OBJECTIVE: To elucidate the mechanism of Lizhong Decoction (LZD) in treating dextran sodium sulfate (DSS)-induced colitis in mice based on metabonomics. METHODS: Thirty-six mice were randomly divided into 6 groups, including normal, model, low- (1.365 g/kg), medium- (4.095 g/kg) and high dose (12.285 g/kg) LZD and salazosulfadimidine (SASP) groups, 6 mice in each group. Colitis model mice were induced by DSS admistration for 7 days, and treated with low, medium and high dose LZD extract and positive drug SASP. Metabolic comparison of DSS-induced colitis and normal mice was investigated by using ultra-performance liquid chromatography coupled to quadrupole time-of-flight mass (UPLC-Q-TOF/MS) combined with Metabolynx™ software. RESULTS: The metabolic profiles of plasma and urine in colitis mice were distinctly ameliorated after LZD treatment (P<0.05). Potential biomarkers (9 in serum and 4 in urine) were screened and tentatively identified. The endogenous metabolites were mainly involved in primary bile acid, sphingolipid, linoleic acid, arachidonic acid, amino acids (alanine, aspartate, and glutamate), butanoate and glycerophospholipid metabolism in plasma, and terpenoid backbone biosynthesis, glycerophospholipid and tryptophan metabolism in urine. After LZD treatment, these markers notably restored to normal levels. CONCLUSIONS The study revealed the underlying mechanism of LZD on amelioration of ulcerative colitis based on metabonomics, which laid a foundation for further exploring the pathological and physiological mechanism, early diagnosis, and corresponding drug development of colitis.
Mice ; Animals ; Colitis, Ulcerative/drug therapy* ; Tryptophan/adverse effects* ; Aspartic Acid ; Dextrans/adverse effects* ; Drugs, Chinese Herbal/adverse effects* ; Colitis/drug therapy* ; Biomarkers/metabolism* ; Amino Acids/adverse effects* ; Glycerophospholipids/therapeutic use* ; Sphingolipids/adverse effects* ; Bile Acids and Salts/adverse effects* ; Glutamates/adverse effects* ; Alanine/adverse effects* ; Arachidonic Acids/adverse effects* ; Linoleic Acids/adverse effects* ; Terpenes

OBJECTIVE: To analyze the effect of conjugated linoleic acid (CLA) on glucose and lipid metabolism in obese diabetic (db/db) mice. METHODS: db/db mice were randomized for treatment with saline or CLA mixture administered intragastrically. The changes in body weight, dietary intake, water intake, oral glucose tolerance, triglyceride and total cholesterol were recorded after the treatments. HE staining and oil red O staining were used to assess liver pathologies and fatty acid content. The expression levels of PPARα, PPARγ, CD36, CHREBP and SREBP-1c were detected using real-time PCR and Western blotting. HepG2 cells were treated with CLA and linoleic acid and the expressions of PPARα, ACC, P-ACC, and CD36 were detected; the level of acetyl-CoA in the cell supernatant was detected using ELISA. RESULTS: CLA treatment obviously reduced the dietary and water intake of db/db mice, effectively reduced the body weight and decreased serum triglyceride and cholesterol levels ( < 0.05). CLA significantly reduced fasting blood glucose, increased glucose tolerance, reduced the accumulation of lipid droplets in the liver and improved lipid metabolism in db/db mice. The mice showed significantly increased expression of PPARα ( < 0.05) and lowered CD36 expression ( < 0.001) in the liver after CLA treatment. Cellular experiments showed that CLA significantly up-regulated PPARα ( < 0.001) and P-ACC and decreased the expression of CD36 ( < 0.01). ELISA showed that acetyl-CoA was significantly up-regulated in the cells after CLA treatment ( < 0.01). CONCLUSIONS The mixture of two conjugated linoleic acid isomers can reduce fasting blood glucose, increase glucose tolerance and improve glycolipid metabolism in db/db mice by enhancing the expression of PPARα, increasing P-ACC and inhibiting CD36 expression.
Animals ; Diabetes Mellitus, Experimental ; Glucose ; Linoleic Acids, Conjugated ; Lipid Metabolism ; Liver ; Mice ; Triglycerides

BACKGROUND/OBJECTIVES: Adequate dietary fatty acid intake is important for toddlers between 12–24 months of age, as this is a period of dietary transition in conjunction with rapid growth and development; however, actual fatty acid intake during this period seldom has been explored. This study was conducted to assess the intake status of n-3 and n-6 polyunsaturated fatty acids by toddlers during the 12–24-month period using 2010–2015 Korea National Health and Nutrition Examination Survey data. SUBJECTS/METHODS: Twenty-four-hour dietary recall data of 12–24-month-old toddlers (n = 544) was used to estimate the intakes of α-linolenic acid (ALA; 18:3n-3), eicosapentaenoic acid (EPA; 20:5n-3), docosahexaenoic acid (DHA; 22:6n-3), linoleic acid (LA; 18:2n-6), and arachidonic acid (AA; 20:4n-6), as well as the major dietary sources of each. The results were compared with the expected intake for exclusively breastfed infants in the first 6 months of life and available dietary recommendations. RESULTS: Mean daily intakes of ALA, EPA, DHA, LA, and AA were 529.9, 22.4, 37.0, 3907.6, and 20.0 mg/day, respectively. Dietary intakes of these fatty acids fell below the expected intake for 0–5-month-old exclusively breastfed infants. In particular, DHA and AA intakes were 4 to 5 times lower. The dietary assessment indicated that the mean intake of essential fatty acids ALA and LA was below the European and the FAO/WHO dietary recommendations, particularly for DHA, which was approximately 30% and 14–16% lower, respectively. The key sources of the essential fatty acids, DHA, and AA were soy (28.2%), fish (97.3%), and animals (53.7%), respectively. CONCLUSIONS: Considering the prevailing view of DHA and AA requirements on early brain development, there remains considerable room for improvement in their intakes in the diets of Korean toddlers. Further studies are warranted to explore how increasing dietary intakes of DHA and AA could benefit brain development during infancy and early childhood.
Animals ; Arachidonic Acid ; Brain ; Diet ; Eicosapentaenoic Acid ; Fatty Acids ; Fatty Acids, Essential ; Fatty Acids, Unsaturated ; Growth and Development ; Humans ; Infant ; Korea ; Linoleic Acid ; Nutrition Surveys

Free fatty acid (FFA) intake regulates blood pressure and vascular reactivity but its direct effect on contractility of systemic arteries is not well understood. We investigated the effects of saturated fatty acid (SFA, palmitic acid), polyunsaturated fatty acid (PUFA, linoleic acid), and monounsaturated fatty acid (MUFA, oleic acid) on the contractility of isolated mesenteric (MA) and deep femoral arteries (DFA) of Sprague–Dawley rats. Isolated MA and DFA were mounted on a dual wire myograph and phenylephrine (PhE, 1–10 µM) concentration-dependent contraction was obtained with or without FFAs. Incubation with 100 µM of palmitic acid significantly increased PhE-induced contraction in both arteries. In MA, treatment with 100 µM of linoleic acid decreased 1 µM PhE-induced contraction while increasing the response to higher PhE concentrations. In DFA, linoleic acid slightly decreased PhE-induced contraction while 200 µM oleic acid significantly decreased it. In MA, oleic acid reduced contraction at low PhE concentration (1 and 2 µM) while increasing it at 10 µM PhE. Perplexingly, depolarization by 40 mM KCl-induced contraction of MA was commonly enhanced by the three fatty acids. The 40 mM KCl-contraction of DFA was also augmented by linoleic and oleic acids while not affected by palmitic acid. SFA persistently increased alpha-adrenergic contraction of systemic arteries whereas PUFA and MUFA attenuated PhE-induced contraction of skeletal arteries. PUFA and MUFA concentration-dependent dual effects on MA suggest differential mechanisms depending on the types of arteries. Further studies are needed to elucidate underlying mechanisms of the various effects of FFA on systemic arteries.
Animals ; Arteries ; Blood Pressure ; Fatty Acids ; Fatty Acids, Unsaturated ; Femoral Artery ; Linoleic Acid ; Mesenteric Arteries ; Oleic Acid ; Oleic Acids ; Palmitic Acid ; Phenylephrine ; Rats ; Receptors, Adrenergic, alpha ; Vasoconstriction

Oenothera biennis with the common name of “evening primrose” is containing a valuable fixed oil with commercial name of EPO. Evening primrose oil has two types of omega-6-fatty acid including linoleic acid (60%–80%) and γ-linoleic acid (8%–14%). Essential fatty acids are considered as essential compounds for body health, especially among women. The aim of this study was to evaluate the efficacy of evening primrose oil in the management of women ailments. The document was prepared by investigation in scientific articles of electronic resources (Google Scholar, PubMed, Science Direct, Wiley, Scopus, and Springer) by keywords of evening primrose oil and women. The results of our investigations showed that evening primrose oil has been the subject of several clinical studies, including premenstrual syndrome (PMS), hot flash, mastalgia, fibroadenomas, gestational diabetes, cervical ripening, and dilation. The major clinical studies are focused on mastalgia, followed by PMS. The results of studies confirmed the evening primrose oil's efficacy in women health, but the immediate response should not be expected from it, therefore, it should be regularly used up to 4 or 6 months.
Cervical Ripening ; Diabetes, Gestational ; Fatty Acids, Essential ; Female ; Fibroadenoma ; Humans ; Linoleic Acid ; Mastodynia ; Oenothera biennis ; Pregnancy ; Premenstrual Syndrome

Studies have reported different changes in the fatty acid composition of red blood cell (RBC) total lipids in patients with various types of cancer. It has been indicated that n-3/n-6 ratio plays a key role in the general consequence of skin photocarcinogenesis. However, to our knowledge there was no study examining the unsaturated fatty acid profile in basal cell carcinoma (BCC) patients. So, we explore the fatty acid composition of RBCs in newly diagnosed BCC patients in a hospital-based case-control study. This study has been conducted on new case BCC patients in Razi Hospital, Tehran, Iran. Fatty acid concentration in erythrocyte membranes defined as relative values after extraction, purification and preparation, by gas chromatography.Analysis revealed that heptadecenoic acid (p = 0.010) and oleic acid (p < 0.001) was significantly higher in BCC patients in comparison with control group. Among polyunsaturated fatty acids (PUFAs), linoleic acid (LA), and arachidonic acid (AA) were significantly higher in BCC patients (p < 0.001). It has been indicated that n-3 was significantly lower (p = 0.040) and n-6 was significantly higher (p = 0.002) in BCC patients. In addition, total PUFA (p < 0.001) and n-6 PUFAs/n-3 PUFAs (p = 0.002) were significantly higher in BCC patients compared to the control group. Here we indicated that new case BCC patient had significantly higher n-6 PUFA and lower n-3 along with other differences in unsaturated fatty acid in comparison with healthy subjects. Our study provides evidence that lipids are important in BCC development.
Arachidonic Acid ; Carcinoma, Basal Cell ; Case-Control Studies ; Erythrocyte Membrane ; Erythrocytes ; Fatty Acids ; Fatty Acids, Unsaturated ; Healthy Volunteers ; Humans ; Iran ; Linoleic Acid ; Oleic Acid ; Skin

Acetic acid, as a main by-product generated in the pretreatment process of lignocellulose hydrolysis, significantly affects cell growth and lipid synthesis of oleaginous microorganisms. Therefore, we studied the tolerance of Rhodotorula glutinis to acetic acid and its lipid synthesis from substrate containing acetic acid. In the mixed sugar medium containing 6 g/L glucose and 44 g/L xylose, and supplemented with acetic acid, the cell growth was not:inhibited when the acetic acid concentration was below 10 g/L. Compared with the control, the biomass, lipid concentration and lipid content of R. glutinis increased 21.5%, 171% and 122% respectively when acetic acid concentration was 10 g/L. Furthermore, R. glutinis could accumulate lipid with acetate as the sole carbon source. Lipid concentration and lipid yield reached 3.20 g/L and 13% respectively with the initial acetic acid concentration of 25 g/L. The lipid composition was analyzed by gas chromatograph. The main composition of lipid produced with acetic acid was palmitic acid, stearic acid, oleic acid, linoleic acid and linolenic acid, including 40.9% saturated fatty acids and 59.1% unsaturated fatty acids. The lipid composition was similar to that of plant oil, indicating that lipid from oleaginous yeast R. glutinis had potential as the feedstock of biodiesel production. These results demonstrated that a certain concentration of acetic acid need not to be removed in the detoxification process when using lignocelluloses hydrolysate to produce microbial lipid by R. glutinis.
Acetic Acid ; Biofuels ; Biomass ; Culture Media ; Fatty Acids ; Hydrolysis ; Industrial Microbiology ; Lignin ; chemistry ; Linoleic Acid ; Lipids ; biosynthesis ; Oleic Acid ; Rhodotorula ; metabolism

Aims: Dietary intake of conjugated linoleic acid (CLA) by human is insufficient to exhibit properties of anti-cancer, antiinflammatory, anti-atherosclerosis, anti-obesity and enhancing immune system. Thus, enrichment of CLA in chicken by bacteria is a suggestion to solve the problem. It would be an advantage to have bacteria capable of producing CLA and has probiotic potential in chicken. Thus, probiotic properties of CLA-producing bacteria were accessed in this study. Methodology and results: In this study, 47 lactic acid bacteria (LAB) isolated from gastrointestinal tract of chickens were screened for conjugated linoleic acid (CLA) production. Lactobacillus salivarius strain P2, Enterococcus faecium strain P1 and Lactobacillus agilis strain P3 were shown to produce 21.97, 23.35 and 31.08 µg/mL of CLA in MRS broth containing free linoleic acid (0.5 mg/mL) and 2% (w/v) Tween 80, respectively. Lactobacillus salivarius strain P2, E. faecium strain P1 and L. agilis strain P3 were found to be able to tolerate 0.3% oxgall (Difco, France) and pH 2.5. Lactobacillus agilis strain P3 and L. salivarius strain P2 showed better acid tolerance compared to E. faecium strain P1. Besides that, L. agilis strain P3 and L. salivarius strain P2 were resistant to two out of eight types of antibiotics tested, able to produce 220.04 mM lactic acid and 200.17 mM of lactic acid, respectively. Enterococcus faecium strain P1 was resistant to five out of eight types of antibiotic tested, produced 90.39 mM lactic acid and showed hemolytic activity. Only L. agilis strain P3 can produce acetic acid at a concentration of 2.71 mM. Conclusion, significance and impact of study: These results showed that the CLA-producing L. salivarius strain P2 and L. agilis strain P3 could be potential probiotic bacteria for chickens, which may eventually lead to production of chicken with better meat quality.
Linoleic Acids, Conjugated ; Probiotics

Conjugated linoleic acids (CLA) are a family of isomers of linoleic acid. CLA increases growth arrest and apoptosis of human colorectal cancer cells through an isomer-specific manner. ATF3 belongs to the ATF/CREB family of transcription factors and is associated with apoptosis in colorectal cancer. The present study was performed to investigate the molecular mechanism by which t10, c12-CLA stimulates ATF3 expression and apoptosis in human colorectal cancer cells. t10, c12-CLA increased an apoptosis in human colorectal cancer cells in dose dependent manner. t10, c12-CLA induced ATF3 mRNA and luciferase activity of ATF3 promoter in a dose-dependent manner. The responsible region for ATF3 transcriptional activation by t10, c12-CLA is located between -147 and -1850 of ATF3 promoter. mRNA stability of ATF3 was not affected by t10, c12-CLA treatment. t10, c12-CLA increases GSK3beta expression and suppresses IGF-1-stimulated phosphorylation of Akt. The knockdown of ATF3 suppressed expression of GSK3beta and NAG-1 and PARP cleavage. The results suggest that t10, c12-CLA induces apoptosis through ATF3-mediated pathway in human colorectal cancer cells.
Activating Transcription Factor 3 ; Apoptosis ; Colonic Neoplasms* ; Colorectal Neoplasms ; Humans ; Linoleic Acid* ; Linoleic Acids, Conjugated ; Luciferases ; Phosphorylation ; RNA Stability ; RNA, Messenger ; Transcription Factors ; Transcriptional Activation

DHA (22:6n-3) is a Ω-3 polyunsaturated fatty acid with 22 carbon atoms and 6 double bonds, which has important biological functions in human body. Human and other mammals synthesize only limited amounts of DHA, more requirements must be satisfied from food resources. However, the natural resources of DHA (Mainly deep-sea fish and other marine products) are prone to depletion. New resources development is still insufficient to satisfy the growing market demand. Previous studies have revealed that the mammals can increase the synthesis of DHA and other long-chain polyunsaturated fatty acids after transgenic procedures. In this study, mammalian cells were transfected with Δ6, Δ5 desaturase, Δ6, Δ5 elongase, Δ15 desaturase (Isolated from nematode Caenorhabditis elegans) and Δ4 desaturase (Isolated from Euglena gracilis), simultaneously. Results show that the expression or overexpression of these 6 enzymes is capable of conversion of the o-6 linoleic acid (LA, 18:2n-6) in DHA (22:6n-3). DHA content has increased from 16.74% in the control group to 25.3% in the experimental group. The strategy and related technology in our research provided important data for future production the valuable DHA (22:6n-3) by using genetically modified animals.
Animals ; Caenorhabditis elegans ; enzymology ; Cells, Cultured ; Docosahexaenoic Acids ; chemistry ; Euglena gracilis ; enzymology ; Fatty Acid Desaturases ; biosynthesis ; Linoleic Acid ; chemistry ; Mammals ; Transfection