Alpha-Tocopherol Transfer Protein (α-TTP)

Yunsook Lim,Maret G. Traber 한국영양학회 2007 Nutrition Research and Practice Vol.1 No.4

Alpha-tocopherol transfer protein (α-TTP) is a liver cytosolic transport protein that faciliates α-tocopherol (α-T) transfer into liver secreted plasma lipoproteins. Genetic defects in α-TTP, like dietary vitamin E deficiency, are associated with infertility, muscular weakness and neurological disorders. Both human and α-TTP deficient (α-TTP<SUP>-/-</SUP>) mice exhibit severe plasma and tissue vitamin E deficiency that can be attenuated by sufficient dietary α-T supplementations. In this review, we summarize the literature concerning studies utilizing the α-TTP<SUP>-/-</SUP> mice. Levels of vitamin E in the α-TTP<SUP>-/-</SUP> mice do not appear to be directly related to the amounts of dietary α-T or to the levels of α-TTP protein in tissues. The α-TTP<SUP>-/-</SUP> mice appear to present a good model for investigating the specific role of α-T in tissue vitamin E metabolism. Furthermore, α-TTP<SUP>-/-</SUP> mice appear to be useful to elucidate functions of α-TTP beyond its well recognized functions of transferring α-T from liver to plasma lipoprotein fractions.

Anti-inflammatory and antiobesity effects of mulberry leaf and fruit extract on high fat diet-induced obesity.

Lim, Hyun Hwa,Lee, Sung Ok,Kim, Sun Yeou,Yang, Soo Jin,Lim, Yunsook The Society 2013 Experimental biology and medicine Vol.238 No.10

<P>The purpose of this study was to investigate the anti-inflammatory and antiobesity effect of combinational mulberry leaf extract (MLE) and mulberry fruit extract (MFE) in a high-fat (HF) diet-induced obese mice. Mice were fed a control diet or a HF diet for nine weeks. After obesity was induced, the mice were administered with single MLE at low dose (133 mg/kg/day, LMLE) and high dose (333 mg/kg/day, HMLE) or combinational MLE and MFE (MLFE) at low dose (133 mg MLE and 67 mg MFE/kg/day, LMLFE) and high dose (333 mg MLE and 167 mg MFE/kg/day, HMLFE) by stomach gavage for 12 weeks. The mulberry leaf and fruit extract treatment for 12 weeks did not show liver toxicity. The single MLE and combinational MLFE treatments significantly decreased plasma triglyceride, liver lipid peroxidation levels and adipocyte size and improved hepatic steatosis as compared with the HF group. The combinational MLFE treatment significantly decreased body weight gain, fasting plasma glucose and insulin, and homeostasis model assessment of insulin resistance. HMLFE treatment significantly improved glucose control during intraperitoneal glucose tolerance test compared with the HF group. Moreover, HMLFE treatment reduced protein levels of oxidative stress markers (manganese superoxide dismutase) and inflammatory markers (monocyte chemoattractant protein-1, inducible nitric oxide synthase, C-reactive protein, tumour necrosis factor-α and interleukin-1) in liver and adipose tissue. Taken together, combinational MLFE treatment has potential antiobesity and antidiabetic effects through modulation of obesity-induced inflammation and oxidative stress in HF diet-induced obesity.</P>

고농도의 감마 토코페롤 보충식이가 흡연에 노출된 쥐의 혈액 및 조직 비타민 E와 대사산물 농도에 미치는 영향

임윤숙(Lim Yunsook) 韓國營養學會 2008 Journal of Nutrition and Health Vol.41 No.2

흡연은 활성 산소/절소종의 생성을 증가시켜 체내 산화적 스트레스를 증가시키고 폐의 염증을 유발한다. 이는 흡연자들의 체내 항산화 영양소들의 감소와 밀접한 관계를 가지는 것으로 알려져 있다. 본 연구에서는 항산화, 항염증 기능을 가진 비타민 E 중 식이에 많이 포함되어 있는 GT를 이용하여 흡연에 의한 항산화, 항염증 작용을 알아보기 위한 선행 연구로 고농도의 GT 식이가 혈액과 간, 폐의 AT, GT농도와 이들의 대사산물인 CEHC 농도에 미치는 영향에 대하여 알아보고자 실시하였다. 연구 결과 고농도 GT 식이는 체내 혈액과 간, 폐 조직에 GT를 축적시키고 G-CEHC의 배설을 증가시켰다. 흡연은 대조군의 혈액과 폐 AT농도는 증가시켰지만, 고농도 GT 군의 혈액과 폐의 GT농도와 간의 G-CEHC의 농도를 감소 시켰다. 이러한 변화는 흡연에 의한 산화적 스트레스 상태에서 각기 다른 기능을 가진 조직의 요구량에 따라, 폐의 이용률을 높이기 위해 혈액으로 운반되는 양을 증가시키고 폐로의 운반을 일시적으로 증가시켜 조직의 AT, GT 농도를 선택적으로 조절하고 GT의 생체 이용률의 증가 때문이라 사료된다. 하지만 정확한 가전에 대한 연구들이 부족한 실정이므로 고농도의 GT 식이가 흡연에 의해 유도된 체내 산화적 스트레스와 폐의 염증 반응에 긍정적인 효과를 알아보기 위한 후속 연구가 절실히 필요한 것으로 사료된다. Cigarette smoke (CS) induces oxidative and nitrosative stress to the respiratory tract (RT) via both oxidants contained in CS and by CS-induced activation of RT inflammatory-immune pro-oxidant processes. CS exposure has been associated with reduced levels of plasma micronutrient antioxidants, in part due to an increased utilization and turnover of alpha-tocopherol (AT). It has been suggested that gamma-tocopherol (GT) may have an expanded spectrum of antioxidant activation compared to alpha-tocopherol (AT). In order to investigate effects of high GT supplementation as compared to AT, C57 BL/6 mice were fed control AT (35 ㎎/㎏ diet) or high GT (1,000 ㎎/㎏ diet) diet for 8-10 weeks and then exposed to 60 ㎎/㎥ CS, 6 hr/day for 3 days. AT and GT levels and their metabolites were measured at endpoints. High GT supplementation significantly reduced AT levels in plasma, liver and lung compared to AT. CS increased levels of AT and GT in plasma and lung of control AT group but decreased GT levels in lung of high GT supplemented group. Moreover, CS significantly decreased GT metabolite, gamma-CEHC. The results suggest that high GT supplementation have selective modulation of concentrations of vitamin E and its metabolite in plasma and lung but not in liver against in vivo CS exposure. (Korean J Nutr 2008; 41 (2): 135~140)

Tocotrienol-rich fraction supplementation reduces hyperglycemia-induced skeletal muscle damage through regulation of insulin signaling and oxidative stress in type 2 diabetic mice

Lee, Heaji,Lim, Yunsook Elsevier 2018 Journal of Nutritional Biochemistry Vol.57 No.-

<P><B>Abstract</B></P> <P>Chronic hyperglycemia induces impairment of muscle growth and development of diabetes mellitus (DM). Since skeletal muscle is the major site for disposal of ingested glucose, impaired glucose metabolism causes imbalance between protein synthesis and degradation which adversely affects physical mobility.</P> <P>In this study, we investigated the effect of tocotrienol-rich fraction (TRF) supplementation on skeletal muscle damage in diabetic mice. Diabetes was induced by a high-fat diet with streptozotocin (STZ) injection (100 mg/kg) in male <I>C57BL/6J</I> mice. After diabetes was induced (fasting blood glucose levels≥250 mg/dl), normal control (CON) and diabetic control (DMC) groups were administrated with olive oil, while TRF treatment groups were administrated with TRF (dissolved in olive oil) at low dose (100 mg/kg BW, LT) or high dose (300 mg/kg BW, HT) by oral gavage for 12 weeks.</P> <P>TRF supplementation ameliorated muscle atrophy, plasma insulin concentration and homeostatic model assessment estimated insulin resistance in diabetic mice. Moreover, TRF treatment up-regulated IRS-1 and Akt levels accompanied by increased translocation of GLUT4. Furthermore, TRF increased mitochondrial biogenesis by activating SIRT1, SIRT3 and AMPK in diabetic skeletal muscle. These changes were in part mechanistically explained by reduced levels of skeletal muscle proteins related to oxidative stress (4-hydroxynonenal, protein carbonyls, Nrf2 and HO-1), inflammation (NFkB, MCP-1, IL-6 and TNF-α), and apoptosis (Bax, Bcl₂ and caspase-3) in diabetic mice. Taken together, these results suggest that TRF might be useful as a beneficial nutraceutical to prevent skeletal muscle atrophy associated with diabetes by regulating insulin signaling via AMPK/SIRT1/PGC1α pathways in type 2 diabetic mice.</P>

Gamma-tocopherol ameliorates hyperglycemia-induced hepatic inflammation associated with NLRP3 inflammasome in alloxan-induced diabetic mice

Lee, Heaji,Lim, Yunsook The Korean Nutrition Society 2019 Nutrition Research and Practice Vol.13 No.5

BACKGROUND/OBJECTIVES: Hyperglycemia-induced hepatic damage has been recognized as one of the major cause of complications in diabetes. Hepatic complications are associated with inflammation and oxidative stress in diabetes. In this study, we investigated the hypothesis that gamma-tocopherol (GT) supplementation ameliorates NLRP3 inflammasome associated hepatic inflammation in diabetes. MATERIALS/METHODS: Diabetes was induced by the intraperitoneal injection of alloxan (150 mg/kg. BW) in ICR mice. All mice were fed with a control diet (AIN-76A). After diabetes was induced (fasting glucose level ${\geq}250mg/dL$), the mice were treated with tocopherol-stripped corn oil or GT-supplemented (35 mg/kg) corn oil, respectively, by gavage for 2 weeks. RESULTS: GT supplementation reduced fasting blood glucose levels in diabetic mice relative to non-treated diabetic mice. Moreover, GT supplementation ameliorated hyperglycemia-induced hepatic damage by regulation of NOD-like receptor protein 3 (NLRP3)-inflammasome associated inflammation represented by NLRP3, apoptosis-associated speck-like protein containing a caspase-recruitment domain, caspase-1, nuclear $factor-{\kappa}B$ pathway as well as oxidative stress demonstrated by nuclear factor erythroid 2-related factor 2, NAD(P)H dehydrogenase quinone 1, catalase and glutathione-dependent peroxidase in diabetic mice. CONCLUSION: The findings suggested that GT supplementation ameliorated hepatic damage by attenuating inflammation and oxidative stress in alloxan-induced diabetic mice. Taken together, GT could be a beneficial nutrient that can ameliorate inflammatory responses associated with NLRP3 inflammasome in hyperglycemia-induced hepatic damage.

Gamma-tocopherol ameliorates hyperglycemia-induced hepatic inflammation associated with NLRP3 inflammasome in alloxan-induced diabetic mice

Heaji Lee,Yunsook Lim 한국영양학회 2019 Nutrition Research and Practice Vol.13 No.5

BACKGROUND/OBJECTIVES: Hyperglycemia-induced hepatic damage has been recognized as one of the major cause of complications in diabetes. Hepatic complications are associated with inflammation and oxidative stress in diabetes. In this study, we investigated the hypothesis that gamma-tocopherol (GT) supplementation ameliorates NLRP3 inflammasome associated hepatic inflammation in diabetes. MATERIALS/METHODS: Diabetes was induced by the intraperitoneal injection of alloxan (150 mg/kg. BW) in ICR mice. All mice were fed with a control diet (AIN-76A). After diabetes was induced (fasting glucose level ≥ 250 mg/dL), the mice were treated with tocopherol-stripped corn oil or GT-supplemented (35 mg/kg) corn oil, respectively, by gavage for 2 weeks. RESULTS: GT supplementation reduced fasting blood glucose levels in diabetic mice relative to non-treated diabetic mice. Moreover, GT supplementation ameliorated hyperglycemia-induced hepatic damage by regulation of NOD-like receptor protein 3 (NLRP3)-inflammasome associated inflammation represented by NLRP3, apoptosis-associated speck-like protein containing a caspase-recruitment domain, caspase-1, nuclear factor-κB pathway as well as oxidative stress demonstrated by nuclear factor erythroid 2-related factor 2, NAD(P)H dehydrogenase quinone 1, catalase and glutathione-dependent peroxidase in diabetic mice. CONCLUSION: The findings suggested that GT supplementation ameliorated hepatic damage by attenuating inflammation and oxidative stress in alloxan-induced diabetic mice. Taken together, GT could be a beneficial nutrient that can ameliorate inflammatory responses associated with NLRP3 inflammasome in hyperglycemia-induced hepatic damage.

Similarities and differences between alpha-tocopherol and gamma-tocopherol in amelioration of inflammation, oxidative stress and pre-fibrosis in hyperglycemia induced acute kidney inflammation

Hanna Shin,Hyeyoon Eo,Yunsook Lim 한국영양학회 2016 Nutrition Research and Practice Vol.10 No.1

BACKGROUND/OBJECTIVES: Diabetes mellitus (DM) is a major chronic disease which increases global health problems. Diabetes-induced renal damage is associated with inflammation and fibrosis. Alpha (AT) and gamma-tocopherols (GT) have shown antioxidant and anti-inflammatory effects in inflammation-mediated injuries. The primary aim of this study was to investigate effects of AT and GT supplementations on hyperglycemia induced acute kidney inflammation in alloxan induced diabetic mice with different levels of fasting blood glucose (FBG). MATERIALS/METHODS: Diabetes was induced by injection of alloxan monohydrate (150 mg/kg, i.p) in ICR mice (5.5-week-old, male) and mice were subdivided according to their FBG levels and treated with different diets for 2 weeks; CON: non-diabetic mice, m-DMC: diabetic control mice with mild FBG levels (250 mg/dl ≤ FBG ≤ 450 mg/dl), m-AT: m-DM mice fed AT supplementation (35 mg/kg diet), m-GT: m-DM mice with GT supplementation (35 mg/kg diet), s-DMC: diabetic control mice with severe FBG levels (450 mg/dl < FBG), s-AT: s-DM mice with AT supplementation, s-GT: s-DM mice with GT supplementation. RESULTS: Both AT and GT supplementations showed similar beneficial effects on NFκB associated inflammatory response (phosphorylated inhibitory kappa B-α, interleukin-1β, C-reactive protein, monocyte chemotactic protein-1) and pre-fibrosis (tumor growth factor β-1 and protein kinase C-II) as well as an antioxidant emzyme, heme oxygenase-1 (HO-1) in diabetic mice. On the other hands, AT and GT showed different beneficial effects on kidney weight, FBG, and oxidative stress associated makers (malondialdehyde, glutathione peroxidase, and catalase) except HO-1. In particular, GT significantly preserved kidney weight in m-DM and improved FBG levels in s-DM and malondialdehyde and catalase in m- and s-DM, while AT significantly attenuated FBG levels in m-DM and improved glutathione peroxidase in m- and s-DM. CONCLUSIONS: the results suggest that AT and GT with similarities and differences would be considered as beneficial nutrients to modulate hyperglycemia induced acute renal inflammation. Further research with careful approach is needed to confirm beneficial effects of tocopherols in diabetes with different FBG levels for clinical applications.

Paeonia japonica, Houttuynia cordata, and Aster scaber Water Extracts Induce Nitric Oxide and Cytokine Production by Lipopolysaccharide-Activated Macrophages

Jin Kim,박창신,Yunsook Lim,김현숙 한국식품영양과학회 2009 Journal of medicinal food Vol.12 No.2

Natural products are increasingly recognized as potential targets for drug discovery and development. We previously reported that Paeonia japonica, Houttuynia cordata, and Aster scaber enhanced macrophage activation both in vitro and in vivo. In the present study we investigated the immunomodulating effects of these plants on lipopolysacharide (LPS)-stimulated macrophages. An aqueous extract of each plant was administered to female BALB/c mice every other day for 4 weeks. Peritoneal macrophages were then collected and incubated to examine the immunoreactivity of macrophages against LPS at different time points. The expression levels of inducible nitric oxide (NO) synthetase (iNOS), cyclooxygenase (COX)-2, and inhibitory factor κB α (IκBα) proteins and the production of NO metabolite (nitrite), prostaglandin (PG) E2, and the pro-inflammatory cytokines interleukin-1β, interleukin-6, and tumor necrosis factor-α were determined in the activated macrophages treated with extracts from each plant individually or combined. High levels of pro-inflammatory cytokines were produced by A. scaber-, P. japonica-, and H. cordata-treated macrophages following 24 hours of LPS stimulation. P. japonica, H. cordata, and A. scaber treatment also induced the production of nitrate by LPS-treated macrophages. Induction of iNOS mRNA and protein was also different in each group. PGE2 secretion was up-regulated by all extract-treated macrophages at early time points; however, no significant differences were observed between the groups by 8 hours post-LPS stimulation. Treatment with A. scaber extract resulted in the highest levels of IκBα degradation. Our findings illustrate that the natural plant products P. japonica, H. cordata, and A. scaber may enhance immune function by modulating ex vivo pro-inflammatory cytokine and NO production as well as the expression of iNOS and COX-2.

Anti-adipogenic effect of mulberry leaf ethanol extract in 3T3-L1 adipocytes

Soo Jin Yang,Na-Young Park,Yunsook Lim 한국영양학회 2014 Nutrition Research and Practice Vol.8 No.6

BACKGROUND/OBJECTIVES: Adipogenesis is part of the cell differentiation process in which undifferentiated fibroblasts (pre-adipocytes) become mature adipocytes with the accumulation of lipid droplets and subsequent cell morphological changes. Several transcription factors and food components have been suggested to be involved in adipogenesis. The aim of this study was to determine whether mulberry leaf ethanol extract (MLEE) affects adipogenesis in 3T3-L1 adipocytes. MATERIALS/METHODS: The 3T3-L1 adipocytes were treated with different doses of MLEE for 8 days starting 2 days post-confluence. Cell viability, fat accumulation, and adipogenesis-related factors including CCAAT-enhancer-binding protein alpha (C/EBPα), peroxisome proliferator-activated receptor gamma (PPARγ), PPARγ coactivator 1 alpha (PGC-1α), fatty acid synthase (FAS), and adiponectin were analyzed. RESULTS: Results showed that MLEE treatments at 10, 25, 50, and 100 μg/ml had no effect on cell morphology and viability. Without evident toxicity, all MLEE treated cells had lower fat accumulation compared with control as shown by lower absorbances of Oil Red O stain. MLEE at 50 and 100 μg/ml significantly reduced protein levels of PPARγ, PGC-1α, FAS, and adiponectin in differentiated adipocytes. Furthermore, protein level of C/EBPα was significantly decreased by the treatment of 100 μg/ml MLEE. CONCLUSION: These results demonstrate that MLEE treatment has an anti-adipogenic effect in differentiated adipocytes without toxicity, suggesting its potential as an anti-obesity therapeutic.

A Study on Food Allergy Practices of Dietitians at Schools in Korea

Yeonsoo Kim(김연수),Eunji Park(박은지),Yunsook Lim(임윤숙) 한국웰니스학회 2014 한국웰니스학회지 Vol.9 No.4

최근들어 성장기 아동과 청소년의 건강과 웰빙이 성인기까지 영향을 미치는 중요한 요인으로 대두되고 있다. 치명적인 위험을 동반한 국내 식품 알러지 발생 빈도가 증가하면서 학교 급식에서 식품 알러지 교육 및 실행 프로그램의 필요성이 증대되고 있다. 본 연구는 학교 급식을 담당하는 영양사들의 식품 알러지와 알러지 발생시 위험에 대처하는 방법들에 대한 지식과 태도를 평 가하고 학교내 식품 알러지 발생시 이에 대처하는 방법 등을 알아보기 위해 실시하였다. 본 연구에서는 서울 시내의 144개교 학 교 급식 영양사를 대상으로 식품 알러지에 대한 지식과 식품 알러지 관련 실태에 관하여 조사하였다. 결과로는 급식 영양사들의 식품 알러지에 대한 지식과 태도는 각각 15점 만점에 10.1, 30 점 만점에 22.6으로 나타났다. 또한, 연구 대상자의 45%만이 학생들 이 가지는 식품 알러지에 대한 조사를 실시하는 것으로 나타났고, 단지 21% 만이 대상 학생이나 학부모들에게 식품 알러지에 대 한 교육을 실시하는 것으로 나타났다. 특히, 연구 대상자들이 근무하는 학교의 10% 만이 식품 알러지를 가지는 학생들에게 대체 식단을 제공하고 있었으며, 학생들 사이에서 식품을 공유하지 못하도록 하거나, 조리 종사자들의 라텍스 장갑 사용을 금지 하는 등에 대한 식품 알러지 예방 규칙은 전혀 없는 것으로 나타났다. 본 연구 결과를 종합해보면, 현재 국내 학교 급식에서 식품 알러지에 대한 관리가 부족한 실정이며, 이를 향상시키기 위한 정 부와 학교의 노력이 더욱 필요한 것으로 사료된다. The prevalence of food allergies has been increasing and food allergy management programs were implemented at schools in Korea to increase public awareness of food allergies and to educate students on the topic of food allergies for their healthy lives and wellness. The objectives of the present study were to identify and to evaluate dietitians' knowledge and attitudes toward food allergies, risk-taking behaviors, and coping strategies with the ultimate goal of protecting against and managing food allergies at school. The study participants included 144 dietitians at schools located in Seoul, Korea. A survey was used to measure dietitians' knowledge and practices with respect to food allergies. Dietitians' knowledge and attitude scores with regard to food allergies were 10.1 out of 15 and 22.6 out of 30, respectively. The results of the study indicate that only 45% of dietitians conducted a survey to identify students with food allergies, and only 21% provided education concerning food allergies, mainly to students with food allergies and their parents. Moreover, only 10% of dietitians offered food substitutions as a strategy to avoid food allergies and did not implement a policy of no sharing foods among students and no use of latex gloves for food service workers when they prepared food substitutions. It seems that the current management of food allergies in school meal service is not sufficient. The findings of the current study could be used to improve prevention and management of food allergies at school.