• Molecules and Cells
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• v.42 no.3
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• pp.252-261
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• 2019

The omega-3 fatty acid docosahexaenoic acid (DHA) is known to induce apoptosis and cell cycle arrest via the induction of reactive oxygen species (ROS) production and endoplasmic reticulum (ER) stress in many types of cancers. However, the roles of DHA in drug-resistant cancer cells have not been elucidated. In this study, we investigated the effects of DHA in cisplatin-resistant gastric cancer SNU-601/cis2 cells. DHA was found to induce ROS-dependent apoptosis in these cells. The inositol 1,4,5-triphosphate receptor ($IP_3R$) blocker 2-aminoethyl diphenylboninate (2-APB) reduced DHA-induced ROS production, consequently reducing apoptosis. We also found that G-protein-coupled receptor 120 (GPR120), a receptor of long-chain fatty acids, is expressed in SNU-601/cis2 cells, and the knockdown of GPR120 using specific shRNAs alleviated DHA-mediated ROS production and apoptosis. GPR120 knockdown reduced the expression of ER stress response genes, similar to the case for the pre-treatment of the cells with N-acetyl-L-cysteine (NAC), an ROS scavenger, or 2-APB. Indeed, the knockdown of C/EBP homologous protein (CHOP), a transcription factor that functions under ER stress conditions, markedly reduced DHA-mediated apoptosis, indicating that CHOP plays an essential role in the anti-cancer activity of DHA. These results suggest that GPR120 mediates DHA-induced apoptosis by regulating $IP_3R$, ROS, and ER stress levels in cisplatin-resistant cancer cells, and that GPR120 is an effective chemotherapeutic target for cisplatin resistance.

• Nutrition Research and Practice
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• v.13 no.4
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• pp.286-294
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• 2019

BACKGROUND/OBJECTIVES: Docosahexaenoic acid (DHA), an n-3 long chain polyunsaturated fatty acid (LCPUFA), is acquired by dietary intake or the in vivo conversion of ${\alpha}$-linolenic acid. Many enzymes participating in LCPUFA synthesis are regulated by peroxisome proliferator-activated receptor alpha ($PPAR{\alpha}$). Therefore, it was hypothesized that the tissue accretion of endogenously synthesized DHA could be modified by $PPAR{\alpha}$. MATERIALS/METHODS: The tissue DHA concentrations and mRNA levels of genes participating in DHA biosynthesis were compared among $PPAR{\alpha}$ homozygous (KO), heterozygous (HZ), and wild type (WT) mice (Exp I), and between WT mice treated with clofibrate ($PPAR{\alpha}$ agonist) or those not treated (Exp II). In ExpII, the expression levels of the proteins associated with DHA function in the brain cortex and retina were also measured. An n3-PUFA depleted/replenished regimen was applied to mitigate the confounding effects of maternal DHA. RESULTS: $PPAR{\alpha}$ ablation reduced the hepatic Acox, Fads1, and Fads2 mRNA levels, as well as the DHA concentration in the liver, but not in the brain cortex. In contrast, $PPAR{\alpha}$ activation increased hepatic Acox, Fads1, Fads2, and Elovl5 mRNA levels, but reduced the DHA concentrations in the liver, retina, and phospholipid of brain cortex, and decreased mRNA and protein levels of the brain-derived neurotrophic factor in brain cortex. CONCLUSIONS: LCPUFA enzyme expression was altered by $PPAR{\alpha}$. Either $PPAR{\alpha}$ deficiency or activation-decreased tissue DHA concentration is a stimulus for further studies to determine the functional significance.

• Asian-Australasian Journal of Animal Sciences
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• v.24 no.1
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• pp.130-136
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• 2011

Methane is known to be one of the major greenhouse gases. On a global scale, livestock farming may contribute 18% of total greenhouse gas emissions. Though methane contribution is less than 2% of all the factors leading to global warming, it plays an important role because it is 21 times more effective than carbon dioxide. Methane emission is a direct result of the fermentation process performed by ruminal microorganisms and, in particular, the archael methanogens. Reducing methane emission would benefit both ruminant production and the environment. Methane generation can be reduced by electron-sink metabolic pathways to dispose of the reducing moieties. An alternative way for methane control in the rumen is to apply inhibitors against methanogens. Generating methane from manure has considerable merit because it appears to offer at least a partial solution to two pressing problems-environmental crisis and energy shortage. An obvious benefit from methane production is the energy value of the gas itself. Control of methane emission by rumen microbes in Korea has mainly been focused on application of various chemicals, such as BES and PMDI, that inhibit the growth and activity of methanogens in the rumen. Alternatives were to apply long-chain polyunsaturated fatty acids and oils with or without organic acids (malate and fumarate). The results for trials with methane reducing agents and the situation of biogas production industries and a typical biogas plant in Korea will be introduced here.

• Pediatric Gastroenterology, Hepatology & Nutrition
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• v.23 no.1
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• pp.98-104
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• 2020

Purpose: To investigate the impact of omega-3-enriched lipid emulsion (LE) on liver enzyme (aspartate transaminase [AST] and alanine aminotransferase [ALT]) and triglyceride (TG) levels of children undergoing gastrointestinal surgery. Methods: This experimental randomized controlled group pretest-posttest design study included 14 children who underwent gastrointestinal surgery due to duodenal atresia, jejunal atresia, esophageal atresia, and need for parenteral nutrition for a minimum of 3 days at RSUD Dr. Soetomo Surabaya between August 2018 and January 2019. These children were divided into two groups, those who received standard intravenous LE (medium-chain triglyceride [MCT]/long-chain triglyceride [LCT]) and those who received intravenous omega-3-enriched LE. Differences in AST, ALT, and TG levels were measured before surgery and 3 days after the administration of parenteral nutrition. Results: Liver enzyme and TG levels in each group did not differ significantly before versus 3 days after surgery. However, TG levels were significantly lower in the omega-3-enriched intravenous LE group (p=0.041) at 3 days after surgery, and statistically significant difference in changes in TG levels was noted at 3 days after surgery between MCT/LCT intravenous LE group and the omega-3-enriched intravenous LE group (p=0.008). Conclusion: The intravenous omega-3-enriched LE had a better TG-lowering effect than the MCT/LCT intravenous LE in children undergoing gastrointestinal surgery.

• Clinical and Experimental Pediatrics
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• v.57 no.9
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• pp.416-419
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• 2014

X-linked adrenoleukodystrophy (X-ALD) is a rare peroxisomal disorder, that is rapidly progressive, neurodegenerative, and recessive, and characteristically primary affects the central nervous system white matter and the adrenal cortex. X-ALD is diagnosed basaed on clinical, radiological, and serological parameters, including elevated plasma levels of very long chain fatty acids (VLCFA), such as C24:0 and C26:0, and high C24:0/C22:0 and C26:0/C22:0 ratios. These tests are complemented with genetic analyses. A 7.5-year-old boy was admitted to Department of Pediatrics, Chungnam National University Hospital with progressive weakness of the bilateral lower extremities. Brain magnetic resonance imaging confirmed clinically suspected ALD. A low dose adrenocorticotropic hormone stimulation test revealed parital adrenal insufficiency. His fasting plasma levels of VLCFA showed that his C24:0/C22:0 and C26:0/C22:0 ratios were significantly elevated to 1.609 (normal, 0-1.390) and 0.075 (normal, 0-0.023), respectively. Genomic DNA was extracted from peripheral whole blood samples collected from the patient and his family. All exons of ABCD1 gene were amplified by polymerase chain reaction (PCR) using specific primers. Amplified PCR products were sequenced using the same primer pairs according to the manufacturer's instructions. We identified a missense mutation (p.Arg163Leu) in the ABCD1 gene of the proband caused by the nucleotide change 488G>T in exon 1. His asymptomatic mother carried the same mutation. We have reported an unpublished mutation in the ABCD1 gene in a patient with X-ALD, who showed increased ratio of C24:0/C22:0 and C26:0/C22:0, despite a normal VLCFA concentrations.

• Journal of the Society of Cosmetic Scientists of Korea
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• v.30 no.3 s.47
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• pp.345-352
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• 2004

There are two paradigms to explain the atopic dermatitis. The first is outside-inside paradigm and the second is inside-outside paradigm. According to the outside-inside paradigm the best way to treat the atopic dermatitis is recovery of skin barrier function. The barrier function is maintained by the specific structure of stratum corneum, which is constructed from corneocytes and intercellular lipids. In terms of lipid structures of SC in atopic dermatitis and lamellar ichthyosis, they contain more fluid hexagonal gel structures in SC and show deficiencies in free fatty acids, especially long chains and certain ceramides. With this reason, moisturizer which has the lamellar structure and restoring function of intrinsic intercellualr long periodicity phase can maintain and restore the lamellar structure of intercellular lipids in SC. The moisturizers containing ceramide or pseudoceramide also seem to be reasonable therapy for atopic dermatitis and several skin diseases, which interrelated with impaired skin harrier. By the way, according to the inside-outside paradigm, immune response including helper T cells, IgE, eosinophils is related. It is effective treatment of atopic dermititis to restore imbalance between Th1 and Th2 cells. Even though several kinds of immune-suppressor were introduced, these can affect the intrinsic immune function. SPC and S1P, metabolites of ceramide, would be interesting because they have the function of wound healing and immune modulating properties.

• Journal of Animal Science and Technology
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• v.46 no.5
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• pp.783-798
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• 2004

This experiment were conducted to determine the formation of fatty acid soaps, digestibility and ruminal characteristics when vegetable oils were added. Three Corriedale${\times}$ 3 Latin square design. Sheep were fed one of three diets consisting of alfalfa hay and concentrates in a ratio of 70:30. Dietary treatments were 1) no oil, 2) 7% soybean oil and 3) 7% corn oil. At the end of each experimental period, rumen contents from each sheep were collected before feeding and at 1, 3, 6 and 9h after feeding. pH decreased up to the 3 hour after feeding and increased until the end of the collection(p<0.0001). Whereas the concentration of $NH_3$-N showed inverse changes to pH(p<0.0001). Type of oil did not affect the molar concentration of total VFA, acetate, propionate and butyrate. Acetic/propionic acid (A/P) ratio decreased with increasing time(P<0.0001), but the ratio at the end of the experiment became similar to the initial value. No effects were found in the digestibility of dry matter, total-N, crude fiber, ash, NFE, NDF and ADF. The formation of fatty acid soaps(FAS) increased after feeding than 1 hour before feeding(P<0.05) and increased in 7% oils than no oil addition(P<0.05). Long chain fatty acids formed mainly FAS. ince the formation of FAS might decrease negative effects on ruminal haracteristics and total tract digestibility.

• Asian-Australasian Journal of Animal Sciences
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• v.22 no.5
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• pp.681-685
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• 2009

L-carnitine promotes mitochondrial ${\beta}$-oxidation of long chain fatty acids and their subsequent transport across the inner mitochondrial membrane. Although the role of L-carnitine in fatty acid metabolism has been extensively studied, its role in live performance and carcass responses of commercial broilers is less understood. The objective of this research was to determine if Lcarnitine fed at various levels in diets differing in CP and amino acids impacted on live performance and carcass characteristics of commercial broilers. Two floor pen experiments were conducted to assess the effect of dietary L-carnitine in grower diets. In Exp. 1, Ross${\times}$Hubbard Ultra Yield broilers were placed in 48 floor pens (12 birds/pen) and fed common diets to d 14. A two (0 or 50 ppm Lcarnitine) by three (173, 187, and 202 g/kg CP) factorial arrangement of treatments was employed from 15 to 35 d of age (8 replications/treatment). An interaction (p<0.05) in carcass yield indicated that increasing CP (187 g/kg) resulted in improved yield in the presence of L-carnitine. Increasing CP from 173 to 202 g/kg increased (p<0.05) BW gain and decreased (p<0.05) feed conversion and percentage abdominal fat. Feeding dietary L-carnitine increased back-half carcass yield which was attributable to an increase (p<0.05) in thigh, but not drumstick, yield relative to carcass. In Exp. 2, $Ross{\times}Ross$ 708 broilers were fed common diets until 29 d. From 30 to 42 d of age, birds were fed one of seven diets: i) 200 g/kg CP, 0 ppm L-carnitine; ii) 200 g/kg CP, 40 ppm L-carnitine; iii) 180 g/kg CP, 0 ppm L-carnitine; iv) 180 g/kg CP, 10 ppm L-carnitine; v) 180 g/kg CP, 20 ppm L-carnitine; vi) 180 g/kg CP, 30 ppm L-carnitine; and vii) 180 g/kg CP, 40 ppm L-carnitine (6 replications of 12 birds each). BW gain, feed conversion, mortality (30 to 42 d), and carcass traits (42 d) were measured on all birds by pen. There were no treatment differences (p<0.05). However, the addition of 40 ppm L-carnitine in the 200 g CP/kg diet increased (p = 0.06) thigh yields relative to BW in comparison to birds fed diets without L-carnitine, which was further confirmed via a contrast analysis (0 vs. 40 ppm L-carnitine in the 200 and 180 g CP/kg diets; p<0.05). These results indicated that dietary L-carnitine may heighten metabolism in dark meat of commercial broilers resulting in increased relative thigh tissue accretion without compromising breast accretion.

• Asian-Australasian Journal of Animal Sciences
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• v.33 no.1
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• pp.148-156
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• 2020

Objective: This study aimed to evaluate the effect of dietary integration with extruded linseed (EL) on fatty acid (FA) and aromatic profile of goat cheese after 60 (T₆₀) days of ripening. Methods: Thirty goats were divided in two groups. The control group (CG) was fed with conventional diet, whereas the experimental group (EL+) was fed with conventional diet supplemented with 10% of EL. Milk samples were collected on 30 and 60 days of trial to determinate chemical-nutritional composition and FA profile. At the end of experiment, six cheese-making sessions (3 for each group) were carried out using a pooled milk sample obtained from the 15 goats of each group. At 60 days of ripening, cheeses were analyzed for chemical-nutritional composition, FA and aromatic profile. Results: An increase in the milk production, protein, fat and lactose were evidenced in the EL+ goats. Conversely, a reduction of somatic cells was observed in the EL+ compared with the CG. However, no variation was observed for urea and casein levels content in milk samples, and no changes in protein and lipid content were found for cheeses in the two experimental groups. Dietary supplementation with EL modified the FA profile of milk. There was a decrease in saturated FAs and an increase in polyunsaturated FAs. Chemical composition of T₆₀ cheese did not differ between the two groups but a different FA profile was observed. In T₆₀ cheese obtained from EL+ milk, an increase in short-chain FA and a decrease in medium and long-chain FA were observed. The EL diet led to cheeses with butanoic acid 2 times higher compared to CG cheeses. Moreover, a greater presence of aldehyde compounds and alcohols were observed in the cheeses of experimental group. Conclusion: The present study pointed out that EL supplementation may improve the chemical and physical qualities of goat milk and cheeses.

• Korean Journal of Poultry Science
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• v.50 no.4
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• pp.283-291
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• 2023

Long-chain fatty acids (LCFAs) are vital in cellular compartments, primarily regulating lipid metabolism. Fatty Acid-Binding Proteins (FABPs) facilitate LCFA transport, lipid synthesis, storage, and act as signaling molecules influencing various pathways, including inflammation. FABP4, in particular, is linked to vascular and cardio-related diseases, and it plays a role in macrophage-mediated inflammatory responses. Previous studies have identified FABP4 as not only a representative biomarker for lipogenesis but also as having correlations with immune responses. This study aims to investigate the regulation of the chicken FABP4 (chFABP4) gene by toll-like receptor 3 (TLR3) activation and determine the signaling pathways that are involved in chFABP4 transcriptional regulation. We analyzed the transcriptional regulation of chFABP4 in TLR3-stimulated DF-1 cells. The results showed that chFABP4 was up-regulated upon stimulation with polyinosinic-polycytidylic acid (PIC), a TLR3 ligand. Notably, chFABP4 transcription was independently regulated in the NF-κB signaling pathway. It was up-regulated in p38 inhibition, demonstrating that the p38 signaling pathway might suppress the transcription of chFABP4 within TLR3-activated DF-1 cells. In contrast, chFABP4 expression was down-regulated in JNK signaling pathway inhibition, suggesting the positive regulation of JNK signaling pathway for chFABP4 transcription in DF-1 cells in response to TLR3 activation, consistent with findings in macrophages. MEK pathway inhibition resulted in a similar regulation to NF-κB signaling. These results suggest that each MAPK contributes differentially to the transcriptional regulation of chFABP4 by in DF-1 cells in response to TLR3 activation.