• Nutrition Research and Practice
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• v.9 no.1
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• pp.30-36
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• 2015

BACKGROUD/OBEJECTIVES: The mechanism of how black garlic effects lipid metabolism remains unsolved. Therefore, the objectives of this study were to determine the effects of black garlic on lipid profiles and the expression of related genes in rats fed a high fat diet. MATERIALS/METHODS: Thirty-two male Sqrague-Dawley rats aged 4 weeks were randomly divided into four groups (n=8) and fed the following diets for 5 weeks: normal food diet, (NF); a high-fat diet (HF); and a high-fat diet + 0.5% or 1.5% black garlic extract (HFBG0.5 or HFBG1.5). Body weights and blood biochemical parameters, including lipid profiles, and expressions of genes related to lipid metabolism were determined. RESULTS: Significant differences were observed in the final weights between the HFBG1.5 and HF groups. All blood biochemical parameters measured in the HFBG1.5 group showed significantly lower values than those in the HF group. Significant improvements of the plasama lipid profiles as well as fecal excretions of total lipids and triglyceride (TG) were also observed in the HFBG1.5 group, when compared to the HF diet group. There were significant differences in the levels of mRNA of sterol regulatory element binding protein-1c (SREBP-1c), acetyl-CoA carboxylase (ACC), fatty acid synthase (FAS), and glucose-6-phosphate dehydrogenase (G6PDH) in the HFBG1.5 group compared to the HF group. In addition, the hepatic expression of (HMG-CoA) reductase and Acyl-CoA cholesterol acyltransferase (ACAT) mRNA was also significantly lower than the HF group. CONCLUSIONS: Consumption of black garlic extract lowers SREBP-1C mRNA expression, which causes downregulation of lipid and cholestrol metahbolism. As a result, the blood levels of total lipids, TG, and cholesterol were decreased.

• 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.

• The Journal of Internal Korean Medicine
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• v.39 no.3
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• pp.302-312
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• 2018

Objectives: This study was performed to investigate the effects of two herbal medicines, Agastachis Herba and Lysimachiae Herba, on a cellular model of non-alcoholic fatty liver diseases (NFLDs). Methods: HepG2 cells were treated with palmitic acid and with various concentrations of Agastachis Herba (AH) or Lysimachiae Herba (LH) extract in water. The lipotoxicity was assessed using EZ-cytox, and the lipoapoptosis was assessed using cell death detection ELISA. Intracellular lipids were measured by oil red O staining. The efficacy of AH and LH on sterol regulatory element-binding transcription factor-1c (SREBP-1c), fatty acid synthase (FAS), and acetyl-CoA carboxylase (ACC) in HepG2 cells was measured by reverse transcription polymerase chain reaction (RT-PCR). Results: Both AH and LH extracts increased lipoapoptosis and decreased lipotoxicity and levels of SREBP-1c, ACC, and FAS (SREBP-1c, ACC, and FAS are factors in lipid synthesis). In the oil red O staining experiment, both extracts also reduced intracellular lipid accumulation; in this instance, LH's efficacy was superior to that of AH. Conclusions: According to the results, both AH and LH are likely to contribute to non-alcoholic fatty liver disease, as both interfere with lipid synthesis.

• Journal of Life Science
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• v.27 no.12
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• pp.1486-1493
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• 2017

Doenjang is a traditional korean fermented soybean paste made from meju (fermented soybean), which are fermented by diverse microorganisms including Bacillus subtilis and molds such as Rizopus, Mucor, and Aspergillus species The purpose of this study was to investigate the antiobesity effect of the black soybean doenjang (Korean fermented soybean pastes) in C57BL/6 mice. The anti-obesity effect was determined by measuring the release of adiponectin, leptin and adipogenic transcription factors by using reverse transcription-polymerase chain reaction and western blot. Weight gain was significantly reduced in the mice fed high fat diets (HFD) plus black soybean doenjang (HBD) compared to HFD mice. The HBD were also effective in improving the lipid profile. They significantly decreased the levels of serum triglyceride and cholesterol. In addition, they had a significantly down regulated impact on antiobesity factors; leptin level and increased adiponectin level. Also, mRNA and protein expression of two adipogenic transcription factors, SREBP-1c and $PPAR-{\gamma}$, in high fat with black soybean fed mice were markedly down regulated. These results indicate that the black soybean doenjang potentiates an anti-obesity effect by modulating lipid metabolism, thereby inhibiting adipogenic transcriptional activation.

• 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.

• 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.

• 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.

• Herbal Formula Science
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• v.28 no.3
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• pp.255-269
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• 2020

Objectives : Hemistepta lyrata Bunge (Bunge) is a wild herb that has been used for managing fever and wound in Korean Traditional Medicine. The present study explored the effects of H. lyrata extract on liver X receptor (LXR) α-dependent lipogenic genes in hepatocyte-derived cells. Methods : After HepG2 cells or Huh7 cells were pre-treated with 1-10 ㎍/mL of H. lyrata extract or its fractionated extract for 0.5 h, the cells were subsequently exposed to LXR ligand for 6-24 h. Cell viability, LXR response element (LXRE)-driven luciferase activity, sterol regulatory element binding protein-response element (SREBP-RE)-driven luciferase activity, SREBP-1c expression, and mRNA levels of LXRα and its-dependent target genes were determined. In addition, LC-MS/MS analysis was conducted to explore major compounds in H. lyrata-chloroform fractionated extract #4 (HL-CF4). Results : Of various H. lyrata extracts tested, chloroform extract and its fractionated extract #4, HL-CF4, significantly decreased T0901317-mediated SREBP-1c expression. In addition, HL-CF4 significantly reduced LXRE atransactivation and LXRα mRNA expression without any cytotoxicity. Moreover, HL-CF4 prevented the SREBP-RE-driven luciferase activity and mRNA levels of fatty acid synthase and stearoyl-CoA desaturase-1 induced by T0901317. Results from LC-MS/MS analysis at positive/negative mode indicated that HL-CF4 contained several compounds showing m/z 197.1176 (C₁₁H₁₇O₃), 693.2913/227.1069 (C₃₈H₄₅O₁₂/C₁₅H₁₅O₂), 203.1797 (C₁₅H₂₃), 181.1225 (C₁₁H₁₇O₂), 591.2957 (C₃₅H₄₃O₈), 379.1040 (C₁₈H₁₉O₉), 409.1509 (C₂₀H₂₅O₉), 309.1348 (C₁₆H₂₁O₆), 391.1404 (C₂₀H₂₃O₈), and 669.2924/389.1248 (C₃₆H₄₅O₁₂/C₂₀H₂₁O₈). Conclusion : Based on its inhibition of the LXRα-dependent signaling pathway, H. lyrata chloroform extract and HL-CF4 have prophylactic potentials for managing non-alcoholic fatty liver.

• 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.

• 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.