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Xibi Fang, Zhihui Zhao, Ping Jiang, Haibin Yu, Hang Xiao, Runjun Yang
Hormone-sensitive lipase (HSL) is an intracellular neutral lipase capable of hydrolysing a variety of esters and is considered to be a candidate gene affecting fat deposition traits. Gene expression profiles of HSL were analysed in various adipose tissues of cattle, and the effect of HSL on lipid metabolism genes was analysed by a PCR array. Novel polymorphisms were identified within the HSL regulatory domain by sequencing, and the relationship between HSL variants and fat deposition traits was analysed. HSL mRNA was highly expressed in the subcutaneous and visceral fat of cattle...
May 6, 2017: Meat Science
Macarena Pozo, Rosalía Rodríguez-Rodríguez, Sara Ramírez, Patricia Seoane-Collazo, Miguel López, Dolors Serra, Laura Herrero, Núria Casals
Carnitine palmitoyltransferase 1C (CPT1C), a brain-specific protein localized in the endoplasmic reticulum of neurons, is expressed in almost all brain regions. Based on global knockout (KO) models, CPT1C has demonstrated relevance in hippocampus-dependent spatial learning as well as in hypothalamic regulation of energy balance. Specifically, it has been shown that CPT1C is protective against high-fat diet-induced obesity (DIO), and that CPT1C KO mice show reduced peripheral fatty acid oxidation (FAO) both during fasting and DIO...
May 3, 2017: Endocrinology
Yixin Chen, Yongtao Wang, Yaoyao Huang, Hang Zeng, Bingfang Hu, Lihuan Guan, Huizhen Zhang, Ai-Ming Yu, Caroline H Johnson, Frank J Gonzalez, Min Huang, Huichang Bi
Carnitine palmitoyltransferase 1C (CPT1C), an enzyme located in the outer mitochondria membrane, has a crucial role in fatty acid transport and oxidation. It is also involved in cell proliferation and is a potential driver for cancer cell senescence. However, its upstream regulatory mechanism is unknown. Peroxisome proliferator activated receptor α (PPARα) is a ligand-activated transcription factor that regulates lipid metabolism and tumor progression. The current study aimed to elucidate whether and how PPARα regulates CPT1C and then affects cancer cell proliferation and senescence...
April 1, 2017: Carcinogenesis
Marcel Blumensatt, Pia Fahlbusch, Rebecca Hilgers, Marlies Bekaert, Daniella Herzfeld de Wiza, Payam Akhyari, Johannes B Ruige, D Margriet Ouwens
Secretory products from epicardial adipose tissue (EAT) from patients with type 2 diabetes (T2D) impair cardiomyocyte function. These changes associate with alterations in miRNA expression, including the induction of miR-208a. Recent studies suggest that activation of the cardiac-specific renin-angiotensin system (RAS) may affect cardiac energy metabolism via induction of miR-208a. This study investigated whether cardiomyocyte dysfunction induced by conditioned media (CM) from EAT-T2D involves activation of the RAS/miR-208a pathway...
January 2017: Basic Research in Cardiology
Won Tae Kim, Seok Joong Yun, Chunri Yan, Pildu Jeong, Ye Hwan Kim, Il Seok Lee, Ho Won Kang, Sunghyouk Park, Sung Kwon Moon, Yung Hyun Choi, Young Deuk Choi, Isaac Yi Kim, Jayoung Kim, Wun Jae Kim
PURPOSE: Our previous high-performance liquid chromatography-quadrupole time-of-flight mass spectrometry study identified bladder cancer (BCA)-specific urine metabolites, including carnitine, acylcarnitines, and melatonin. The objective of the current study was to determine which metabolic pathways are perturbed in BCA, based on our previously identified urinary metabolome. MATERIALS AND METHODS: A total of 135 primary BCA samples and 26 control tissue samples from healthy volunteers were analyzed...
July 2016: Yonsei Medical Journal
Johanneke E Oosterman, Denise D Belsham
Specific neurons in the hypothalamus are regulated by peripheral hormones and nutrients to maintain proper metabolic control. It is unclear if nutrients can directly control clock gene expression. We have therefore utilized the immortalized, hypothalamic cell line mHypoE-37, which exhibits robust circadian rhythms of core clock genes. mHypoE-37 neurons were exposed to 0.5 or 5.5 mM glucose, comparable to physiological levels in the brain. Per2 and Bmal1 mRNAs were assessed every 3 hours over 36 hours. Incubation with 5...
2016: PloS One
Aritro Nath, Christina Chan
Reprogramming of cellular metabolism is a hallmark feature of cancer cells. While a distinct set of processes drive metastasis when compared to tumorigenesis, it is yet unclear if genetic alterations in metabolic pathways are associated with metastatic progression of human cancers. Here, we analyzed the mutation, copy number variation and gene expression patterns of a literature-derived model of metabolic genes associated with glycolysis (Warburg effect), fatty acid metabolism (lipogenesis, oxidation, lipolysis, esterification) and fatty acid uptake in >9000 primary or metastatic tumor samples from the multi-cancer TCGA datasets...
January 4, 2016: Scientific Reports
Núria Casals, Victor Zammit, Laura Herrero, Rut Fadó, Rosalía Rodríguez-Rodríguez, Dolors Serra
Carnitine palmitoyltransferase 1 (CPT1) C was the last member of the CPT1 family of genes to be discovered. CPT1A and CPT1B were identified as the gate-keeper enzymes for the entry of long-chain fatty acids (as carnitine esters) into mitochondria and their further oxidation, and they show differences in their kinetics and tissue expression. Although CPT1C exhibits high sequence similarity to CPT1A and CPT1B, it is specifically expressed in neurons (a cell-type that does not use fatty acids as fuel to any major extent), it is localized in the endoplasmic reticulum of cells, and it has minimal CPT1 catalytic activity with l-carnitine and acyl-CoA esters...
January 2016: Progress in Lipid Research
Haruka Shinohara, Minami Kumazaki, Yosuke Minami, Yuko Ito, Nobuhiko Sugito, Yuki Kuranaga, Kohei Taniguchi, Nami Yamada, Yoshinori Otsuki, Tomoki Naoe, Yukihiro Akao
In Ph-positive leukemia, imatinib brought marked clinical improvement; however, further improvement is needed to prevent relapse. Cancer cells efficiently use limited energy sources, and drugs targeting cellular metabolism improve the efficacy of therapy. In this study, we characterized the effects of novel anti-cancer fatty-acid derivative AIC-47 and imatinib, focusing on cancer-specific energy metabolism in chronic myeloid leukemia cells. AIC-47 and imatinib in combination exhibited a significant synergic cytotoxicity...
February 1, 2016: Cancer Letters
Ali Yasrebi, Anna Hsieh, Kyle J Mamounis, Elizabeth A Krumm, Jennifer A Yang, Jason Magby, Pu Hu, Troy A Roepke
Ghrelin's receptor, growth hormone secretagogue receptor (GHSR), is highly expressed in the arcuate nucleus (ARC) and in neuropeptide Y (NPY) neurons. Fasting, diet-induced obesity (DIO), and 17β-estradiol (E2) influence ARC Ghsr expression. It is unknown if these effects occur in NPY neurons. Therefore, we examined the expression of Npy, Agrp, and GHSR signaling pathway genes after fasting, DIO, and E2 replacement in ARC and pools of NPY neurons. In males, fasting increased ARC Ghsr and NPY Foxo1 but decreased NPY Ucp2...
February 15, 2016: Molecular and Cellular Endocrinology
Mónica Lopes-Marques, Inês L S Delgado, Raquel Ruivo, Yan Torres, Sri Bhashyam Sainath, Eduardo Rocha, Isabel Cunha, Miguel M Santos, L Filipe C Castro
The Carnitine palmitoyltransferase I (Cpt1) gene family plays a crucial role in energy homeostasis since it is required for the occurrence of fatty acid β-oxidation in the mitochondria. The exact gene repertoire in different vertebrate lineages is variable. Presently, four genes are documented: Cpt1a, also known as Cpt1a1, Cpt1a2; Cpt1b and Cpt1c. The later is considered a mammalian innovation resulting from a gene duplication event in the ancestor of mammals, after the divergence of sauropsids. In contrast, Cpt1a2 has been found exclusively in teleosts...
2015: PloS One
Rut Fadó, David Soto, Alfredo J Miñano-Molina, Macarena Pozo, Patricia Carrasco, Natalia Yefimenko, José Rodríguez-Álvarez, Núria Casals
The regulation of AMPA-type receptor (AMPAR) abundance in the postsynaptic membrane is an important mechanism involved in learning and memory formation. Recent data suggest that one of the constituents of the AMPAR complex is carnitine palmitoyltransferase 1C (CPT1C), a brain-specific isoform located in the endoplasmic reticulum of neurons. Previous results had demonstrated that CPT1C deficiency disrupted spine maturation in hippocampal neurons and impaired spatial learning, but the role of CPT1C in AMPAR physiology had remained mostly unknown...
October 16, 2015: Journal of Biological Chemistry
Ashraf Virmani, Luigi Pinto, Otto Bauermann, Saf Zerelli, Andreas Diedenhofen, Zbigniew K Binienda, Syed F Ali, Feike R van der Leij
The carnitine palmitoyl transferase (CPT) system is a multiprotein complex with catalytic activity localized within a core represented by CPT1 and CPT2 in the outer and inner membrane of the mitochondria, respectively. Two proteins, the acyl-CoA synthase and a translocase also form part of this system. This system is crucial for the mitochondrial beta-oxidation of long-chain fatty acids. CPT1 has two well-known isoforms, CPT1a and CPT1b. CPT1a is the hepatic isoform and CPT1b is typically muscular; both are normally utilized by the organism for metabolic processes throughout the body...
October 2015: Molecular Neurobiology
Sirui Zhou, Lan Xiong, Pingxing Xie, Amirthagowri Ambalavanan, Cynthia V Bourassa, Alexandre Dionne-Laporte, Dan Spiegelman, Maude Turcotte Gauthier, Edouard Henrion, Ousmane Diallo, Patrick A Dion, Guy A Rouleau
BACKGROUND: Nunavik Inuit (northern Quebec, Canada) reside along the arctic coastline where for generations their daily energy intake has mainly been derived from animal fat. Given this particular diet it has been hypothesized that natural selection would lead to population specific allele frequency differences and unique variants in genes related to fatty acid metabolism. A group of genes, namely CPT1A, CPT1B, CPT1C, CPT2, CRAT and CROT, encode for three carnitine acyltransferases that are important for the oxidation of fatty acids, a critical step in their metabolism...
2015: PloS One
Yong Wu, Marianna Sarkissyan, Eva Mcghee, Sangkyu Lee, Jaydutt V Vadgama
Targeting glycolysis for cancer treatment has been investigated as a therapeutic method but has not offered a feasible chemotherapeutic strategy. Our aim was to examine whether AMP-activated protein kinase (AMPK), a conditional oncogene, rescues the energetic stress and cytotoxicity induced by 2-deoxyglucose (2-DG), a glycolytic inhibitor, and the related mechanisms. Luciferin/luciferase adenosine triphosphate (ATP) determination, Western analysis, qRT-PCR analyses, MTT growth assay, clonogenic assay, and statistical analysis were performed in this study...
June 2015: Breast Cancer Research and Treatment
Carlo Rinaldi, Thomas Schmidt, Alan J Situ, Janel O Johnson, Philip R Lee, Ke-Lian Chen, Laura C Bott, Rut Fadó, George H Harmison, Sara Parodi, Christopher Grunseich, Benoît Renvoisé, Leslie G Biesecker, Giuseppe De Michele, Filippo M Santorelli, Alessandro Filla, Giovanni Stevanin, Alexandra Dürr, Alexis Brice, Núria Casals, Bryan J Traynor, Craig Blackstone, Tobias S Ulmer, Kenneth H Fischbeck
IMPORTANCE: The family of genes implicated in hereditary spastic paraplegias (HSPs) is quickly expanding, mostly owing to the widespread availability of next-generation DNA sequencing methods. Nevertheless, a genetic diagnosis remains unavailable for many patients. OBJECTIVE: To identify the genetic cause for a novel form of pure autosomal dominant HSP. DESIGN, SETTING, AND PARTICIPANTS: We examined and followed up with a family presenting to a tertiary referral center for evaluation of HSP for a decade until August 2014...
May 2015: JAMA Neurology
Esther Gratacòs-Batlle, Natalia Yefimenko, Helena Cascos-García, David Soto
AMPARs mediate the vast majority of fast excitatory synaptic transmission in the brain and their biophysical and trafficking properties depend on their subunit composition and on several posttranscriptional and posttranslational modifications. Additionally, in the brain AMPARs associate with auxiliary subunits, which modify the properties of the receptors. Despite the abundance of AMPAR partners, recent proteomic studies have revealed even more interacting proteins that could potentially be involved in AMPAR regulation...
2014: Frontiers in Cellular Neuroscience
Tomihiro Wakamiya, Satoshi O Suzuki, Hideomi Hamasaki, Hiroyuki Honda, Masahiro Mizoguchi, Koji Yoshimoto, Toru Iwaki
Fatty acid synthase (FASN) and carnitine palmitoyltransferase 1C (CPT1C), a brain-specific isoform of the CPT1 family, are upregulated in certain types of cancers, including gliomas. Acetyl-CoA carboxylase (ACC) catalyzes the carboxylation of acetyl-CoA to malonyl-CoA, the rate-limiting step in fatty acid synthesis, and its phosphorylated form inhibits lipid synthesis. We examined the expression and subcellular localization of these fatty acid metabolism-related molecules in human gliomas. We performed immunostaining of two glioma cell lines (U373MG and U87MG) and 41 surgical specimens of diffuse gliomas with various histological grades (21 with the isocitrate dehydrogenase 1(IDH1) R132H mutation and 20 without the mutation)...
October 2014: Neuropathology: Official Journal of the Japanese Society of Neuropathology
Alessandra Cirillo, Anna Di Salle, Orsolina Petillo, Mariarosa A B Melone, Giovanna Grimaldi, Alfredo Bellotti, Giovanni Torelli, Maria Serena De' Santi, Giovanna Cantatore, Alfredo Marinelli, Umberto Galderisi, Gianfranco Peluso
The diagnosis of glioblastoma is still based on tumor histology, but emerging molecular diagnosis is becoming an important part of glioblastoma classification. Besides the well-known cell cycle-related circuitries that are associated with glioblastoma onset and development, new insights may be derived by looking at pathways involved in regulation of epigenetic phenomena and cellular metabolism, which may both be highly deregulated in cancer cells. We evaluated if in glioblastoma patients the high grade of malignancy could be associated with aberrant expression of some genes involved in regulation of epigenetic phenomena and lipid metabolism...
June 1, 2014: Cancer Biology & Therapy
Osamu Maeda, Takafumi Ando, Naoki Ohmiya, Kazuhiro Ishiguro, Osamu Watanabe, Ryoji Miyahara, Yoko Hibi, Taku Nagai, Kiyofumi Yamada, Hidemi Goto
The mechanisms of drug resistance in cancer are not fully elucidated. To study the drug resistance of gastric cancer, we analyzed gene expression and DNA methylation profiles of 5-fluorouracil (5-FU)- and cisplatin (CDDP)-resistant gastric cancer cells and biopsy specimens. Drug-resistant gastric cancer cells were established with culture for >10 months in a medium containing 5-FU or CDDP. Endoscopic biopsy specimens were obtained from gastric cancer patients who underwent chemotherapy with oral fluoropyrimidine S-1 and CDDP...
April 2014: Oncology Reports
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