• Journal of Nutrition and Health
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• v.34 no.8
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• pp.865-871
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• 2001

The adipose tissue hormone leptin has been proposed to be involved in the regulation of flood intake and energy expenditure via thermogenesis by uncoupling protein(UCP) in brown adipose tissue(BAT). The objective of the study was to examine the effects of high fat diet on the serum leptin levels, BAT UCPl expression and the body fat mass in rats after weaning. During experimental period of 12 weeks, 4 male Sprague-Dawley rats were killed for the baseline experiment at 4 weeks of age while the remaining rats were fed the two different diets: the control diet AIN-76A(n = 20), high fat(beef tallow) diet(n = 20) ad libitum, which provided 11.7% or 40% of calories as fat, respectively. At 16 weeks of age, the increase in the food efficiency ratio(FER) was related to fat mass in rats on high fat diet. Serum leptin level was increased by age and dietary high fat. There was no difference in serum insulin level between groups until 10 weeks of age, but rats fed high fat diet for 12 weeks showed hyperinsulinemia. The amount of body fat pads was increased significantly in high fat group compared to normal diet group. Visceral fat mass affected acutely by high fat diet, as a result, it was higher in rats fed high fat diet for 2 weeks than normal diet. At 16 weeks of age, BAT and visceral fat mass were significantly high in high fat group. Also, the serum leptin levels reflected the amount of body fat mass. BAT UCPI mRNA expression increased with age and dietary high fat. This study demonstrates that dietary high fat increased serum leptin levels, BAT UCPI expression and body fat mass. Futhermore, in rats fed high fat diets, the increases in leptin and UCPI expression counteracts only in part the excess adiposity and obesity.

• Journal of Korean Biological Nursing Science
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• v.18 no.4
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• pp.305-317
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• 2016

Purpose: Recent studies demonstrated disruption of the circadian clock gene is associated with the development of obesity and metabolic syndrome. Obesity is often caused by the high calorie intake, In addition, the chronic stress tends to contribute to the increased risk for obesity. To evaluate the molecular mechanisms, we examined the expression of circadian clock genes in high fat diet-induced mice models with the chronic stress. Methods: C57BL/6J mice were fed with a 45% or 60% high fat diet for 8 weeks. Daily immobilization stress was applied to mice fed with a 45% high fat for 16 weeks. We compared body weight, food consumption, hormone levels and metabolic variables in blood. mRNA expression levels of metabolic and circadian clock genes in both fat and liver were determined by quantitative RT-PCR. Results: The higher fat content induced more severe hyperglycemia, hyperlipidemia and hyperinsulinemia, and these results correlated with their relevant gene expressions in fat and liver tissues. Chronic stress had only minimal effects on metabolic variables, but it altered the expression patterns of metabolic and circadian clock genes. Conclusion: These results suggest that the fat metabolism regulates the function of the circadian clock genes in peripheral tissues, and stress hormones may contribute to its regulation.

• Korean Journal of Pharmacognosy
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• v.33 no.4 s.131
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• pp.384-388
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• 2002

The effects of the ethanol (EtOH)-extract of Allium wageki were studied on the changes of body weight (BW), systolic blood pressure (SBP), triacylglycerol (TG), cholesterol, and insulin levels in Sprague-Dawley rats in which high fructose feeding elicited hyperinsulinemia, hypertriglyceridemia, and hypertension. SBP and BW were measured for 7 weeks on the fructose diet, fructose/EtOH-extract, vehicle- treated, or vehicle/EtOH-treated rats. The EtOH-extract of Allium wageki blocked the increases of SBP ($119.4{\pm}3.7\;mmHg$ in fructose/EtOH-extract of Allium wageki; $141{\pm}4.3 \;mmHg$ in fructose diet, p<0.01) and BW ($368{\pm}11.4\;g$ in fructose/EtOH-extract of Allium wageki; $402{\pm}15.7\;g$ in fructose diet, p<0.05) by high fructose-diet. The increases of TG, total cholesterol, and insulin levels were also blocked by administration of EtOH-extract of Allium wageki in fructose-induced hypertensive rats. These results suggest that EtOH-extract of Allium wageki has protect effects on the increases of TG, total cholesterol, insulin level, and blood pressure in fructose-induced hypertensive rats.

• Preventive Nutrition and Food Science
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• v.7 no.2
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• pp.174-178
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• 2002

The influence of physical forms of gelatinized rice products on enzymatic hydrolysis in vitro and glycemic and insulinemic responses in normal subjects were studied. Densities of garaedu, bagsulgi, and cooked rice were 1.20, 1.18 and 1.11 g/mL, respectively, while moisture contents of garaeduk, bagsulgi, and cooked rice were 47.5, 43.1 and 66.0% (wt.), respectively. The highest initial rate of in vitro hydrolysis by porcine pancreatic $\alpha$-amylase was observed in bagsulgi followed by cooked rice and garaeduk. However, time for complete hydrolysis seemed to reach a plateau value. Postprandial glucose and insulin responses and satiety of rice products were studied in 12 normal subjects (mean age 23.2 $\pm$ 2.4 years, 6 men and 6 women). Postprandial serum glucose and insulin levels, after consumption of the rice products, reached a peak at 30 min. Garaeduk showed significantly less incremental responses for glucose (1627.5$\pm$134.9 mg.min/dL) and insulin (2041$\pm$287.0 uU.min/mL) than did bagsulgi for glucose (2407.4$\pm$208.3 mg.min/dL) and insulin (3582$\pm$264.4 uU.min/mL). Satiety responses to the rice products were not significantly different. Therefore, it can be concluded that garaeduk may be more beneficial in controlling postprandial hyperglycemia and hyperinsulinemia than bagsulgi. These results also suggest that physical properties of starch products, acquired by the specific processing methods, affect postprandial metabolism of carbohydrate foods.

• Journal of Microbiology and Biotechnology
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• v.14 no.4
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• pp.796-804
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• 2004

We found previously that dietary high fat caused obesity, and levan supplementation to the regular diet reduced adiposity and serum lipids. In the present study, we examined the effects of levan [high-molecular-mass $\beta$-(2,6)-linked fructose polymer] supplement on the development of obesity and lipid metabolism in rats fed with high-fat diet. Thus, to determine whether the dietary levan may have the anti-obesity and hypolipidemic effects, 4-wk-old Sprague Dawley male rats were fed with high-fat diet for 6 wk to induce obesity, and subsequently fed with 0, 1, 5, or 10% levan supplemented high-fat diets (w/w) for another 4 wk. For the comparison, a normal control group was fed with AIN-76A diet. Supplementation with levan resulted in a significant reduction of high-fat-induced body weight gain, white fat (i.e., epididymal, visceral, and peritoneal fat) development, adipocyte hypertrophy, and the development of hyperinsulinemia and hyperlipidemia in a dose-dependent manner. Serum triglyceride and free fatty acid levels were greatly reduced by levan supplementation. Serum total cholesterol level was reduced, whereas the HDL cholesterol level was increased by dietary levan. The expression of uncoupling protein (UCP) was increased by dietary high fat, and was further induced by levan supplementation. The mRNA level of UCP1, 2, and 3 in brown adipose tissue (BAT) and UCP3 in skeletal muscle was upregulated in rats fed with dietary levan. In conclusion, upregulated UCP mRNA expression may contribute to suppression of development of obesity through increased energy expenditure. The present results suggest that levan supplementation to the diet is beneficial in suppressing diet-induced obesity and hyperlipidemia.

• The Korean Journal of Physiology and Pharmacology
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• v.22 no.5
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• pp.493-501
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• 2018

The present study was carried out with the hypothesis that combination of canagliflozin and omega-3 fatty acid may have potential effect on insulin level, insulin resistance, cardiac biomarkers, inflammatory cytokines and histological studies in type 2 diabetes mellitus (DM). Type 2 DM was induced by injecting nicotinamide (120 mg/kg, i.p.) 15 min before STZ (60 mg/kg) injection. Canagliflozin (5 and 10 mg/kg) and omega-3 fatty acid (300 mg/kg) were given for 28 days after confirmation of diabetes. Biochemical estimations revealed elevated levels of glucose, insulin, HOMA-R and inflammatory cytokines in diabetic group. Daily dosing of alone canagliflozin and omega-3 fatty acid slightly reduced elevated levels of glucose, insulin, HOMA-R and inflammatory cytokines ($IL-1{\beta}$, IL-2, and $TNF{\alpha}$), whereas canagliflozin and omega-3 fatty acid combination has reduced these biochemical parameters significantly when compared with diabetic group. Similarly in diabetic group the levels of cardiac biomarkers such as lipid profile, LDH, CKMB and troponin were significantly increased. Elevated levels of cardiac biomarkers were significantly reduced after daily dosing of alone canagliflozin and omega-3 fatty acid. Canagliflozin and omega-3 fatty acid combination has offered better improvement in cardiac biomarkers compared to alone canagliflozin and omega-3 fatty acid. Histopathological analysis also supported the above hypothesis that combination therapy (canagliflozin and omega-3 fatty acid) offered better protection against degenerative changes in ${\beta}-cells$ of pancreas as compared to alone treatment with these drugs. Thus the present study revealed that canagliflozin and omega-3 fatty acid can be used as potential combination therapy in type 2 DM along with cardiac complication.

• Journal of Life Science
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• v.10 no.4
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• pp.388-396
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• 2000

The effect of the traditional herbal medicine Yukmijihwangtang-Jahage(YJ) on the improvement of insulin resistance and lipid profile was studied using a model for non-insulin dependent diabetes mellitus, lean (Fa/-) and obese (fa/fa) Zucker rats. Yukmijihwangtang-Jahage feeding for 4 weeks resulted in a significant decrease in the concentration of plasma triglyceride in both lean and obese Zucker rats. Furthermore, Yukmijihwangtang-Jahage markedly decreased both plasma cholesterol and fasting plasma insulin, and significantly decreased the postprandial glucose level at 30 min during oral glucose tolerance test in obese Zucker rats. Although there was no statistical significance, the crude glucose transporter 4 protein level of Yukmijihwangtang-Jahage dieted obese rats tended to increase when compared to that of obese control rats. Therefore, the present results suggested that Yukmijihwangtang-Jahage may be useful in prevention and improvement of metabolic disorders characterized by hyperinsulinemia states such as non-insulin dependent diabetes mellitus, syndrome X and coronary artery disease.

• Journal of Physiology & Pathology in Korean Medicine
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• v.22 no.2
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• pp.350-356
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• 2008

Etiological studies of diabetes and its complications showed that oxidative stress might play a major role. Therefore, many efforts have been tried to regulate free oxygen radicals for treating diabetes and its complications. Cheonghyul-san has been known to be effective for the antidiabetic, antihyperlipidemic and antiobesitic prescription, and composed of four crude herbs. In male ob/ob mouse with severe obesity, hyperinsulinemia, hypergiycemia, hyperlipidemia, the acting mechanisms of Cheonghyul-san were examined. Mice were grouped and treated for 5 weeks as follows. Both the lean (C57/BL6J black mice) and diabetic (ob/ob mice) control groups received standard chow. The experimental groups were fed with a diet of chow supplemented with 7.5, 15 and 30 mg Cheonghyul-san per 1 kg of body weight for 14 days. The effects of Cheonghyul-san extract on the ob/ob mice were observed by measuring the serum levels of glucose, insulin, lipid components, and the kidney levels of reactive oxygen species (ROS), MDA+HAE, GSH and also the enzyme activities involved in polyol pathway. Cheonghyul-san lowered the levels of serum glucose and insulin in a dose dependent manner. Total cholesterol, triglyceride and free fatty acid levels were decreased, while the HDL-cholesterol level was increased, in Cheonghyul-san treated groups. Renal aldose reductase and sorbitol dehydrogenase activities were increased in the ob/ob mice, whereas those were inhibited in the Cheonghyul-san-administered groups. Cheonghyul-san inhibited the generation of ROS in the kidney. Finally, MDA+HAE level was increased and the GSH level was decreased in the ob/ob mice, whereas those were improved in the Cheonghyul-san-administered groups. The results suggested that Cheonghyul-san exerted the antidiabetic and antihyperlipidemic activities by regulating the activities of polyol pathway enzymes, scavenging ROS, regulating the MDA+HAE and GSH levels in the ob/ob mice.

• Toxicological Research
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• v.29 no.1
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• pp.7-14
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• 2013

Betaine supplementation has been shown to alleviate altered glucose and lipid metabolism in mice fed a high-fat diet or a high-sucrose diet. We investigated the beneficial effects of betaine in diabetic db/db mice. Alleviation of endoplasmic reticulum (ER) and oxidative stress was also examined in the livers and brains of db/db mice fed a betaine-supplemented diet. Male C57BL/KsJ-db/db mice were fed with or without 1% betaine for 5 wk (referred to as the db/db-betaine group and the db/db group, respectively). Lean non-diabetic db/+ mice were used as the control group. Betaine supplementation significantly alleviated hyperinsulinemia in db/db mice. Betaine reduced hepatic expression of peroxisome proliferator-activated receptor gamma coactivator 1 alpha, a major transcription factor involved in gluconeogenesis. Lower serum triglyceride concentrations were also observed in the db/db-betaine group compared to the db/db group. Betaine supplementation induced hepatic peroxisome proliferator-activated receptor alpha and carnitine palmitoyltransferase 1a mRNA levels, and reduced acetyl-CoA carboxylase activity. Mice fed a betaine-supplemented diet had increased total glutathione concentrations and catalase activity, and reduced lipid peroxidation levels in the liver. Furthermore, betaine also reduced ER stress in liver and brain. c-Jun N-terminal kinase activity and tau hyperphosphorylation levels were lower in db/db mice fed a betaine-supplemented diet, compared to db/db mice. Our findings suggest that betaine improves hyperlipidemia and tau hyperphosphorylation in db/db mice with insulin resistance by alleviating ER and oxidative stress.

• Journal of Animal Science and Technology
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• v.59 no.1
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• pp.1.1-1.11
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• 2017

Background: Intrauterine environment plays a pivotal role in the origin of fatal diseases such as the metabolic syndrome. Diabetes is associated with low-grade inflammatory state and dysregulated adipokines production. The aim of this study is to investigate the effect of maternal diabetes on adipocytokines (adiponectin, leptin and TNF-${\alpha}$) production in F1 offspring in rats. Methods: The offspring groups were as follows: F1 offspring of control mothers under control diet (CD) (CF1-CD), F1 offspring of control mothers under high caloric diet (HCD) (CF1-HCD), F1 offspring of diabetic mothers under CD (DF1-CD), and F1 offspring of diabetic mothers under HCD (DF1-HCD). Every 5 weeks post-natal, 10 pups of each subgroup were culled to obtain blood samples for biochemical analysis. Results: The results indicate that DF1-CD and DF1-HCD groups exhibited hyperinsulinemia, dyslipidemia, insulin resistance and impaired glucose homeostasis compared to CF1-CD (p > 0.05). DF1-CD and DF1-HCD groups had high hepatic and muscular depositions of TGs. The significant elevated NEFA level only appeared in offspring of diabetic mothers that was fed HCD. DF1-CD and DF1-HCD groups demonstrated low serum levels of adiponectin, high levels of leptin, and elevated levels of TNF-${\alpha}$ compared to CF1-CD (p > 0.05). These results reveal the disturbed metabolic lipid profile of offspring of diabetic mothers and could guide further characterization of the mechanisms involved. Conclusion: Dysregulated adipocytokines production could be a possible mechanism for the transgenerational transmittance of diabetes, especially following a postnatal diabetogenic environment. Moreover, the exacerbating effects of postnatal HCD on NEFA in rats might be prone to adipcytokine dysregulation. Furthermore, dysregulation of serum adipokines is a prevalent consequence of maternal diabetes and could guide further investigations to predict the development of metabolic disturbances.