• Journal of Physiology & Pathology in Korean Medicine
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• v.29 no.1
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• pp.11-17
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• 2015

Overconsumption of fructose results in dyslipidemia, hypertension, which have documented as a risk of cardiovascular diseases. This experimental study was designed to investigate the beneficial effects of Rubus coreanus Miq.(RCM) in high-fructose diet-induced metabolic syndrome. Animals were divided into three groups; Control group fed regular diet and tap water, fructose groups were fed the 65% high-fructose (HF) diet with/without RCM 100 mg/kg/day for 8 weeks, respectively. Chronic treatment with RCM significantly decreased body weight, fat weight and adipocyte size. Moreover, RCM significantly prevented the development of the metabolic disturbances such as hyperlipidemia and hypertension. RCM also led to increase in high density lipoprotein level in the HF group. In addition, RCM suppressed vascular cell adhesion molecule-1 (VCAM-1) expression and significantly recovered the levels of endothelial nitric oxide synthase (eNOS) expression in aorta. These results demonstrates that RCM may be a beneficial therapeutic for metabolic syndrome through the improvement of hyperlipidemia, obesity, and hypertension.

• Journal of Nutrition and Health
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• v.48 no.5
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• pp.381-389
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• 2015

Purpose: The objective of this study was to investigate the effects of a high fructose and fat diet on bone growth and maturation in growing female rats. Methods: Three-week-old female SD rats were randomly assigned to four experimental groups; the control group (CON: fed control diet based on AIN-93G, n = 8); the high-fructose diet group (HFrc: fed control diet with 30% fructose, n = 8); the high-fat diet group (Hfat: fed control diet with 45 kcal% fat, n = 8); and the high-fat diet plus high fructose group (HFrc + HFat: fed diets 45 kcal% fat with 30% fructose, n = 8). Each group was assigned their respective diets for the remaining eight weeks. Bone-related parameters (bone mineral density (BMD) and structural parameters, osteocalcin (OC), deoxypyridinoline (DPD)) and morphologic changes of kidney were analyzed at the end of the experiment. Results: Final body weights and weight gain were higher in the HFat and HFrc + HFat groups and showed higher tendency in the HFrc group compared with those of the CON group (p < 0.05); however, no significant difference in caloric intake was observed among the four experimental groups. The serum OC levels of the HFrc and HFrc + HFat groups were lower than those of the CON and HFat groups (p < 0.05). Urinary levels of DPD did not differ among the experimental groups. BV/TV and Tb.N of trabecular bone were higher in the HFrc + HFat group and showed a higher tendency in the HFrc group than those of the CON and HFat groups (p < 0.05). Tb.Pf of trabecular bone were lower in the HFrc + HFat group than those in the CON and HFat groups (p < 0.05). However, no difference in trabecular BMD was observed among the experimental groups. Cortical bone volume was higher in the HFat and HFrc + HFat groups than in the CON and HFrc groups (p < 0.05). No morphology change in kidney was observed among the experimental groups. Conclusion: Our study suggests that 8 weeks of high-fructose and high fat intake could improve the bone quality (Structural parameters) of trabecular and cortical bone of tibia in growing female rats.

• Molecules and Cells
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• v.46 no.8
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• pp.496-512
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• 2023

A fructose-enriched diet is thought to contribute to hepatic injury in developing non-alcoholic steatohepatitis (NASH). However, the cellular mechanism of fructose-induced hepatic damage remains poorly understood. This study aimed to determine whether fructose induces cell death in primary hepatocytes, and if so, to establish the underlying cellular mechanisms. Our results revealed that treatment with high fructose concentrations for 48 h induced mitochondria-mediated apoptotic death in mouse primary hepatocytes (MPHs). Endoplasmic reticulum stress responses were involved in fructose-induced death as the levels of phosho-eIF2α, phospho-C-Jun-N-terminal kinase (JNK), and C/EBP homologous protein (CHOP) increased, and a chemical chaperone tauroursodeoxycholic acid (TUDCA) prevented cell death. The impaired oxidation metabolism of fatty acids was also possibly involved in the fructose-induced toxicity as treatment with an AMP-activated kinase (AMPK) activator and a PPAR-α agonist significantly protected against fructose-induced death, while carnitine palmitoyl transferase I inhibitor exacerbated the toxicity. However, uric acid-mediated toxicity was not involved in fructose-induced death as uric acid was not toxic to MPHs, and the inhibition of xanthine oxidase (a key enzyme in uric acid synthesis) did not affect cell death. On the other hand, treatment with inhibitors of the nicotinamide adenine dinucleotide (NAD)⁺-consuming enzyme CD38 or CD38 gene knockdown significantly protected against fructose-induced toxicity in MPHs, and fructose treatment increased CD38 levels. These data suggest that CD38 upregulation plays a role in hepatic injury in the fructose-enriched diet-mediated NASH. Thus, CD38 inhibition may be a promising therapeutic strategy to prevent fructose-enriched diet-mediated NASH.

• Journal of Korean Medicine for Obesity Research
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• v.5 no.1
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• pp.121-131
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• 2005

During last few decades dietary guidelines for the weight management mainly have focused on a low-fat, high carbohydrate diet. Carbohydrate was supposed to be low-dense, highly satiating as well as it affects little on the lipogenesis. Although low-fat diet has significant weight-reducing effect, the loss was modest and usually regained after cessation of the diet. Furthermore, low-fat, modest-carbohydrate diet did not impact on the ever increasing rates of overweight and obesity. Alternative approaches include low-carbohydrate diet, high-carbohydrate diet and low-glycemic index diet. Although none of above mentioned diet have sufficient evidence for standard weight management diet, short-term efficacy and safety are being approved continuously. Low-carbohydrate diet contains less than 45% of carbohydrate in daily energy consumption, it is claimed to have more satiating effect and to improve metabolism. However, low compliance due to the limitation of food choice should be considered on prescribing the diet. High-carbohydrate which contains 90% of carbohydrate in total daily energy consumption, is effective in providing satiety and lowering total calorie intake and cholesterol. On the other hand, nutritional unbalance should be took into account. Low-glycemic index diet is based on the theory that contemporary diet contains significantly less fiber and unrefined carbohydrate, therefore insulin secretion is disturbed. Because low glycemic index food slowly increase blood glucose and insulin level, it induces much satiating effect and may decrease calorie ultimate intake. However, poor standardization of glycemic index is one of the main obstacle for the diet to be applied in the clinic. Meanwhile, high fructose food and beverage should be discouraged because it has little satiating effect and may cause insulin resistance. High fiber food is another recommendation for healthy, lean diet.

• Preventive Nutrition and Food Science
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• v.21 no.3
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• pp.171-180
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• 2016

Non-alcoholic fatty liver disease (NAFLD) is one of the most prevalent liver diseases associated with an altered lifestyle, besides genetic factors. The control and management of NAFLD mostly depend on lifestyle modifications, due to the lack of a specific therapeutic approach. In this context, we assessed the effect of carrot juice on the development of high fructose-induced hepatic steatosis. For this purpose, male weanling Wistar rats were divided into 4 groups, fed either a control (Con) or high fructose (HFr) diet of AIN93G composition, with or without carrot juice (CJ) for 8 weeks. At the end of the experimental period, plasma biochemical markers, such as triglycerides, alanine aminotransferase, and ${\beta}$-hydroxy butyrate levels were comparable among the 4 groups. Although, the liver injury marker, aspartate aminotransferase, levels in plasma showed a reduction, hepatic triglycerides levels were not significantly reduced by carrot juice ingestion in the HFr diet-fed rats (HFr-CJ). On the other hand, the key triglyceride synthesis pathway enzyme, hepatic stearoyl-CoA desaturase 1 (SCD1), expression at mRNA level was augmented by carrot juice ingestion, while their protein levels showed a significant reduction, which corroborated with decreased monounsaturated fatty acids (MUFA), particularly palmitoleic (C16:1) and oleic (C18:1) acids. Notably, it also improved the long chain n-3 polyunsaturated fatty acid, docosahexaenoic acid (DHA; C22:6) content of the liver in HFr-CJ. In conclusion, carrot juice ingestion decreased the SCD1-mediated production of MUFA and improved DHA levels in liver, under high fructose diet-fed conditions. However, these changes did not significantly lower the hepatic triglyceride levels.

• The Korean Journal of Physiology and Pharmacology
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• v.25 no.1
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• pp.39-49
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• 2021

High fructose diet is associated with the global metabolic syndrome (MtS) pandemic. MtS develops in early life, depending on prenatal and postnatal nutritional status. We hypothesized that ovariectomy increases the chances of developing MtS in adult offspring following high fructose intake by the mother. Pregnant C57BL/6J mouse dams drank water with or without 20% fructose during pregnancy and lactation. After weaning, the pups were fed regular chow. The offspring were evaluated until they were 7 months of age after the mice in each group, both sexes, were gonadectomized at 4 weeks of age. The offspring (both sexes) of the dams who had high fructose intake developed MtS. In the offspring of dams who drank tap water, orchiectomy increased the body weight gain and body fat accumulation, while ovariectomy increased the body fat accumulation as compared to the sham controls. In the offspring of dams with high fructose intake, orchiectomy decreased the body weight gain, body fat accumulation, visceral adiposity, and glucose intolerance, while ovariectomy exacerbated all of them as compared to the sham operations. These data indicate that ovariectomy encourages the development of MtS in adult offspring after maternal high fructose intake, while orchiectomy prevents the development of MtS. The sex difference indicates that male and female sex hormones play contradictory roles in the development of MtS.

• Journal of Physiology & Pathology in Korean Medicine
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• v.26 no.5
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• pp.724-731
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• 2012

This study was designed to elucidate whether combination with Korean red ginseng and Morus alba L. (MPM), traditional treatment for diabetes, ameliorates on high fructose-induced steatohepatitis and vascular inflammation. Animals were divided into four groups; Control receiving tap water, fructose-fed, rosiglitazone-treated fructose-fed rats, and MPM-treated fructose-fed rats both receiving supplemented with 60% fructose (n=10). The MPM or rosiglitazone groups initially received a high-fructose diet alone for 8 weeks, with supplementation with MPM or rosiglitazone, peroxisome proliferators-activated receptor gamma ($PPAR{\gamma}$) agonist, occurring during the final 6 weeks. Treatment with MPM significantly prevented the increase in c-reactive protein (CRP) levels in the high fructose group. MPM suppressed high fructose diet-induced vascular inflammation marker expression such as intracellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1), and E-selectin. MPM also reduced intima/media thickness of thoracic aorta. Histologic observation and oil red O staining demonstrated hepatic tissue damage and lipid accumulation were severe in high fructose group. Treatment with MPM ameliorated hepatic tissue morphology with minimized steatosis. In addition, MPM attenuated hepatitis by inhibition of monocyte chemoattractant protein-1 (MCP-1) expression. MPM-fed group showed lower serum GOT and GPT levels comparing with high fructose group. MPM and rosiglitazone (positive control) significantly decreased the size of epididymal adipocytes. Taken together, the administration of MPM inhibited high fructose-induced steatohepatitis and vascular inflammation. These results suggested that MPM is useful in the prevention or treatment of metabolic syndrome-related disorders such as fatty acid metabolism and vascular homeostasis.

• Nutrition Research and Practice
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• v.7 no.5
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• pp.366-372
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• 2013

The application of polyphenols has attracted great interest in the field of functional foods and nutraceuticals due to their potential health benefits in humans. However, the effectiveness of polyphenols depends on their bioactivity and bioavailability. In the present study, the bioactive component from green tea extract (GTE) was administrated orally (50 mg/kg body weight/day) as free or in a microencapsulated form with maltodextrin in rats fed a high fructose diet. High fructose diet induced features of metabolic syndrome including hypertriglyceridemia, hyperuricemia, increased serum total cholesterol, and retroperitoneal obesity. In addition, myocardial fibrosis was increased. In rats receiving high fructose diet, the lowering of blood triglycerides, total cholesterol, non esterified fatty acid (NEFA) and uric acid, as well as the reduction in final body weight and retroperitoneal fat weight associated with the administration of GTE, led to a reversal of the features of metabolic syndrome (P < 0.05). In particular, the administration of microencapsulated GTE decreased myocardial fibrosis and increased liver catalase activity consistent with a further alleviation of serum NEFA, and hyperuricemia compared to administration of GTE. Taken together, our results suggest that microencapsulation of the bioactive components of GTE might have a protective effect on cardiovasucular system by attenuating the adverse features of myocardial fibrosis, decreasing uric acid levels and increasing hepatic catalase activity effectively by protecting their bioactivities.

• The Korea Journal of Herbology
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• v.30 no.2
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• pp.11-18
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• 2015

Objectives : Polygoni Multiflori Radix (Jeokhasuo in Korean) is a Oriental traditional herbs widely used in East Asian countries. Overconsumption of fructose results in hypertension, dyslipidemia, obesity and impaired glucose tolerance which have documented as a risk of cardiovascular diseases. This experimental study was designed to investigate the beneficial effects of an ethanol extract from Polygoni Multiflori Radix (PMR) in high-fructose (HF) diet-induced metabolic syndrome rat model. Methods : Sprague-Dawley (SD) rats were divided into three groups; Control group, receiving regular diet and tap water, HF group, and HF + PMR group both receiving supplemented with 65% fructose (n=10), respectively. The HF + PMR group initially received HF diet with PMR (100 mg/kg/day) for 8 weeks. Results : PMR significantly prevented the metabolic disturbances such as hyperlipidemia, hypertension and impaired glucose tolerance. Chronic treatment with PMR significantly decreased body weight, fat weight and adipocyte size, suggesting a role of anti-obesity effect. PMR led to improve the hyperlipidemia through the increase in HDL cholesterol level as well as the decrease in triglyceride and LDL cholesterol level. In addition, PMR suppressed adhesion molecules and endothelin-1 (ET-1) expression in aorta resulting in the decrease of hypertension. In muscle tissue, PMR significantly recovered the HF-induced insulin resistance through increase of insulin receptor substrate-1 (IRS-1), p-$AMPK{\alpha}1/2$, and p-Akt expression. PMR improved HF-induced metabolic disorders and its action was caused by energy metabolism-mediated insulin signaling activation. Conclusions : These results demonstrate that PMR may be a beneficial therapeutic for metabolic syndrome through the improvement of hyperlipidemia, obesity, insulin resistance and hypertension.

• Journal of Nutrition and Health
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• v.56 no.6
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• pp.629-640
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• 2023

Purpose: Non-alcoholic fatty liver disease (NAFLD) is characterized by the accumulation of fat in the liver which is not a result of excessive alcohol consumption. Its global prevalence was estimated to be approximately 32% in the years 1994-2019. More than half of obese individuals and patients with diabetes are reported to have NAFLD as a comorbidity. This study aimed to investigate the impact of the autumn olive (Elaeagnus umbellata Thunb.) berry on insulin resistance and steatosis in rats fed a high-fructose diet. Methods: Six-week-old Wistar rats were divided into four groups. The control group received a diet consisting of 65% corn starch, while the fructose and experimental groups were fed a diet comprising 65% fructose (FRU) and an FRU diet containing 0.5% (low-dose autumn olive berry group; LAO) or 1.0% (high-dose autumn olive berry group; HAO) ethanol extract of autumn olive berry, respectively, for 10 weeks. Results: The HAO group exhibited significantly lower blood glucose levels compared to the fructose-fed group. Both the LAO and HAO groups showed a substantial reduction in serum insulin levels and insulin resistance when compared to the fructose-fed group. The consumption of LAO and HAO significantly ameliorated dyslipidemia and reduced the levels of triglycerides in the liver compared to the fructose-fed group. Additionally, the consumption of HAO resulted in lower serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) activities compared to the fructose group. The hepatic expression of the sterol regulatory element-binding protein-1c (SREBP-1c) and carbohydrate-responsive element-binding protein (ChREBP) was significantly reduced in the LAO and HAO groups compared to the fructose group. Conclusion: Autumn olive berries improved steatosis by ameliorating insulin resistance and down-regulating the lipogenesis proteins in rats fed on high fructose diet.