• Asian-Australasian Journal of Animal Sciences
• /
• v.32 no.11
• /
• pp.1789-1800
• /
• 2019

Objective: Although alveolar macrophages play a key role in the respiratory immunity of livestock, studies on the mechanism of differentiation and survival of alveolar macrophages are lacking. Therefore, we undertook to investigate changes in the lipid metabolism and survival rate, using 3D4/31 macrophages and Dudleya brittonii which has been used as a traditional asthma treatment. Methods: 3D4/31 macrophages were used as the in vitro porcine alveolar macrophages model. The cells were activated by exposure to phorbol 12-myristate 13-acetate (PMA). Dudleya brittonii extraction was performed with distilled water. For evaluating the cell survival rate, we performed the water-soluble tetrazolium salt cell viability assay and growth curve analysis. To confirm cell death, cell cycle and intracellular reactive oxygen species (ROS) levels were measured using flow cytometric analysis by applying fluorescence dye dichlorofluorescein diacetate and propidium iodide. Furthermore, we also evaluated cellular lipid accumulation with oil red O staining, and fatty acid synthesis related genes expression levels using quantitative polymerase chain reaction (qPCR) with SYBR green dye. Glycolysis, fatty acid oxidation, and tricarboxylic acid (TCA) cycle related gene expression levels were measured using qPCR after exposure to Dudleya brittonii extract (DB) for 12 h. Results: The ROS production and cell death were induced by PMA treatment, and exposure to DB reduced the PMA induced downregulation of cell survival. The PMA and DB treatments upregulated the lipid accumulation, with corresponding increase in the acetyl-CoA carboxylase alpha, fatty acid synthase mRNA expressions. DB-PMA co-treatment reduced the glycolysis genes expression, but increased the expressions of fatty acid oxidation and TCA cycle genes. Conclusion: This study provides new insights and directions for further research relating to the immunity of porcine respiratory system, by employing a model based on alveolar macrophages and natural materials.

• BMB Reports
• /
• v.55 no.9
• /
• pp.413-416
• /
• 2022

Ferroptosis is a type of programmed cell death distinct from apoptosis or necroptosis. Ferroptosis is well characterized by an iron-dependent accumulation of lipid peroxides and disruption of cellular membrane integrity. Many metabolic alterations can prevent or accelerate ferroptosis induction. Recent advances in analytical techniques of mass spectrometry have allowed high-throughput analysis of metabolites known to be critical for understanding ferroptosis regulatory metabolism. In this review, we introduce mass spectrometry-based analytical methods contributing to recent discovery of various metabolic pathways regulating ferroptosis, focusing on cysteine metabolism, antioxidant metabolism, and poly-unsaturated fatty acid metabolism.

• Asian-Australasian Journal of Animal Sciences
• /
• v.33 no.7
• /
• pp.1167-1179
• /
• 2020

Objective: This study was conducted to fathom the underlying mechanisms of nutrition intervention and redox sensitive transcription factors regulated by Antrodia cinnamomea fermented product (FAC) dietary supplementation in broiler chickens. Methods: Four hundreds d-old broilers (41±0.5 g/bird) assigned to 5 groups were examined after consuming control diet, or control diet replaced with 5% wheat bran (WB), 10% WB, 5% FAC, and 10% FAC. Liver mRNA expression of antioxidant, inflammatory and lipid metabolism pathways were analyzed. Prostaglandin E2 (PGE₂) concentration in each group were tested in the chicken peripheral blood mononuclear cells (cPBMCs) of 35-d old broilers to represent the stress level of the chickens. Furthermore, these cells were stimulated with 2,2'-Azobis(2-amidinopropane) dihydrochloride (AAPH) and lipopolysaccharide (LPS) to evaluate the cell stress tolerance by measuring cell viability and oxidative species. Results: Heme oxygenase-1, glutathione S-transferase, glutamate-cysteine ligase, catalytic subunit, and superoxide dismutase, and nuclear factor (erythroid-derived 2)-like 2 (Nrf2) that regulates the above antioxidant genes were all up-regulated significantly in FAC groups. Reactive oxygen species modulator protein 1 and NADPH oxygenase 1 were both rather down-regulated in 10% FAC group as comparison with two WB groups. Despite expressing higher level than control group, birds receiving diet containing FAC had significantly lower expression level in nuclear factor-kappa B (NF-κB) and other genes (inducible nitric oxide synthase, tumor necrosis factor-α, interleukin-1β, nucleotide-binding domain, leucine-richcontaining family, pyrin domain-containing-3, and cyclooxygenase 2) involving in inflammatory pathways. Additionally, except for 3-hydroxy-3-methyl-glutaryl-coenzyme A reductase that showed relatively higher in both groups, the WB, lipoprotein lipase, Acetyl-CoA carboxylase, fatty acid synthase, fatty acid binding protein, fatty acid desaturase 2 and peroxisome proliferator-activated receptor alpha genes were expressed at higher levels in 10% FAC group. In support of above results, promoted Nrf2 and inhibited NF-κB nuclear translocation in chicken liver were found in FAC containing groups. H₂O₂ and NO levels induced by LPS and AAPH in cPBMCs were compromised in FAC containing diet. In 35-d-old birds, PGE₂ production in cPBMCs was also suppressed by the FAC diet. Conclusion: FAC may promote Nrf2 antioxidant pathway and positively regulate lipid metabolism, both are potential inhibitor of NF-κB inflammatory pathway.

• Journal of Nutrition and Health
• /
• v.33 no.2
• /
• pp.124-133
• /
• 2000

This study evaluated the effects of chronic ethanol consumption and/or taurine supplementation on hepatic total, phospholipid fatty acid composition and the metabolism of rats fed one of three purified liquid diets for 8 weeks. the rats followed either the control diet (CD, ethanol-free and taurine-free diet); ethanol diet (ED, CD+ 50g ethanol/L) or ethanol-taurine diet (ETD, ED+3.75g taurne/L). Chronic ethanol consumption and/or dietary taurine supplementation were associated with altered hepatic total and phospholipid fatty acid composition. compared to the values for the control rats, ED or ETD significantly decreased the percentage of total monounsaturated fatty acids ($\Sigma$MUFA), and increased the percentage of total polyunsaturated fatty acids ($\Sigma$PUFA) of hepatic total lipids(p〈0.01). Percentages of 14:0(P〈0.01) and 16:0(p〈0.001) were sigificantly lower, and those of 18:0(p〈0.01), 20:0(p〈0.001), 20:3$\omega$6(p〈0.01) and 22:4$\omega$6(p〈0.01) in hepatic total fatty acid compositions were oserved in rats fed ETD versus those fed ED or ETD. No significant differences in hepatic total fatty acid compositions were observed in rats fed ETD versus those fed ED. Percentages of 24:0(p〈0.01), 16:1(p〈0.05), 20:1(p〈0.01), 18:2$\omega$6(p〈0.01) and 18:3$\omega$3(p〈0.05) in hepati phospholipids were significantly higher, and those of 14:0(p〈0.01), 16:0(p〈0.001), 20:3$\omega$3(p〈0.05) in hepatic phospholipids were significantly higher, and those of 14:0(p〈0.01), 16:0(p〈0.001), 20:3$\omega$3(p〈0.001), 22:6$\omega$3(p〈0.001) and $\Sigma$$\omega$3(P〈0.001) were significantly lower in rats fed ED or ETD compared to the values for the control rats. The Δ5 desaturation index(20:3$\omega$6⇒20:4$\omega$6) and elongation index (20:5$\omega$3⇒22:5$\omega$3) of hepatic phospholipid index (20:3$\omega$6⇒20:4$\omega$6) and decreased Δ4 desaturation index (22:5$\omega$3⇒22:6$\omega$3) compared to the values for the ED rats. These changes in hepatic fatty acid composition induced by chronic ethanol consumption and/or taurine supplementation might be associated with the modulations of physical properties of the hepatic cell membrane and its sensitivity to peroxidation damage.

• Journal of Ginseng Research
• /
• v.47 no.3
• /
• pp.376-384
• /
• 2023

Background: Hepatic lipid disorder impaired mitochondrial homeostasis and intracellular redox balance, triggering development of non-alcohol fatty liver disease (NAFLD), while effective therapeutic approach remains inadequate. Ginsenosides Rc has been reported to maintain glucose balance in adipose tissue, while its role in regulating lipid metabolism remain vacant. Thus, we investigated the function and mechanism of ginsenosides Rc in defending high fat diet (HFD)-induced NAFLD. Methods: Mice primary hepatocytes (MPHs) challenged with oleic acid & palmitic acid were used to test the effects of ginsenosides Rc on intracellular lipid metabolism. RNAseq and molecular docking study were performed to explore potential targets of ginsenosides Rc in defending lipid deposition. Wild type and liver specific sirtuin 6 (SIRT6, 50721) deficient mice on HFD for 12 weeks were subjected to different dose of ginsenosides Rc to determine the function and detailed mechanism in vivo. Results: We identified ginsenosides Rc as a novel SIRT6 activator via increasing its expression and deacetylase activity. Ginsenosides Rc defends OA&PA-induced lipid deposition in MPHs and protects mice against HFD-induced metabolic disorder in dosage dependent manner. Ginsenosides Rc (20mg/kg) injection improved glucose intolerance, insulin resistance, oxidative stress and inflammation response in HFD mice. Ginsenosides Rc treatment accelerates peroxisome proliferator activated receptor alpha (PPAR-α, 19013)-mediated fatty acid oxidation in vivo and in vitro. Hepatic specific SIRT6 deletion abolished ginsenoside Rc-derived protective effects against HFD-induced NAFLD. Conclusion: Ginsenosides Rc protects mice against HFD-induced hepatosteatosis by improving PPAR-α-mediated fatty acid oxidation and antioxidant capacity in a SIRT6 dependent manner, and providing a promising strategy for NAFLD.

• Journal of Nutrition and Health
• /
• v.33 no.1
• /
• pp.23-32
• /
• 2000

The purpose of this study was to investigate the effcts of n-3, n-6 fatty arid and d-limonene on histopathological and biochemical changes in experimental rat hepatocarcinogenesis. To attain the above objectives, weanling Sprague-Dawley female rats were intraperitoneally injected twice with a dose of diethylnitrosamine(DEN, 50mg/kg body weight) and after 1 week 0.05% phenobarbital was provided with water. Sardine oil rich in n-3 fatty acids and corn oil rich in n-6 fatty acids were fed at 15% by weight and 5% d-limonene was added to the diet in each group. Ten weeks or 20 weeks after DEN treatment, rats were sacrifirced. The formation of glutathione S-transferase placental form positive(GST-P$\^$+/) foci was significantly decreased by the treatment of either sardine oil or d-limonene HMG-CoA reductase activity was not affected by dietary oils and d-limonene. Protein kinase C (PKC) activity was decreased by either sardine oil or d-limonene. Particularly d-limonene decreased the membrane PKC activity. Membrane Cholesterol/Phospholipid(Chol/PL) ratio was significantly decreased by d-limonene in sardine oil group. The data showed that GST-P$\^$+/ foci number was positively correlated with membrane PKC activity and serum cholesterol and negatively correlated with liver cholesterol level. These results suggest informations about the correlation between histopathological and biochemical changes such as cholesterol metabolism and PKC activity in experimental hepatocarcinogenesis and thereby can elucidate the possible mechanism related to the cancer inhibition.(Korean J Nutrition 33(1) : 23-32, 2000)

• Asian-Australasian Journal of Animal Sciences
• /
• v.23 no.8
• /
• pp.1013-1021
• /
• 2010

This study was conducted to determine the effects of amino acid-enriched ruminally protected fatty acid (AARPFA) on plasma fatty acids and amino acids, growth performance and carcass characteristics of Korean native steers (Hanwoo) by simultaneous supply of fatty acids and limiting amino acids (methionine and lysine). Eighteen finishing Hanwoo steers, 18 months of age and weighing an average of $459.0{\pm}38.9\;kg$, were used for studies of the metabolism of plasma fatty acids and amino acids during supplementation of AARPFA. Also, 45 finishing Hanwoo steers, 16 months of age and weighing an average of $408.6{\pm}26.5\;kg$, were used for growth performance and carcass characteristics during supplemention of AARPFA. There were three treatments which comprised a basal diet supplemented with AARPFA at 0 g (T1), 50 g (T2) or 100 g (T3), respectively. Concentrations of saturated, unsaturated and total fatty acids in plasma were increased in T3 compared with other treatments (p<0.05). Concentrations of methionine and lysine in plasma were linearly increased with increasing levels of AARPFA (p<0.01). Average daily gain, dry matter intake and feed conversion ratio were not different among the treatments. Marbling score measured by ultra-sound scanning was higher in T3 than in T1 at 24 months of age (p<0.05). Rib eye area, back fat thickness, yield index and yield grade score were similar across the treatments. Marbling score and quality grade score were higher in T3 compared with other treatments (p<0.01). Thus, plasma fatty acids, methionine and lysine metabolism were affected by supplementing with 100 g of AARPFA which also had positive effects on marbling score and meat quality grade of finishing Hanwoo steers.

• Journal of the Korean Society of Food Science and Nutrition
• /
• v.27 no.6
• /
• pp.1253-1261
• /
• 1998

Effects of dietary cholesterol and taurine supplementation on hepatic total and phospholipid fatty acid compositions were evaluated in rats fed one of the following semisynthetic diets for 5 weeks : control diet(CD, cholesterol free and taurine free diet); high cholesterol diet(HCD, CD＋1.5% cho lesterol); high cholesterol, high taurine diet(HCHTD, HCD＋1.5% taurine). Diet induced changes in hepatic total fatty acid compositions were very similar to those in hepatic phospholipid fatty acid compositions. The HCD significantly decreased the percentage of total saturated fatty acids(SFA), and increased the percentage of total monounsaturated fatty acids(MUFA) of hepatic total lipids and phospholipids as compared to the values for the control rats(p<0.001). HCHTD significantly elevated the percentage of $\Sigma$SFA and lowered the percentage of $\Sigma$MUFA compared to the values for the HCD(p<0.001). Percentages of hepatic total and phospholipid 18:3$\omega$3, 20:5$\omega$3, 18:2$\omega$6 and 20:3$\omega$6 were significantly higher in rats fed the HCD than the values for the control rats, and the percentages of their elongation and desaturation products(22:5$\omega$3, 22:6$\omega$3, 20:4$\omega$6, 22l:4$\omega$6 and 22: 5$\omega$6) were significantly lower in rats fed the HCD compared to those for the control rats. HCD significantly lowered the Δ5 desaturation(20:3$\omega$6⇒20:4$\omega$6) and Δ4 desaturation(22:4$\omega$6⇒22:5$\omega$6) indices, and the elongation index of $\omega$3 fatty acid(20:5 $\omega$3⇒22:5$\omega$3) in rat liver. HCHTD reversed the cholesterol induced changes in the compositions of $\omega$3 and $\omega$6 fatty acids. These results suggest the possibility that dietary cholesterol and taurine supplementations affect plasma and liver lipid levels, at least in part, by changing the hepatic phospholipid fatty acid compositions and thereby modulating the physical characteristics of the membrane and the activities of microsomal enzymes involved in lipid metabolism.

• Biomedical Science Letters
• /
• v.16 no.3
• /
• pp.151-159
• /
• 2010

The peroxisome proliferator-activated receptor $\alpha$ (PPAR$\alpha$) is a nuclear transcription factor that plays a central role in lipid metabolism and obesity. Exercise also is a powerful modifier of the manifestations of the lipid metabolism and obesity in animal models and humans with obesity and metabolic syndrome. However, effects of exercise on lipid metabolism and obesity in normal-weight younger female subjects, having functional ovaries and not metabolic disease, remain unexplained. To explore the effects of exercise on the development of obesity and its molecular mechanism in high fat diet-fed female C57BL/6J mice, we experimented the effects of swim training on body weight, adipose tissue mass, serum lipid levels, morphological changes of adipocytes and the expression of PPAR$\alpha$ target genes involved in fat oxidation in skeletal muscle tissue of female C57BL/6J mice. Swim-trained mice had significantly decreased body weight, adipose tissue mass, serum triglycerides compared with female control mice. Histological studies showed that swim training significantly decreased the average size of adipoctyes in parametrial adipose tissue. Swim training did not affect the expression of PPAR$\alpha$ mRNA in skeletal muscle. Concomitantly, swim training did not increase mRNA levels of PPAR$\alpha$ target genes responsible for fatty acid $\beta$-oxidation, such as carnitine palmitoyltransferase 1, medium chain acyl-CoA dehydrogenase, enoyl-CoA hydratase/3-hydroxyacyl-CoA dehydrogenase, and thiolase in skeletal muscle. In conclusion, these results indicate that swim training regulates lipid metabolism and obesity in high fat diet fed-female mice although swim training did not increase mRNA levels of PPAR$\alpha$ target genes involved in fatty acid $\beta$-oxidation in skeletal muscle, suggesting that swim training may prevent obesity and improve fitness through other mechanisms in female with ovaries, not through the activation of skeletal muscle PPAR$\alpha$.

• The Journal of Korean Medicine
• /
• v.23 no.4
• /
• pp.64-72
• /
• 2002

Objective: Ramulus mori (RM) has been known to be effective for the treatment of obesity. To show the effectiveness of RM in a more scientific way, RM extract was prepared and evaluated in high fat diet rats by measuring the changes of body weight and lipid metabolism as described briefly below. Methods: 200 g of crushed RM was extracted withmethyl alcohol. The extract was evaporated under reduced pressure to give 33.4 g. For 10 weeks, control group rats were fed a high fat diet, while the test group rats were fed with the same diet plus RM extract. The normal group was fed with a normal diet. 150 mg of RM extract per 1 kg of body weight was added to the diet in the test group rats. Results: The control group rats on the high fat diet gained weight significantly, whereas the test group rats on the high fat diet plus RM extract gamed less weight. The significant increase of liver weight caused by the high fat diet was also inhibited by the RM extract treatment. Total lipid, triglyceride and total cholesterol levels of serum in the high fat diet rats were remarkably increased, whereastheir levels on the high fat diet plus RM extract were less increased. While serum HDL-cholesterol levels were remarkably decreased in the high fat diet, its level was less decreased in the high fat diet plus RM extract. Furthermore, we observed that the activities of hepatic acetyl-CoA carboxylase and fatty acid synthetase increased under the high fat diet, while their activities under the high fat diet plus RM extract were getting back nearly to the normal levels of the normal diet rats. Conclusions: These result show that the obesity caused by a high fat diet was effectively inhibited by an RM extract. Our results also showed that the abnormal lipid metabolism caused by a high fat diet was effectively cured by adding RM extract.