: Comparative Biochemistry and Physiology. Toxicology & Pharmacology: CBP
Kenji Yamada, Hideaki Shiraishi, Eishin Oki, Mika Ishige, Toshiyuki Fukao, Yusuke Hamada, Norio Sakai, Fumihiro Ochi, Asami Watanabe, Sanae Kawakami, Kazuyo Kuzume, Kenji Watanabe, Koji Sameshima, Kiyotaka Nakamagoe, Akira Tamaoka, Naoko Asahina, Saki Yokoshiki, Takashi Miyakoshi, Kota Ono, Koji Oba, Toshiyuki Isoe, Hiroshi Hayashi, Seiji Yamaguchi, Norihiro Sato
Introduction: Fatty acid oxidation disorders (FAODs) are rare diseases caused by defects in mitochondrial fatty acid oxidation (FAO) enzymes. While the efficacy of bezafibrate, a peroxisome proliferator-activated receptor agonist, on the in vitro FAO capacity has been reported, the in vivo efficacy remains controversial. Therefore, we conducted a clinical trial of bezafibrate in Japanese patients with FAODs. Materials and methods: This trial was an open-label, non-randomized, and multicenter study of bezafibrate treatment in 6 patients with very long-chain acyl-CoA dehydrogenase (VLCAD) deficiency and 2 patients with carnitine palmitoyltransferase-II (CPT-2) deficiency (median age, 8...
June 2018: Molecular Genetics and Metabolism Reports
Dan Wei, Ningning Zheng, Lanyan Zheng, Leting Wang, Liang Song, Luning Sun
Background: Metabolic syndrome (MS) is a global epidemic that has great socioeconomic and public health implications. This study reports observed effects of the Shexiang Baoxin Pill (SBP) in a rat model of MS and explores its underlying mechanisms of action. Methods: A diet-induced rat model of MS was established according to accepted methods, and the rats were randomly divided into two groups: a control group (0.9% NaCl, 100 mg/kg• d) and a SBP-treated group (SBP, 100 mg/kg• d). Systolic blood pressures, fasting blood glucose (FBS) levels, triglyceride (TG) levels, high-density lipoprotein cholesterol (HDL-C) levels, body weights, and abdominal perimeters were dynamically monitored and analyzed...
2018: Frontiers in Pharmacology
Sarah Cohen
Long considered inert fat storage depots, it has become clear that lipid droplets (LDs) are bona fide organelles. Like other organelles, they have a characteristic complement of proteins and lipids, and undergo a life cycle that includes biogenesis, maturation, interactions with other organelles, and turnover. I will discuss recent insights into mechanisms governing the life cycle of LDs, and compare and contrast the LD life cycle with that of other metabolic organelles such as mitochondria, peroxisomes, and autophagosomes, highlighting open questions in the field...
2018: International Review of Cell and Molecular Biology
P Kurowska, J Chmielinska, A Ptak, A Rak
The peroxisome proliferator-activated receptors (PPARs) are a family of transcription factors which are involved in the regulation of different processes such as lipid metabolism, inflammation, angiogenesis, tissue remodeling and steroidogenesis. Our previous data described the ovarian expression of PPAR isoforms (-α, -γ and -β), and the increase of PPAR-α and PPAR-γ in porcine ovarian follicles during the estrous cycle. The current studies were undertaken to test the hypothesis that gonadotropin and steroid hormones can regulate the expression of PPAR isoforms in the ovary...
December 2017: Journal of Physiology and Pharmacology: An Official Journal of the Polish Physiological Society
Martyna Pakuła, Justyna Mikuła-Pietrasik, Łukasz Stryczyński, Paweł Uruski, Sebastian Szubert, Rafał Moszyński, Dariusz Szpurek, Stefan Sajdak, Andrzej Tykarski, Krzysztof Książek
Very little is known about the mechanisms by which malignant ascites modulates the cancer-promoting activity of human peritoneal mesothelial cells (HPMCs). Because malignant ascites induces pro-tumoral senescence in HPMCs, here we examined if this effect could be driven by oxidative stress. The study showed that malignant ascites generated by serous ovarian tumors induced oxidative damage to the DNA (γH2A.X, 53BP1, 8-hydroxy-2'-deoxyguanosine) and lipids (8-isoprostane) in HPMCs as well as increased the production of mitochondrial superoxides and cellular peroxides in these cells...
March 14, 2018: International Journal of Biochemistry & Cell Biology
Jian Bi, Kang Sun, Hao Wu, Xiuli Chen, Haiying Tang, Jingwei Mao
Peroxisome proliferator-activated receptor gamma (PPARγ) participates in the process of insulin resistance (IR), a crucial pathophysiology in non-alcoholic fatty liver disease (NAFLD). Meanwhile, suppressor of cytokine signaling3 (SOCS3) also regulates IR in NAFLD. Both PPARγ and SOCS3 play a role in NAFLD through regulating IR, while it is unclear whether these two proteins interact to regulate hepatic steatosis. PPARγ, SOCS3 and its associated JAK2/STAT3 pathway were analyzed using Kuppfer cells (KCs) treatment with LPS and BRL-3A cells treatment with palmitic acid, KC-conditioned medium (KCCM), PPARγ agonist rosiglitazone (ROZ) or JAK2 inhibitor AG490 to demonstrate the role of PPARγ and SOCS3 in hepatocytes steatosis...
March 14, 2018: Biochemical and Biophysical Research Communications
Jinpeng Li, Megumi Kanasaki, Ling Xu, Munehiro Kitada, Kenji Nagao, Yusuke Adachi, Hiroko Jinzu, Yasushi Noguchi, Miyuki Kohno, Keizo Kanasaki, Daisuke Koya
Muscle biology is important topic in diabetes research. We have reported that a diet with ketogenic amino acids rich replacement (KAAR) ameliorated high-fat diet (HFD)-induced hepatosteatosis via activation of the autophagy system. Here, we found that a KAAR ameliorated the mitochondrial morphological alterations and associated mitochondrial dysfunction induced by an HFD through induction of the AKT/4EBP1 and autophagy signaling pathways in both fast and slow muscles. The mice were fed with a standard HFD (30% fat in food) or an HFD with KAAR (HFDKAAR )...
March 14, 2018: Biochimica et Biophysica Acta
C P Hawkes, S Mostoufi-Moab
The relationship between fat, bone and systemic metabolism is a growing area of scientific interest. Marrow adipose tissue is a well-recognized component of the bone marrow milieu and is metabolically distinct from current established subtypes of adipose tissue. Despite recent advances, the functional significance of marrow adipose tissue is still not clearly delineated. Bone and fat cells share a common mesenchymal stem cell (MSC) within the bone marrow, and hormones and transcription factors such as growth hormone, leptin, and peroxisomal proliferator-activated receptor γ influence MSC differentiation into osteoblasts or adipocytes...
March 14, 2018: Bone
Enrico Gugliandolo, Roberta Fusco, Giovanna Ginestra, Ramona D'amico, Carlo Bisignano, Giuseppina Mandalari, Salvatore Cuzzocrea, Rosanna Di Paola
BACKGROUND: Colonization with Pseudomonas aeruginosa (PA), the most common pathogen isolated mainly in patients with cystic fibrosis, is particularly difficult to eradicate and is associated with acceleration of decline in lung function and with poorer prognosis. PA LPS is recognized by toll like receptors 4 (TLR4) and has been shown to induce lung inflammation in vivo. In addition, regulation of this process is essential for proper pathogen clearance and to prevent excessive inflammatory response resulting in tissue damage...
March 15, 2018: Shock
Tian-Xing Chen, Xiao-Ying Cheng, Yun Wang, Wu Yin
Toosendanin (TSN), a triterpenoid extracted from Melia toosendan, has been reported to possess anti-oxidant, anti-inflammatory, anti-allergic, and anti-arthritic activities. However, its anti-adipogenic effect remains unknown. Here, we found that TSN dose-dependently attenuated lipid accumulation in preadipocytes 3T3-L1 as evidenced by Oil Red O staining. TSN also significantly downregulated mRNA and protein levels of adipocytokines (adiponectin and leptin), CCAAT/enhancer binding proteins α (C/EBP-α), peroxisome proliferator-activated receptor γ (PPAR-γ), fatty acid synthase, and acetyl-CoA carboxylase in adipocytes...
March 15, 2018: Scientific Reports
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