Topiramate stimulates glucose transport through AMP-activated protein kinase-mediated pathway in L6 skeletal muscle cells

Ha, E,Yim, S V,Jung, K H,Yoon, S H,Zheng, L T,Kim, M J,Hong, S J,Choe, B K,Baik, H H,Chung, J H,Kim, J W Nature Publishing Group 2006 The pharmacogenomics journal Vol.6 No.5

The use of topiramate (TPM) in the treatment of binge-eating disorder, bulimia nervosa, and antipsychotic-induced weight gain has recently increased, however, the exact molecular basis for its effects on body weight reduction and improved glucose homeostasis, is yet to be elucidated. Here we investigated the effect and signaling pathway of TPM on glucose uptake in L6 rat skeletal muscle cells, which account for >70% of glucose disposal in the body. Intriguingly, we found that TPM (10 μM) stimulated the rate of glucose uptake up to twofold increase. And TPM-stimulated glucose transport was inhibited with the overexpression of dominant-negative form of AMP-activated protein kinase (AMPK), an important mediator in glucose transport, implicating that AMPK-mediated pathway is involved. The TPM-stimulated glucose transport was blocked by SB203580, a specific inhibitor of AMPK downstream mediator, p38 mitogen-activated protein kinase (MAPK) protein. LY294002, an inhibitor of phosphatidylinositol (PI) 3-kinase, which is another crucial mediator in independent glucose transport pathway, did not inhibit TPM-stimulated glucose transport. We also found that TPM increased the phosphorylation level of AMPK and p38 MAPK, whereas no effect on the activity of PI 3-kinase of TPM, when assessed by PI 3-kinase assay, was observed. These results together suggest that TPM stimulates glucose transport, not via PI 3-kinase mediated, but via AMPK-mediated pathway in skeletal muscle cells, thereby contributing to the body weight regulation and glucose homeostasis.The Pharmacogenomics Journal (2006) 6, 327–332. doi:10.1038/sj.tpj.6500366; published online 17 January 2006

항암제 CLA의 기능성 농·축·수산물 생산을 위한 신 기능성소재로서의 역할

하영래,박구부,강석중,박원석,박경아 경상대학교 농업자원이용연구소 1998 심포지엄 자료집 Vol.1998 No.1

Conjugated linoleic acid (CLA)는 여러 동물실험에서 항암성을 나타내었다. 항암성 외에도 CLA는 항동맥경화 효과, 면역촉진 효과, 체지방감소 효과와 같은 생리활성을 나타내었다. 주요 CLA source는 반추동물로부터 유래되는 고기 (쇠고기 등)와 유제품이다. 최근 이러한 생리 활성을 갖는 CLA를 사효첨가제 또는 식품첨가제로 이용하여 CLA-달걀, CLA-닭고기, CLA-돼지고기, CLA-쇠고기, CLA-우럭, CLA-새우, CLA-감자 등과 같은 여러가지 기능성 농·축·수산물을 생산하는 연구가 수행되고 잇다. CLA는 생체 내에서 함암성과 같은 생리활성을 나타냄은 물론, 기능성 식품에서 cholesrerol의 함량감소, 지방감소 및 저장성 증진효과를 나타내었다. 특히 CLA는 우럭종묘의 활력을 증가시켰다. 그러나 CLA의 합성단가가 높아, CLA 함유 기능성 식품 생상네는 고비용이 소요되고 있다. 따라서 CLA의 생산단가를 낮출 수 있는 연구가 수행되어야 할 것이다. Conjugated linoleic acid (CLA) exhibited anticarcinogenic activity for several animal models:7,12-dimethylbenz-[a]anthracene (DMBA)-induced mouse epidermal carcino-genesis, benzo[a]pyrene (BP)-un-duced mouse forestomach tumorigenesis, DMBA-induced rat mammary carcinogenesis, 2-amino-3-methylimidazo[4,5-f]euinoline (IQ)-induced rat colon carcinogenesis, and S-180 in-duced mouse ascites cancer. In addition, CLA showed activities of anti-atherosclerosis, immune stimulation, and body fat reduction in animal models and human as well. Major sources of CLA was meats and dairy products derived from ruminant animals. currently, lots of attempts have being conducted to produce CLA-containing functional products of agricultures, meats and marine fish by dietary CLA or adding CLA during prcessings. The typical CLA-containing functional products were eggs (CLA-eggs), chickens (CLA- chickens), porks (CLA-porks), beef patties (CLA-beef patties), eels (CLA-eels), rockfish (CLA-rockfish), shrimps (CLA-shrimps) and potatoes (CLA-potatoes). The functions of CLA in these products were appeared to be the reduction of cholesterol content in CLA-eggs, CLA-porks and CLA-shrimps, reduction of total fat content in CLA-porks, exten- sion of storage stability in CLA-pork and CLA-beef patties, enhancement of survival rate of rockfish seeds in CLA-rockfish, and inhibition of browning reaction in CLA-potatoes. One of shortcomings for the production of these functional products was found to be the high cost for manufacturing CLA from plant seed oils containing relatively higher linoleic acid; hence, methods to synthesize CLA at lower cost should be developed for utilization of CLA as feed ingredients. We believe that functionally active CLA-containing agri-cultural, animal and marine products should appear on market soon.

Conjugated Linoleic Acid(CLA) 급여기간이 계육의 CLA 함량과 지방산 조성에 미치는 영향

이정일,박구부,하정기,하영래,주선태,최병대 한국축산학회 1999 한국축산학회지 Vol.41 No.3

To investigate the effects of conjugated linoleic acid (CLA)-added diet feeding on CLA accumulation and fatty acid composition of chicken, a total of 150 Bramas broiler was fed both CLA-free and CLA-added (1, 2.5 and 5%) diet for 2-8 weeks of age weeks. The CLA used to add in diet was chemically synthesized by alkaline isomerization method with safflower oil. The pH, peroxide value (POV), thiobarbituric acid reactive substances (TBARS), cholesterol content, fatty acids composition and CLA concentration in breast and leg of chicken were measured. Samples from CLA-treated group showed higher pH and lower POV value than control group, and the both values were significantly affected by CLA levels in diet and/or feeding periods. Also the cholesterol content of meat was decreased with increasing CLA level in diet and/or feeding period. CLA was not detected in control chicken. However, the CLA concentration in meat from CLA-added diet was increased with increasing of CLA level in diet and feeding period. The highest CLA concentration in chicken breast was detected after feeding 5% CLA-added diet for 5 weeks. The fatty acid composition was changed with increasing CLA concentration in the meat that the proportion of palmitic acid was increased whereas that of linoleic acid and arachidonic acid were decreased. It was suggested that CLA could be accumulated in chicken meat by dietary CLA supplementation, and the CLA concentration and fatty acid composition in the meat could be affected by CLA level in diet and feeding period.

Conjugated Linoleic Acid(CLA)의 생리활성과 축산식품

허선진,이정일,하영래,박구부,주선태 한국동물자원과학회 2002 한국축산학회지 Vol.44 No.4

Conjugated linoleic acid (CLA) is collective term for a group of positional (c8, c10; c9, c11; c10, c12, and c11, c13) and geometric(cis,cis; cis,trans; trans,cis; and trans,trans) isomers of octadecadienoic acid (linoleic acid) with conjugated double bond system. CLA has been shown to have a variety of biological effects. Major effects of CLA on health, such as anti-cancer, anti-oxidation, anti-atherosclerosis and improving immuno-responses, might be derived or partially derived from the alternated lipid metabolism after CLA feeding. Most of studies on the effect of CLA on fat metabolism are concentrated on rats, mice, pigs and other mammals. The CLA inhibited carcinogen-induced neoplasia in several animal models and inhibited the proliferation of human malignant melanoma, colorectal and breast cancer cells and CLA reduced the atherosclerosis. Several studies have determined the antioxidant property of CLA; however, the property still remains controversial. Some of the studies have shown that CLA acted as an antioxidant, whereas some other studies have demonstrated that CLA might be a prooxidant. Several studies suggested that CLA could reduce fat accumulation in mammals. CLA was suggested to promote muscle growth and reduce fat deposition in mouse, and improve feed efficiency in rats. CLA has been shown to inhibit the activity of stearoyl-CoA reductase. CLA also reduced the content of arachidonic acid. Since arachidonic acid, and eicosapentaenoic acid (EPA) and docosahexenoic acid (DHA) are synthesized by different pathways, reducing the synthesis of arachidonic acid may not mean reducing that of EPA and DHA. Many sutdies have been shown biological effects of CLA . Therefore, further research is needed to answer the following question; 1) how to synthesize the new CLA by new methods, 2) why CLA has shown biological effects. 3) how to increase CLA effects in animal products.

NOVEL ANTICARCINOGENIC COMPOUNDS ISOLATED FROM ARTEMISIA CAPILLARIS

Bahn, Kyeong N.,Lee, Eun J.,Lee, Jung M.,Byun, Jae I.,Park, Sook J.,Yang, Min S.,Ha, Yeong L. Plant Molecular Biology & Biotechnology Research C 1994 Plant molecular biology and biotechnology research Vol.1994 No.

Chloroform fraction of hot-methanol soluble materials from Artemisia capaillaris, which inhibited DMBA-induced mouse skin carcinogenesis (Bahn et al., 1993), was further fractionated into F1 fraction by combination of solvent partition and TLC procedures. From the F1 fraction exhibited a strong cytotoxicity (ED_(50):<0.08vg/ml) for both L1210 and S- 180 mouse cancer cells, achillin and its isomer were identified as the major anticarcinogenic compounds.

Moutan radix 의 mouse sarcoma 180 cell 로 유발한 mouse ascites cancer 에 대한 항암효과

반경녀(Kyeong N . Bahn),이은주(Eun J . Lee),양민석(Min S . Yang),김정옥(Jeong O . Kim),하영래(Yeong L . Ha) 한국응용생명화학회 1995 Applied Biological Chemistry (Appl Biol Chem) Vol.38 No.4

Anticarcinogenic activity of Moutan radix for mouse ascites cancer induced by mouse Sarcoma 180 (S-180) cells was investigated. Methanol extract of Moutan radix including other folk medicinal plants (Taxus cuspidata, Curcuma Tonga, Artemisia capillaris, Ligrstri fructus, and Liriope platyphylla) used to remedy or cure many chronic human diseases like cancer was fractionated into hexane, chloroform (CHCl₃), ethylacetate (EtOAc), and butanol (BuOH) fractions. Anticarcinogenic activity of the fractions, exhibited a strong cytotoxicity for L1210 and S-180 cells, was examined for mouse ascites cancer induced by S-180 cells. Male ICR mice (7 mice/treatment, 5∼6 weeks of age, 23±1 g) were injected i.p. with S-180 cells (1×10^7 cell/1 ㎖ PBS). One day later, each mouse was given 0.1 ㎖ of 10% DMSO containing sample (30 ㎍/g body weight) every day for 10 consecutive days. Control mice were only given 0.1 ㎖ S-180 cells and 0.1 ㎖ 10% DMSO. Mice treated with EtOAc fraction of Moutan radix showed 28.7 days of life, which is 167% of control mice`s life. Based on the dose-dependant experiment, mice treated with 30 ㎍ showed longer life relative to mice treated with other doses (5, 15, 60 ㎍) and mice treated with 60 ㎍ exhibited toxic symptoms. Body weight of mice treated with Moutan radix was significantly reduced relative to that of control mice (p$lt;0.05). GC-MS analysis in conjunction with silica-gel column chromatography revealed that the EtOAc fraction contained 2-methoxylphenol, benzoic acid, 1-(4-hydroxy-3-methoxyphenyl)ethanone, 8-methyl-2,4(1H,3H)pteridinedione and 2,5-furan-dicarboxylic dimethyl ester as regards to the anticarcinogenic property of the EtOAc fraction. These results suggest that Moutan radix might be included as an anticarcinogenic medicinal plant for treatment of ascites cancer.

Enhanced biomass and lipid production by supplement of myo-inositol with oceanic microalga Dunaliella salina

Cho, K.,Kim, K.N.,Lim, N.L.,Kim, M.S.,Ha, J.C.,Shin, H.H.,Kim, M.K.,Roh, S.W.,Kim, D.,Oda, T. Pergamon ; Elsevier Science Ltd 2015 Biomass & bioenergy Vol.72 No.-

We investigated the effects of inositols, which are well-known plant growth-promoting agents, on the growth of the oceanic microalga Dunaliella salina. Of the four inositol derivatives tested (myo-inositol, scyllo-inositol, d-chiro-inositol, and l-chiro-inositol), myo-inositol (MI) showed the greatest growth-promoting effect in a concentration-dependent manner. The yield of biomass from the alga cultured with 500 mg L<SUP>-1</SUP> of MI was 1.48-times that of the control culture. No significant effect of MI on the total carotenoid content was observed, but neutral lipid content was significantly increased, 1.34-times greater than the control. MI also influenced the fatty acid methyl ester composition, with the levels of linoleic, linolenic, and linolelaidic acids significantly higher than those of the control culture. To the best of our knowledge, this is the first demonstration that MI promotes the growth of a marine microalga. Our results suggest that MI has potential for enhancing the efficiency of biofuel production by D. salina through growth promotion and increasing lipid productivity.

검정종료돈의 체중변화에 따른 일당중체량, 등지방두께 및 정육율의 반복력과 상관

김현철,김병우,송광림,오하식,손창준,하동우,이정규 한국동물자원과학회 2002 한국축산학회지 Vol.44 No.5

본 연구는 1999년 8월부터 2000년 2월까지 공인 제2종돈능력검정소에서 검정 종료된 Duroc종, Landrace종 및 Yorkshire종에 대하여 체중, 등지방두께, 일당증체량 및 정육율을 측정하여, 동일 개체의 반복측정치 간의 반복력과, 상관 및 순위상관을 추정하였으며, 그 결과를 요약하면 다음과 같다. 1. 평균능력은 측정시 체중이 각각 91.0, 114.7, 123.2㎏이였으며, 측정시 일령은 각각 142.1, 173.7, 182.5일이였으며, 정육율은 각각 57.9, 56.2 55.2%였으며, 등지방두께는 각각 1.33, 1.61, 1.63㎝였으며, 일당증체량은 각각 946.6, 879.2, 879.4g으로 나타났다. 2. 각 형질의 측정차수간 상관은 정육율의 경우, 1차와 2차, 1차와 3차, 2차와 3차간 각각 0.493, 0.471, 0.619로 나타났고, 등지방두께의 경우, 각각 0.424, 0.424, 0.700으로 나타났으며, 일당증체량의 경우, 각각 0.716, 0.601, 0.861로 모든 형질에서 1차와 2차간, 1차와 3차간 보다는 2차와 3차간에 높게 추정되었다. 3. 각 측정차수의 형질간 상관은 1차 측정의 경우, 정육율과 등지방두께, 정육율과 일당증체량, 등지방두께와 일당증체량이 각각 -0.597, -0.291, 0.303으로 나타났고, 2차 측정의 경우, 각각 -0.667, -0.292, 0.396으로 나타났으며, 3차 측정의 경우, 각각 -0.711, -0.369, 0.409로 정육율과 등지방두께 및 일당증체량은 부의 상관관계에 있으며, 등지방두께와 일당증체량은 정의 상관관계에 있고, 일령이 증가할수록 상관이 높게 추정되었다. 4. 각 형질의 반복력 추정치를 살펴보면, 등지방두께가 0.374, 정육율이 0.428, 일당증체량이 0.673으로 추정되었으며, 일당증체량의 반복력은 상당히 높게 추정되어, 110㎏까지 검정의 필요성이 인정되지 않으나, 등지방두께와 정육율의 추정치는 낮게 추정되어 더욱 많은 연구가 필요할 것으로 사료된다. The respeatability, correlation and rank correlation coefficients among average daily gain, backfat thickness and lean percent were estimated on the basis of records tested from August 1999 to February 2000 with 695 pigs of Duroc, Landrace and Yorkshire boars and gilts tested at 2nd Korea Swine Test Station located in Ha-dong, Kyeongnam Province. The effect of the sex, breed and month of measured were estimated by the least square method. The repeatabilities were estimated from the component of variance among repeated measurements of the trait for the same animal. The results obtained are summarized as follow ; 1. The means of the major economic traits studied were 142.1 days, 173.7 days and 182.5 days for age at 1st, 2nd and 3rd measure, 57.9%, 56.2% and 55.2% for lean percent at 1st. 2nd and 3rd mesure, 1.33㎝, 1.61㎝ and 1.63㎝ for backfat thickness at 1st. 2nd and 3rd measure, 946.6g, 879.2g and 879.4g for average daily gain at 1st. 2nd and 3rd measure, respectively. 2. The correlation coefficients between the backfat thickness measured at 1st and 2nd, at 2nd and 3rd, at 1st and 3rd were 0.424, 0.700 and 1.424, respectively. The correlation coefficients between the lean percent measured at 1st and 2nd, at 2nd and 3rd, at 1st and 3rd were 0.493, 0.619 and 0.471, respectively. The correlation coefficients between the average daily gain measured at 1st and 2nd, at 2nd and 3rd, at 1st and 3rd were 0.716, 0.861 and 0.601, respectively. 3. The rank correlation coefficients between backfat thickness measured at 1st and 2nd, at 2nd and 3rd, at 1st and 3rd were 0.438, 0.693 and 0.441, respectively. The rank correlation coefficients between lean percent measured at1st and 2nd, at 2nd and 3rd, at 1st and 3rd were 0.508, 0.593 and 0.478, respectively. The rank correlation coefficients between average daily gain measured at 1st and 2nd, at 2nd and 3rd, at 1st and 3rd were 0.704, 0.834 and 0.571, respectively. 4. The estimated repeatabilities of the traits studied were 0.428 for the lean percent, 0.374 for the backfat thickness and 0.673 for the average daily gain, respectively.

Compensation of motion artifacts in catheter-based optical frequency domain imaging

Ha, J. Y.,Shishkov, M.,Colice, M.,Oh, W. Y.,Yoo, H.,Liu, L.,Tearney, G. J.,Bouma, B. E. Optical Society of America 2010 Optics express Vol.18 No.11

<P>A novel heterodyne Doppler interferometer method for compensating motion artifacts caused by cardiac motion in intracoronary optical frequency domain imaging (OFDI) is demonstrated. To track the relative motion of a catheter with regard to the vessel, a motion tracking system is incorporated with a standard OFDI system by using wavelength division multiplexing (WDM) techniques. Without affecting the imaging beam, dual WDM monochromatic beams are utilized for tracking the relative radial and longitudinal velocities of a catheter-based fiber probe. Our results demonstrate that tracking instantaneous velocity can be used to compensate for distortion in the images due to motion artifacts, thus leading to accurate reconstruction and volumetric measurements with catheter-based imaging.</P>

The Depigmentation Effect of A New Material Extracted from Paper Mulberry and its Comparison by Three Colorimetric Instruments

( Ha J. H ),( Jo N. S ),( Lee H. K ),( Kim J. L ),( Lee B. G ),( Park W. J ) 대한화장품학회 1996 대한화장품학회지 Vol.22 No.2