Release of ischemia in paced rat Langendorff hearts by supply of L-carnitine: Role of endogenous long-chain acylcarnitine

1996 ◽  
Vol 156 (1) ◽  
Author(s):  
W.C. Hulsmann ◽  
A. Peschechera ◽  
F. Serafini ◽  
L.E. Ferrari
Keyword(s):  
Langendorff Hearts ◽  
Long Chain

scholarly journals Evidence for an essential role of long chain acyl-CoA synthetase in animal cell proliferation

1991 ◽  
Vol 266 (7) ◽  
pp. 4214-4219
Author(s):  
H Tomoda ◽  
K Igarashi ◽  
J C Cyong ◽  
S Omura
Keyword(s):  
Cell Proliferation ◽  
Essential Role ◽  
Animal Cell ◽  
Chain Acyl ◽  
Long Chain

scholarly journals FSMP-15. EVALUATING THE ROLE OF LONG-CHAIN FATTY ACID METABOLISM IN PROMOTING GLIOBLASTOMA GROWTH

2021 ◽  
Vol 3 (Supplement_1) ◽  
pp. i19-i19
Author(s):  
Divya Ravi ◽  
Carmen del Genio ◽  
Haider Ghiasuddin ◽  
Arti Gaur
Keyword(s):  
Fatty Acids ◽  
Fatty Acid ◽  
Survival Rate ◽  
Tumor Progression ◽  
Acid Synthesis ◽  
Normal Brain ◽  
Acid Uptake ◽  
Exogenous Fatty Acid ◽  
Long Chain

Abstract Glioblastomas (GBM) or Stage IV gliomas, are the most aggressive of primary brain tumors and are associated with high mortality and morbidity. Patients diagnosed with this lethal cancer have a dismal survival rate of 14 months and a 5-year survival rate of 5.6% despite a multimodal therapeutic approach, including surgery, radiation therapy, and chemotherapy. Aberrant lipid metabolism, particularly abnormally active de novo fatty acid synthesis, is recognized to have a key role in tumor progression and chemoresistance in cancers. Previous studies have reported a high expression of fatty acid synthase (FASN) in patient tumors, leading to multiple investigations of FASN inhibition as a treatment strategy. However, none of these have developed as efficacious therapies. Furthermore, when we profiled FASN expression using The Cancer Genome Atlas (TCGA) we determined that high FASN expression in GBM patients did not confer a worse prognosis (HR: 1.06; p-value: 0.51) and was not overexpressed in GBM tumors compared to normal brain. Therefore, we need to reexamine the role of exogenous fatty acid uptake over de novofatty acid synthesis as a potential mechanism for tumor progression. Our study aims to measure and compare fatty acid oxidation (FAO) of endogenous and exogenous fatty acids between GBM patients and healthy controls. Using TCGA, we have identified the overexpression of multiple enzymes involved in mediating the transfer and activation of long-chain fatty acids (LCFA) in GBM tumors compared to normal brain tissue. We are currently conducting metabolic flux studies to (1) assess the biokinetics of LCFA degradation and (2) establish exogenous versus endogenous LCFA preferences between patient-derived primary GBM cells and healthy glial and immune cells during steady state and glucose-deprivation.

scholarly journals Specialized Pro-Resolving Lipid Mediators in Neonatal Cardiovascular Physiology and Diseases

Antioxidants ◽  
2021 ◽  
Vol 10 (6) ◽  
pp. 933
Author(s):  
Andrea Gila-Diaz ◽  
Gloria Herranz Carrillo ◽  
Pratibha Singh ◽  
David Ramiro-Cortijo
Keyword(s):  
Tissue Repair ◽  
Cardiovascular Health ◽  
Critical Role ◽  
Potential Effect ◽  
Lipid Mediators ◽  
Physiological Effects ◽  
Therapeutic Approaches ◽  
The Impact ◽  
Long Chain

Cardiovascular disease remains a leading cause of mortality worldwide. Unresolved inflammation plays a critical role in cardiovascular diseases development. Specialized Pro-Resolving Mediators (SPMs), derived from long chain polyunsaturated fatty acids (LCPUFAs), enhances the host defense, by resolving the inflammation and tissue repair. In addition, SPMs also have anti-inflammatory properties. These physiological effects depend on the availability of LCPUFAs precursors and cellular metabolic balance. Most of the studies have focused on the impact of SPMs in adult cardiovascular health and diseases. In this review, we discuss LCPUFAs metabolism, SPMs, and their potential effect on cardiovascular health and diseases primarily focusing in neonates. A better understanding of the role of these SPMs in cardiovascular health and diseases in neonates could lead to the development of novel therapeutic approaches in cardiovascular dysfunction.

Jumping on the Omega-3 Bandwagon: Distinguishing the Role of Long-Chain and Short-Chain Omega-3 Fatty Acids

2012 ◽  
Vol 52 (9) ◽  
pp. 795-803 ◽  
Author(s):  
Giovanni M. Turchini ◽  
Peter D. Nichols ◽  
Colin Barrow ◽  
Andrew J. Sinclair
Keyword(s):  
Fatty Acids ◽  
Short Chain ◽  
Omega 3 Fatty Acids ◽  
Omega 3 ◽  
Long Chain

Immunometabolic role of long-chain omega-3 fatty acids in obesity-induced inflammation

2013 ◽  
Vol 29 (6) ◽  
pp. 431-445 ◽  
Author(s):  
Michael R. Flock ◽  
Connie J. Rogers ◽  
K. Sandeep Prabhu ◽  
Penny M. Kris-Etherton
Keyword(s):  
Fatty Acids ◽  
Omega 3 Fatty Acids ◽  
Omega 3 ◽  
Long Chain

scholarly journals Self-assembly of alkyl chains of fatty acids in papermaking systems: A review of related pitch issues, hydrophobic sizing, and pH effects

BioResources ◽  
2020 ◽  
Vol 15 (2) ◽  
pp. 4591-4635
Author(s):  
Martin A. Hubbe ◽  
Douglas S. McLean ◽  
Karen R. Stack ◽  
Xiaomin Lu ◽  
Anders Strand ◽  
...  
Keyword(s):  
Fatty Acids ◽  
Self Assembly ◽  
Review Article ◽  
Ph Effects ◽  
Monolayer Films ◽  
Alkyl Chains ◽  
Ph Values ◽  
Self Association ◽  
Long Chain

This review article considers the role of fatty acids and the mutual association of their long-chain (e.g. C18) alkyl and alkenyl groups in some important aspects of papermaking. In particular, published findings suggest that interactions involving fatty acids present as condensed monolayer films can play a controlling role in pitch deposition problems. Self-association among the tails of fatty acids and their soaps also helps to explain some puzzling aspects of hydrophobic sizing of paper. When fatty acids and their soaps are present as monolayers in papermaking systems, the pH values associated with their dissociation, i.e. their pKa values, tend to be strongly shifted. Mutual association also appears to favor non-equilibrium multilayer structures that are tacky and insoluble, possibly serving as a nucleus for deposition of wood extractives, such, as resins and triglyceride fats, in pulp and paper systems.

scholarly journals Multiple Myeloma Cells Induce Lipolysis in Adipocytes and Uptake Fatty Acids through Fatty Acid Transporter Proteins

Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 41-42
Author(s):  
Cristina Panaroni ◽  
Keertik Fulzele ◽  
Tomoaki Mori ◽  
Chukwuamaka Onyewadume ◽  
Noopur S. Raje
Keyword(s):  
Multiple Myeloma ◽  
Bone Marrow ◽  
Fatty Acid ◽  
Board Of Directors ◽  
Metabolic Reprogramming ◽  
Glycerol Production ◽  
Advisory Committees ◽  
Myeloma Cells ◽  
Long Chain

Multiple myeloma (MM) originates in the bone marrow where adipocytes occupy 65% of the cellular volume in a typical myeloma patient. Cancer associated adipocytes support the initiation, progression, and survival of solid tumors via mechanisms including adipokine secretion, modulation of the tumor microenvironment, and metabolic reprogramming of cancer cells. Although MM cells are surrounded by abundant bone marrow adipocytes (BMAd), the nature of their interaction remains unclear. Recent studies have elucidated the role of BMAds in supporting the survival of MM cells, in part, through secreted adiponectin. Increased fatty acid (FA) metabolism may result in metabolic reprogramming of cancer cells impacting their growth and survival. Here, we hypothesize that MM cells extract FA from adipocytes for their growth. We first characterized mesenchymal stem cells (MSCs) from MGUS, smoldering MM (SMM), and newly diagnosed MM (NDMM) patients by flow cytometry analysis. MSCs showed significant increase in Pref1, leptin receptor and perilipin A, suggesting increased adipogenic commitment. MSCs from healthy donors (HD), MGUS, SMM, and NDMM patients were induced to differentiate into adipocytes and then co-cultured with human MM MM.1S cells. After 72 hr of co-culture, CyQUANT assay demonstrated significant increase in proliferation of MM.1S cells in the presence of BMAd from HD; this was further increased in the presence of BMAd from MGUS/SMM and NDMM. These data suggest that the BMAd support the growth of MM cells and this effect is more pronounced in patient derived BMAd. A PCR-array targeting lipid metabolism on BM fat aspirates showed significant deregulation of genes involved in FA synthesis and lipolysis. Taken together, our data suggest that BMAd in MM patients are altered to further support the aggressive expansion of MM cells. The proliferative-supportive role of adipocytes was further validated in co-culture of OP9 murine BM stromal preadipocytes with 5TGM1 murine MM cells. To study the bidirectional interaction of MM/ BMAd, mature OP9 adipocytes were co-cultured with 5TGM1 or human OPM2 MM cells for 24 hr. Intracellular lipid droplets were labelled with Deep Red LipidTox stain. The lipid droplet sizes were significantly decreased in the presence of both 5TGM1 and OPM2 cells compared to OP9 alone. The decrease in lipid size suggested that MM cells may induce lipolysis in adipocytes. Indeed, 24hr co-culture of 5TGM1 cells with OP9 mature adipocytes significantly increased lipolysis 3-fold as measured by glycerol secretion in conditioned media. Co-culture of OP9 adipocytes with other MM cell lines of human origin, MM.1S, INA6, KMS-12 PE, and OPM2 also significantly increased the glycerol production as much as 4-fold. Taken together these data indicate that MM cells induce lipolysis in adipocytes. In contrast, treatment of 5TGM1 cells with synthetic catecholamine isoproterenol did not induce lipolysis, or glycerol production, indicating lack of triglyceride storage. Next, we hypothesized that the free FAs released from adipocytes are taken up by MM cells for various biological processes. To test this, 5TGM1, MM.1S and OPM2 cells were incubated with BODIPY-C12 and BODIPY-C16, the BODIPY-fluorophore labelled 12-carbon and 16-carbon long chain FA. All MM cells showed saturated uptake of the FA within 10 minutes suggesting that MM cells have efficient FA transporters. To confirm this uptake, unstained 5TGM1, OPM2 and KMS12 PE cells were co-cultured with the LipidTox-labelled OP9 mature adipocytes. After 24 hours, flow cytometric analysis showed LipidTox signal in MM cells. These data demonstrate that FAs released by MM induced adipocyte lipolysis are taken up by MM cells. Long-chain FAs such as BODIPY-C12 and BODIPY-C16 are transported into cells through FA transporter protein (FATP) family of lipid transporters. We therefore analyzed patient samples which showed that CD138+ plasmacells and myeloma cells expressed high levels of FATP1 and FATP4 whereas, their expression was absent in lineage-sibling T-cells. Moreover, pretreatment with Lipofermata, a FATP inhibitor, was able to decrease the uptake of BODIPY-C12 and -C16 in 5TGM1 cells. Taken together, our data show that myeloma cells induce lipolysis in adipocytes and the released free FAs are then uptaken by myeloma cells through FATPs. Inhibiting myeloma cell induced lipolysis or uptake of FA through FATPs may be a potential anti-tumor strategy. Disclosures Fulzele: FORMA Therapeutics, Inc: Current Employment, Other: Shareholder of Forma Therapeutics. Raje:Amgen: Consultancy; bluebird bio: Consultancy, Research Funding; Caribou: Consultancy, Membership on an entity's Board of Directors or advisory committees; Immuneel: Membership on an entity's Board of Directors or advisory committees; Bristol Myers Squibb: Consultancy; Celgene: Consultancy; Immuneel: Consultancy; Janssen: Consultancy; Karyopharm: Consultancy; Takeda: Consultancy.

The Ecological Role of Sulfate-Reducing Bacteria in Anaerobic Degradation of a Long-Chain Fatty Acid.

1995 ◽  
Vol 18 (6) ◽  
pp. 499-510 ◽  
Author(s):  
Takashi YAMAGUCHI ◽  
Hideki HARADA ◽  
Kiyoshi MOMONOI ◽  
I-Cheng TSENG
Keyword(s):  
Fatty Acid ◽  
Anaerobic Degradation ◽  
Sulfate Reducing Bacteria ◽  
Chain Fatty Acid ◽  
Ecological Role ◽  
Long Chain Fatty Acid ◽  
Sulfate Reducing ◽  
Reducing Bacteria ◽  
Long Chain

Abstract 16607: Age-induced Endoplasmic Reticulum Stress in the Heart: Role of Increased Very Long-chain Ceramides

Circulation ◽  
2020 ◽  
Vol 142 (Suppl_3) ◽  
Author(s):  
Qun Chen ◽  
Anna Kovilakath ◽  
Jeremy Allegood ◽  
Lauren A Cowart ◽  
Edward J Lesnefsky
Keyword(s):  
Er Stress ◽  
Mitochondrial Dysfunction ◽  
Acyl Chain ◽  
Membrane Domains ◽  
Ceramide Synthase ◽  
Age Related ◽  
Chain Lengths ◽  
Endoplasm Reticulum ◽  
Long Chain

Introduction: Mitochondrial function is impaired in aged hearts. Increased endoplasm reticulum (ER) stress contributes to the mitochondrial dysfunction observed during aging. Ceramides (CRMD) are sphingolipid metabolites that contribute key roles in cell signaling. Increased CRMD can lead to ER stress. Ceramide synthase enzymes (CerS) generate chain length specific CRMD with the CerS isoform 2 (Cers2) forming very long chain CRMD of ≥ 20 carbon acyl chain lengths. Hypothesis: An increase in CRMD content during aging contributes to age-related ER stress. Methods: Male mice (3, 18, 24 mo.) from the NIA colony were studied. Cardiac mitochondria (MITO), mitochondrial associated membranes (MAM), and ER were isolated from mouse hearts. CRMD content was measured using LC-MS. The contents of CerS enzymes were measured by immunoblotting in myocardial homogenates. Results: ER stress increased progressively during aging with increased contents of cleaved ATF6 and CHOP, indicators of increased ER stress, evident at 18 and 24 mo. (Panel A) (all data mean±SEM; *p<0.05 vs. 3 mo., † p<0.05 vs. 18 mo.). Aging increased very long-chain CRMD (≥C20) in ER (Panel B) at 18 and 24 mo. Similar CRMD trends were observed MAM (Panel C), shared membrane domains where ER and MITO interact. The content of CerS2 was increased at 24 mo. compared to 3 mo. (Panel D, n=4 each age). In contrast, the contents of CerS isoforms 4 and 5, that generate shorter chain CRMD (<C20) were unchanged (not shown). CRMD contents in MITO were unaltered with age (not shown). Thus, increased generation of very long chain CRMD in the ER is the likely mechanism of increased ER stress in the aged heart. Conclusion: Aging increased ER CRMD content by enhancing the formation of very long chain CRMD in ER by an increase in CerS2 content, concomitant with the onset of ER stress. The increase in age-induced ER stress, in turn, leads to mitochondrial dysfunction in the aged heart.

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