• 약학회지
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• 제56권6호
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• pp.364-365
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• 2012

Liver is the major organ to regulate the systemic glucose homeostasis and insulin resistance. Excess energy intake leads to triglyceride accumulation in adipose tissue first and subsequent accumulation in liver, resulting in obesity and type 2 diabetes. The representative pathological animal model for obesity associated insulin resistance is a high fat diet (HFD) fed mice model. Given the essential role of liver fat accumulation in developing systemic insulin resistance in obesity, I measured the liver triglyceride contents in HFD fed mice as a function of time. As such, in this report, I show the cause and effect relationship with regard to time during a HFD feeding between a variety of factors that are related to systemic insulin resistance including glucose intolerance, plasma insulin level and inflammatory gene expression in liver and adipose tissue.

• BMB Reports
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• 제51권1호
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• pp.33-38
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• 2018

Sterol regulatory element-binding protein-1c (SREBP1c) plays an important role in triglyceride (TG) homeostasis. Although our previous study showed that hepatitis C virus core-binding protein 6 (HCBP6) regulates SREBP1c expression to maintain intracellular TG homeostasis, the mechanism underlying this regulation is unclear. In the present study, we found that HCBP6 increased intracellular TG levels by upregulating SREBP1c expression. HCBP6 increased SREBP1c transcription by directly binding to the SREBP1c promoter (at the -139- to +359-bp region). Moreover, we observed that HCBP6 interacted with $C/EBP{\beta}-binding$ site in the SREBP1c promoter both in vitro and in vivo. These results indicate that HCBP6 upregulates human SREBP1c expression by binding to the $C/EBP{\beta}-binding$ site in the SREBP1c promoter.

• 동의생리병리학회지
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• 제24권2호
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• pp.266-271
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• 2010

Obesity occurred by energy imbalance, is increasing regardless of race, sex, age, and related to the metabolic syndrome, diabetes and cardiovascular disease. Since adipose tissue plays a critical role in regulating energy homeostasis, understanding of adipogenesis pathway and finding of regulatory mechanism for adipogenesis can be helpful to manage obesity as well as obesity-related diseases. In this study, to investigate the effects of Chestnut Inner Shell(CIS) extract on the adipogenesis in 3T3-L1 preadipocytes, 3T3-L1 preadipocytes were differentiated with adipogenic reagents for 9 days in the absence or presence of CIS extract ranging from 10 - 100 ${\mu}g/m{\ell}$. The effect of CIS extract on 3T3-L1 differentiation was examined by measuring intracelluar lipid droplet and triglyceride contents. CIS extract remarkably inhibited lipid accumulation(about 45% inhibition at 100 ${\mu}g/m{\ell}$ of CIS extract) and slightly decreased triglyceride contents(about 15% decrease at 100 ${\mu}g/m{\ell}$ of CIS extract) in 3T3-L1 preadipocytes at the concentration showing no cytotoxicity. These results demonstrated that CIS extract significantly inhibit adipogenesis and can be used for the regulation of obesity.

• Molecules and Cells
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• 제41권6호
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• pp.603-611
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• 2018

Triglyceride homeostasis is a key process of normal development and is essential for the maintenance of energy metabolism. Dysregulation of this process leads to metabolic disorders such as obesity and hyperlipidemia. Here, we report a novel function of the Drosophila flightless-I (fliI) gene in lipid metabolism. Drosophila fliI mutants were resistant to starvation and showed increased levels of triglycerides in the fat body and intestine, whereas fliI overexpression decreased triglyceride levels. These flies suffered from metabolic stress indicated by increased levels of trehalose in hemolymph and enhanced phosphorylation of eukaryotic initiation factor 2 alpha ($eIF2{\alpha}$). Moreover, upregulation of triglycerides via a knockdown of fliI was reversed by a knockdown of desat1 in the fat body of flies. These results indicate that fliI suppresses the expression of desat1, thereby inhibiting the development of obesity; fliI may, thus, serve as a novel therapeutic target in obesity and metabolic diseases.

• 산업식품공학
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• 제21권1호
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• pp.1-11
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• 2017

Dyslipidemia, defined as elevated triglyceride (TG), total- and LDL-C, and/or decreased HDL-C levels, is considered a principal risk factor for cardiovascular disease. The low-density lipoprotein receptor (LDLR) family has been considered a key player in the prevention of dyslipidemia. The LDLR family consists of cytoplasmic membrane proteins and plays an important role not only in ligand-receptor binding and uptake, but also in various cell signaling pathways. Emerging reports state that various functional ingredients dynamically modulate the function of the LDLR family. For instance, oats stimulated the LDLR function in vivo, resulting in decreased body weight and improved serum lipid profiles. The stimulation of LRP6 by functional ingredients in vitro activated the Wnt/${\beta}-catenin$ pathway, subsequently suppressing the intracellular TG via inhibition of SREBP1, $PPAR{\gamma}$, and $C/EBP{\alpha}$. Furthermore, the extract of Cistanchetubulosa enhanced the expression of the mRNA of VLDLR, followed by a reduction in the serum cholesterol level. In addition, fermented soy milk diminished TG and total cholesterol levels while increasing HDL-C levels via activation of LRP1. To summarize, modulating the function of the LDLR family by diverse functional ingredients may be a potent therapeutic remedy for the treatment of dyslipidemia and cardiovascular diseases.

• BMB Reports
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• 제49권2호
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• pp.105-110
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• 2016

Ursodeoxycholic acid (UDCA), a natural, hydrophilic nontoxic bile acid, is clinically effective for treating cholestatic and chronic liver diseases. We investigated the chronic effects of UDCA on age-related lipid homeostasis and underlying molecular mechanisms. Twenty-week-old C57BL/6 male and female mice were fed a diet with or without 0.3% UDCA supplementation for 25 weeks. UDCA significantly reduced weight gain, adiposity, hepatic triglyceride, and hepatic cholesterol without incidental hepatic injury. UDCA-mediated hepatic triglyceride reduction was associated with downregulated hepatic expression of peroxisome proliferator-activated receptor-γ, and of other genes involved in lipogenesis (Chrebp, Acaca, Fasn, Scd1, and Me1) and fatty acid uptake (Ldlr, Cd36). The inflammatory cytokines Tnfa, Ccl2, and Il6 were significantly decreased in liver and/or white adipose tissues of UDCA-fed mice. These data suggest that UDCA exerts beneficial effects on age-related metabolic disorders by lowering the hepatic lipid accumulation, while concurrently reducing hepatocyte and adipocyte susceptibility to inflammatory stimuli.

• Preventive Nutrition and Food Science
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• 제14권1호
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• pp.1-7
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• 2009

Control of hyperglycemia and dyslipidemia is strongly correlated with decreased risk for cardiovascular disease, the most common and fatal diabetic complication. The purpose of this study is to determine the effects of garlic and aged black garlic on glycemic control and blood lipid profile in animal model of type 2 diabetes. Three week-old db/db mice (C57BL/Ks, n=21) were fed AIN-93G semipurified diet or diet containing 5% freeze-dried garlic or aged black garlic for 7 weeks after 1 week of adaptation. Fasting serum glucose, insulin, triglyceride, total cholesterol, and HDL-cholesterol and blood glycated hemoglobin were measured. Body weight and food intake of garlic and aged black garlic group were not significantly different from those of the control group. Fasting serum glucose and blood glycated hemoglobin levels were significantly decreased and insulin level was significantly increased in garlic group compared with control group (p<0.05). Consumption of aged black garlic significantly decreased homeostasis model assessment for insulin resistance (HOMA-IR) and tended to decrease serum glucose. Garlic consumption significantly decreased total cholesterol, while aged black garlic significantly reduced serum total cholesterol and triglyceride and increased HDL-cholesterol levels. These results suggest that garlic exerts hypoglycemic and hypocholesterolemic effect and aged black garlic improved insulin sensitivity and dyslipidemia in db/db mice.

• Nutrition Research and Practice
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• 제8권2호
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• pp.172-176
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• 2014

BACKGROUND/OBJECTIVES: Non-alcoholic fatty liver disease (NAFLD) is becoming an important public health problem as metabolic syndrome and type 2 diabetes have become epidemic. In this study we investigated the protective effect of Cordyceps militaris (C. militaris) against NAFLD in an obese mouse model. MATERIALS/METHODS: Four-week-old male ob/ob mice were fed an AIN-93G diet or a diet containing 1% C. militaris water extract for 10 weeks after 1 week of adaptation. Serum glucose, insulin, free fatty acid (FFA), alanine transaminase (ALT), and proinflammatory cytokines were measured. Hepatic levels of lipids, glutathione (GSH), and lipid peroxide were determined. RESULTS: Consumption of C. militaris significantly decreased serum glucose, as well as homeostasis model assessment for insulin resistance (HOMA-IR), in ob/ob mice. In addition to lowering serum FFA levels, C. militaris also significantly decreased hepatic total lipids and triglyceride contents. Serum ALT activities and tumor necrosis factor-${\alpha}$ (TNF-${\alpha}$) and interleukin-6 (IL-6) levels were reduced by C. militaris. Consumption of C. militaris increased hepatic GSH and reduced lipid peroxide levels. CONCLUSIONS: These results indicate that C. militaris can exert protective effects against development of NAFLD, partly by reducing inflammatory cytokines and improving hepatic antioxidant status in ob/ob mice.

• Nutrition Research and Practice
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• 제6권3호
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• pp.221-225
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• 2012

Zinc deficiency is known to be associated with insulin resistance in obese individuals. This study was performed to evaluate the effect of zinc supplementation on insulin resistance and metabolic risk factors in obese Korean women. Forty obese women (body mass index (BMI) ${\geq}25kg/m^2$) aged 19-28 years were recruited for this study. Twenty women of the study group took 30 mg/day of supplemental zinc as zinc gluconate for 8 weeks and 20 women of control group took placebo. Usual dietary zinc intake was estimated from 3-day diet records. Insulin resistances were measured using Homeostasis model assessment (HOMA) indices, and insulin sensitivities Matsuda indices, which were calculated using oral glucose tolerance test data. Metabolic risk factors, such as waist circumference, blood pressure, fasting glucose, triglyceride, high density lipoprotein (HDL) cholesterol, and adipocyte hormones such as leptin, and adiponectin were also measured. At the beginning of study, dietary zinc averaged 7.31 mg/day and serum zinc averaged $12.98{\mu}mol/L$ in the study group. Zinc supplementation increased serum zinc by 15% and urinary zinc by 56% (P < 0.05). HOMA values tended to decrease and insulin sensitivity increased slightly in the study group, but not significantly so. BMI, waist circumference, blood pressure, blood glucose, triglyceride, HDL cholesterol, and adipocyte hormones did not change in either the study or control group. These results suggest that zinc status may not affect insulin resistance and metabolic risk factors in obese Korean women. Further research is required on a larger cohort with a longer follow-up to determine the effects of zinc status on insulin resistance and metabolic variables.

• 동의생리병리학회지
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• 제24권4호
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• pp.646-652
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• 2010

Gambejaeseup-tang (GBJST) have recently been used as an anti-obesity herbal medicine but their effect and mechanism of action have not been studied. We modified ingredients of GBJST based on the previous experiments about exploring herbs to suppress triglyceride accumulation in 3T3-L1 adipocytes. We investigated the effects of modified GBJST on energy, glucose and lipid homeostasis using female rats with diet-induced obesity and their action mechanism was also determined. Rats fed a high-fat diet (HFD) were divided into 3 groups: rats in each group received 0.2 or 2 g water extracts of modified GBJST (L-GBJST or H-GBJST) or 2 g cellulose per kg body weight (a negative control) on a daily basis. A further group was fed a low-fat diet (LFD) as a positive control. We found that modified GBJST dose-dependently decreased body weight and mesenteric and retroperitoneal fat more than the control. This decrease was due to the reduction in energy intake and the increase of energy expenditure. HFD increased fat oxidation more than LFD and modified GBJST further increased fat oxidation as a major energy source more than the control in a dose-dependent manner. In addition, H-GBJST improved glucose tolerance without changing serum insulin levels during an oral glucose tolerance test. H-GBJST also suppressed the increase of serum total and LDL cholesterol and triglyceride levels by HFD. In conclusion, modified GBJST have a good anti-obesity effect by decreasing energy intake and increasing energy expenditure mainly as fat in female rats with diet-induced obesity. It also improves glucose tolerance and lipid metabolism.