• Nutrition Research and Practice
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• v.7 no.4
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• pp.287-293
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• 2013

This study determined the effects of fucoxanthin on gene expressions related to lipid metabolism in rats with a high-fat diet. Rats were fed with normal fat diet (NF, 7% fat) group, high fat diet group (HF, 20% fat), and high fat with 0.2% fucoxanthin diet group (HF+Fxn) for 4 weeks. Body weight changes and lipid profiles in plasma, liver, and feces were determined. The mRNA expressions of transcriptional factors such as sterol regulatory element binding protein (SREBP)-1c, Carnitine palmitoyltransferase-1 (CPT1), Cholesterol $7{\alpha}$-hydroxylase1 (CYP7A1) as well as mRNA expression of several lipogenic enzymes were determined. Fucoxanthin supplements significantly increased plasma high density lipoprotein (HDL) concentration (P < 0.05). The hepatic total lipids, total cholesterols, and triglycerides were significantly decreased while the fecal excretions of total lipids, cholesterol, and triglycerides were significantly increased in HF+Fxn group (P < 0.05). The mRNA expression of hepatic Acetyl-CoA carboxylase (ACC), Fatty acid synthase (FAS), and Glucose-6-phosphate dehydrogenase (G6PDH) as well as SREBP-1C were significantly lower in HF+Fxn group compared to the HF group (P < 0.05). The hepatic mRNA expression of Hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) and Acyl-CoA cholesterol acyltransferase (ACAT) were significantly low while lecithin-cholesterol acyltransferase (LCAT) was significantly high in the HF+Fxn group (P < 0.05). There was significant increase in mRNA expression of CPT1 and CYP7A1 in the HF+Fxn group, compared to the HF group (P < 0.05). In conclusion, consumption of fucoxanthin is thought to be effective in improving lipid and cholesterol metabolism in rats with a high fat diet.

• The Journal of Korean Medicine
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• v.37 no.1
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• pp.77-89
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• 2016

Objectives: The present study was conducted to examine whether Haedoksamul-tang (HS), a traditional oriental herbal medicine, have beneficail effects on anti-inflammation and dyslipidemia in lipopolysaccharide (LPS)-induced ICR mouse. Methods: Twenty four 8-week old male ICR mouse were divided into four groups: normal untreated; LPS treatment only; HS 10 mg/kg plus LPS treatment; and HS 30 mg/kg plus LPS treatment. HS was orally administered per day for 2days. Twenty-four hours after LPS injection (10 mg/kg/day, i.p.), all the mice were sacrificed, and serological changes were evaluated. The levels of nuclear factor-${\kappa}B$ (NF-${\kappa}B$), sterol regulatory element-binding transcription protein 1 (SREBP-1) activity and cyclooxygenase-2 (COX-2), inducible nitric oxide synthase (iNOS), tumor necrosis factor a (TNF-a), monocyte chemotactic protein 1 (MCP-1), acetyl-CoA carboxylase a (ACCa) expression were analyzed in Western blot analysis. Results: HS inhibited oxidative stress in the liver of LPS-induced ICR mice. The LPS-induced ICR mice exhibited the increase of NF-${\kappa}B$ activity and COX-2, iNOS, TNF-a, MCP-1 expressions in the liver, while HS treatment significantly inhibited them. Moreover, The administration of HS significantly decreased the elevated serum triglyceride and down-regulated the levels of SREBP-1, ACCa in the liver of LPS-induced ICR mice. Conclusions: In conclusion, HS could have hepato-protective effects against the oxidative stress-related inflammation and abnormal lipid metabolism.

• Journal of Nutrition and Health
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• v.52 no.1
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• pp.17-25
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• 2019

Purpose: Obesity is a major health problem of global significance because it is clearly associated with an increased risk of health problems, such as nonalcoholic fatty liver disease (NAFLD), diabetes, cardiovascular diseases, and cancer. Lonicera caerulea (LC) originates from high mountains or wet areas and has been used as a traditional medicine in northern Russia, China, and Japan. LC contains a range of bioactive constituents, such as vitamins, minerals, and polyphenols. This study examined the anti-obesity effects of LC during differentiation in preadipocytes. Methods: The cell viability assay was performed after the differentiation of 3T3-L1 cells for 7 days. Oil Red O staining was used to visualize the changes in lipid droplets in 3T3-L1 cells and mouse adipose-derived stem cells (MADSCs). The mRNA expression of obesity-related genes was determined by quantitative real-time PCR. Results: According to the results of Oil Red O staining, the lipid levels and size of lipid droplets in the adipocytes were reduced and the LC extract (LCE, 0.25-1 mg/mL) markedly inhibited adipogenesis in a dose-dependent manner. The treatment of LCE also decreased the mRNA expression of peroxisome proliferator-activated receptor ${\gamma}$ ($PPAR{\gamma}$), CCAAT/enhancer binding protein-${\alpha}$ ($C/EBP{\alpha}$), and sterol regulatory element binding protein 1 (SREBP1) in 3T3-L1 cells. Western blot analysis showed that the $PPAR{\gamma}$, $C/EBP{\alpha}$, and SREBP1 protein levels in both 3T3-L1 and MADSC were reduced in a dose-dependent manner. Conclusion: These results suggest that LCE can inhibit adipogenic differentiation through the regulation of adipogenesis-related markers.

• Journal of Life Science
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• v.29 no.9
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• pp.964-971
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• 2019

Hepatic lipid accumulation and insulin resistance increases in patients with non-alcoholic fatty liver disease. Piperine is a major compound found in black pepper (Piper nigrum) and long pepper (P. longum). Piperine has been used in fine chemical for its anti-cancer, anti-obesity, anti-diabetic, anti-inflammatory and anti-oxidant properties. However, the signaling-based mechanism of piperine and its role as an inhibitor of lipogenesis and insulin resistance in human hepatocyte cells remains ill-defined. In the present study, we explored the effects of piperine on lipid accumulation and insulin resistance, and explored the potential underlying molecular mechanisms in palmitate-treated HepG2 cells. Piperine treatment resulted in a significant reduction of triglyceride content. Furthermore, piperine treatment decreased palmitate-treated intracellular lipid deposition by inhibiting the lipogenic target genes, sterol-regulatory-element-binding protein 1c (SREBP-1c) and fatty acid synthase (FAS); whereas the expression of carnitine palmitoyl transferase (CPT-1) and phosphorylation of acetyl coenzyme A carboxylase (ACC) gene involved in fatty acid oxidation was increased. Moreover, piperine also inhibited the phosphorylation of insulin receptor substrate (IRS)-1 (Ser307). Piperine treatment modulated palmitate-treated lipid accumulation and insulin resistance in HepG2 cells with concomitant reduction of lipogenic target genes, such as SREBP-1 and FAS, and induction of CPT-1-ACC and phosphorylation of IRS-1 (Tyr632)-Akt pathways. Therefore, piperine represents a promising treatment for the prevention of lipid accumulation and insulin resistance.

• Journal of Korean Medicine Rehabilitation
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• v.32 no.2
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• pp.19-36
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• 2022

Objectives This study is to investigate the effects and mechanisms of Imyo-san (IMS) on the obese mice model induced by high-fat diet. Methods Antioxidative capacity was measured by in vitro method. C57BL/6 mice were randomly assigned into 5 groups (n=7). Normal group was fed general diet (Normal). The other 4 groups were fed high fat diet (HFD) with water (Control), with Garcinia gummi-gutta (GG, Garcinia gummi-gutta 200 mg/kg), with low-dose IMS (IMSL, Imyo-san 0.54 g/kg) and with high-dose IMS (IMSH, Imyo-san 1.08 g/kg). Results IMS showed high radical scavenging activity. After 6 week experiment, body weight, food intake, food efficiency ratio (FER), epididymal fat and liver weight, triglyceride (TG), total cholesterol (TC), high density lipoprotein (HDL) cholesterol, low density lipoprotein (LDL) cholesterol, very low density lipoprotein (VLDL) cholesterol, sterol regulatory element-binding protein-1 (SREBP-1), phospho-acetyl-CoA carboxylase (p-ACC), fatty acid synthase (FAS), stearoyl-CoA desaturase-1 (SCD-1), SREBP-2, 3-hydroxy-3-methylglutaryl-CoA reductase (HMGCR), phospho-liver kinase B1 (p-LKB1), phospho-AMP-activated protein kinase (p-AMPK), peroxisome proliferator-activated receptor 𝛼 (PPAR𝛼), peroxisome proliferator-activated receptor 𝛾 coactivator-1𝛼 (PGC-1𝛼), uncoupling protein-2 (UCP-2), carnitine palmitoyltransferase 1A (CPT-1A), and histology of liver and epididymal fat were measured and analysed. Body weight gain, FER, liver and epididymal fat weight of IMS groups were significantly decreased. There were significant improvements in blood lipids with less TG, TC, LDL-cholesterol, VLDL-cholesterol and more HDL-cholesterol. Proteins associated with lipid synthesis (SREBP-1, p-ACC, FAS, SCD-1) and cholesterol (SREBP-2, HMGCR) was improved. Factors regulating lipid synthesis and lipid catabolism (p-LKBI, p-AMPK, PPARα, PGC-1α, UCP-2, CPT-1A) were increased. In histological examinations, IMS group had smaller fat droplets than control group. All results increased depending on concentration. Conclusions It can be suggested that IMS has anti-obesity effects with improving lipid metabolism.

• Korean Journal of Food Science and Technology
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• v.46 no.6
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• pp.762-768
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• 2014

In this study, the ameliorating effects of lactic acid-fermented garlic extract (LAFGE) on non-alcoholic fatty liver were investigated using oleic acid-induced steatotic HepG2 cells. The ameliorating mechanism was analyzed by RT-PCR and Western blot. Treatment with 1 mg/mL LAFGE decreased intracellular lipid accumulation approximately 1.5-fold, compared to that achieved with non-fermented garlic extract. LAFGE reduced fatty acid influx into hepatocytes through down-regulation of FAT/CD36 mRNA expression in the steatotic HepG2 cells. $PPAR{\alpha}$ and CPT-1 mRNA expression was significantly up-regulated by LAFGE treatment of HepG2 cells as a consequence of activation of beta oxidation. Additionally, the treatment with 1 mg/mL LAFGE highly down-regulated mRNA expression of SREBP-1c and FAS to 51% and 35%, respectively. LAFGE showed concentration-dependent down-regulation patterns in protein expression of SREBP-1c and FAS, as determined by Western blot. These results suggest that LAFGE treatment improves hepatic steatosis triggered by the imbalance of hepatic lipid metabolism owing to oleic acid treatment.

• Asian-Australasian Journal of Animal Sciences
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• v.26 no.8
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• pp.1080-1088
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• 2013

Our previous results showed that kisspeptin-10 (Kp-10) injections via intraperitoneal (i.p.) once daily for three weeks notably promoted the egg laying rate in quails. In order to investigate the mechanism behind the effects of Kp-10 on enhancing the egg laying rate in birds, this study focused on the alternations of lipids synthesis in liver after Kp-10 injections. 75 female quails (22 d of age) were allocated to three groups randomly, and subjected to 0 (control, Con), 10 nmol (low dosage, L) and 100 nmol (high dosage, H) Kp-10 injections via i.p. once daily for three weeks, respectively. At d 52, quails were sacrificed and sampled for further analyses. Serum $E_2$ concentration was increased by Kp-10 injections, and reached statistical significance in H group. Serum triglyceride (TG) concentrations were increased by 46.7% in L group and 36.8% in H group, respectively, but did not reach statistical significance, and TG contents in liver were significantly elevated by Kp-10 injections in a dose-dependent manner. Serum total cholesterol (Tch) concentrations significantly decreased in H group, while in H group the hepatic Tch content was markedly increased. The level of non-esterified fatty acid (NEFA), apolipoprotein A1 and B (apoA1 and apoB) were not altered by Kp-10 injections. The genes expression of sterol regulatory element binding protein-1 (SREBP-1), fatty acid synthetase (FAS), apolipoprotein VLDL-II (apoVLDL-II), cholesterol $7{\alpha}$-hydroxylase (CYP7A1) and vitellogenin II (VTG-II) were significantly up-regulated by high but not low dosage of Kp-10 injection compared to the control group. However, the expression of SREBP-2, acetyl-CoA carboxylase ($ACC_{\alpha}$), malic enzyme (ME), stearoyl-CoA (${\Delta}9$) desaturase 1 (SCD1), apolipoprotein A1 (apoA1), fatty acid binding protein 2 (FABP2), 3-hydroxyl-3-methyl glutaryl-coenzyme A reductases (HMGCR), estrogen receptor ${\alpha}$, ${\beta}$($ER{\alpha}$ and ${\beta}$) mRNA were not affected by Kp-10 treatment. In line with hepatic mRNA abundance, hepatic SREBP1 protein content was significantly higher in H group. Although the mRNA expression was not altered, the content of $ER{\alpha}$ protein in liver was also significantly increased in H group. However, SREBP-2 protein content in liver was not changed by Kp-10 treatment. In conclusion, exogenous Kp-10 consecutive injections during juvenile stage significantly advanced the tempo of egg laying in quails, which was associated with the significant elevation in hepatic lipids synthesis and transport.

• Proceedings of the Plant Resources Society of Korea Conference
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• 2023.04a
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• pp.55-55
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• 2023

With the COVID-19 pandemic, there is increasing interest in anti-obesity strategies. According to the National Statistical Office, the obesity rate in Korea was 38.3% in 2020 and 37.1% in 2021. Obesity is a risk factor for several severe diseases, including stroke, heart disease, type 2 diabetes, and certain types of cancer. Pinus rigida × Pinus taeda is a hybrid of Pinus rigida Mill and Pinus taeda Linn, and its cones are considered a by-product. Although previous studies have investigated their pharmacological effects on antioxidant activity and protection against oxidative DNA damage, few researchers have explored their potential as functional natural materials. Therefore, we evaluated the anti-obesity effects of the cone of ethyl acetate fraction of P. rigida × P. taeda (ERT), specifically its ability to inhibit lipid accumulation. Our analysis showed that ERT contains phytochemicals (catechin and caffeic acid) which are known to improve immune function and inhibit cell damage. ERT inhibited lipid droplet accumulation at the cellular levels through Oil Red O staining. Furthermore, ERT suppressed the expression of adipogenic transcription factors (PPARγ and CEBP/α) as well as downstream lipogenic target genes (FAS and SREBP-1) thereby inhibiting adipogenesis. ERT also down-regulated key adipogenic markers, including aP2α, while inducing the phosphorylation of AMPK. It has been reported that PPARγ and CEBP/α are expressed in the early stages of adipose differentiation, while SREBP-1 is expressed in the late stage. Therefore, our findings suggest that ERT activates AMPK signaling pathways, which inhibits adipogenic transcription factors (PPARγ, C/EBPα, and SREBP1) and lipogenic genes (FAS and aP2α), thereby blocking lipid accumulation and preventing obesity and related disorders. ERT showed potential as a new resource for developing a functional material for anti-obesity agents.

• Journal of Life Science
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• v.29 no.10
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• pp.1144-1151
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• 2019

Non-alcoholic fatty liver disease (NAFLD) is a chronic liver disease associated with various metabolic syndromes, such as obesity, dyslipidemia, hypertension, and diabetes. Cudrania tricuspidata is a medicinal plant distributed widely in Asia and has been used in clinical practice to treat various diseases. The aim of this study is to determine the lipid-lowering effects of C. tricuspidata fruit extract (CTE) using a cell model induced by free fatty acids (FFAs). HepG2 cells were exposed to 1mM FFAs (palmitic acid:oleic acid = 2:1) for 24 hr to simulate the conditions of NAFLD in vitro. CTE attenuated the increases of lipid accumulation, intracellular triglyceride, and cholesterol content and inhibited 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMG-CoA reductase) activity in the HepG2 cells in a dose-dependent manner. Also, CTE inhibited the protein expression of lipogenesis-related genes, such as sterol regulatory element-binding protein-1/-2 (SREBP-1/-2), fatty acid synthase (FAS), and stearoyl CoA desaturase-1 (SCD-1) in FFAs-induced lipid accumulation in HepG2 cells. In addition, CTE-induced adenosine monophosphate-activated protein kinase (AMPK) phosphorylation in HepG2 cells. These results suggest that CTE attenuates hepatic lipid accumulation by inhibiting lipogenesis through the modulation of the AMPK signaling pathway on FFAs-induced lipogenesis in HepG2 cells and may potentially prevent NAFLD.

• BMB Reports
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• v.43 no.2
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• pp.140-145
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• 2010

The present study investigated whether the mammalian target of rapamycin (mTOR) signal pathway is involved in the regulation of high glucose-induced intramuscular adipogenesis in porcine muscle satellite cells. High glucose (25 mM) dramatically increased intracellular lipid accumulation in cells during the 10-day adipogenic differentiation period. The expressions of CCAAT/enhancer binding protein-$\alpha$ (C/EBP-$\alpha$) and fatty acid synthase (FAS) protein were gradually enhanced during the 10-day duration while mTOR phosphorylation and sterol-regulatory- element-binding protein (SREBP)-1c protein were induced on day 4. Moreover, inhibition of mTOR activity by rapamycin resulted in a reduction of SREBP-1c protein expression and adipogenesis in cells. Collectively, our findings suggest that the adipogenic differentiation of porcine muscle satellite cells and a succeeding extensive adipogenesis, which is triggered by high glucose, is initiated by the mTOR signal pathway through the activation of SREBP-1c protein. This process is previously uncharacterized and suggests a cellular mechanism may be involved in ectopic lipid deposition in skeletal muscle during type 2 diabetes.