• Journal of Nutrition and Health
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• 제30권6호
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• pp.658-668
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• 1997

Path of a small hydrophobic molecule through the aqueous cytoplasma is not linear. Partition may favor membrane binding by several orders of magnitude : thus significant membrane association will markedly decrease the cytosolic transport rate. The presence of high concentration of soluble binding proteins for these hydrophobic molecules would compete with membrane association and thereby increase transport rate. For long chain fatty acid molecules, a family of cytosolic binding proteins collectively known as the fatty acid binding proteins(FABP), are thought to act as intracellular transport proteins. This paper examines the mechanism of transfer of fluorescent antyroyloxy-labeled fatty acids(AOFA) from purified FABPs to phosholipid membranes. With the exception of the liver FABP, AOFA is transferred from FABP by collisional interaction of the protein with a acceptor membrane. The rate of transfer increased markedly when membranes contain anionic phospholipids. This suggests that positively charged residues on the surface of the FABP may interact with the membranes. Neutralization of the surface lysine residues of adipocyte FABP decreased fatty acid transfer rate, and transfer was found to proceed via aqueous diffusion rather than collisional interaction. Site specific mutagenesis has further shown that the helix-turn-helix domain of the FABP is critical for interaction with anionic acceptor membranes. Thus cytosolic FABP may function in intracellular transport of fatty acid to decrease their membranes association as well as to target fatty acid to specific subcellular sites of utilization.

• Molecules and Cells
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• 제43권8호
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• pp.686-693
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• 2020

Autophagy is an intracellular degradation system that breaks down damaged organelles or damaged proteins using intracellular lysosomes. Recent studies have also revealed that various forms of selective autophagy play specific physiological roles under different cellular conditions. Lipid droplets, which are mainly found in adipocytes and hepatocytes, are dynamic organelles that store triglycerides and are critical to health. Lipophagy is a type of selective autophagy that targets lipid droplets and is an essential mechanism for maintaining homeostasis of lipid droplets. However, while processes that regulate lipid droplets such as lipolysis and lipogenesis are relatively well known, the major factors that control lipophagy remain largely unknown. This review introduces the underlying mechanism by which lipophagy is induced and regulated, and the current findings on the major roles of lipophagy in physiological and pathological status. These studies will provide basic insights into the function of lipophagy and may be useful for the development of new therapies for lipophagy dysfunction-related diseases.

• 한국임상약학회지
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• 제28권4호
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• pp.273-278
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• 2018

Bile acids are major constituents of bile and known to help absorb dietary fat and fat-soluble vitamins in the gastrointestinal tract. In the past few decades, many studies have shown that bile acids not only play a role in fat digestion but also function as broad range of signal transduction hormones by binding to various receptors present in cell membranes or nuclei. Bile acid receptors are distributed in a wide range of organs and tissues in the human body. They perform multitudes of physiological functions with complex mechanisms. When bile acids bind to their receptors, they regulate fat and glucose metabolism in a tissue-specific way. In addition, bile acids are shown to inhibit inflammation and fibrosis in the liver. Considering the roles of bile acids as metabolic regulators, bile acids and their receptors can be very attractive targets in treating metabolic disorders. In the future, if roles of bile acids and their receptors are further clarified, they will be the novel target of drugs in the treatment of various metabolic diseases.

• Journal of Preventive Medicine and Public Health
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• 제29권1호
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• pp.43-50
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• 1996

We experienced a case of nephropathy in chronic lead poisoning. The patient was 43-year-old male who has been working in secondary lead smelting plant for 14 years. On admission, blood pressure was 160/90 mmHg and the others were non-specific. In past history, he received chelating agent administration for lead poisoning irregularly and medicated for gout, and the blood lead concentration was $180.0{\mu}g/dl$ on 2 months before admission. Smoking habit has been 1 pack per day for 15 years and drinking habit has been 1 bottle of Soju per day but less flow. In liver function test, AST/ALT were 27/28 IU/l and $\gamma-GT$ was 456 IU/l. In blood test, Hb : 11.5 g/dl, Hct : 34.0% and basophilic stipplings were found in peripheral blood smear. Chest PA was normal and abdominal ultrasonographic finding was non-specific except fatty liver. In the test of lead exposure indices, $PbB:83.0{\mu}g/dl,\;PbU:28.3{\mu}g/l$, and blood ZPP was $300.0{\mu}g/dl$. And in renal function test, BUN : 31.4 mg/dl, blood creatinine : 2.7mg/dl, blood uric acid. 9.1 mg/dl, urinary albumin : 100.0 mg/g creatinine, urinary $\alpha_1-microglobulin$ : 120.5 mg/g creatinine, urinary $\beta_2-microglobulin$ : $183.8{\mu}g/g$ creatinine, and 24 hours urinary creatinine clearance was 31.9 ml/min. The ultrasonoguided renal biopsy showed the global sclerosis of glomerulus, moderate atrophy and loss of tubule, and interstitial fibrosis in light microscopy. There were diffuse losses of brush border of proximal tubule in electronmicroscopy.

• Journal of Ginseng Research
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• 제47권3호
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• pp.376-384
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• 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 Biomedical and Translational Research
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• 제19권4호
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• pp.116-124
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• 2018

Korean Native Pig (KNP) has a uniform black coat color, excellent meat quality, white colored fat, solid fat structure and good marbling. However, its growth performance is low, while the western origin Yorkshire pig has high growth performance. To take advantage of the unique performance of the two pig breeds, we raised crossbreeds (KNP ${\times}$ Yorkshire to make use of the heterotic effect. We then analyzed the liver transcriptome as it plays an important role in fat metabolism. We sampled at two stages: 10 weeks and at 26 weeks. The stages were chosen to correspond to the change in feeding system. A total of 16 pigs (8 from each stage) were sampled and RNA sequencing was performed. The reads were mapped to the reference genome and differential expression analysis was performed with edgeR package. A total of 324 genes were found to be significantly differentially expressed (${\left|log2FC\right|}$ > 1 & q < 0.01), out of which 180 genes were up-regulated and 144 genes were down-regulated. Principal Component Analysis (PCA) showed that the samples clustered according to stages. Functional annotation of significant DEGs (differentially expressed genes) showed that GO terms such as DNA replication, cell division, protein phosphorylation, regulation of signal transduction by p53 class mediator, ribosome, focal adhesion, DNA helicase activity, protein kinase activity etc. were enriched. KEGG pathway analysis showed that the DEGs functioned in cell cycle, Ras signaling pathway, p53 signaling pathway, MAPK signaling pathway etc. Twenty-nine transcripts were also part of the DEGs, these were predominantly Cys2His2-like fold group (C2H2) family of zinc fingers. A protein-protein interaction (PPI) network analysis showed that there were three highly interconnected clusters, suggesting an enrichment of genes with similar biological function. This study presents the first report of liver tissue specific gene regulation in a cross-bred Korean pig.

• 한국양식학회지
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• 제20권4호
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• pp.248-254
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• 2007

멸종위기 천연기념물 어류 어름치(Hemibarbus mylodon)를 대상으로한 어름치 유전자 은행 구축 연구의 일환으로 뇌, 소화관, 근육, 간, 신장, 난소 및 정소 조직으로부터 expressed sequence tag (EST) library들을 구축하고 발현 유전자의 탐색을 실시하였다. EST 탐색을 통해 총 3,383개의 발현 유전자 염기서열 단편을 확보하였고 이들로부터 1,354개의 EST를 포함하는 총 333개의 contig들이 형성됨으로써 비교적 높은 빈도(69.8%)의 unigene 확보율을 나타내었다. EST의 조직 별 출현 양상은 orthologue들과의 상동성 정도 및 유추 기능의 대분류를 기준으로 분석할 때 각 조직들은 서로 다른 특징을 나타내었다. 어름치에서 발굴된 EST들은 zebrafish의 유전자들과 가장 높은 match 빈도를 나타내었다. 본 연구를 통해 확보된 EST library들과 염기서열 정보는 본 종의 장외 복원을 위한 효율적인 인공증식 기술 개발에 유용한 기초 정보로 활용될 수 있을 것이다.

• 대한의생명과학회지
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• 제11권3호
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• pp.311-318
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• 2005

Grp78, discovered as one of the putative target genes of Hoxc8, is a highly conserved stress protein and functions as a molecular chaperone in the endoplasmic reticulum (ER). In order to see the stage-specific expression pattern of Grp78 during development, mouse embryos from day 7.5 to 17.5 p.c. were isolated, and RT-PCR as well as in situ hybridization was performed. When RT-PCR was performed using Grp78 specific primers, periodic expression pattern was detected. And also a region-specific expression pattern was detected with a strong expression in the trunk part of day 11.5 p.c. embryo, like that of Hoxc8. When in situ hybridization was performed, Grp78 was revealed to be expressed in the endoderm, somite, neuroepithelium cells of neural tube in early embryos. In the case of late embryos, Grp78 expression was detected in the liver, segmental bronchus within cranial lobe of lung, ossification center within the cartilage primordium of rib and vertebra, submandibular gland, as well as metanephros. These expression patterns are very much similar to those of Hoxc8. Since Hoxc8 has been reported to regulate apoptosis during organogenesis, it might be possible that the apoptotic function could have been conveyed through the expression of Grp78, implying that the Grp78 is one of the Hoxc8 downstream target genes.

• 대한한방내과학회지
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• 제39권1호
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• pp.9-21
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• 2018

Objective: Graves' disease, the most common cause of primary hyperthyroidism, is a thyroid specific autoimmune disorder. When resistance to medication is shown in spite of long term therapy with anti-thyroid drugs, radioactive iodine therapy would be chosen in Western medicine. However, this therapy has often been reported to cause patients have hypothyroidism, thus requiring them to take levothyroxine for the rest of their lives. In this study, we evaluate the clinical efficacy and safety of Ahnjeonbaekho-tang (AJBHT) on patients with Graves' disease. Methods: We prescribed AJBHT for 3 months to two groups: patients who had been taking antithyroid drugs were administered AJBHT after discontinuing the antithyroid drugs ($Com-Tx{\rightarrow}Single-Tx$), and patients who had not been taking antithyroid drugs were started with AJBHT (Single-Tx) immediately. We evaluated the thyroidal function test (TFT) and visual analogue scale (VAS) for clinical symptoms for 3 months. Results: Serum T3 and fT4 were significantly decreased in both groups and remission rate of thyroidal hormones were significantly improved in the Single-Tx group. The clinical symptoms of palpitation, fatigue, and heat intolerance were significantly improved in both groups. In the safety analysis, all patients were in normal range of liver, renal function blood test and common blood count. Conclusion: From these results, we suggested that AJBHT was effective on TFT and clinical symptoms of Graves' disease. The study supports that AJBHT may be a useful agent for patients with Graves' disease who are resistant to antithyroid medication or radioactive iodine therapy, and for patients at first diagnosis.

• 대한한의학회지
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• 제26권2호
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• pp.231-240
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• 2005

Objectives: In order to investigate the efficacy and safety of the newly developed herbal medicine Jetongdan, a placebo­controlled, randomized clinical trial of patients with osteoarthritis of the knee was undertaken. Methods: Data were obtained from 80 patients with OA of the knee. After enrollment, they were asked to answer a disease-specific questionnaire (Western Ontario and McMaster Universities (WOMAC) OA index) and analyzed with the erythrocyte sedimentation rate (ESR) in order to evaluate the efficacy of Jetongdan, and analyzed for aspartate transaminase (AST) level, alanine transaminase (ALT) level, blood mea nitrogen (BUN) level, and creatinine (Cr) level in order to evaluate the safety of Jetongdan. Results: The liver function and renal function did not deteriorate after treatment with Jetongdan. Composite WOMAC score and physical function subscale was improved, but pain subscale, stiffness subscale, and ESR were not improved by. This was possibly because the baseline characteristics of the two groups were not homogenized after randomization. Conclusions: Jetongdan could be a promising treatment option for osteoarthritis of the knee. Further study in a larger population with appropriate severity grades is recommended.