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Journal of Nuclear Medicine : Official... Dec 1984Uptake and turnover of 15-(p-[123I]iodophenyl)pentadecanoic acid (I-PPA), a radioiodinated free-fatty-acid analog, was examined in heart, lung, liver, kidneys, and... (Comparative Study)
Comparative Study
Uptake and turnover of 15-(p-[123I]iodophenyl)pentadecanoic acid (I-PPA), a radioiodinated free-fatty-acid analog, was examined in heart, lung, liver, kidneys, and spleen and compared with that of [1-14C]palmitic acid (PA). High cardiac uptake of both I-PPA (4.4% dose/g) and PA (2.8% dose/g) was followed by a two-component tracer clearance. Kinetics of I-PPA were linked to those of PA in tissues with primary oxidation of free fatty acids or their preferential storage. Tissue lipids of all organs investigated were labeled concordantly by both tracers. Fractional distributions of PA and I-PPA incorporation in tissue lipids were significantly correlated. Thus general pathways of FFA tissue metabolism are traced by this radioiodinated free-fatty-acid analog. High-quality metabolic imaging of the heart is possible by means of I-PPA with conventional scintigraphic equipment or cross-sectional imaging with single photon emission computerized tomography facilities.
Topics: Animals; Carbon Radioisotopes; Dogs; Heart; Iodobenzenes; Lipid Metabolism; Male; Palmitic Acid; Palmitic Acids; Rats; Rats, Inbred Strains; Tissue Distribution; Tomography, Emission-Computed
PubMed: 6334144
DOI: No ID Found -
Journal of Nuclear Cardiology :... 1995Although fatty acid is a major energy source in the normal myocardium, fatty acid oxidation is easily suppressed in a variety of cardiac disorders. Therefore assessment... (Review)
Review
Although fatty acid is a major energy source in the normal myocardium, fatty acid oxidation is easily suppressed in a variety of cardiac disorders. Therefore assessment of fatty acid metabolism may hold an important role for early detection of myocardial abnormalities and provide insights into cardiac pathologic states. C-11 palmitate is a well-established PET tracer to probe myocardial fatty acid metabolism. On the other hand, a variety of iodinated fatty acid compounds have been introduced for assessment of fatty acid metabolism with conventional gamma cameras. These include straight-chain, such as iodopheyl pentadecanoic acid (IPPA), and branch-chain fatty acid compounds, such as beta-methyl iodopheyl pentadecanoic acid (BMIPP). This review article includes the characterization of these tracers and clinical experiences with these tracers for detection and characterizing patients with ischemic heart disease and cardiomyopathy.
Topics: Animals; Animals, Domestic; Carbon Radioisotopes; Fatty Acids; Heart; Humans; Iodine Radioisotopes; Iodobenzenes; Myocardium; Palmitic Acid; Tomography, Emission-Computed, Single-Photon
PubMed: 9420796
DOI: 10.1016/s1071-3581(05)80063-7 -
Journal of Nuclear Medicine : Official... Apr 1993The kinetics of 17-[123I]iodoheptadecanoic acid (IHDA), 15-(p-[125I]iodophenyl)pentadecanoic acid (pIPPA) and 15-(p-[131I]iodophenyl)-3,3-dimethylpentadecanoic acid... (Comparative Study)
Comparative Study
Comparison of uptake, oxidation and lipid distribution of 17-iodoheptadecanoic acid, 15-(p-iodophenyl)pentadecanoic acid and 15-(p-iodophenyl)-3,3-dimethylpentadecanoic acid in normal canine myocardium.
The kinetics of 17-[123I]iodoheptadecanoic acid (IHDA), 15-(p-[125I]iodophenyl)pentadecanoic acid (pIPPA) and 15-(p-[131I]iodophenyl)-3,3-dimethylpentadecanoic acid (DMIPPA) were investigated in normal canine myocardium. After simultaneous intravenous injection, myocardial biopsy specimens and samples of arterial blood were taken over 80 min. IHDA showed the highest myocardial uptake (995 +/- 248 dpm/mg.mCi versus pIPPA: 785 +/- 197 dpm/mg.mCi, ns) and the largest size of oxidation (74% +/- 4% versus pIPPA: 65% +/- 5%, p < 0.05). Myocardial activity of IHDA decreased with a half-time value of 11.2 min (pIPPA: 13.2 min). Phospholipids were the main lipid fraction into which IHDA was incorporated, whereas pIPPA was predominantly incorporated into triacylglycerols. DMIPPA myocardial activity remained constant during the assay period and instead of being oxidized, DMIPPA was mainly incorporated into triacylglycerols (55% +/- 12%). The myocardium-to-blood ratios of DMIPPA were greater than 10:1. The ratios at peak for IHDA and pIPPA were 4.1:1 and 3.9:1, respectively (both p < 0.0001 versus DMIPPA). In conclusion, differences have been found in the myocardial uptake, oxidation and lipid distribution of IHDA, pIPPA and DMIPPA. DMIPPA is a promising tracer for fatty acid uptake studies with single-photon emission computerized tomography because of its prolonged retention and high myocardium-to-blood ratios.
Topics: Animals; Dogs; Fatty Acids; Heart; Iodine Radioisotopes; Iodobenzenes; Myocardium; Tomography, Emission-Computed, Single-Photon
PubMed: 8455083
DOI: No ID Found -
The Journal of Physical Chemistry. B Jan 2022Langmuir monolayers consisting of fatty acids with relatively short alkyl chains (CHCOOH (pentadecanoic acid), CHCOOH (palmitic acid), and CHCOOH (heptadecanoic acid))...
Langmuir monolayers consisting of fatty acids with relatively short alkyl chains (CHCOOH (pentadecanoic acid), CHCOOH (palmitic acid), and CHCOOH (heptadecanoic acid)) are stable at a neutral pH (pH ≈ 6) but become unstable at a high pH (pH ≈ 11). Further addition of a small amount of divalent salt in subphase water was found to recover the monolayer at a high pH because binding of the divalent cations to the carboxylic headgroups renders the molecule more stable against dissolution in subphase water. This revival of the monolayer was observed via a pressure-area isotherm measurement and sum-frequency generation spectrum in the CH and OH ranges. Fatty acids with longer alkyl chains needed less amount of MgCl to recover the monolayer at a high pH. A much lower concentration of Mg as compared to Ca is required to revive fatty acid molecules to the surface. Monovalent and trivalent salts were compared with the above divalent salts on the ability to recover the fatty acid monolayers.
Topics: Fatty Acids; Palmitic Acid; Salts; Spectrum Analysis; Surface Properties; Water
PubMed: 35026947
DOI: 10.1021/acs.jpcb.1c08028 -
Nutrients Apr 2023Epidemiological studies found that the intake of dairy products is associated with an increased amount of circulating odd-chain fatty acids (OCFA, C15:0 and C17:0) in...
Epidemiological studies found that the intake of dairy products is associated with an increased amount of circulating odd-chain fatty acids (OCFA, C15:0 and C17:0) in humans and further indicate that especially C17:0 is associated with a lower incidence of type 2 diabetes. However, causal relationships are not elucidated. To provide a mechanistic link, mice were fed high-fat (HF) diets supplemented with either milk fat or C17:0 for 20 weeks. Cultured primary mouse hepatocytes were used to distinguish differential effects mediated by C15:0 or C17:0. Despite an induction of OCFA after both dietary interventions, neither long-term milk fat intake nor C17:0 supplementation improved diet-induced hepatic lipid accumulation and insulin resistance in mice. HF feeding with milk fat actually deteriorates liver inflammation. Treatment of primary hepatocytes with C15:0 and C17:0 suppressed JAK2/STAT3 signaling, but only C15:0 enhanced insulin-stimulated phosphorylation of AKT. Overall, the data indicate that the intake of milk fat and C17:0 do not mediate health benefits, whereas C15:0 might be promising in further studies.
Topics: Humans; Animals; Mice; Insulin Resistance; Diabetes Mellitus, Type 2; Fatty Acids; Fatty Liver; Diet, High-Fat
PubMed: 37432205
DOI: 10.3390/nu15092052 -
Journal of Nuclear Medicine : Official... Oct 1990The human myocardium retains oPPA as opposed to pPPA. Therefore turnover of oPPA was compared with that of pPPA in rat hearts and in man, the latter by using substrates... (Comparative Study)
Comparative Study
The human myocardium retains oPPA as opposed to pPPA. Therefore turnover of oPPA was compared with that of pPPA in rat hearts and in man, the latter by using substrates double-labeled with 123/131I and 14C. Moreover, substrate binding to coenzyme-A was tested in vitro. In rats, oPPA remained mainly in the pool of free fatty acids, as opposed to pPPA, which was metabolized by mitochondrial beta-oxidation. Binding to coenzyme-A at maximum was 62% for oPPA, 81% for pPPA and 90% for palmitic acid. In man, after i.v. and intracoronary injection of double-labeled oPPA, the two radionuclides reappeared together in venous blood and in coronary sinus respectively, in an unchanged ratio but at a significantly lower rate than with pPPA. It can be concluded that oPPA is bound to coenzyme-A and is retained in the cytosolic lipid pool, while pPPA is metabolized by mitochondrial beta-oxidation. A dual-tracer application of oPPA and pPPA has the potential of being a specific probe for the function of the carnitine shuttle.
Topics: Animals; Carbon Radioisotopes; Coenzyme A; Fatty Acids; Heart; Humans; In Vitro Techniques; Iodine Radioisotopes; Iodobenzenes; Kinetics; Male; Myocardium; Radionuclide Imaging; Rats; Rats, Inbred Strains
PubMed: 2213181
DOI: No ID Found -
Frontiers in Endocrinology 2023Diabetic sarcopenia (DS) is characterized by muscle atrophy, slower nerve conduction, reduced maximum tension generated by skeletal muscle contraction, and slower...
INTRODUCTION
Diabetic sarcopenia (DS) is characterized by muscle atrophy, slower nerve conduction, reduced maximum tension generated by skeletal muscle contraction, and slower contraction rate. Hence, DS can cause limb movement degeneration, slow movement, reduced balance, reduced metabolic rate, falls, fractures, etc. Moreover, the relevant early biological metabolites and their pathophysiological mechanism have yet to be characterized.
METHOD
The current cross-sectional study employed serum metabolomics analysis to screen potential noninvasive biomarkers in patients with diabetic sarcopenia. A total of 280 diabetic patients were enrolled in the study (n = 39 sarcopenia [DS], n = 241 without sarcopenia [DM]). Ten patients were randomly selected from both groups. Non-targeted metabolomic analysis was performed by ultra-high-performance liquid chromatography-electrospray ionization tandem mass spectrometry.
RESULTS
A total of 632 differential metabolites were identified, including 82 that were significantly differentially abundant ( < 0.05, VIP > 1, FC > 1.2 or FC < 0.8). Compared with the DM group, the contents of pentadecanoic acid, 5'-methylthioadenosine (5'-MTA), N,N-dimethylarginine (asymmetric dimethylarginine, ADMA), and glutamine in the DS group were significantly increased, while that of isoxanthohumol was decreased.
DISCUSSION
Based on receiver operating characteristic curve analysis, pentadecanoic acid, 5'-MTA, ADMA, and glutamine may serve as potential biomarkers of DS. Moreover, ATP-binding cassette (ABC) transporters and the mammalian target of the rapamycin signaling pathway were found to potentially have important regulatory roles in the occurrence and development of DS (P < 0.05). Collectively, the differential metabolites identified in this study provide new insights into the underlying pathophysiology of DS and serve as a basis for therapeutic interventions.
Topics: Humans; Biomarkers; Cross-Sectional Studies; Diabetes Mellitus; Glutamine; Sarcopenia; Diabetes Complications; Metabolome
PubMed: 37033246
DOI: 10.3389/fendo.2023.1119782 -
Nuclear Medicine and Biology Oct 1995The purpose of this study was to compare by planar myocardial scintigraphy the kinetics of iodine-123-15-(iodophenyl)pentadecanoic acid (123I-pPPA and 123I-oPPA), and of... (Comparative Study)
Comparative Study
Planar myocardial imaging in the baboon model with iodine-123-15-(iodophenyl)pentadecanoic acid (IPPA) and iodine-123-15-(P-iodophenyl)-3-R,S-methylpentadecanoic acid (BMIPP), using time-activity curves for evaluation of metabolism.
The purpose of this study was to compare by planar myocardial scintigraphy the kinetics of iodine-123-15-(iodophenyl)pentadecanoic acid (123I-pPPA and 123I-oPPA), and of iodine-123-(p-iodophenyl)-3-R,S-methyl-pentadecanoic acid (BMIPP), firstly in normal baboons, and subsequently after blocking fatty acid oxidation by a carnitine palmitoyl transferase I(CPT1) inhibitor. The induced changes in myocardial metabolism were reflected in the dynamic behaviour of the three tracers. pPPA and oPPA to a large extent, provided information on beta-oxidation changes in the myocardium: beta-oxidation participation changed from 47% and 50%, respectively to 17% and 23% after inhibition. BMIPP provided better images and reflected largely on changed tracer incorporation into the neutral lipid pools. The beta-oxidation contributed only about 10% towards the metabolic pathway of BMIPP. The information obtained in this study could help determine the tracer of choice for SPECT, whereby myocardial viability could optimally be revealed.
Topics: Animals; Carnitine O-Palmitoyltransferase; Decanoic Acids; Enzyme Inhibitors; Epoxy Compounds; Fatty Acids; Heart; Hypoglycemic Agents; Iodine Radioisotopes; Iodobenzenes; Liver; Male; Myocardium; Oxidation-Reduction; Papio; Structure-Activity Relationship; Tomography, Emission-Computed, Single-Photon
PubMed: 8547881
DOI: 10.1016/0969-8051(95)00015-p -
Journal of Nuclear Cardiology :... 1999We used beta-methyl iodophenyl pentadecanoic acid (BMIPP) single photon emission computed tomography (SPECT) to evaluate fatty acid metabolism in patients who were...
BACKGROUND
We used beta-methyl iodophenyl pentadecanoic acid (BMIPP) single photon emission computed tomography (SPECT) to evaluate fatty acid metabolism in patients who were candidates for permanent pacemaker implantation and in patients with atrioventricular (AV) synchronous pacing.
METHODS AND RESULTS
We performed BMIPP SPECT studies in 66 patients with bradyarrhythmia, of whom 11 patients were candidates for permanent pacemaker implantation, 27 patients had atrial pacing (atrial sensing, inhibited mode, simple programmable [AAI]), and 28 patients had atrial synchronous ventricular inhibited pacing (ventricular pacing, 2-chamber sensing, atrial-triggered and ventricular-inhibited, multiprogrammable [VDD]) or atrial and ventricular pacing in sequence (atrial and ventricular sensing, atrial-inhibited and atrial-triggered, ventricular-inhibited, multiprogrammable [DDD]). A qualitative assessment revealed that the BMIPP uptake at the septal, inferior, and apical regions was significantly decreased in the patients with VDD/DDD compared with both the candidates for permanent pacemaker implantation and the patients with AAI. The total extent score (ES) and severity score (SS) were significantly higher in the patients with VDD/DDD than in the other 2 groups. Significant regional differences of both ES and SS values were observed at the septal and inferior regions in the patients with VDD/DDD compared with the other groups. No differences were found between the qualitative and quantitative measures of BMIPP uptake in the candidates for permanent pacemaker implantation and those in the patients with AAI.
CONCLUSION
Our study suggests that AV synchronous right ventricular pacing resulting in the delayed conduction and depolarization of myocardial cells may directly interfere with regional cellular free fatty acid uptake and metabolism.
Topics: Aged; Aged, 80 and over; Bradycardia; Cardiac Pacing, Artificial; Electrocardiography; Fatty Acids; Female; Heart; Humans; Iodine Radioisotopes; Iodobenzenes; Male; Middle Aged; Myocardium; Tomography, Emission-Computed, Single-Photon
PubMed: 10070839
DOI: 10.1016/s1071-3581(99)90063-6 -
Biochimie Jul 2021The dysregulation of histone deacetylases (HDACs) is closely associated with tumorigenesis and has emerged as a promising target for anti-cancer drugs. Some odd-chain...
The dysregulation of histone deacetylases (HDACs) is closely associated with tumorigenesis and has emerged as a promising target for anti-cancer drugs. Some odd-chain fatty acids are present in trace levels in human tissue. Despite limited health benefits, there is increasing experimental evidence of nutritional benefits of odd-chain fatty acids. This study examines the effects of five odd-chain fatty acids (valeric, heptanoic, nonanoic, undecanoic, and pentadecanoic acid) as novel HDAC6 inhibitors. Examination of these fatty acids on the proliferation and clonogenic ability in various cancer cell lines revealed that pentadecanoic and undecanoic acid can strongly inhibit cancer cell proliferation. Heptanoic and nonanoic acid showed moderate anti-proliferative effects, while valeric acid demonstrated weak anti-proliferative effects. HDAC6 inhibitory activities were in the order of pentadecanoic acid (C15:0) > undecanoic acid (C11:0) > nonanoic acid (C9:0) > heptanoic acid (C7:0) > valeric acid (C5:0), consistent with the anti-proliferative assay results. All of these fatty acids promoted the acetylation of α-tubulin in MCF-7 breast and A549 lung cancer cells dose-dependently. In-silico molecular docking analysis showed that increasing the aliphatic carbon chain length facilitates binding to HDAC6 residues, which might be important for the inhibitory potential of HDAC6. This study shows the potential utility of odd-chain fatty acids for epigenetic-based cancer therapy.
Topics: A549 Cells; Antineoplastic Agents; Fatty Acids; Hep G2 Cells; Histone Deacetylase 6; Histone Deacetylase Inhibitors; Humans; MCF-7 Cells; Molecular Docking Simulation; Neoplasm Proteins; Neoplasms
PubMed: 33965456
DOI: 10.1016/j.biochi.2021.04.011