• 대한임상검사과학회지
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• 제49권3호
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• pp.248-255
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• 2017

대사적으로 건강한 비만인(metabolically healthy obese, MHO)은 대사적 합병증을 동반하지 않으며, 과도한 체지방에도 불구하고 인슐린 감수성을 유지하는 비만의 표현형이다. 이 연구는 20세 이상 70세 이하의 남성을 대상으로 비만과 대사적 이상 유무에 따라 MHNO, MHO와 MAO군으로 분류하여 간 효소의 차이를 알아보고 대사적으로 건강한 비만남성에서 간 효소가 대사적 이상을 예측할 수 있는 지표인지 그 임상적 의의를 확인하고자 하였다. Executive Summary of The Third Report of The National Cholesterol Education Program Adult Treatment Panel III (NCEP-ATP III) 진단기준으로 대사적 이상을 평가하였으며, 비만 진단기준은 WHO에서 제시하는 아시아인의 기준을 따라 세 군으로 분류하였다. 최종 연구 대상자 9,683명 중 대사적으로 건강한 정상체중군(metabolically healthy non obese, MHNO) 2,878명, 대사적으로 건강한 비만군(metabolically healthy obese, MHO) 5,427명, 대사적으로 이상이 있는 비만군(metabolically abnormal obese, MAO) 1,378명 이었다. AST, ALT, GGT는 MAO군보다 MHO군에서 통계적으로 유의하게 낮았으나(각각 p<0.001), MHO군은 MHNO군보다는 간 효소치가 높게 나타났다(각각 p<0.001). 또한 간 효소는 대사증후군 위험요인과 관련이 있으며, 허리둘레, 공복혈당, 총콜레스테롤, 중성지방, HDL-C은 AST, ALT, GGT에 영향을 미치는 위험요인으로 나타났다. 결론적으로 대사적으로 건강한 비만남성에서 간 효소가 대사적 이상을 예측할 수 있는 지표인 것을 확인하였다.

• 한국식품영양과학회지
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• 제38권4호
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• pp.415-422
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• 2009

고 fructose 식이를 섭취시켜 제 2형 당뇨를 유발한 쥐에서 ZA의 섭취가 혈당 조절에 미치는 기전을 밝히고자 하였다. 4주 동안의 실험기간 중 Control군(normal chow diet), Fructose군(high-fructose diet)과 Fructose+ZA군(highfructose diet+ZA treatment) 간의 체중, 먹이 및 물의 섭취량에는 유의한 차이를 나타내지 않았다(p<0.05). 기저상태 (basal state)에서 혈장 포도당, 인슐린 농도 및 간의 포도당 생성률을 측정한 결과 Control군과 Fructose군 및 Fructose+ZA군 간의 차이를 나타내지 않았다. 인슐린 감수성을 알아보기 위한 hyperinsulinemic euglycemic clamp 실험에서 인슐린 농도와 포도당 농도는 군 간의 차이를 나타내지 않았다. 또한 인슐린 감수성 지표인 포도당 흡수(glucose uptake)에서도 역시 군 간의 차이를 발견하지 못하였다. 그러나 간의 인슐린 감수성 지표인 간의 포도당 생성률(HGO)에서는 Fructose군이 Control군에 비하여 유의적으로 증가되었고 (p<0.05), Fructose+ZA군이 대조군의 수준으로 감소되었다. 이것으로 미루어 볼 때 fructose 식이는 간에서 인슐린감수성을 감소시켰으나 당뇨는 유발되지 않았으며, ZA 섭취가 간의 포도당 생성률을 억제하는 것으로 보아 인슐린 감수성을 증가시키지만, 말초조직의 포도당 이용에는 영향을 미치지 않는 것으로 사료된다.

• Journal of Ginseng Research
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• 제42권4호
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• pp.419-428
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• 2018

Background: Despite the large number of studies on ginseng, pharmacological activities of ginseng seed oil (GSO) have not been established. GSO is rich in unsaturated fatty acids, mostly oleic and linoleic acids. Unsaturated fatty acids are known to exert a therapeutic effect in nonalcoholic fatty liver disease (NAFLD). In this study, we investigated the protective effect and underlying mechanisms of GSO against NAFLD using in vitro and in vivo models. Methods: In vitro lipid accumulation was induced by free fatty acid mixture in HepG2 cells and by 3 wk of high fat diet (HFD)-feeding in Sprague-Dawley rats prior to hepatocyte isolation. The effects of GSO against diet-induced hepatic steatosis were further examined in C57BL/6J mice fed a HFD for 12 wk. Results: Oil Red O staining and intracellular triglyceride levels showed marked accumulation of lipid droplets in both HepG2 cells and rat hepatocytes, and these were attenuated by GSO treatment. In HFD-fed mice, GSO improved HFD-induced dyslipidemia and hepatic insulin resistance. Increased hepatic lipid contents were observed in HFD-fed mice and it was lowered in GSO (500 mg/kg)-treated mice by 26.4% which was evident in histological analysis. Pathway analysis of hepatic global gene expression indicated that GSO increased the expression of genes associated with ${\beta}$-oxidation (Ppara, Ppargc1a, Sirt1, and Cpt1a) and decreased the expression of lipogenic genes (Srebf1 and Mlxipl), and these were confirmed with reverse transcription and quantitative polymerase-chain reaction. Conclusion: These findings suggest that GSO has a beneficial effect on NAFLD through the suppression of lipogenesis and stimulation of fatty acid degradation pathway.

• Nutrition Research and Practice
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• 제4권2호
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• pp.106-113
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• 2010

In this study, we compared corn gluten hydrolyzates, BCAAs, and leucine for their effects on body weight reduction in high fat-induced obese rats in order to determine the major active components in the corn gluten hydrolyzates. After obesity was induced for 13 weeks with high fat diet, the overweight-induced SD rats (n = 64) were stratified according to body weight, randomly blocked into eight treatments, and raised for 8 weeks. Four groups were changed to a normal diet and the other groups remained on the high fat diet. Each of the groups within both diets was fed either casein, corn gluten hydrolyzates, leucine, or branched chain amino acids, respectively. Daily food intake, body weight gain, and food efficiency ratio were significantly lower in the corn gluten hydrolyzate groups compared to the other groups, regardless of the high fat diet or normal fat diet. The rats fed the corn gluten hydrolyzates diet had the lowest perirenal fat pad weights whereas muscle weight was significantly increased in the corn gluten hydrolyzates groups. Plasma triglyceride, hepatic total lipid, and total cholesterol contents were significantly reduced in the corn gluten hydrolyzates groups. Other lipid profile measurements were not significantly changed. Plasma triglyceride and hepatic total lipid were also significantly reduced in the BCAA and leucine groups. Leptin levels were significantly lower and adiponectin was significantly higher in the corn gluten hydrolyzates groups. Fasting blood glucose, insulin, C-peptide, and HOMA-IR levels were also significantly reduced in the corn gluten hydrozylates groups, regardless of fat level.

• Nutrition Research and Practice
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• 제11권3호
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• pp.206-213
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• 2017

BACKGROUN/OBJECTIVES: Although studies have revealed that black garlic is a potent antioxidant, its antioxidant mechanism remains unclear. The objective of this study was to determine black garlic's antioxidant activities and possible antioxidant mechanisms related to nuclear factor erythroid 2-like factor 2 (Nrf2)-Keap1 complex. METHODS/MATERIALS: After four weeks of feeding rats with a normal fat diet (NF), a high-fat diet (HF), a high-fat diet with 0.5% black garlic extract (HF+BGE 0.5), a high-fat diet with 1.0% black garlic extract (HF+BGE 1.0), or a high-fat diet with 1.5% black garlic extract (HF+BGE 1.5), plasma concentrations of glucose, insulin,homeostatic model assessment of insulin resistance (HOMA-IR) were determined. As oxidative stress indices, plasma concentrations of thiobarbituric acid reactive substances (TBARS) and 8-isoprostaglandin $F2{\alpha}$ (8-iso-PGF) were determined. To measure antioxidant capacities, plasma total antioxidant capacity (TAC) and activities of antioxidant enzymes in plasma and liver were determined. The mRNA expression levels of antioxidant related proteins such as Nrf2, NAD(P)H: quinone-oxidoreductase-1 (NQO1), heme oxygenase-1 (HO-1), glutathione reductase (GR), and glutathione S-transferase alpha 2 (GSTA2) were examined. RESULTS: Plasma glucose level, plasma insulin level, and HOMA-IR in black garlic supplemented groups were significantly (P < 0.05) lower than those in the HF group without dose-dependent effect. Plasma TBARS concentration and TAC in the HF+BGE 1.5 group were significantly decreased compared to those of the HF group. The activities of catalase and glutathione peroxidase were significantly (P < 0.05) increased in the HF+BGE 1.0 and HF+BGE 1.5 groups compared to those of the HF group. The mRNA expression levels of hepatic Nrf2, NQO1, HO-1, and GSTA2 were significantly (P < 0.05) increased in the HF with BGE groups compared to those in the HF group. CONCLUSIONS: The improvements of blood glucose homeostasis and antioxidant systems in rats fed with black garlic extract were related to mRNA expression levels of Nrf2 related genes.

• 대한의생명과학회지
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• 제14권4호
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• pp.225-231
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• 2008

Non-alcoholic fatty liver disease (NAFLD) is associated with various metabolic abnormalities, including central obesity, type 2 diabetes, dyslipidemia, and high blood pressure. This suggests that NAFLD may represent the hepatic manifestation of the metabolic syndrome. In this study, we investigated unfavorable effects NAFLD on components of metabolic syndrome in post-menopause women. Eight hundred sixty-nine postmenopausal women were recruited for this study. The diagnosis of fatty liver was based on the results of abdominal ultrasonography. Serum levels of fasting glucose, total cholesterol, triglyceride, and HDL-cholesterol were measured. The prevalence of component of metabolic syndrome such as hypertension, hyperglycemia, hypertriglyceridemia, and low-HDL-cholesterol was significantly higher in subjects with NAFLD as compared with those without NAFLD. The moderate to severe grade of NAFLD presented higher levels of serum fasting glucose, fasting insulin, HOMA-IR, total cholesterol, and triglycerides than the mild NAFLD and the normal group. In conclusion, metabolic syndrome risk was increased in post-menopause women with NAFLD as compared with those without NAFLD. The severity of NAFLD affected metabolic syndrome risk factors. The optimal strategy for the treatment of NAFLD is likely to include lifestyle modifications and therapy to improve insulin resistance.

• 대한의생명과학회지
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• 제12권2호
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• pp.65-72
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• 2006

Thiazolidinediones (TZDs) are widely used antidiabetic drugs that activate the nuclear peroxisome proliferator-activated receptor ${\gamma}(PPAR{\gamma})$, and thereby improve the metabolic abnormalities linking hypertriglyceridemia to diabetes, hyperglycemia, insulin resistance, and cardiovascular disease. To determine whether the $PPAR{\gamma}$ ligand troglitazone regulates lipid metabolism with sexual dimorphism, we examined the effects of troglitazone on circulating lipids, body weight and the expression of hepatic genes responsible for lipid metabolism in both sexes of C57BL/6J mice. Compared to mice fed a low fat control diet, both sexes of mice fed a troglitazone-treated low fat diet for 14 weeks did not exhibit changes in body weight gain, serum total cholesterol, HDL-cholesterol and LDL-cholesterol levels. However, serum triglycerides were significantly reduced in both sexes of mice, although these effects were more pronounced among males. Furthermore, troglitazone regulated the expression of hepatic genes critical for lipid and lipoprotein metabolism, the magnitudes of which were much higher in males compared to females, as evidenced by results for increased acyl-CoA oxidase and decreased apolipoprotein C-III mRMA levels. These results suggest that $PPAR{\gamma}$ activator troglitazone may exert sexually dimorphic control of serum triglycerides in part through the differential activation of $PPAR{\gamma}$ in liver between male and female mice.

• Food Science and Biotechnology
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• 제18권1호
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• pp.172-178
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• 2009

Fermented ginseng (FG) is an ethanol extract of ginseng radix processed with $\beta$-galactosidase. It was hypothesized that FG may exert anti-hyperlipidemic and anti-diabetic activities through modulating AMP-activated protein kinase (AMPK) in HepG2 human hepatoma cells. In this study, we showed that AMPK phosphorylation was stimulated by FG. These effects were abolished by pretreatment with an AMPK inhibitor, compound C. In addition, FG regulated the expression of genes associated with lipogenesis and lipolysis, thus causing suppression of hepatic triglyceride accumulation. In vivo study using db/db mice, FG reduced fasting plasma glucose, HbAlc, and insulin resistance index, when compared to diabetic control. FG also increased the phospho-AMPK and glucose transporter 4 (GLUT4) expressions in liver and skeletal muscle, respectively. In liver, expressions of lipogenic gene were decreased whereas expressions of lipolytic genes were induced, when compared to diabetic control. Taken together, we may suggest that FG ameliorates hyperglycemia and hyperlipidemia through activation of AMPK and could be developed as a health functional food or therapeutic agent for type 2 diabetic patients.

• Pediatric Gastroenterology, Hepatology & Nutrition
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• 제10권2호
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• pp.185-192
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• 2007

목 적: 본 연구에서는 소아 비만 환자에서 발생하는 비알코올성 지방간 질환의 발병에 TNF-${\alpha}$, adiponectin, leptin 등의 adipokine들이 미치는 영향을 알아보며, 이들 adipokine과 체지방분포 및 인슐린 저항성과의 연관성을 함께 살펴보고자 하였다. 방 법: 2004년 3월에서 2005년 6월까지 분당서울대병원 소아과에 내원한 비만한 소아 61명을 대상으로 하여 비알코올성 지방간 질환의 상태에 따라 대상 환자들을 지방간 질환이 없는 소아 비만 환자(n=23), 단순 지방간(n=20), 그리고 비알코올성 지방간염(n=18)의 세군으로 나누고, 각 환자에서 혈중 TNF-${\alpha}$, leptin, adiponectin 농도를 측정하고 인슐린 저항성의 지표로서 HOMA-IR을 계산하였으며 복부 전산화단층촬영에서 VSR (visceral-subcutaneous fat ratio)을 산출하였다. 결 과: 총 61명(남 : 여=42 : 19, 평균 연령 11.2${\pm}$1.3세)의 환아를 대상으로 지방간 질환에 따라 세 군으로 나누었을 때, 세 군 간의 성별, 연령별 차이는 없었다(p=0.422, p=0.119). 각 군의 혈중 TNF-${\alpha}$ 농도는 유의한 차이가 없었고(22.13${\pm}$6.37 vs. 21.35${\pm}$6.95 vs. 25.17${\pm}$9.30; p=0.342), leptin 농도에도 유의한 차이가 없었으나 (20.29${\pm}$8.57 vs. 16.42${\pm}$6.85 vs. 20.10${\pm}$7.86; p=0.330), adiponectin은 유의한 차이를 보여 비알코올성 지방간염에서 혈중농도가 의미 있게 감소하였다 (6.08${\pm}$1.38 vs. 5.69${\pm}$0.79 vs. 4.93${\pm}$1.75; p=0.026). 복부 전산화단층 촬영에서 산출한 VSR도 지방간염군에서 유의하게 증가된 소견을 보였다(0.31${\pm}$0.08 vs. 0.32${\pm}$0.11 vs. 0.47${\pm}$0.14; p=0.001). HOMA-IR도 세 군에서 유의한 차이를 보였다(4.77${\pm}$3.67 vs. 6.89${\pm}$7.05 vs. 10.42${\pm}$6.73; p=0.000). 그러나 adiponectin과 HOMA-IR 또는 VSR간에 유의한 상관관계는 보이지 않았다(r=-0.117; p=0.450 & r=-0.106; p=0.499). 결 론: 인슐린 저항성은 비만한 소아에서 간 내 지방 축적과 지방간염으로의 진행과정에 모두 영향을 미칠 것으로 추정되며, 비만한 소아의 지방조직에서 분비되는 adipokine 중에서 adiponectin이 단순지방간에서 지방간염으로의 이행하는 기전에 관여할 것으로 여겨진다.

• Journal of Nutrition and Health
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• 제55권4호
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• pp.462-475
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• 2022

본 연구는 팔미트산으로 인슐린 저항성을 유도한 C2C12 근육세포주에서 ADLE의 인슐린 저항성개선효과를조사하고이에대한조절기전을확인하고자하였다. C2C12 근육세포주에 ADLE를 처리 시, AMPK의 활성화를 통해 포도당흡수 (glucose uptake)가 증가되었으며, 이는 미토콘드리아-매개 에너지 생합성 조절단백질인 PGC1α, UCP3, CS 활성을 증가시킴과 동시에 지방산 합성인자인 ACC, FAS, SREBP-1의 발현을 억제함을 알 수 있었다. 세포주에서 확인된 결과들을 고지방식이 유도 당뇨마우스의 근육조직에서 조사한 결과, 고지방식이와 ADLE를 동시에 처리한 그룹에서 AMPK 활성화, GLUT4 발현증가와 미토콘드리아 에너지 대사증가, 지방산 합성 감소효과를 보였다. 이상의 결과들로, ADLE가 근육 내 에너지 대사 관련 경로의 상위유전자인 AMPK를 활성화하여 GLUT4의 세포막 이동을 증진시켜 당대사 조절에 관여하는 것을 관찰하였으며, AMPK의 인산화 증가는 PGC1α의 활성화에 관여하고, 이를 통해 열 발산 대사와 관련된 UCP3의 증가 및 CS 활성을 증가시키고, 지방산 합성 관련 유전자 발현을 억제시킴을 알 수 있었다. 본 결과로부터 ADLE는 대사증후군에서 공통적으로 나타나는 인슐린 저항성을 개선시킬 수 있으며, 이는 근육세포에서의 AMPK의 활성화를 통한 에너지생성기전과 관련이 있음을 알 수 있었다. ADLE는 비만, 당뇨 등의 다양한 부작용을 가진 약제와는 다른 안전성을 보장할 수 있는 이점을 가지고 있어 인슐린 저항성 및 제2형 당뇨병 치료를 위한 기능성 식품 소재로의 활용 가능성도 충분히 가지고 있음을 확인할 수 있었다.