• The Korean Journal of Physiology and Pharmacology
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• v.21 no.5
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• pp.519-529
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• 2017

Sodium butyrate (SB) has various metabolic actions. However, its effect on dipeptidyl peptidase 4 (DPP-4) needs to be studied further. We aimed to evaluate the metabolic actions of SB, considering its physiologically relevant concentration. We evaluated the effect of SB on regulation of DPP-4 and its other metabolic actions, both in vitro (HepG2 cells and mouse mesangial cells) and in vivo (high fat diet [HFD]-induced obese mice). Ten-week HFD-induced obese C57BL/6J mice were subjected to SB treatment by adding SB to HFD which was maintained for an additional 16 weeks. In HepG2 cells, SB suppressed DPP-4 activity and expression at sub-molar concentrations, whereas it increased DPP-4 activity at a concentration of $1,000{\mu}M$. In HFD-induced obese mice, SB decreased blood glucose, serum levels of insulin and $IL-1{\beta}$, and DPP-4 activity, and suppressed the increase in body weight. On the contrary, various tissues including liver, kidney, and peripheral blood cells showed variable responses of DPP-4 to SB. Especially in the kidney, although DPP-4 activity was decreased by SB in HFD-induced obese mice, it caused an increase in mRNA expression of $TNF-{\alpha}$, IL-6, and $IL-1{\beta}$. The pro-inflammatory actions of SB in the kidney of HFD-induced obese mice were recapitulated by cultured mesangial cell experiments, in which SB stimulated the secretion of several cytokines from cells. Our results showed that SB has differential actions according to its treatment dose and the type of cells and tissues. Thus, further studies are required to evaluate its therapeutic relevance in metabolic diseases including diabetes and obesity.

• The Korea Journal of Herbology
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• v.36 no.6
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• pp.39-46
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• 2021

Objectives : AMP-activated protein kinase (AMPK) is a key metabolic regulator that reduces lipogenesis. AMPK is mainly activated via phosphorylation of liver kinase B (LKB) 1 under energy stress. Here, we highlighted the anti-obesity effect and underlying mechanism of Coix lacryma-jobi var. mayuen Stapf sprout water extract (CSW) sprout extract in connection with the LKB1/AMPK signaling pathway. Methods : C57BL/6 mice (20~25 g) fed HFD to induce obesity and at the same time administered CSW 100 mg/kg (CSWL; (CSWL; CSW low concentration) or CSW 200 mg/kg (CSWH; CSW high concentration) or Garcinia extract (Garcinia) 200 mg/kg orally for 6 weeks. Body weight and food intake were measured at the same time each day. After 6 weeks of CSW administration, liver tissue and serum were obtained through an autopsy. After the end of the experiment, biochemical analysis (triglycerides (TG), total cholesterol (TC), HDL-cholesterol, and LDL-cholesterol) was performed on the serum. And then, protein levels related to TG and TC synthesis were measured through western blot analysis in liver tissue. Results : As a result, serum TG, TC, and LDL-cholesterol levels were significantly increased in the control group and significantly decreased in the CSW administration group. On the other hand, the HDL-cholesterol level was increased in the CSW-administered group. And as a result of Western blot analysis, CSW significantly increased the phosphorylation of LKB1 & AMPK, and remarkably decreased the expression of factors related to TG and TC synthesis. Conclusions : Our findings suggest that CSW influences the TG and TC synthesis to positively affect HFD-induced obesity in C57BL/6 mice.

• Korean Journal of Food Science and Technology
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• v.49 no.6
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• pp.649-658
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• 2017

The potential of the ethyl acetate fraction from Pteridium aquilinum (EFPA) to improve the cognitive function in high-fat diet (HFD)-induced diabetic mice was investigated. EFPA-treatment resulted in a significant improvement in the spatial, learning, and memory abilities compared to the HFD group in behavioral tests, including the Y-maze, passive avoidance, and Morris water maze. The diabetic symptoms of the EFPA-treated groups, such as fasting glucose and glucose tolerance, were alleviated. The administration of EFPA reduced the acetylcholinesterase (AChE) activity and malondialdehyde (MDA) content in mice brains, but increased the acetylcholine (ACh) and superoxide dismutase (SOD) levels. Finally, kaempferol-3-o-glucoside, a major physiological component of EFPA, was identified by using high-performance liquid chromatography coupled with a hybrid triple quadrupole-linear ion trap mass spectrometer (QTRAP LC-MS/MS).

• Journal of the Korean Society of Food Science and Nutrition
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• v.44 no.7
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• pp.953-960
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• 2015

This study evaluated the effects of Rubus coreanus Miq. oil on the plasma lipid profile of high fat diet (HFD)-induced obese mice. Animals were randomly divided into 4 groups (n=10). After completion of the 5-week experimental period, we measured bodyweight gain, food intake, adipose tissue mass, and plasma lipid profile. We also analyzed the activities of carnitine and superoxide dismutase (SOD) involved in ${\beta}$-oxidation and antioxidation, respectively. Our results show that HFD-induced weight gain in animals in the R. coreanus Miq. oil diet group (RCO) and corn oil diet group (CO) was significantly lower compared to animals in the HFD group; RCO supplementation had a more noticeable effect than CO. Visceral and back fat weights were lower in the RCO and CO groups while plasma HDL cholesterol (HDL-C) and HDL-C per total cholesterol [HDL-C/TC (%)] ratio were significantly higher in the RCO group. The contents of acid-soluble acylcarnitine and total carnitine as well as SOD activation were significantly higher in the RCO group, but no significant difference was observed between the RCO and CO groups. In conclusion, RCO effectively averted elevation of total body weight and fat weight in HFD-induced obese mice and promoted increased HDL-C. Therefore, R. coreanus Miq. oil might play an anti-obesity role in obese people and could be used as an effective oil supplement.

• Journal of the East Asian Society of Dietary Life
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• v.23 no.1
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• pp.31-38
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• 2013

This study was designed to evaluate the effect of a rice-based diet on body weight and serum lipid levels. Thirty male C57BL/6 mice were randomly divided into three groups and fed a high-fat diet (HFD), rice-based diet (RD), or bread-based diet (BD) for five weeks. Our results showed that the RD group had a significantly lower final body weight, although there was no significant difference in daily food intake among the groups. There was a reduction in body weight gains, adipose tissues weight, and adipocyte size of epididymal adipose tissue in the RD group (p<0.05). Also, serum triglycerides and total cholesterol in the RD group were significantly decreased compared to the BD group. RD also reduced fasting glucose and insulin levels. These results indicate that the intake of RD attenuates increases in body weight and serum lipid concentrations in mice, suggesting its benefits for the dietary control of obesity and hyperlipidemia.

• Journal of the Korean Society of Food Science and Nutrition
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• v.29 no.2
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• pp.252-256
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• 2000

Coronary heart disease (CHD) is caused by elevated blood lipids and the death rate from CHD is continuously increasing in recent years. In Korea, death rate from CHD is more than 30%. Recently, it has been reported that Job's tear decreaseds blood cholesterol level. However, most of the reports used Job's tear itself. Therefore, we have examined the effect of extruded Job's-tear cereal on blood and liver lipid levels in rats fed with a high fat diet for 5 weeks. The energy intake and body weight gain were higher in Job's tear cereal group (JFD) than in high fat fed group(HFD). Blood triglyceride concentration was significantly reduced in JFD group (p<0.05). And Atherogenic Index was decreased about 20% in JFD suggesting favorable effect of Job's-tear cereal on hyperlipidemia. Liver lipids levels were not affected by Job's-tear cereal.

• Journal of Nutrition and Health
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• v.43 no.4
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• pp.333-341
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• 2010

The aim of this study was to investigate the hypolgycemic activity of water extract of fermented yacon (Smallanthus sonchifolius) leaves tea (Yacon LWE) in high-fat diet (HFD)/streptozotocin (STZ)-induced diabetic mice. Male ICR mice were fed with a HFD (37% calories from fat) for 4 weeks prior to intraperitoneal injection with STZ (100 mg/kg body weight). Diabetic mice were supplemented with two doses of Yacon LWE (0.16% and 0.8%, wt/wt) for 6 weeks. The supplementation of high-dose Yacon LWE significantly lowered blood glucose levels and plasma ALT and AST activities compared with the control group. High-dose Yacon LWE also improved the insulin tolerance without any changes in plasma and pancreatic insulin concentrations in HFD/STZ-induced diabetic mice. Yacon LWE supplementation increased the insulin staining of pancreatic $\beta$-cells in a dose-dependent manner. Both 0.16% and 0.8% of Yacon LWE significantly elevated plasma leptin concentration, hepatic glucokinase activity and glucokinase/glucose-6-phosphatase ratio compared with the control group. However, glycosylated hemoglobin concentration was not different among the groups. These results suggest that high-dose Yacon LWE lowers the blood glucose level partly by enhancing insulin sensitivity and hepatic glucose metabolism in type 2 diabetic mice.

• Journal of Applied Biological Chemistry
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• v.64 no.4
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• pp.399-405
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• 2021

A number of studies have been conducted to prevent obesity due to the worldwide increasing rate of obesity and its adverse effects on our health. Recently, a relationship between obesity and gut microbiome has been reported. Fecal and cecal microbiota are generally targeted for examining the gut microbiome during dietary interventions. There is, however, no common understanding on which microbiota and how results elucidated from the data would differ. In this study, we conducted dietary induced obesity study and compared fecal and cecal microbiota affected by dietary interventions. Normal Diet and high fat diet were fed to 6 weeks old mice for 12 weeks, and 16 S rRNA genes amplified from fecal and cecal DNA were sequenced using MiSeq. Our results show that the 𝛼-diversity showed significant differences between the dietary interventions as well as cecal and fecal microbiota. The difference in the taxonomic compositions between cecal and fecal microbiota had become clearer at the family and genus level. At the genus level, Faecalibaculum and Lactobacillus were more abundant in the cecal and fecal microbiota, respectively. In general dietary intervention studies, dietary effects are more significant than type difference. However, the microbiota analysis results should be interpreted carefully, considering both diet and samples (feces/caecum).

• Biomolecules & Therapeutics
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• v.25 no.2
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• pp.140-148
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• 2017

Hyperlipidemia, which is closely associated with a fatty diet and aging, is commonly observed in the western and aged society. Therefore, a novel therapeutic approach for this disease is critical, and an immunological view has been suggested as a novel strategy, because hyperlipidemia is closely associated with inflammation and immune dysfunction. In this study, the effects of an aqueous extract of Rubus occidentalis (RO) in obese mice were investigated using immunological indexes. The mice were fed a high-fat diet (HFD) to induce hyperlipidemia, which was confirmed by biochemical analysis and examination of the mouse physiology. Two different doses of RO and rosuvastatin, a cholesterol synthesis inhibitor used as a control, were orally administered. Disturbances in immune cellularity as well as lymphocyte proliferation and cytokine production were significantly normalized by oral administration of RO, which also decreased the elevated serum tumor necrosis factor $(TNF)-{\alpha}$ level and total cholesterol. The specific immune-related actions of RO comprised considerable improvement in cytotoxic T cell killing functions and regulation of antibody production to within the normal range. The immunological evidence confirms the significant cholesterol-lowering effect of RO, suggesting its potential as a novel therapeutic agent for hyperlipidemia and associated immune decline.

• Journal of Ginseng Research
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• v.48 no.1
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• pp.89-97
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• 2024

Background: Ginsenoside F2 (GF2), the protopanaxadiol-type constituent in Panax ginseng, has been reported to attenuate metabolic dysfunction-associated steatotic liver disease (MASLD). However, the mechanism of action is not fully understood. Here, this study investigates the molecular mechanism by which GF2 regulates MASLD progression through liver X receptor (LXR). Methods: To demonstrate the effect of GF2 on LXR activity, computational modeling of protein-ligand binding, Time-resolved fluorescence resonance energy transfer (TR-FRET) assay for LXR cofactor recruitment, and luciferase reporter assay were performed. LXR agonist T0901317 was used for LXR activation in hepatocytes and macrophages. MASLD was induced by high-fat diet (HFD) feeding with or without GF2 administration in WT and LXRα^-/- mice. Results: Computational modeling showed that GF2 had a high affinity with LXRα. LXRE-luciferase reporter assay with amino acid substitution at the predicted ligand binding site revealed that the S264 residue of LXRα was the crucial interaction site of GF2. TR-FRET assay demonstrated that GF2 suppressed LXRα activity by favoring the binding of corepressors to LXRα while inhibiting the accessibility of coactivators. In vitro, GF2 treatments reduced T0901317-induced fat accumulation and pro-inflammatory cytokine expression in hepatocytes and macrophages, respectively. Consistently, GF2 administration ameliorated hepatic steatohepatitis and improved glucose or insulin tolerance in WT but not in LXRα^-/- mice. Conclusion: GF2 alters the binding affinities of LXRα coregulators, thereby interrupting hepatic steatosis and inflammation in macrophages. Therefore, we propose that GF2 might be a potential therapeutic agent for the intervention in patients with MASLD.