• Title/Summary/Keyword: Hepatic lipid

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The PNPLA3 rs738409 Variant but not MBOAT7 rs641738 is a Risk Factor for Nonalcoholic Fatty Liver Disease in Obese U.S. Children of Hispanic Ethnicity

  • Mansoor, Sana;Maheshwari, Anshu;Guglielmo, Matthew Di;Furuya, Katryn;Wang, Makala;Crowgey, Erin;Molle-Rios, Zarela;He, Zhaoping
    • Pediatric Gastroenterology, Hepatology & Nutrition
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    • v.24 no.5
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    • pp.455-469
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    • 2021
  • Purpose: The rs641738 C>T in membrane-bound O-acyltransferase domain-containing protein 7 (MBOAT7) is implicated, along with the rs738409 C>G polymorphism in patatin-like phospholipase domain-containing protein 3 (PNPLA3), in nonalcoholic fatty liver disease (NAFLD). The association of these polymorphisms and NAFLD are investigated in Hispanic children with obesity. Methods: Obese children with and without NAFLD were enrolled at a pediatric tertiary care health system and genotyped for MBOAT7 rs641738 C>T and PNPLA3 rs738409 C>G. NAFLD was characterized by the ultrasonographic presence of hepatic steatosis along with persistently elevated liver enzymes. Genetic variants and demographic and biochemical data were analyzed for the effects on NAFLD. Results: Among 126 enrolled subjects, 84 in the case group had NAFLD and 42 in the control group did not. The two groups had similar demographic distribution. NAFLD was associated with abnormal liver enzymes and elevated triglycerides and cholesterol (p<0.05). Children with NAFLD had higher percentage of PNPLA3 GG genotype at 70.2% versus 31.0% in non-NAFLD, and lower MBOAT7 TT genotype at 4.8% versus 16.7% in non-NAFLD (p<0.05). PNPLA3 rs738409 C>G had an additive effect in NAFLD; however, MBOAT7 rs641738 C>T had no effects alone or synergistically with PNPLA3 polymorphism. NAFLD risk increased 3.7-fold in subjects carrying PNPLA3 GG genotype and decreased in MBOAT7 TT genotype. Conclusion: In Hispanic children with obesity, PNPLA3 rs738409 C>G polymorphism increased the risk for NAFLD. The role of MBOAT7 rs641738 variant in NAFLD is less evident.

Fermented ginseng, GBCK25, ameliorates steatosis and inflammation in nonalcoholic steatohepatitis model

  • Choi, Naeun;Kim, Jong Won;Jeong, Hyeneui;Shin, Dong Gue;Seo, Jeong Hun;Kim, Jong Hoon;Lim, Chae Woong;Han, Kang Min;Kim, Bumseok
    • Journal of Ginseng Research
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    • v.43 no.2
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    • pp.196-208
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    • 2019
  • Background: Nonalcoholic steatohepatitis (NASH) is one of the chronic inflammatory liver diseases and a leading cause of advanced liver fibrosis, cirrhosis, and hepatocellular carcinoma. The main purpose of this study was to clarify the effects of GBCK25 fermented by Saccharomyces servazzii GB-07 and pectinase, on NASH severity in mice. Methods: Six-wk-old male mice were fed either a normal diet (ND) or a Western diet (WD) for 12 wks to induce NASH. Each group was orally administered with vehicle or GBCK25 once daily at a dose of 10 mg/kg, 20 mg/kg, 100 mg/kg, 200 mg/kg, or 400 mg/kg during that time. The effects of GBCK25 on cellular damage and inflammation were determined by in vitro experiments. Results: Histopathologic analysis and hepatic/serum biochemical levels revealed that WD-fed mice showed severe steatosis and liver injury compared to ND-fed mice. Such lesions were significantly decreased in the livers of WD-fed mice with GBCK25 administration. Consistently, mRNA expression levels of NASH-related inflammatory-, fibrogenic-, and lipid metabolism-related genes were decreased in the livers of WD-fed mice administered with GBCK25 compared to WD-fed mice. Western blot analysis revealed decreased protein levels of cytochrome P450 2E1 (CYP2E1) with concomitantly reduced activation of c-Jun N-terminal kinase (JNK) in the livers of WD-fed mice administered with GBCK25. Also, decreased cellular damage and inflammation were observed in alpha mouse liver 12 (AML12) cells and RAW264.7 cells, respectively. Conclusion: Administration of GBCK25 ameliorates NASH severity through the modulation of CYP2E1 and its associated JNK-mediated cellular damage. GBCK25 could be a potentially effective prophylactic strategy to prevent metabolic diseases including NASH.

Allomyrina dichotoma larva extract attenuates free fatty acid-induced lipotoxicity in pancreatic beta cells

  • Kim, Kyong;Kwak, Min-Kyu;Bae, Gong-Deuk;Park, Eun-Young;Baek, Dong-Jae;Kim, Chul-Young;Jang, Se-Eun;Jun, Hee-Sook;Oh, Yoon Sin
    • Nutrition Research and Practice
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    • v.15 no.3
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    • pp.294-308
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    • 2021
  • BACKGROUD/OBJECTIVES: Allomyrina dichotoma larva (ADL), one of the many edible insects recognized as future food resources, has a range of pharmacological activities. In a previous study, an ADL extract (ADLE) reduced the hepatic insulin resistance of high-fat diet (HFD)-induced diabetic mice. On the other hand, the associated molecular mechanisms underlying pancreatic beta-cell dysfunction remain unclear. This study examined the effects of ADLE on palmitate-induced lipotoxicity in a beta cell line of a rat origin, INS-1 cells. MATERIALS/METHODS: ADLE was administered to high-fat diet treated mice. The expression of apoptosis-related molecules was measured by Western blotting, and reactive oxidative stress generation and nitric oxide production were measured by DCH-DA fluorescence and a Griess assay, respectively. RESULTS: The administration of ADLE to HFD-induced diabetic mice reduced the hyperplasia, 4-hydroxynonenal levels, and the number of apoptotic cells while improving the insulin levels compared to the HFD group. Treatment of INS-1 cells with palmitate reduced insulin secretion, which was attenuated by the ADLE treatment. Furthermore, the ADLE treatment prevented palmitate-induced cell death in INS-1 cells and isolated islets by reducing the apoptotic signaling molecules, including cleaved caspase-3 and PARP, and the Bax/Bcl2 ratio. ADLE also reduced the levels of reactive oxygen species generation, lipid accumulation, and nitrite production in palmitate-treated INS-1 cells while increasing the ATP levels. This effect corresponded to the decreased expression of inducible nitric oxide synthase (iNOS) mRNA and protein. CONCLUSIONS: ADLE helps prevent lipotoxic beta-cell death in INS-1 cells and HFD-diabetic mice, suggesting that ADLE can be used to prevent or treat beta-cell damage in glucose intolerance during the development of diabetes.

Effects of Steaming Process on Liriopis Tuber to Antioxidant Activities and Hyperlipidemia Induced Rats. (맥문동(麥門冬)의 증숙(蒸熟)에 따른 항산화 효능 및 고지혈증 유발 흰쥐에 대한 효능 연구)

  • Ku, Garam;Lee, Hyun-In;Kim, SuJi;Shin, Mi-Rae;Lee, AhReum;Park, Hae-Jin;Roh, Seong-Soo;Seo, Young Bae
    • The Korea Journal of Herbology
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    • v.33 no.5
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    • pp.89-103
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    • 2018
  • Objectives : This study is aimed to compare the changes in Antioxidative capacity of Liriopis Tuber by steaming process and to compare the effects in hyperlipidemia induced rats fed high cholesterol diet between Simvastatin and Liriopis Tuber by steaming process. Methods : The SD rats were divided into six groups: normal diet (Nor), high cholesterol diet (Veh), high cholesterol diet plus Simvastatin 5 mg/kg (Sim), high cholesterol diet plus LT0 extract 200 mg/kg (LT0), high cholesterol diet plus LT6 extract 200 mg/kg (LT6) and high cholesterol diet plus LT9 extract 200 mg/kg (LT9). We compared the total cholesterol (TC), triglyceride (TG), high density lipoprotein cholesterol (HDL), low density lipoprotein cholesterol (LDL) contents and reactive oxygen species (ROS) from each serums. Protein expression in liver tissues related to antioxidant and cholesterol was analyzed. Results : The Antioxidant activity of Liriopis Tuber increased by steaming process. In vivo, TC, TG, LDL-c, atherogenic index (AI) and cardiac risk factor (CRF) decreased and HDL-c increased with increasing steaming frequency. aspartate aminotransferase (AST), alanine aminotransferase (ALT), creatinine, and blood urea nitrogen (BUN) decreased with increasing steaming frequency. ROS decreased only in LT9, and SOD, catalase and glutathione peroxidase (GPx) increased with increasing steaming frequency. phospho-AMP-activated protein kinase (p-AMPK) increased and sterol regulatory element-binding protein 2 (SREBP-2), Phospho-Acetyl-CoA Carboxylase (p-ACC) and HMG-CoA reductase (HMGCR) decreased with increasing steaming frequency. Liver staining showed a decrease in hepatic fat accumulation of LT9. LT9 showed significant results in all experiments. Conclusions : LT9 showed significance of anti-lipid effect and improved fatty liver of hyperlipemia induced rats fed on high cholesterol diet, In conclusion, LP9 can be effectively used for the treatment of hyperlipidemia.

Effect of Bambusae Caulis in Liquamen on Lipid Metabolism in Rats Fed High Fat Diet (죽력(Bambusae Caulis in Liquamen)이 고지방식이를 급여한 흰쥐의 체내 지질대사에 미치는 영향)

  • Choi Hyun-Sook;Ha Jin-Ok;Choo Myung-Hi;Na Myung-Soon;Lee Myung-Yul
    • Food Science and Preservation
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    • v.11 no.3
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    • pp.373-382
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    • 2004
  • The purposes of this study were to investigate effects of Bambusae Caulis in Liquamen(BCL) on antioxidant activities and inhibitory activities of HMG-CoA reductase of in vitro, and lipid metabolism in rats fed the high cholesterol diet in vivo. Sprague-Dawley male rats weighing l00$\pm$10 g were devided into five groups ; normal group(NOR), the high cholesterol diet administered group(1 $\%$ cholesterol and 0.25$\%$ sodium cholate)(CON), 5$\%$ BCL administered group (5BL), the high cholesterol diet and 5$\%$ BCL administered group (5BCB) and the high cholesterol diet and 10\$\%$ BCL administered group (10BCB), respectively. In antioxidative activities of BCL using Rancimat in vitro, 1.25 diulent and original solution were more excellent activities than the control group, and in inhibiting activities of HMG-CoA reductase, BCL was shown inhibitory effects compared with the control, in dose dependent manners, especially 57.9$\%$ in original solution and 36.0$\%$ in 1.25 diulent. The growth rate of the control group was higher than the normal group, wheras the group given 5$\%$ BCL and 10$\%$ BCL were gradually decreased, especially the most excellent effect in 10$\%$ BCL. Serum levels of total cholesterol, LDL-cholesterol, triglyceride and free cholesterol were significantly decreased, whereas levels of HDL-cholesterol and phospholipid were increased, but not significantly. BCL administered group was increased in HDL-cholesterol/total cholesterol ratio and lowered antherogenic index. The activities of AST in serum were rather lowered in the BCL administration group than the cholesterol diet group, but not in ALT and ALP. The hepatic contents of total cholesterol were lowered significantly than control group, but not in triglyceride. Therefore, it might be expected that BCL is believed to be a possible protective or curative effects for fatty livers and hyperlipidemia-induced by a hi~h cholesterol diet.

The Biological Effects of β-Cyclodextrin on Antithrombotic Activity and Plasma Lipid Metabolism in Rats (흰쥐에서 혈액지질 대사 및 항혈전작용에 관한 베타사이클로덱스트린의 생물학적 효과)

  • Park, B. S.
    • Journal of Animal Science and Technology
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    • v.45 no.2
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    • pp.199-210
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    • 2003
  • The effect of feeding a cyclic oligosaccharide, $\beta$-cyclodextrin($\beta$CD) on plasma cholesterol and triacylglyceride concentrations and on antithrombotic activity were investigated in rats fed a control chow diet, or one either high in cholesterol or in saturated fat. The bleeding time of $\beta$CD-fed groups was significantly prolonged by 293%, 157% and 218% in normal, high cholesterol and high fat diet fed groups, respectively, as compared to the control group(p<0.05). The whole blood clotting time was significantly increased by 202%, 168% and 211% in normal, high cholesterol and high fat diet fed groups as compared to control group, respectively(p<0.05). The $\beta$CD diet caused a marked decrease in plasma total lipid(TL), triacylglyceride(TAG), total cholesterol (TC) and low density lipoprotein- cholesterol (LDL-C) concentrations. The plasma TL concentration was significantly decreased by 70%, 82% and 87% in normal, high cholesterol and high fat diet fed groups as compared to the control group, respectively(p<0.05). The plasma TAG concentration was significantly decreased by 89%, 43% and 59% in normal, high cholesterol and high fat diet fed groups, respectively, as compared to the control group(p<0.05). The plasma TC concentration was significantly decreased by 28%, 62% and 36% in normal, high cholesterol and high fat diet fed groups, respectively, as compared to the control group(p<0.05). The LDL-C concentration was significantly decreased by 39%, 54% and 25% in normal, high cholesterol and high fat diet fed groups as compared to control group, respectively(p<0.05). The plasma total bile acids contents of $\beta$CD group was significantly increased by 66%, 95% and 97% in normal, high cholesterol and high fat diet fed groups as compared to control group, respectively(p<0.05). The hepatic HMG-CoA reductase activity was significantly lowered by 41% in the $\beta$CD-fed group compared to normal diet fed rats(p<0.05). The fecal steroid excretions of the $\beta$CD groups was significantly increased by 167% in normal diet fed rats(p<0.05). These results suggest that the $\beta$CD has a biological active function on antithrombotic activity and is hypolipidemic, hypotriglyceridemic and hypocholesterolimic agents. These are all effects that can help to prevent obesity and coronary heart disease in humans.

Effects of Liquid Culture of Coriolus Versicolor on Lipid Metabolism and Enzyme Activities in Rats Fed High Fat Diet (운지버섯 균사체 배양액이 고지방 식이를 급여한 흰쥐의 지질대사 및 효소활성에 미치는 영향)

  • 문상필;고진복
    • Journal of Nutrition and Health
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    • v.37 no.2
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    • pp.88-94
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    • 2004
  • The effects of liquid culture of Coriolus versicolor on weight gain, food intakes, food efficiency ratios, serum and hepatic lipid concentrations, serum protein levels and serum enzyme activities, were studied in growing male rats. Sprague-Dawley rats were given four different types of diets for a succeeding period of 5 weeks, respectively: a normal diet group (7% corn oil), a high fat diet group (7% corn oil+15% lard), a 20% or 30% C. versicolor diet groups (high fat diet+20% or 30% C. versicolor in water) according to the levels of C. versicolor supplementation. The body weight gains of the rats fed the 30% C. versicolor diets were lower than those in the rats fed high fat diet. The epididymal fat pad weight of the rats fed high fat diet and 20% or 30% C. versicolor diets were significantly higher than that of the rats fed normal diet. The concentrations of triglyceride in the serum and the liver of the rats fed the 30% C. versicolor diets were more significantly decreased compared to rats on the high fat diet. The concentrations of total cholesterol in the serum and the liver of rats fed the high fat diet, 20% and 30% C. versicolor diets were similar to those of rats fed the normal diet. The HDL-cholesterol concentration and the HDL-cholesterol/total-cholesterol ratio of the rats fed 20% and 30% C. versicolor diets were significantly lower than those of the rats fed high fat diet. But the antherogenic index of the rats fed 20% or 30% C. versicolor diets were significantly higher than those of the rats fed high fat diet. There were no differences in the activities of glutamic oxaloacetic transaminase, glutamic pyruvic transaminase and alkaline phosphatase in the serum among the experimental groups. These results showed that the 30% C. versicolor diet feeding decreased the triglyceride in serum and liver of the rats.

Effects of coffee powder supplementation on the blood glucose and antioxidative enzyme activity of liver tissue in STZ-induced diabetic rats (커피가루 첨가식이가 당뇨 쥐의 혈당 및 간 조직 항산화효소 활성에 미치는 영향)

  • Bae, Jihyun;Jung, Yun-Jung;Choi, Mi-Ja
    • Journal of Nutrition and Health
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    • v.48 no.2
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    • pp.140-148
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    • 2015
  • Purpose: The purpose of this study was to evaluate the role of coffee in diabetic rats in order to prevent hyperglycemia and hyperlipidemia, and to improve antioxidant enzyme activity in streptozotocin induced diabetic rats. Methods: Thirty two male Sprague-Dawley rats (body weight $200{\pm}5g$) were divided into two groups; diabetic and nondiabetic groups. The groups were each randomly divided into two subgroups; fed control and coffee (5 g coffee powder/kg diet) diets. Diabetes was induced by intramuscular injection of 50 mg streptozotocin/kg body weight. Rats with blood glucose concentrations ${\geq}300mg/dL$ were considered diabetic for these experiments. All rats were fed an experimental diet and deionized water ad libitum for 4 weeks. Results: The results of this study indicate that body weight gain was significantly lower in diabetic groups than in nondiabetic groups regardless of diet. Mean food intake was significantly higher in diabetic groups than in nondiabetic groups, and significantly higher in the coffee group than in the control group in diabetic rats. Food efficiency ratio (FER) was significantly lower in diabetic groups than in nondiabetic groups regardless of diet. The fasting blood glucose of coffee supplemented groups was significantly lower compared with the control group in diabetic and nondiabetic rats. The levels of serum LDL-cholesterol and atherogenic index were significantly lower in the coffee group than in the control group in diabetic and nondiabetic rats, and serum HDL-cholesterol was significantly higher in the coffee group than in control groups. The contents of hepatic triglyceride were significantly lower in the coffee group than in the control group in diabetic and nondiabetic rats. The lipid peroxidation of malondialdehyde (MDA) contents was significantly lower in the coffee group than in the control group in diabetic and nondiabetic rats. Activity of superoxide dismutase (SOD), glutathione peroxidase (GPx) and catalase in liver was not significantly different by experimental diets among all groups. Conclusion: In conclusion, effects of 0.5% coffee powder supplemented diet were beneficial on blood glucose and lipids in diabetic rats.

Lipolytic Effect of Sparassis crispa Extracts in Differentiated 3T3-L1 Cells and High Fat Diet-induced Obese Mice (분화된 3T3-L1 세포와 비만유도 쥐에 꽃송이버섯 추출물의 지질분해 효과)

  • Lee, Mi-Ae;Park, Jin-Kyung;Um, Mi-Hyang;Jeon, Jung-Woo;Lee, Jung-Min;Park, Yoo-Kyoung
    • Journal of the Korean Society of Food Science and Nutrition
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    • v.41 no.12
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    • pp.1708-1715
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    • 2012
  • The purpose of this study was to investigate whether water extracts of Sparassis crispa (SC) have anti-obesity effects. Treatment of mature adipocytes with SC caused a decrease in lipid accumulation (assessed by Oil Red O staining) and an increase in glycerol release. Mice were induced to obesity by a high fat diet (45% fat in total kcal) and experimental groups were treated with two different dosages of SC extracts, a low SC (LSC, 100 mg/kg/day) or high SC (HSC, 300 mg/kg/day). SC extracts were administered by gavages for 10 weeks in the experimental groups, while the control group was fed with distilled water. The body weight gain of mice fed SC was significantly reduced (11.88% lower in LSC, 14.54% lower in HSC) compared to the control group. Additionally, there were significantly reduced serum levels of triglycerides (13.57% lower in LSC, 19.46% lower in HSC), total cholesterol (32.22% lower in LSC, 24.67% lower in HSC) and glucose (28.85% lower in LSC, 25.82% lower in HSC) in mice fed SC compared to the control group. Hepatic triglycerides in mice fed SC were lower (9.68% lower in LSC, 14.24% lower in HSC) than the control group and total cholesterol levels were also lower in mice fed SC (38.72% lower in LSC, 35.20% in HSC). These results demonstrate that the water extract of SC may enhance lipolysis and up-regulate the expression of lipolytic enzymes in vitro and reduce body weight in vivo. These significant effects were found for both low and high doses of SC treatment, and suggest SC can be used as potential therapeutic substances for the prevention and treatment of obesity.

Changes of Serum Fatty Acid and Carnitine Levels after Administration of L-carnitine in Rats (흰쥐에서 L-carnitine 투여 후에 혈청 지방산과 Carnitine의 농도 변화)

  • Lee, Jae Won;Hong, Young Mi
    • Clinical and Experimental Pediatrics
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    • v.45 no.9
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    • pp.1075-1082
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    • 2002
  • Purpose : Obesity is known to be associated with hypertension, dyslipidemia, and fatty liver and is thought to be associated with increased levels of free fatty acids. One of the strategies for decreasing free fatty acid levels is stimulation of hepatic lipid oxidation with L-carnitine. Carnitine is an essential cofactor for transport of long-chain fatty acid into mitochondria for oxidation. This study was designed to evaluate the changes of serum fatty acids and carnitine levels after exogenous injection of L-carnitine. Methods : Sprague Dawley rats were divided into two groups. Group A was control. Group B was given intraperitoneal injection with L-carnitine(200 mg/kg) daily for two weeks. Serum lipid (total cholesterol, triglyceride, HDL-cholesterol, LDL-cholesterol) and fatty acid levels were analyzed on the first day of the first and second weeks after injection of L-carnitine. Total, free, and acyl carnitine levels also were performed by a enzymatic cycling techniques at the same day intervals. Results : There was no significant difference between the two groups in total cholesterol, HDL-cholesterol, LDL-cholesterol levels before and after the administration of L-carnitine. But triglyceride levels were significantly decreased at the first week in group B compared with group A. Among free fatty acids, linoleic acid showed significant decrement(A group : $131.3{\pm}31.3mg/dL$ vs B group : $90.0{\pm}7.0mg/dL$) at the first week. Total, free, and acyl carnitine levels showed significant increments at all days intervals, but only free carnitine showed significant increments according to cumulative doses of carnitine. Conclusion : Plasma linoleic acid, a long-chain fatty acid, showed significant decrement after administration of L-carnitine in the first week. This may suggest that L-carnitine can be used as an antilipidemic agent for obese patients. A prospective study will investigate obese children in the future.