Pentadecanoic acid

[123I]-汕-Methyl iodophenyl-pentadecanoic acid

Under normal conditions the myocardium can metabolize several different types of substrates for energy. Although fatty acids supply almost 66% of the energy requirements of this tissue, the myocardium can also metabolize glucose (the second most preferred substrate), lactate, amino acids, and ketone bodies (1). Either through 汕-oxidation or glycolysis the fatty acids and glucose are, respectively, broken down to acetyl-coenzyme A (CoA), which is further oxidized through the tricarboxylic acid cycle to produce energy. Certain pathological conditions, such as ischemia, are known to alter myocardial metabolism, and the reduced availability of oxygen shifts the myocardium into an anaerobic mode that leads to an increased utilization of glucose for energy because glycolysis requires less oxygen in comparison to 汕-oxidation (2). Therefore, different imaging agents are used to assess myocardial changes observed during heart disease. For example, radioactive fluorodeoxyglucose ([18F]-FDG) is often used to evaluate glucose metabolism, labeled acetate is used to assess oxygen consumption, and fatty acids labeled with iodine (123I) are used for single-photon emission computed tomography (SPECT) of the heart (1).

Among the fatty acids, [123I]-汕-methyl iodophenyl-pentadecanoic acid ([123I]-BMIPP), used as a racemic mixture ([125I]-3(R,S)-BMIPP), is used most frequently for SPECT imaging of the heart because the methyl group at the 汕 position of the molecule slows 汕-oxidation of the fatty acid, which results in prolonged retention and improved quantitative imaging of the organ (3). Animal and clinical studies have shown that the CD36 molecule on the cell membrane plays an important role in the transport of BMIPP into the cell (4). It is then converted to BMIPP-CoA and rapidly incorporated into triglycerides (5). Using a dual mixture of [125I]-3(R)-BMIPP and [131I]-3(S)-BMIPP as surrogate molecules for [123I]-BMIPP to study the effect of BMIPP molecular configuration on its uptake and metabolism in the rat myocardium, it was shown that uptake of the 3(R)-BMIPP isomer was higher compared to 3(S)-BMIPP but the two isomers were metabolized in the same manner in the rat myocardium (6, 7). Morishita et al. proved that BMIPP was metabolized in the mitochondria of the tissue (8). Other investigators studying the metabolism of branched-chain fatty acids in the myocardium of rats with streptozotocin-induced acute or chronic diabetes mellitus concluded that the uptake of BMIPP was reduced in rats with chronic diabetes mellitus because the mitochondrial function was not normal in the myocardium of these animals (9).

In humans, [123I]-BMIPP was shown to be a superior cardiac SPECT imaging agent compared to its dimethyl analog, and it has been used extensively for this purpose in Japan and Europe (1, 7, 10). Akashi et al. investigated the significance of [123I]-BMIPP imaging in cardiac patients and concluded that this radiochemical enhanced the assessment of fatty acid metabolism disorders in the myocardium both under normal and diseased conditions (11). Nishimura and colleagues have shown that [123I]-BMIPP scintigraphy can be used to detect asymptomatic coronary artery disease and predict cardiac death and coronary artery stenosis in hemodialysis patients (12-14). In the United States, [123I]-BMIPP has been used for the imaging of ischemic heart and coronary artery disease as well as acute coronary syndrome in clinical trials approved by the U.S. Food and Drug Administration. The use of [123I]-BMIPP for diagnostic imaging has been patented in the United States (15).

Pentadecanoic acid promotes basal and insulin-stimulated glucose uptake in C2C12 myotubes

Background: Saturated fatty acids (SFAs) generally have been thought to worsen insulin-resistance and increase the risk of developing type 2 diabetes mellitus (T2DM). Recently, accumulating evidence has revealed that SFAs are not a single homogeneous group, instead different SFAs are associated with T2DM in opposing directions. Pentadecanoic acid (C15:0, PA) is directly correlated with dairy products, and a negative association between circulating PA and metabolic disease risk was observed in epidemiological studies. Therefore, the role of PA in human health needs to be reinforced. Whether PA has a direct benefit on glucose metabolism and insulin sensitivity needs further investigation.
Objective: The present study aimed to investigate the effect and potential mechanism of action of PA on basal and insulin stimulated glucose uptake in C2C12 myotubes.
Methods: Glucose uptake was determined using a 2-(N-[7-nitrobenz-2-oxa-1,3-diazol-4-yl] amino)-2-deoxyglucose (2-NBDG) uptake assay. Cell membrane proteins were isolated and glucose transporter 4 (GLUT4) protein was detected by western blotting to examine the translocation of GLUT4 to the plasma membrane. The phosphorylation levels of proteins involved in the insulin and 5'-adenosine monophosphate-activated protein kinase (AMPK) pathways were examined by western blotting.
Results: We found that PA significantly promoted glucose uptake and GLUT4 translocation to the plasma membrane. PA had no effect on the insulin-dependent pathway involving insulin receptor substrate 1 (Tyr632) and protein kinase B (PKB/Akt), but increased phosphorylation of AMPK and Akt substrate of 160 kDa (AS160). Compound C (an AMPK inhibitor) blocked PA-induced AMPK activation and reversed PA-induced GLUT4 translocation, indicating that PA promotes glucose uptake via the AMPK pathway in vitro. Moreover, PA significantly promoted insulin-stimulated glucose uptake in myotubes. Under insulin stimulation, PA did not affect the insulin-dependent pathway, but still activated AMPK.
Conclusion: PA, an odd-chain SFA, significantly stimulates glucose uptake via the AMPK-AS160 pathway and exhibits an insulin-sensitizing effect in myotubes.

Pentadecanoic acid against Candida albicans-Klebsiella pneumoniae biofilm: towards the development of an anti-biofilm coating to prevent polymicrobial infections

The ability to form biofilms is a common feature of microorganisms, which can colonize a variety of surfaces, such as host tissues and medical devices, resulting in infections highly resistant to conventional drugs. This aspect is particularly critical in polymicrobial biofilms involving both fungi and bacteria, therefore, to eradicate such severe infections, new and effective anti-biofilm strategies are needed. The efficacy of pentadecanal and pentadecanoic acid as anti-biofilm agents has been recently reported against different bacterial strains. Their chemical similarity with diffusible signal factors (DSFs), plus the already known ability of fatty acids to act as anti-biofilm agents, suggested to explore their use against Candida albicans and Klebsiella pneumoniae mixed biofilm. In this work, we demonstrated the ability of both molecules to prevent the formation and destabilize the structure of the dual-species biofilm. Moreover, the pentadecanoic acid anti-biofilm coating, previously developed through the adsorption of the fatty acid on polydimethylsiloxane (PDMS), was proved to prevent the polymicrobial biofilm formation in dynamic conditions by confocal laser scanning microscopy analysis. Finally, the evaluation of the expression levels of some biofilm-related genes of C. albicans and K. pneumoniae treated with pentadecanoic acid provided some insights into the molecular mechanisms underpinning its anti-biofilm effect.

Effects of Combined Pentadecanoic Acid and Tamoxifen Treatment on Tamoxifen Resistance in MCF-7/SC Breast Cancer Cells

Estrogen receptors are indicators of breast cancer adaptability to endocrine therapies, such as tamoxifen. Deficiency or absence of estrogen receptor 汐 (ER-汐) in breast cancer cells results in reduced efficacy of endocrine therapy. Here, we investigated the effect of combined tamoxifen and pentadecanoic acid therapy on ER-汐-under-expressing breast cancer cells. Drug resistance gene expression patterns were determined by RNA sequencing analysis and in vitro experiments. For the first time, we demonstrate that the combined treatment of pentadecanoic acid, an odd-chain fatty acid, and tamoxifen synergistically suppresses the growth of human breast carcinoma MCF-7 stem cells (MCF-7/SCs), which were found to be tamoxifen-resistant and showed reduced ER-汐 expression compared with the parental MCF-7 cells. In addition, the combined treatment synergistically induced apoptosis and accumulation of sub-G1 cells and suppressed epithelial-to-mesenchymal transition (EMT). Exposure to this combination induces re-expression of ER-汐 at the transcriptional and protein levels, along with suppression of critical survival signal pathways, such as ERK1/2, MAPK, EGFR, and mTOR. Collectively, decreased ER-汐 expression was restored by pentadecanoic acid treatment, resulting in reversal of tamoxifen resistance. Overall, pentadecanoic acid exhibits the potential to enhance the efficacy of endocrine therapy in the treatment of ER-汐-under-expressing breast cancer cells.

Iodofiltic Acid I 123

Information in this record refers to the use of iodofiltic acid I 123 (beta-methyl-15-(4-iodophenyl) pentadecanoic acid; I 123 BMIPP) as a diagnostic agent. The International Commission on Radiological Protection states that breastfeeding should be interrupted for more than 3 weeks following diagnostic use of I 123 BMIPP because of possible contamination with other iodine isotopes.[1] Because this contamination does not occur with modern production methods, discontinuation of nursing is not necessary, especially if a thyroid blocking agent is given to the mother.[2,3]

Mothers concerned about the level of radioactivity in their milk could ask to have it tested at a nuclear medicine facility at their hospital. When the radioactivity is at a safe level, she may resume breastfeeding. A method for measuring milk radioactivity and determining the time when a mother can safely resume breastfeeding has been published.[4]