• Journal of Animal Science and Technology
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• v.64 no.1
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• pp.97-109
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• 2022

Species are facing strong selection pressures to adapt to inhospitable high-altitude environments. Yaks are a valuable species and an iconic symbol of the Qinghai-Tibet Plateau. Extensive studies of high-altitude adaptation have been conducted, but few have focused on metabolism. In the present study, we determined the differences in the serum metabolomics between yaks and the closely related species of low-altitude yellow cattle and dairy cows. We generated high-quality metabolite profiling data for 36 samples derived from the three species, and a clear separation trend was obtained between yaks and the other animals from principal component analysis. In addition, we identified a total of 63 differentially expressed metabolites among the three species. Functional analysis revealed that differentially expressed metabolites were related to the innate immune activation, oxidative stress-related metabolism, and energy metabolism in yaks, which indicates the important roles of metabolites in high-altitude adaptation in yaks. The results provide new insights into the mechanism of adaptation or acclimatization to high-altitude environments in yaks and hypoxia-related diseases in humans.

• Journal of the Korean Chemical Society
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• v.63 no.4
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• pp.253-259
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• 2019

5-Aminoimidazole-4-carboxamide ribonucleotide (AICAR), a structural analog of adenosine monophosphate (AMP), promotes oxidative remodeling in muscle cells. AICAR activates AMP-dependent protein kinase (AMPK), thus increasing lipid metabolism, respiration, and mitochondrial counts. This process is called oxidative remodeling, which enhances the physical endurance of mice. To test this drug on an invertebrate that is genetically similar to humans, we used the small water crustacean Daphnia magna, which is sensitive to changes in water conditions. We tested the effects of pH on the efficacy of AICAR using two methods. One method measured oxygen consumption of Daphnia in oxygen chambers. The other method determined lipid levels of Daphnia through fluorescent tagging of lipids. The results showed that when exposed to AICAR at pH 6.58, D. magna consumed more oxygen and had lower overall levels of lipids, which is consistent with the expected effects of AICAR, such as increased respiration and lipid metabolism.

• Journal of Microbiology and Biotechnology
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• v.18 no.2
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• pp.270-282
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• 2008

The yeast Saccharomyces cerevisiae has defense mechanisms identical to higher eukaryotes. It offers the potential for genome-wide experimental approaches owing to its smaller genome size and the availability of the complete sequence. It therefore represents an ideal eukaryotic model for studying cellular redox control and oxidative stress responses. S. cerevisiae Yap1 is a well-known transcription factor that is required for $H_2O_2$-dependent stress responses. Yap1 is involved in various signaling pathways in an oxidative stress response. The Gpx3 (Orp1/PHGpx3) protein is one of the factors related to these signaling pathways. It plays the role of a transducer that transfers the hydroperoxide signal to Yap1. In this study, using extensive proteomic and bioinformatics analyses, the function of the Gpx3 protein in an adaptive response against oxidative stress was investigated in wild-type, gpx3-deletion mutant, and gpx3-deletion mutant overexpressing Gpx3 protein strains. We identified 30 proteins that are related to the Gpx3-dependent oxidative stress responses and 17 proteins that are changed in a Gpx3-dependent manner regardless of oxidative stress. As expected, $H_2O_2$-responsive Gpx3-dependent proteins include a number of antioxidants related with cell rescue and defense. In addition, they contain a variety of proteins related to energy and carbohydrate metabolism, transcription, and protein fate. Based upon the experimental results, it is suggested that Gpx3-dependent stress adaptive response includes the regulation of genes related to the capacity to detoxify oxidants and repair oxidative stress-induced damages affected by Yap1 as well as metabolism and protein fate independent from Yap1.

• Journal of Ginseng Research
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• v.44 no.4
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• pp.664-671
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• 2020

Background: Ginsenoside compound-Mc1 (Mc1) is a member of the deglycosylated ginsenosides obtained from ginseng extract. Although several ginsenosides have a cardioprotective effect, this has not been demonstrated in ginsenoside Mc1. Methods: We treated H9c2 cells with hydrogen peroxide (H₂O₂) and ginsenoside Mc1 to evaluate the antioxidant effects of Mc1. The levels of antioxidant molecules, catalase, and superoxide dismutase 2 (SOD2) were measured, and cell viability was determined using the Bcl2-associated X protein (Bax):B-cell lymphoma-extra large ratio, a cytotoxicity assay, and flow cytometry. We generated mice with high-fat diet (HFD)-induced obesity using ginsenoside Mc1 and assessed their heart tissues to evaluate the antioxidant effect and the fibrosis-reducing capability of ginsenoside Mc1. Results: Ginsenoside Mc1 significantly increased the level of phosphorylated AMP-activated protein kinase (AMPK) in the H9c2 cells. The expression levels of catalase and SOD2 increased significantly after treatment with ginsenoside Mc1, resulting in a decrease in the production of H₂O₂-mediated reactive oxygen species. Treatment with ginsenoside Mc1 also significantly reduced the H₂O₂-mediated elevation of the Bax:Bcl2 ratio and the number of DNA-damaged cells, which was significantly attenuated by treatment with an AMPK inhibitor. Consistent with the in vitro data, ginsenoside Mc1 upregulated the levels of catalase and SOD2 and decreased the Bax:B-cell lymphoma-extra large ratio and caspase-3 activity in the heart tissues of HFD-induced obese mice, resulting in reduced collagen deposition. Conclusion: Ginsenoside Mc1 decreases oxidative stress and increases cell viability in H9c2 cells and the heart tissue isolated from HFD-fed mice via an AMPK-dependent mechanism, suggesting its potential as a novel therapeutic agent for oxidative stress-related cardiac diseases.

• Journal of Nutrition and Health
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• v.40 no.5
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• pp.413-418
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• 2007

The present study was designed to observe the effect of chronically ingested ethanol on the level of fatty acid ethyl esters (FAEEs), which is a non-oxidative metabolite of ethanol metabolism in tissues, and its correlation to the status of oxidative stress in rats. Forty male Sprague Dawley rats weighing 145 - 155 g were divided into 2 groups, Control and EtOH. All rats were fed Lieber-DeCarli liquid diet for 4 weeks by pair-feeding. An isocaloric maltose dextrin was added in replace of 50 g ethanol (36%kcal) in the control diet. Chronically ingested ethanol significantly increased the content of FAEEs in pancreas and liver, but not in brain. The level of 2-thiobarbituric acid reactive substances (TBARS) was significantly increased, but ${\alpha}-tocopherol$ level was significantly decreased in pancreas and liver. However, the levels of TBARS and ${\alpha}-tocopherol$ in brain were not significantly affected by ethanol ingestion. Therefore, chronically ingested ethanol might cause tissue damage by increasing the levels of FAEEs and TBARS and dissipating more ${\alpha}-tocopherol$ in tissues.

• Clinical Nutrition Research
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• v.11 no.4
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• pp.316-330
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• 2022

Iron plays a role in energy metabolism as a component of vital enzymes and electron transport chains (ETCs) for adenosine triphosphate (ATP) synthesis. The tricarboxylic acid (TCA) cycle and oxidative phosphorylation are crucial in generating ATP in mitochondria. At the mitochondria matrix, heme and iron-sulfur clusters are synthesized. Iron-sulfur cluster is a part of the aconitase in the TCA cycle and a functional or structural component of electron transfer proteins. Heme is the prosthetic group for cytochrome c, a principal component of the respiratory ETC. Regarding fat metabolism, iron regulates mitochondrial fat oxidation and affects the thermogenesis of brown adipose tissue (BAT). Thermogenesis is a process that increases energy expenditure, and BAT is a tissue that generates heat via mitochondrial fuel oxidation. Iron deficiency may impair mitochondrial fuel oxidation by inhibiting iron-containing molecules, leading to decreased energy expenditure. Although it is expected that impaired mitochondrial fuel oxidation may be restored by iron supplementation, its underlying mechanisms have not been clearly identified. Therefore, this review summarizes the current evidence on how iron regulates energy metabolism considering the TCA cycle, oxidative phosphorylation, and thermogenesis. Additionally, we relate iron-mediated metabolic regulation to obesity and obesity-related complications.

• Asian-Australasian Journal of Animal Sciences
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• v.32 no.1
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• pp.137-143
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• 2019

Objective: The aim of this study was to compare male and female geese of two contrasting genotypes in terms of fatty acid composition, indexes related to human health, lipid metabolism and oxidative stability of the meat. Methods: The experiment was carried out on total of 120 geese of two different genotypes; the native breed Czech goose (CG) and commercial hybrid Novohradska goose (NG). One-d-old goslings were divided into 4 groups according to genotype and sex, and 8 birds from each group were slaughtered at 8 weeks of age. Results: The effects of the interactions between genotype and sex were observed on growth performance and carcass traits. Final body weight (p<0.001), daily weight gain (p<0.001), daily feed intake (p<0.001), slaughter weight (p<0.001), and cold carcass weight (p<0.001) were highest in NG males and lowest in CG females. The meat fatty acid composition results showed effects of both genotype and sex on the total n-6 and the total polyunsaturated fatty acid (PUFA) content, as well as the PUFA n-6/PUFA n-3 ratio. Regarding genotype, the total n-6, the total PUFA content and the PUFA n-6/PUFA n-3 ratio were higher in CG, and higher values were found in females. In terms of the lipid metabolism, ${\Delta}^5-{\Delta}^6$ desaturase (p = 0.006) was higher in males. The meat oxidative stability results revealed an interaction between genotype, sex and storage time (p<0.001). The highest (13.85 mg/kg) malondialdehyde content was measured in the meat of CG females after 5 days of storage and was presumably related to a higher PUFA content. Conclusion: NG had a relatively higher growth rate and meat oxidative stability, whereas the advantage of CG meat is its favourable fatty acid profile characterized by a higher PUFA content.

• Biomolecules & Therapeutics
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• v.26 no.1
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• pp.4-9
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• 2018

Cancer metabolism as a field of research was founded almost 100 years ago by Otto Warburg, who described the propensity for cancers to convert glucose to lactate despite the presence of oxygen, which in yeast diminishes glycolytic metabolism known as the Pasteur effect. In the past 20 years, the resurgence of interest in cancer metabolism provided significant insights into processes involved in maintenance metabolism of non-proliferating cells and proliferative metabolism, which is regulated by proto-oncogenes and tumor suppressors in normal proliferating cells. In cancer cells, depending on the driving oncogenic event, metabolism is re-wired for nutrient import, redox homeostasis, protein quality control, and biosynthesis to support cell growth and division. In general, resting cells rely on oxidative metabolism, while proliferating cells rewire metabolism toward glycolysis, which favors many biosynthetic pathways for proliferation. Oncogenes such as MYC, BRAF, KRAS, and PI3K have been documented to rewire metabolism in favor of proliferation. These cell intrinsic mechanisms, however, are insufficient to drive tumorigenesis because immune surveillance continuously seeks to destroy neo-antigenic tumor cells. In this regard, evasion of cancer cells from immunity involves checkpoints that blunt cytotoxic T cells, which are also attenuated by the metabolic tumor microenvironment, which is rich in immuno-modulating metabolites such as lactate, 2-hydroxyglutarate, kynurenine, and the proton (low pH). As such, a full understanding of tumor metabolism requires an appreciation of the convergence of cancer cell intrinsic metabolism and that of the tumor microenvironment including stromal and immune cells.

• Toxicological Research
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• v.35 no.3
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• pp.241-248
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• 2019

Pesticide exposure may induce biochemical alterations including oxidative stress and lipid peroxidation. However, in the context of developmental origin of health and disease, putative trans-generational effect of exposure to pesticides are insufficiently studied. We therefore aimed to evaluate the biochemical effect of gestational exposure to four pesticides on female Wistar rats and their offspring at adult age. We studied 30 female nulliparous Wistar rats divided into 5 equal groups. Group 1 served as the control group and received distilled water while group 2, 3, 4 and 5 received orally pesticide 1 (imidacloprid), pesticide 2 (chlorpyrifos), pesticide 3 (imidacloprid + lambda cyhalothrin) and pesticide 4 (oxamyl) respectively once daily throughout gestation at a dose equivalent to 1/10 lethal dose 50. The mothers were followed up until one month post gestation. The offspring were followed up from birth until adult age (12 weeks). In all animals at each time point we evaluated malondialdehyde (MDA), oxidative stress and liver function enzymes. There was similar variation of total body weight in all the groups during and after gestation. However, Female Wistar rats of the exposed groups had significant alterations in liver SOD (-30.8% to +64.1%), catalase (-38.8% to -85.7%) and GSH (-29.2% to -86.5%) and; kidney catalase (> 100%), GSH (> 100%). Moreover, MDA, alanine transaminase (ALT) and aspartate transaminase (AST) levels were significantly higher in pesticide exposed rats compared to the control group. Similar alterations in antioxidant enzymes, MDA and liver function enzymes were observed in offspring of treated rats evidenced at weaning and persisting until adult age. Exposure to pesticides causes oxidative stress and lipid peroxidation in exposed female Wistar rats and their offspring. The persistence in offspring at adult age suggests transgenerational adverse effects.

• Nutrition Research and Practice
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• v.9 no.2
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• pp.137-143
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• 2015

BACKGROUND/OBJECTIVES: Mulberry leaves contain quercetin derivatives, which have the effects of reducing obesity and improving lipid and glucose metabolism in mice with obesity. It is not clear whether or not mulberry leaves can directly affect metabolic disorders, in the presence of obesity, because of the interaction between obesity and metabolic disorders. The aim of the current study was to assess the direct action of quercetin derivatives on metabolic disorders in non-obese conditions in short-term high-fat diet fed mice. MATERIALS/METHODS: C57BL/6N mice were fed a high-fat diet, supplemented with either 0% (control), 1%, or 3% mulberry leaf powder (Mul) or 1% catechin powder for five days. Anthropometric parameters and blood biochemistry were determined, and hepatic gene expression associated with lipid and glucose metabolism was analyzed. RESULTS: Body and white fat weights did not differ among the four groups. Plasma triglycerides, total cholesterol, and free fatty acids in the 1%, 3% Mul and catechin groups did not differ significantly from those of the controls, however, plasma glucose and 8-isoprostane levels were significantly reduced. Liver gene expression of gp91phox, a main component of NADPH oxidase, was significantly down-regulated, and PPAR-${\alpha}$, related to ${\beta}$-oxidation, was significantly up-regulated. FAS and GPAT, involved in lipid metabolism, were significantly down-regulated, and Ehhadh was significantly up-regulated. Glucose-metabolism related genes, L-PK and G6Pase, were significantly down-regulated, while GK was significantly up-regulated in the two Mul groups compared to the control group. CONCLUSIONS: Our results suggest that the Mul quercetin derivatives can directly improve lipid and glucose metabolism by reducing oxidative stress and enhancing ${\beta}$-oxidation. The 1% Mul and 1% catechin groups had similar levels of polyphenol compound intake ($0.4{\times}10^{-5}$ vs $0.4{\times}10^{-5}$ mole/5 days) and exhibited similar effects, but neither showed dose-dependent effects on lipid and glucose metabolism or oxidative stress.