• BMB Reports
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• 제45권7호
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• pp.419-424
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• 2012

High-fat diets (HFD) and high-carbohydrate diets (HCD)-induced obesity through different pathways, but the metabolic differences between these diets are not fully understood. Therefore, we applied proton nuclear magnetic resonance ($^1H$ NMR)-based metabolomics to compare the metabolic patterns between C57BL/6 mice fed HCD and those fed HFD. Principal component analysis derived from $^1H$ NMR spectra of urine showed a clear separation between the HCD and HFD groups. Based on the changes in urinary metabolites, the slow rate of weight gain in mice fed the HCD related to activation of the tricarboxylic acid cycle (resulting in increased levels of citrate and succinate in HCD mice), while the HFD affected nicotinamide metabolism (increased levels of 1-methylnicotineamide, nicotinamide-N-oxide in HFD mice), which leads to systemic oxidative stress. In addition, perturbation of gut microflora metabolism was also related to different metabolic patterns of those two diets. These findings demonstrate that $^1H$ NMR-based metabolomics can identify diet-dependent perturbations in biological pathways.

• Journal of Ginseng Research
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• 제42권4호
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• pp.419-428
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• 2018

Background: Despite the large number of studies on ginseng, pharmacological activities of ginseng seed oil (GSO) have not been established. GSO is rich in unsaturated fatty acids, mostly oleic and linoleic acids. Unsaturated fatty acids are known to exert a therapeutic effect in nonalcoholic fatty liver disease (NAFLD). In this study, we investigated the protective effect and underlying mechanisms of GSO against NAFLD using in vitro and in vivo models. Methods: In vitro lipid accumulation was induced by free fatty acid mixture in HepG2 cells and by 3 wk of high fat diet (HFD)-feeding in Sprague-Dawley rats prior to hepatocyte isolation. The effects of GSO against diet-induced hepatic steatosis were further examined in C57BL/6J mice fed a HFD for 12 wk. Results: Oil Red O staining and intracellular triglyceride levels showed marked accumulation of lipid droplets in both HepG2 cells and rat hepatocytes, and these were attenuated by GSO treatment. In HFD-fed mice, GSO improved HFD-induced dyslipidemia and hepatic insulin resistance. Increased hepatic lipid contents were observed in HFD-fed mice and it was lowered in GSO (500 mg/kg)-treated mice by 26.4% which was evident in histological analysis. Pathway analysis of hepatic global gene expression indicated that GSO increased the expression of genes associated with ${\beta}$-oxidation (Ppara, Ppargc1a, Sirt1, and Cpt1a) and decreased the expression of lipogenic genes (Srebf1 and Mlxipl), and these were confirmed with reverse transcription and quantitative polymerase-chain reaction. Conclusion: These findings suggest that GSO has a beneficial effect on NAFLD through the suppression of lipogenesis and stimulation of fatty acid degradation pathway.

• 한국축산식품학회지
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• 제39권2호
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• pp.179-196
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• 2019

We investigated the effect of high density lipoprotein from egg yolk (EYHDL) on serum, hepatic and fecal lipid and fatty acids (FAs) levels and on gene expression involved in FAs metabolism. Male KM mice were fed either normal diet (ND; n=20), high fat diet (HFD; n=20), or high fat diet containing EYHDL (EYHDL; 0.6 mg/g, every day by oral gavage, n=20) for 100 days. At the end of the experiment, the effects of treatments on biochemical parameters, FAs profiles and involved gene expression were analyzed. Our results revealed that EYHDL markedly suppressed the body weight gain, accumulation of abdominal fat tissues, serum concentrations of LDL-cholesterol (LDL-C) and triglycerides, hepatic triglycerides and cholesterol accumulation, while increased serum concentration of HDL-cholesterol (HDL-C). EYHDL intake also increased total cholesterol (TC) excretions compared with HFD group. Moreover, it alleviated the severity of fatty liver and improved glucose and insulin tolerance compared with HFD. More importantly, EYHDL partially normalized FAs profiles in serum, liver and fecaces and neutralized the HFD-induced upregulation of SREBP-1c, Acaca, Fasn, GPAT and Scd1. In conclusion, our findings indicate that EYHDL may have the potential to improve metabolic disturbances that occur in HFD mice and can be considered as an appropriate dietary recommendation for the treatment of metabolic syndrome (MetS).

• Nutrition Research and Practice
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• 제15권3호
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• pp.279-293
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• 2021

BACKGROUND/OBJECTIVES: The steamed ginger has been shown to have antioxidative effects and a protective effect against obesity. In the present study, we investigated the effects of ethanolic extract of steamed ginger (SGE) on adipogenesis in 3T3-L1 preadipocytes and diet-induced obesity (DIO) mouse model. MATERIALS/METHODS: The protective effects of SGE on adipogenesis were examined in 3T3-L1 adipocytes by measuring lipid accumulations and genes involved in adipogenesis. Male C57BL/6J mice were fed a normal diet (ND, 10% fat w/w), a high-fat diet (HFD, 60% fat w/w), and HFD supplemented with either 40 mg/kg or 80 mg/kg of SGE for 12 weeks. Serum chemistry was measured, and the expression of genes involved in lipid metabolism was determined in the adipose tissue. Histological analysis and micro-computed tomography were performed to identify lipid accumulations in epididymal fat pads. RESULTS: In 3T3-L1 cells, SGE significantly decreased lipid accumulation, with concomitant decreases in the expression of adipogenesis-related genes. SGE significantly attenuated the increase in body, liver, and epididymal adipose tissue weights by HFD. Serum total cholesterol and triglyceride levels were significantly lower in SGE fed groups compared to HFD. In adipose tissue, SGE significantly decreased adipocyte size than that of HFD and altered adipogenesis-related genes. CONCLUSIONS: In conclusion, steamed ginger exerted anti-obesity effects by regulating genes involved in adipogenesis and lipogenesis in 3T3-L1 cell and epididymal adipose tissue of DIO mice.

• 생약학회지
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• 제46권1호
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• pp.65-71
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• 2015

Although it has recently been reported that Acanthopanax senticosus has a protective effect against the development of metabolic disorders such as diabetes and hyperlipidemia, its underlying molecular mechanisms have remained to be elucidated. In this study, we observed that treatment of an extract of A. senticosus (ASE) reduced body weight and adiposity and improved glucose tolerance in high-fat diet (HFD)-induced obese mice. HFD-induced weight gain in white adipose tissues and liver was also significantly reduced in ASE-treated HFD-fed mice, which was found to be contributed by suppression of mRNA expression of genes involved in fatty-acid uptake and fat synthesis in white adipose tissue. ASE treatment also attenuated M1 macrophage activation, increased regulatory T ($T_{reg}$) cell population, and modulated leptin/adiponectin profile that might alleviate chronic inflammation to protect against HFD-induced insulin resistance. Our findings suggest a therapeutic potential of ASE for prevention and treatment of type 2 diabetes without adverse effects such as weight gain and dyslipidemia.

• Clinical and Experimental Reproductive Medicine
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• 제47권1호
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• pp.20-33
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• 2020

Objective: The differences between type 1 and type 2 diabetes mellitus (T1DM and T2DM) in terms of their adverse effects on male reproductive parameters have never been elucidated. This study aimed to distinguish between the effects of the DM types in mice treated with multiple low doses of streptozotocin (STZ) to mimic human T1DM and coadministered a high-fat diet (HFD) to mimic human T2DM. Methods: The T1DM mice were intraperitoneally injected with STZ (40 mg/kg body weight) for 5 days. The T2DM mice received an HFD for 14 days prior to STZ injection (85 mg/kg body weight), followed by continuous feeding of an HFD. Male reproductive parameters were evaluated. Results: The reproductive organs of the DM mice weighed significantly less than those of controls, and the seminal vesicles plus prostates of the T1DM mice weighed less than those of the T2DM mice. Increased sperm abnormalities and incomplete DNA packaging were observed in the DM groups. Sperm concentration and the proportion of normal sperm were significantly lower in the T1DM group. The seminiferous histopathology of DM mice was classified into seven types. The penises of the DM mice were smaller than those of the controls; however, tunica albuginea thickness and the amount of penile collagen fibers were increased in these mice. Round germ cells were abundant in the epididymal lumens of the mice with DM. Conclusion: T1DM adversely affected reproductive parameters to a greater extent than T2DM.

• 생명과학회지
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• 제29권1호
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• pp.18-28
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• 2019

최근 비만에 의해 과발현된 신경세포형 산화질소 생성효소(neuronal nitric oxide synthase, nNOS)가 정서적 행동을 조절하는 중요한 인자라는 보고되었다. 이와 관련한 최근의 연구에서 운동이 비만에 의해 과발현된 nNOS를 억제하고 정서적 우울감과 항불안 효과를 감소시켰다는 연구결과가 보고되었다. 운동은 nNOS를 억제하여 뇌의 기능을 향상시킬 수 있는 효과적인 전략으로 보이지만 운동은 강도에 따라 면역 반응에 큰 차이가 있다. 따라서 본 연구에서는 고지방식이(high-fat diet, HFD)로 유도된 비만 마우스에서 다른 강도의 운동을 실시하여 해마의 nNOS 발현의 차이를 분석하고자 하였다. 실험동물은 C57BL/6 마우스를 사용하였다. 대조군(CON, n=14)을 제외한 마우스(n=35)에게 6주 동안 60%의 고지방식이를 섭취시켜 비만을 유도하였다. 6주간의 비만유도 기간이 종료된 후 CON과 비만이 유도된 동물 각각 7마리씩 희생하여 비만유도를 확인하는데 사용되었다. 나머지 동물은 8주간의 운동중재 연구에 이용되었다. 이 때 CON을 제외하고 비만이 유도된 동물들은 고지방대조군(HFD) 그리고 저강도운동군(HFD-LI, n=7) 중강도운동군(HFD-MI, n=7) 그리고 HFD-고강도(HFD-HI, n=7)로 나누어졌다. HFD-LI는 12 m/min으로 75분, HFD-MI는 15 m/min으로 60분 그리고 HFD-HI는 18 m/min으로 50분 동안 동물용 트레드밀에서 운동이 수행되었다(동등한 운동량, 900 m). 해마(hippocampus)의 nNOS 단백질의 발현은 CON에 비해 HFD에서 유의하게 높았고(p<0.01), CON과 운동을 실시한 모든 그룹과 차이가 없었다. 하지만 HFD-LI에 비해 HFD-HI가 유의하게 nNOS 발현이 낮았다(p<0.05). 대뇌피질에서는 CON에 비해 HFD에서 유의하게 높았으나(p<0.01), 다른 그룹 간에 차이는 없었다. nNOS의 생성을 조절할 수 있는 인산화된 Akt (pAkt)의 발현이 CON과 HFD에 비해 운동을 실시한 나머지 그룹 모두에서 유의하게 높았다. 대뇌피질에서의 pAkt의 발현에서는 차이가 모든 그룹 간에 차이가 없었고, 소뇌에서는 CON에 비해 HFD-HI에서 유의하게 높았다(p<0.05). 소뇌에서는 각 그룹 간에 차이가 없었다. 결론적으로 nNOS는 고지방식이와 비만에 의해 과발현된 것으로 보여지고 이를 운동을 통하여 낮출 수 있는 것으로 보여지며, 이 때 운동량이 같다는 가정하에 상대적으로 높은 강도가 효과적일 가능성이 있다.

• Nutrition Research and Practice
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• 제12권6호
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• pp.503-511
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• 2018

BACKGROUND/OBJECTIVES: Ginger, a root vegetable, is known to have antioxidant and antiobesity effects. Preparation, such as by steaming, can affect the chemical composition of prepared root vegetables or herbs and can change their functional activities. In the present study, we investigated the protective effects of steamed ginger against oxidative stress and steatosis in C57BL/6J mice fed a high-fat diet. MATERIAL/METHODS: The levels of polyphenols and flavonoids in two different extracts of steamed ginger, i.e., water extract (SGW) and ethanolic extract (SGE); as well, their antioxidant activities were examined. Forty male C57BL/6J mice were fed a normal diet (ND, n = 10), high-fat diet (HFD, 60% fat, w/w, n = 10), HFD supplemented with 200 mg/kg of SGE or garcinia (GAR) by weight (SGED or GARD, respectively, n = 10) for 12 weeks. Serum chemistry was examined, and the expressions of genes involved in lipid metabolism were determined in the liver. Histological analysis was performed to identify lipid accumulations in epididymal fat pads and liver. RESULTS: The SGE had higher contents of polyphenols and flavonoids and higher DPPH and $ABTS^+$ free radical scavenging activities compared to those of SGW. Treatment with SGE or GAR significantly decreased the HFD-induced weight gain. Both SGE and GAR significantly reduced the high serum total cholesterol (TC), triglyceride (TG) and low-density lipoprotein levels induced by HFD. Compared to ND, HFD significantly increased hepatic TC and TG levels. SGE or GAR supplementation significantly decreased the increase of hepatic lipids by HFD. Interestingly, SGE had a more significant effect in reducing hepatic TC and TG levels than GAR. Furthermore, hepatic genes involved in lipogenesis and lipolysis were altered in both the SGED and GARD groups. CONCLUSIONS: The present study indicates that steamed ginger supplementation can decrease plasma TC and TG and can inhibit liver steatosis by regulating the expressions of hepatic genes.

• Journal of Ginseng Research
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• 제47권3호
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• pp.376-384
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• 2023

Background: Hepatic lipid disorder impaired mitochondrial homeostasis and intracellular redox balance, triggering development of non-alcohol fatty liver disease (NAFLD), while effective therapeutic approach remains inadequate. Ginsenosides Rc has been reported to maintain glucose balance in adipose tissue, while its role in regulating lipid metabolism remain vacant. Thus, we investigated the function and mechanism of ginsenosides Rc in defending high fat diet (HFD)-induced NAFLD. Methods: Mice primary hepatocytes (MPHs) challenged with oleic acid & palmitic acid were used to test the effects of ginsenosides Rc on intracellular lipid metabolism. RNAseq and molecular docking study were performed to explore potential targets of ginsenosides Rc in defending lipid deposition. Wild type and liver specific sirtuin 6 (SIRT6, 50721) deficient mice on HFD for 12 weeks were subjected to different dose of ginsenosides Rc to determine the function and detailed mechanism in vivo. Results: We identified ginsenosides Rc as a novel SIRT6 activator via increasing its expression and deacetylase activity. Ginsenosides Rc defends OA&PA-induced lipid deposition in MPHs and protects mice against HFD-induced metabolic disorder in dosage dependent manner. Ginsenosides Rc (20mg/kg) injection improved glucose intolerance, insulin resistance, oxidative stress and inflammation response in HFD mice. Ginsenosides Rc treatment accelerates peroxisome proliferator activated receptor alpha (PPAR-α, 19013)-mediated fatty acid oxidation in vivo and in vitro. Hepatic specific SIRT6 deletion abolished ginsenoside Rc-derived protective effects against HFD-induced NAFLD. Conclusion: Ginsenosides Rc protects mice against HFD-induced hepatosteatosis by improving PPAR-α-mediated fatty acid oxidation and antioxidant capacity in a SIRT6 dependent manner, and providing a promising strategy for NAFLD.

• Nutrition Research and Practice
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• 제11권3호
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• pp.198-205
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• 2017

BACKGROUND/OBJECTIVES: The anti-diabetic activity of pear through inhibition of ${\alpha}-glucosidase$ has been demonstrated. However, little has been reported about the effect of pear on insulin signaling pathway in obesity. The aims of this study are to establish pear pomace 50% ethanol extract (PPE)-induced improvement of insulin sensitivity and characterize its action mechanism in 3T3-L1 cells and high-fat diet (HFD)-fed C57BL/6 mice. MATERIALS/METHODS: Lipid accumulation, monocyte chemoattractant protein-1 (MCP-1) secretion and glucose uptake were measure in 3T3-L1 cells. Mice were fed HFD (60% kcal from fat) and orally ingested PPE once daily for 8 weeks and body weight, homeostasis model assessment of insulin resistance (HOMA-IR), and serum lipids were measured. The expression of proteins involved in insulin signaling pathway was evaluated by western blot assay in 3T3-L1 cells and adipose tissue of mice. RESULTS: In 3T3-L1 cells, without affecting cell viability and lipid accumulation, PPE inhibited MCP-1 secretion, improved glucose uptake, and increased protein expression of phosphorylated insulin receptor substrate 1 [p-IRS-1, ($Tyr^{632})$)], p-Akt, and glucose transporter type 4 (GLUT4). Additionally, in HFD-fed mice, PPE reduced body weight, HOMA-IR, and serum lipids including triglyceride and LDL-cholesterol. Furthermore, in adipose tissue, PPE up-regulated GLUT4 expression and expression ratio of p-IRS-1 ($Tyr^{632})/IRS$, whereas, down-regulated p-IRS-1 ($Ser^{307})/IRS$. CONCLUSIONS: Our results collectively show that PPE improves glucose uptake in 3T3-L1 cells and insulin sensitivity in mice fed a HFD through stimulation of the insulin signaling pathway. Furthermore, PPE-induced improvement of insulin sensitivity was not accompanied with lipid accumulation.