Endogenous Metabolite; Na+/K+ ATPase

人体脂肪细胞和其他组织中最常见的不饱和肥料（FA）是油酸。油酸可增加 β-氧化介导的 AMPK 激活介导的细胞增殖和高度转移细胞的迁移。油酸抑制低增殖肿瘤的生长和死亡，包括乳腺癌 MCF-7 细胞系以及 SGC7901 [1]。

日粮中油酸的摄入可改善小鼠的跑步耐力，并随肌肉纤维类型份额的变化而变化。本研究阐明了油酸在骨骼肌纤维类型中的一种新功能。需要进一步的研究来阐明潜在的机制。我们的发现有可能通过营养方法为健康和体育科学领域做出贡献，例如开发旨在改善肌肉功能的补充剂。[3]

油红O染色和甘油三酯测定[2]
用油红O对脂滴进行染色。在0.3%的2-丙醇中制备储备溶液，用水（3∶2）稀释储备溶液，制备新的工作溶液。固定后，将细胞在PBS中洗涤两次，并分别用油红O和苏木精染色15分钟和1分钟。用PBS洗涤细胞，并在光对比显微镜下获得图像。根据制造商推荐的方案，使用甘油三酯测定试剂盒（GPO-POD）测定细胞内甘油三酯

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耗氧量的测定[2]
将五百万个细胞重悬在用21%氧气预平衡的1ml新鲜温热培养基中，并放置在配备有恒温器控制、微搅拌装置和Clark型氧电极盘的密封呼吸室中。持续监测细胞悬浮培养基中的氧含量10分钟，并记录氧消耗速率

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ATP分析[2]
用ATPlite测定试剂盒测定细胞内ATP水平。将细胞在含有或不含有400µM OA的无血清培养基中孵育48小时，用PBS洗涤三次，在ATP提取缓冲液中裂解，并在4°C中离心。根据制造商的说明书，使用市售的荧光素/荧光素酶试剂在光度计（TD-20/20）上通过光度法测量ATP。将数据归一化为总蛋白质。

细胞活力测定[2]
用不同的应激源处理48孔板中密度为每孔10000个细胞的细胞。根据制造商的方案，使用3-[4,5-二甲基噻唑-2-基]-2,5-二苯基溴化四氮唑（MTT）测定法测量细胞活力

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BrdU掺入测定[2]
根据制造商的说明书，通过使用BrdU掺入测定法测量BrdU的掺入来测定细胞增殖。简言之，用10uM BrdU对接种在96孔板中的5000个细胞/孔进行脉冲标记2小时。将细胞与稀释的过氧化物酶缀合的抗BrdU抗体一起孵育30分钟。使用ELISA读取器在450nm处测量吸光度值

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迁移测定[2]
使用Transwell室（8µm孔径的聚碳酸酯膜）进行细胞迁移测定。将总共50个K细胞接种到200µl含有BSA或400µM BSA结合油酸的无血清培养基中的插入物中，并允许其在指定的时间段内从上部室向下部室以15%的FBS梯度迁移。迁移后，通过擦洗去除膜上表面上的非迁移细胞，并将膜固定在缓冲的4%多聚甲醛中，并在室温下用0.1%结晶紫染色。然后对迁移的细胞进行计数。迁移值表示为来自三个独立膜实验的每次测定的六个场上每个显微镜场迁移的细胞的平均数量。

All animal experiments were conducted in strict accordance with the Guidelines for Proper Conduct of Animal Experiments published by the Science Council of Japan and with the approval of the Animal Care and Use Committee of Kitasato University (approval no. 20-007). And all methods were performed in accordance with guidelines and regulations at Kitasato University, as well as complying with ARRIVE guidelines for the reporting of animal experiments. Eight-week-old male C57BL/6JJcl mice were purchased from CLEA Japan, Inc. The experimental design is illustrated in Fig. 5. The mice were housed in plastic cages in an animal room at 22 ± 2 °C and 50 ± 10% humidity under an artificial lighting system of 12-h light/12-h dark cycle. They were acclimated to the environment for one week. Following the acclimatization period, the mice were fed a CE-2 diet supplemented with 10% (w/w) palmitic acid (control diet) or oleic acid for 4 weeks. Palmitic acid was chosen as control fatty acid because it is a representative saturated fatty acid commonly found in soybean oil and olive oil, which has been used in previous studies. Although we considered using linoleic acid as a control, we decided against it because unsaturated fatty acids have ligand activity for PPARs. In our previous study, we reported the results of an 8-week feeding test, and in a preliminary study we confirmed similar changes in skeletal muscle characteristics even with a 4-week period. Therefore, we chose a shorter period of 4 weeks for this study. Nutritional and fatty acid compositions of experimental diets are shown in Table 2 and 3, respectively. Running endurance tests and serum biochemical analyses were performed on the last day of week 3 and the first day of week 4, respectively. After a 4-week feeding period, the mice were euthanized by cervical dislocation under inhalation anesthesia with isoflurane. The adipose tissues, liver, and skeletal muscles (soleus, EDL, and gastrocnemius muscles) were harvested and weighed immediately. The growth performance and tissue weight are shown in Table 1. All tissues were stored at –80 °C until further analysis [3].

Absorption, Distribution and Excretion
Fatty acid uptake by different tissues may be mediated via passive diffusion to facilitated diffusion or a combination of both. Fatty acids taken up by tissues are then stored in the form of triglycerides or oxidized. Oleic acid was shown to penetrate rat skin. Following oral administration of Brucea javanica oil emulsion in rats, the time of oleic acid to reach peak plasma concentration was approximately 15.6 hours.
Following oral administration of trace amounts of oleic acid, less than 10% of total oleic acid was found to be eliminated via fecal excretion.
Radio-labelled oleic acid was detected in the heart, liver, lung, spleen, kidney, muscle, intestine, adrenal, blood, and lymph, and adipose, mucosal, and dental tissues. Oleic acid is primarily transported via the lymphatic system.
No pharmacokinetic data available.
Radioactivity has been traced to the heart, liver, lung, spleen, kidney, muscle, intestine, adrenal, blood, and lymph, and adipose, mucosal, and dental tissues after administration of radioactive oleic, palmitic, and stearic acids.
Simultaneous ingestion of trace amounts of 14C-triolein (10 uCi) and 3H-oleic acid (20 uCi) in 42 g of carrier fat by patients with normal fecal fat excretion resulted in estimated fecal excretion of less than 10% of both substances. Gastrointestinal transit times for 14C-triolein, 3H-oleic acid, and a nonabsorbable marker, CrCl3, did not differ significantly.
Oleic Acid has been reported to penetrate the skin of rats. On histological examination, fluorescence from absorbed oleic acid was found in epidermal cell layers of skin removed from treated rats within 10 min of its application. The path of penetration was suggested to be via the hair follicles. Only minute amounts of oleic acid were visualized in the blood vessels throughout the experiment. Skin permeability was shown to increase with the lipophilic nature of a compound.
METABOLISM OF TRITIATED OLEIC ACID WAS STUDIED IN RATS DURING 600 DAYS. DURING FIRST 4 DAYS, HALF ACTIVITY IS FIXED TO WATER & HALF IS STORED IN ADIPOSE TISSUE WHICH IT LEAVES QUICKLY, THEN MORE SLOWLY WITH T/2 OF ABOUT 200 DAYS.
For more Absorption, Distribution and Excretion (Complete) data for OLEIC ACID (10 total), please visit the HSDB record page.

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Metabolism / Metabolites
Like most fatty acids, oleic acid may undergo oxidation via beta-oxidation and tricarboxylic acid cycle pathways of catabolism, where an additional isomerization reaction is required for the complete catabolism of oleic acid. Via a series of elongation and desaturation steps, oleic acid may be converted into longer chain eicosatrienoic and nervonic acid.
Proposed mechanisms for fatty acid uptake by different tissues range from passive diffusion to facilitated diffusion or a combination of both. Fatty acids taken up by the tissues can either be stored in the form of triglycerides (98% of which occurs in adipose tissue depots) or they can be oxidized for energy via the beta-oxidation and tricarboxylic acid cycle pathways of catabolism.
The beta-oxidation of fatty acids occurs in most vertebrate tissues (except the brain) using an enzyme complex for the series of oxidation and hydration reactions resulting in the cleavage of acetate groups as acetyl-CoA (coenzyme A). An additional isomerization reaction is required for the complete catabolism of Oleic Acid. Alternate oxidation pathways can be found in the liver (omega-oxidation) and in the brain (alpha-oxidation).
Fatty acid biosynthesis from acetyl-CoA takes place primarily in the liver, adipose tissue, and mammary glands of higher animals. Successive reduction and dehydration reactions yield saturated fatty acids up to a 16-carbon chain length. Stearic Acid is synthesized by the condensation of palmitoyl-CoA and acetyl-CoA in the mitochondria, and Oleic Acid is formed via a mono-oxygenase system in the endoplasmic reticulum.
The normal metabolic pathway of palmitic and stearic acids in mammals produces oleic acid. Oleic acid, on a series of elongation and desaturation steps, may be converted into longer chain eicosatrienoic and nervonic acid.
Weanling rats were fed diets containing rapeseed, canbra or ground nut oils for 8 or 60 days. They received simultaneously (14)C erucate and (3)H2 oleate by iv application. Animals were killed 2 or 19 hr after injection, lungs were removed and the distribution of (14)C and (3)H radioactivities was determined in pulmonary lipid fractions and in fatty acids of phospholipids and neutral lipids. More (14)C than (3)H radioactivity was recovered in lung lipids 3 and 19 hr after admin of labelled fatty acids. (14)C and (3)H radioactivity in the phospholipid fraction was larger than in the triglyceride fraction, the inverse was observed after 19 hr. The main part of (14)C radioactivity was present in the monounsaturated fatty acids, in decr order: 18:1, 24:1, 16:1 and 20:1. Erucic acid was slightly esterified in phospholipids.
Oleic acid has known human metabolites that include 18-Hydroxyoleic acid and 17-Hydroxyoleic acid.

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Biological Half-Life
No pharmacokinetic data available.
METABOLISM OF TRITIATED OLEIC ACID WAS STUDIED IN RATS DURING 600 DAYS. /ELIMINATION OCCURED/ SLOWLY WITH T/2 OF ABOUT 200 DAYS.

Protein Binding
As with other fatty acids originating from adipose tissue stores, oleic acid may bind to serum albumin or remain unesterified in the blood.

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Interactions
LOW CONCN OF ... OLEIC ACID ... CAUSED CONSIDERABLE INCREASE IN THE INTESTINAL ABSORPTION OF AMORPHOUS & POLYMORPHIC CHLORAMPHENICOL IN THE CAT.
LIVER TRITIATED-LABELED OLEATE SHOWED ACCUMULATION OF NEWLY SYNTHESIZED TRIGLYCERIDES WITHOUT ANY EFFECT ON PHOSPHOLIPIDS, AFTER SINGLE INJECTION OF CEROUS CHLORIDE IN RATS. /TRITIATED-LABELED OLEATE/
ALTERATIONS IN PHOSPHOLIPID COMPOSITION IN BRAIN & HEART OCCURS IN RESPONSE TO ETHANOL IN THOSE STRAINS OF MICE THAT SHOW RAPID TOLERANCE TO ETHANOL. AN INCREASE IN LIVER PHOSPHOLIPIDS CONTAINING OLEIC ACID WERE FOUND IN ALL STRAINS.
AFTER 16 MIN OF BRAIN ISCHEMIA IN RATS, BRAIN OLEATE INCREASED 2.5-FOLD. POSTISCHEMIA THERAPY WITH THIOPENTAL ACCELERATED THE RATE OF FALL OF BRAIN OLEATE. /OLEATE/
For more Interactions (Complete) data for OLEIC ACID (11 total), please visit the HSDB record page.

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Non-Human Toxicity Values
LD50 Rat oral 74 g/kg
LD50 Rat iv 2.4 mg/kg
LD50 Mouse iv 230 mg/kg
LD50 Guinea pig dermal >3000 mg/kg

[1]. Jack-Hays MG, et al. Activation of Na+/K(+)-ATPase by fatty acids, acylglycerols, and related amphiphiles: structure-activity relationship. Biochim Biophys Acta. 1996 Feb 21;1279(1):43-8.
[2]. Li S, et al. High metastaticgastric and breast cancer cells consume oleic acid in an AMPK dependent manner. PLoS One. 2014 May 13;9(5):e97330.
[3]. Sci Rep. 2024 Jan 8;14(1):755. doi: 10.1038/s41598-023-50464-y.

Therapeutic Uses
/EXPTL THER/ Ten Japanese boys with childhood adrenoleukodystrophy (ALD), one adult patient with adrenomyeloneuropathy (AMN), and two presymptomatic ALD boys were treated with dietary erucic acid (C22:1) for more than 12 months; except in a case of childhood ALD patient who died 7 months after beginning erucic acid therapy. During erucic acid therapy, the serum levels of very long-chain fatty acid (VLCFA) (C24:0/C22:0) decreased within 1-2 months in all patients, and these levels in four of the patients decreased to the normal range. Neurological examination and MRI findings in all 10 of the childhood ALD patients showed progression of the disease while they were receiving the dietary therapy. However, the mean interval between the onset of awkward gait and a vegetative state in diet-treated patients was significantly longer than that in the untreated patients. One AMN patient showed slight improvement of spastic gait and lessened pain in the lower limbs due to spasticity. The two presymptomatic ALD boys remained intact on clinical examination and on MRI findings for 38 and 23 months, respectively, after starting the diet.
/EXPL THER/ An open 2 yr trial of oleic and erucic acids (Lorenzos oil) included 14 men with adrenomyeloneuropathy, 5 symptomatic heterozygous women and 5 boys with preclinical adrenomyeloneuropathy. No evidence of a clinically relevant benefit from dietary treatment in patients with adrenomyeloneuropathy (accumulation of very-long-chain fatty acids) could be found. /Lorenzos oil/

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Drug Warnings
40 male and 6 female patients with adrenoleukodystrophy received Lorenzos oil (20% erucic acid and 80% oleic acid). In 19 of these patients the platelet count decr significantly. In 6 patients with thrombocytopenia, platelet counts became normal within 2 to 3 mo after erucic acid was omitted from the diet. Observations suggested that strategies for the dietary management of adrenoleukodystrophy requiring the admin of large amt of erucic acid may be associated with thrombocytopenia and that the erucic acid component of Lorenzos oil is the cause of the thrombocytopenia. Patients treated with erucic acid should be followed closely with determinations of the platelet count. /Lorenzos oil: 20% erucic acid and 80% oleic acid/
15 men with adrenoleukodystrophy and 3 symptomatic heterozygous women were admin oleic and erucic acids (Lorenzos oil). Asymptomatic thrombocytopenia developed in 5 patients (platelet counts ranged between 37000 and 84000 per cu mm) but was reversed within 2 to 3 wk after erucic acid was omitted. In addition, long-term treatment with Lorenzos oil (for 24 to 43 mo) was associated with lymphocytopenia in these 5 patients. The observations suggested that the long-term treatment of adrenoleukodystrophy with Lorenzos oil can induce severe lymphocytopenia with immunosuppression and recurrent infections. /Lorenzos oil/

C18H34O2

282.468

282.255

C, 76.54; H, 12.13; O, 11.33

112-80-1

Sodium oleate;143-19-1;Oleic acid-13C;82005-44-5;Oleic acid-d2;5711-29-5;Glycerol Monoleate;25496-72-4;Oleic acid-13C18;287100-82-7;Oleic acid-d17;223487-44-3;Oleic acid-13C-1;2483735-58-4;Oleic acid-d9;2687960-84-3

445639

Colorless to light yellow liquid

0.9±0.1 g/cm3

360.0±0.0 °C at 760 mmHg

13-14 °C(lit.)

270.1±14.4 °C

0.0±1.7 mmHg at 25°C

1.467

Endogenous Metabolite

7.7

37.3

1

2

15

20

234

0

O([H])C(C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])/C(/[H])=C(/[H])\C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H])=O

ZQPPMHVWECSIRJ-KTKRTIGZSA-N

InChI=1S/C18H34O2/c1-2-3-4-5-6-7-8-9-10-11-12-13-14-15-16-17-18(19)20/h9-10H,2-8,11-17H2,1H3,(H,19,20)/b10-9-

9-Octadecenoic acid (9Z)-

D 100 Oleic acid9-cis-Octadecenoic acid9Z-Octadecenoic acid

2934.99.9001

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

Ethanol : ~100 mg/mL (~354.03 mM)
0.1 M NaOH : ~100 mg/mL (~354.03 mM)
DMSO : ≥ 62.5 mg/mL (~221.27 mM)

配方 1 中的溶解度: ≥ 2.5 mg/mL (8.85 mM) (饱和度未知) in 10% EtOH + 40% PEG300 + 5% Tween80 + 45% Saline (这些助溶剂从左到右依次添加，逐一添加), 澄清溶液。
例如，若需制备1 mL的工作液，可将100 μL 25.0 mg/mL 澄清 EtOH 储备液加入到400 μL PEG300中，混匀；再向上述溶液中加入50 μL Tween-80，混匀；然后加入450 μL 生理盐水定容至1 mL。
*生理盐水的制备：将 0.9 g 氯化钠溶解在 100 mL ddH₂O中，得到澄清溶液。

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配方 2 中的溶解度: ≥ 2.5 mg/mL (8.85 mM) (饱和度未知) in 10% EtOH + 90% (20% SBE-β-CD in Saline) (这些助溶剂从左到右依次添加，逐一添加), 澄清溶液。
例如，若需制备1 mL的工作液，可将 100 μL 25.0 mg/mL 澄清乙醇储备液加入 900 μL 20% SBE-β-CD 生理盐水溶液中，混匀。
*20% SBE-β-CD 生理盐水溶液的制备（4°C，1 周）：将 2 g SBE-β-CD 溶解于 10 mL 生理盐水中，得到澄清溶液。

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配方 3 中的溶解度: ≥ 2.5 mg/mL (8.85 mM) (饱和度未知) in 10% EtOH + 90% Corn Oil (这些助溶剂从左到右依次添加，逐一添加), 澄清溶液。
例如，若需制备1 mL的工作液，可将 100 μL 25.0 mg/mL 澄清乙醇储备液添加到 900 μL 玉米油中并混合均匀。

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配方 4 中的溶解度: ≥ 2.08 mg/mL (7.36 mM) (饱和度未知) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (这些助溶剂从左到右依次添加，逐一添加), 澄清溶液。
例如，若需制备1 mL的工作液，可将100 μL 20.8 mg/mL澄清的DMSO储备液加入400 μL PEG300中，混匀；再向上述溶液中加入50 μL Tween-80，混匀；然后加入450 μL生理盐水定容至1 mL。
*生理盐水的制备：将 0.9 g 氯化钠溶解在 100 mL ddH₂O中，得到澄清溶液。

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配方 5 中的溶解度: ≥ 2.08 mg/mL (7.36 mM) (饱和度未知) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (这些助溶剂从左到右依次添加，逐一添加), 澄清溶液。
例如，若需制备1 mL的工作液，可将100μL 20.8mg/mL澄清的DMSO储备液加入到900μL 20％SBE-β-CD生理盐水中，混匀。
*20% SBE-β-CD 生理盐水溶液的制备（4°C，1 周）：将 2 g SBE-β-CD 溶解于 10 mL 生理盐水中，得到澄清溶液。

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配方 6 中的溶解度: ≥ 2.08 mg/mL (7.36 mM) (饱和度未知) in 10% DMSO + 90% Corn Oil (这些助溶剂从左到右依次添加，逐一添加), 澄清溶液。
例如，若需制备1 mL的工作液，可将 100 μL 20.8 mg/mL 澄清 DMSO 储备液加入到 900 μL 玉米油中并混合均匀。

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请根据您的实验动物和给药方式选择适当的溶解配方/方案：
1、请先配制澄清的储备液(如：用DMSO配置50 或 100 mg/mL母液(储备液));
2、取适量母液，按从左到右的顺序依次添加助溶剂，澄清后再加入下一助溶剂。以 下列配方为例说明 (注意此配方只用于说明，并不一定代表此产品 的实际溶解配方):
10% DMSO → 40% PEG300 → 5% Tween-80 → 45% ddH2O (或 saline);
假设最终工作液的体积为 1 mL, 浓度为5 mg/mL: 取 100 μL 50 mg/mL 的澄清 DMSO 储备液加到 400 μL PEG300 中，混合均匀/澄清；向上述体系中加入50 μL Tween-80，混合均匀/澄清；然后继续加入450 μL ddH2O (或 saline)定容至 1 mL；
3、溶剂前显示的百分比是指该溶剂在最终溶液/工作液中的体积所占比例;
4、 如产品在配制过程中出现沉淀/析出，可通过加热(≤50℃)或超声的方式助溶;
5、为保证最佳实验结果，工作液请现配现用！
6、如不确定怎么将母液配置成体内动物实验的工作液，请查看说明书或联系我们;
7、 以上所有助溶剂都可在 Invivochem.cn网站购买。