• The Journal of Internal Korean Medicine
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• v.37 no.3
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• pp.442-452
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• 2016

Objectives: This study was performed to investigate the anti-lipogenic effect and the mechanism of Jungmanbunso-hwan extract (JMBSH) on a cellular model of non-alcoholic fatty liver disease (NAFLD) caused by palmitate in HepG2 cells.Methods: The JMBSH was prepared, andHepG2 cells were treated with various concentrations of JMBSH in order to perform an MTT assay. The HepG2 cells were cultivated in palmitate-containing media with or without extract of JMBSH. The intracellular lipid content in the HepG2 cells was examined. The effects of JMBSH on sterol regulatory element-binding transcription factor-1c (SREBP-1c), acetyl-CoA carboxylase (ACC), fatty acid synthase (FAS), stearoyl-CoA desaturase-1 (SCD-1), and AMP-activated protein kinase (AMPK) activation in HepG2 cells were measured.Results: JMBSH did not reduce HepG2 cell viability under 1,000 μg/mL. JMBSH considerably decreased intracellular lipid accumulation caused by palmitate in HepG2 cells. JMBSH repressed expression of SREBP-1c, which mediates the induction of lipogenic genes (ACC, FAS, and SCD-1). JMBSH also activated AMPK, which plays animportant role in the regulation of hepatic lipid metabolism.Conclusions: This study suggested that JMBSH relieves hepatic steatosis by repressing SREBP-1c, which mediates the induction of lipogenic genes. The anti-lipogenic effect of JMBSH may also be related to the activation of AMPK. Therefore, JMBSH could potentially be applied to NAFLD treatment after further clinical studies.

• Journal of Physiology & Pathology in Korean Medicine
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• v.22 no.3
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• pp.642-648
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• 2008

The aim of this study is to investigate Chegameuiin-tang water extracts (CETE) have potent anti-obesity activities in a high fat diet-induced obesity mouse model. In this study, we designed three group (normal diet group, high fat diet group, high fat diet plus CETE group for 13-week oral administration). Increases in body weight and fat storage were inhibited by 13-week oral administration of CETE at a 500 mg/kg concentration in this animal model, while the amount of food intake was not affected. Results from blood lipid analysis showed that the levels of triglyceride, total cholesterol and LDL-cholesterol were significantly lowered by CETE administration, also HDL-cholesterol was increased more than high fat diet-induced obese mouse. To understand the underlying mechanism at the molecular level, the effects of CETE were examined on the expression of the genes involved in lipogenesis and lipolysis by real-time PCR. In epididymal fat of CETE-treated mice, the mRNA level of lipogenic genes such as sterol regulatory element binding protein 1 and fatty acid synthase were decreased, which was well correlated with the reduction of the epididymal fat weight. Also, CETE administration inhibited decreases of the hormone-sensitve lipase and lipoprotein lipase mRNA expressions, which are genes related with lipolysis. These results suggest that Chegameuiin-tang may have great potential as a novel anti-obesity agent.

• Journal of Food Hygiene and Safety
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• v.28 no.2
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• pp.89-94
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• 2013

The present study was undertaken to elucidate the mechanisms underlying the cholesterol-lowering effect of S-allylmercaptocysteine (SAMC) derived from aged garlic. Rat hepotocytes and HepG2 cells were used to determine the short-term effects of SAMC on [$^{14}C$] acetate incorporation into cholesterol, and several enzymatic steps. The cells were grown in Dulbecco's modified Eagle's medium supplemented with 10% fetal bovine serum and treated with 20, 40, 60 and 80 ${\mu}g/ml$ of SAMC. At concentration of 20~40 ${\mu}g/ml$, no significant cells viability effect was noted during those incubation periods. However, at a concentration 60 ${\mu}g/ml$, cell viability decreased approximately 50% compared with the control. The treatment of cells with 5, 10, 15, and 20 ${\mu}g/ml$ of SAMC resulted in a marked of [$^{14}C$]-acetate incorporation into cholesterol. At concentration of 15 ${\mu}g/ml$, the cholesterol synthesis was inhibited 79% in cells. The activities of lipogenic enzymes, fatty acid synthase (FAS), and glucose-6-phosphate dehydrogenase (G3PDH) were measured in culture hepatocytes treated with the inhibitors. The activity of FAS in cells treated with 0.95 nmol SAMC was 19% lower than that of nontreated cells, and no affected G6PDH activity, 3-hydroxy-3-methylglutaryl Co A activity was decreased at concentration dependant manner. The present study demonstrates that SAMC is effective in inhibiting cholesterol biosynthesis.

• Journal of the Korean Society of Food Science and Nutrition
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• v.46 no.4
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• pp.401-408
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• 2017

Salvia plebeia R. Br. (Lamiaceae) has been used in folk medicines in Asian countries, including Korea and China, to treat inflammatory diseases. The focus of our research was on the anti-adipogenic activity of ethanol extract from Salvia plebeia R. Br. (SPE) in 3T3-L1 adipocytes. This study investigated inhibition of differentiation and lipogenesis upon SPE treatment in 3T3-L1 cells. The results reveal that SPE at non-cytotoxic concentration significantly suppressed triglyceride accumulation and reduced expression of peroxisome proliferator-activated receptor gamma, CCAAT/enhancer-binding protein-alpha, and sterol regulatory element-binding protein as adipogenic transcription factors in 3T3-L1 adipocytes compared to non-treated control cells. Inducible phosphorylation of AMP-activated protein kinase, acetyl CoA carboxylase, and hormone-sensitive lipase as well as carnitine palmitoyltransferase-1 mRNA expression increased upon SPE treatment, which suppressed expression of fatty acid synthase. In conclusion, these results demonstrate that SPE can inhibit expression of adipogenic genes in 3T3-L1 adipocytes. Our study suggests that SPE has potential anti-obesity effects and is a novel therapeutic functional agent with anti-adipogenic activity via reduction of lipogenesis.

• Biomolecules & Therapeutics
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• v.27 no.5
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• pp.457-465
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• 2019

Patients with diabetes mellitus (DM) often suffer from diverse skin disorders, which might be attributable to skin barrier dysfunction. To explore the role of lipid alterations in the epidermis in DM skin disorders, we quantitated 49 lipids (34 ceramides, 14 free fatty acids (FFAs), and cholesterol) in the skin epidermis, liver, and kidneys of db/db mice, a Type 2 DM model, using UPLC-MS/MS. The expression of genes involved in lipid synthesis was also evaluated. With the full establishment of hyperglycemia at the age of 20 weeks, remarkable lipid enrichment was noted in the skin of the db/db mice, especially at the epidermis and subcutaneous fat bed. Prominent increases in the ceramides and FFAs (>3 fold) with short or medium chains ($LXR{\alpha}/{\beta}$ and $PPAR{\gamma}$, nuclear receptors promoting lipid synthesis, lipid synthesis enzymes such as elongases 1, 4, and 6, and fatty acid synthase and stearoyl-CoA desaturase were highly expressed in the skin and livers of the db/db mice. Collectively, our study demonstrates an extensive alteration in the skin and systemic lipid profiles of db/db mice, which could contribute to the development of skin disorders in DM.

• Journal of Nutrition and Health
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• v.56 no.2
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• pp.123-139
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• 2023

Purpose: This study was conducted to establish whether an ethanol extract of Lycium barbarum leaves (LLE) and an ethanol extract of Lycium barbarum leaves from which chlorophyll has been removed, denoted as LLE(Ch^-), have a protective effect against hepatic fat accumulation. Methods: The inhibitory effects of LLE and LLE(Ch^-) on liver fat accumulation were examined in C57BL/6 mice with non-alcoholic fatty liver disease (NAFLD) induced by an methionine and choline deficient diet and in HepG2 cells with palmitic acid-induced fat accumulation. Results: The plasma triglyceride, aspartate aminotransferase, and alanine aminotransferase levels were lower in the LLE(Ch^-) group, whereas the plasma ALT activity decreased significantly in the LLE group. In both the LLE and the LLE(Ch^-) groups, the triglyceride and cholesterol contents in the hepatic tissue were significantly reduced. A greater inhibitory effect on tissue fat accumulation was observed in the LLE(Ch^-) group than in the LLE group. In HepG2 cells, LLE and LLE(Ch^-) were non-toxic up to a concentration of 1,000 ㎍/mL. Compared to the control group, intracellular fat accumulation in the LLE and LLE(Ch^-) groups were significantly reduced at concentrations of 200 ㎍/mL and 500 ㎍/mL, respectively. The expression of phosphorylated adenosine monophosphate-activated protein kinase and phosphorylated acetyl-CoA carboxylase in both LLE groups increased at the concentrations of 100 ㎍/mL and 500 ㎍/mL. The fatty acid synthase expression was suppressed in a concentration-dependent manner at 10 ㎍/mL. Conclusion: The examined two ethanol extracts of LLE inhibit hepatic fat accumulation in NAFLD. This effect was more pronounced in the LLE(Ch^-) group. Therefore, these 2 extracts have an anti-steatosis effect and can be used for NAFLD treatment.

• Asian-Australasian Journal of Animal Sciences
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• v.20 no.9
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• pp.1417-1423
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• 2007

The present study was conducted to investigate the supplementation effects of $C_{18:2}$ rich-soybean oil or $C_{18:3}$ rich-perilla oil (7% of total diet, DM basis) for 12 weeks on plasma metabolites, fatty acid profile, in vitro lipogenesis, and activities of LPL and FAS in adipose tissue of sheep. The treatments were basal diet (Control), $C_{18:2}$ rich-soybean oil supplemented diet (SO-D) and $C_{18:3}$ rich-perilla oil supplemented diet (PO-D). All the sheep were fed the diets consisting of roughage to concentrate in the ratio of 40:60 (DM basis). Oil supplemented diets (SO-D and PO-D) slightly increased contents of triglyceride (TG) and total cholesterol (TC), proportions of both cis-9 trans-11 and trans-10 cis-12 CLA and TVA, but lowered (p<0.01) those of $C_{18:0}$ compared to the control diet. No differences were observed in the contents of TG and TC and proportions of fatty acids in plasma between supplemented oils. Oil supplemented diets slightly increased the proportions of cis-9 trans-11 and trans-10 cis-12 types of CLA in subcutaneous adipose tissue of sheep compared to the control diet. The rate of lipogenesis with acetate was higher (p<0.01) for intermuscular- and subcutaneous adipose tissues than that for intramuscular adipose tissue, while that with glucose did not differ among fat locations in sheep fed SO-D. No differences were observed in the rate of lipogenesis between substrates in all fat locations. The rates of lipogenesis with glucose increased only in the intermuscular- (p<0.01) and subcutaneous adipose tissue (p<0.005) compared to those with acetate. The rates of lipogenesis with acetate were the highest in the intermuscular and intramuscular adipose tissue of the sheep fed PO-D. Oil supplemented diets slightly increased the rate of lipogenesis with glucose for all fat locations. Supplementation of oils to the diet numerically increased the fatty acid synthase activity but did not affect the lipoprotein lipase activity in subcutaneous adipose tissue.

• Asian-Australasian Journal of Animal Sciences
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• v.31 no.8
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• pp.1088-1097
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• 2018

Objective: It is commonly accepted that adiponectin binds to its two receptors to regulate fatty acid metabolism in adipocytes. To better understand their functions in the regulation of intramuscular adipogenesis in goats, we cloned the three genes (adiponectin [AdipoQ], adiponectin receptor 1 [AdipoR1], and AdipoR2) encoding these proteins and detected their mRNA distribution in different tissues. We also determined the role of AdipoQ in the adipogenic differentiation of goat skeletal muscle satellite cells (SMSCs). Methods: SMSCs were isolated using 1 mg/mL Pronase E from the longissimus dorsi muscles of 3-day-old female Nanjiang brown goats. Adipogenic differentiation was induced in satellite cells by transferring the cells to Dulbecco's modified Eagle's medium supplemented with an isobutylmethylxanthine, dexamethasone and insulin cocktail. The pEGFP-N1-AD plasmid was transfected into SMSCs using Lipofectamine 2000. Expression of adiponectin in tissues and SMSCs was detected by quantitative polymerase chain reaction and immunocytochemical staining. Results: The three genes were predominantly expressed in adipose and skeletal muscle tissues. According to fluorescence and immunocytochemical analyses, adiponectin protein expression was only observed in the cytoplasm, suggesting that adiponectin is localized to the cytoplasm of goat SMSCs. In SMSCs overexpressing the AdipoQ gene, adiponectin promoted SMSC differentiation into adipocytes and significantly (p<0.05) up-regulated expression of AdipoR2, acetyl-CoA carboxylase, fatty-acid synthase, and sterol regulatory element-binding protein-1, though expression of CCAAT/enhancer-binding $protein-{\alpha}$, peroxisome proliferator-activated receptor ${\gamma}$, and AdipoR1 did not change significantly. Conclusion: Adiponectin induced SMSC differentiation into adipocytes, indicating that adiponectin may promote intramuscular adipogenesis in goat SMSC.

• Journal of Nutrition and Health
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• v.55 no.2
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• pp.227-239
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• 2022

Purpose: This study investigated the effects of water-soluble mulberry leaf extract (ME) on hepatic lipid accumulation in high-fat diet-fed rats via the regulation of hepatic microRNA (miR)-221/222 and inflammation. Methods: Male Sprague-Dawley rats (4 weeks old) were randomly divided into 3 groups (n = 7 each) and fed with 10 kcal% low-fat diet (LF), 45 kcal% high-fat diet (HF), or HF + 0.8% ME for 14 weeks. Lipid profiles and cytokine levels of the liver and serum were measured using commercial enzymatic colorimetric and enzyme-linked immunosorbent assay, respectively. The messenger RNA (mRNA) and miR levels in liver tissue were assayed by real-time quantitative reverse-transcription polymerase chain reaction. Results: Supplementation of ME reduces body weight and improves the liver and serum lipid profiles as compared to the HF group. The mRNA levels of hepatic peroxisome proliferator-activated receptor-gamma, sterol regulatory element binding protein-1c, fatty acid synthase, and fatty acid translocase, which are genes involved in lipid metabolism, were significantly downregulated in the ME group compared to the HF group. In contrast, the mRNA level of hepatic carnitine palmitoyl transferase-1 (involved in fatty acid oxidation) was upregulated by ME supplementation. Furthermore, administration of ME significantly downregulated the mRNA levels of inflammatory mediators such as hepatic tumor necrosis factor alpha (TNF-α), interleukin 6 (IL-6), monocyte chemoattractant protein-1, and inducible nitric oxide synthase. The serum levels of TNF-α, IL-6, and nitric oxide were also significantly reduced in ME group compared to the HF group. Expression of hepatic miR-221 and miR-222, which increase in the inflammatory state of the liver, were also significantly inhibited in the ME group compared to the HF group. Conclusion: These results indicate that ME has the potential to improve hepatic lipid accumulation in high-fat diet-fed rats via modulation of inflammatory mediators and hepatic miR-221/222 expressions.

• Animal Bioscience
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• v.37 no.8
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• pp.1483-1494
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• 2024

Objective: This study was conducted to investigate the effect of slaughter age on carcass traits, meat quality, and the relative mRNA levels of lipid metabolism-related genes in different muscles of Taihang black goats. Methods: In this study, the triceps brachii (TB), longissimus dorsi (LD) and gluteus (GL) muscles of 15 grazing Taihang black goats slaughtered at the age of 2, 3, and 4 (designated as 2-year-old, 3-year-old, and 4-year-old, respectively) were collected. The differences in carcass shape, meat quality, amino acid composition and lipid metabolism gene expression among Taihang black goats of different ages and from different plant parts were compared. Results: Compared with goats at other ages, goats slaughtered at the age of 4 had greater live and carcass weights, meat weights, bone weights and skin areas (p<0.05). LD in the 4-years-old had the lowest cooking loss and moisture content. The crude protein content in the LD of 2-year-old was significantly greater than that in the other age group, and at the age of 2, the LD had the highest crude protein content than TB and GL. The highest fat content was in LD, followed by TB, for goats slaughtered at the age of 4. Eight out of 9 essential amino acids had higher content in the TB compared with other muscles, regardless of age. The total essential amino acid content was highest in the 4-year-old and lowest in the GL muscle at the age of 3. The sterol regulatory element-binding protein-1c (SREBP-1c) and adipose triglyceride lipase (ATGL) genes were significantly more abundant in the TB muscle than in the other muscles for goats slaughtered at the age of 2. At the age of 4, the ATGL and peroxisome proliferator-activated receptor γ (PPARγ) genes were significantly more abundant in the GL than in the LD, while the fatty acid synthase (FAS) genes were significantly less abundant in the GL than in the other muscles. Similarly, compared with those in goats of other ages, the relative mRNA expression levels of the FAS and heart-type fatty acid binding protein (H-FABP) genes in goats slaughtered at the age of 4 were the highest, and the relative mRNA expression of the PPARγ gene was the lowest (p<0.05). The relative mRNA expression of the H-FABP and FAS genes was positively correlated with the intramuscular fat (IMF) content, while the relative mRNA expression levels of the PPARγ and ATGL genes was negatively correlated with the IMF content. Conclusion: Overall, a better nutritional value was obtained for TB from 4-year-old goats, in which the total essential amino acid and fat contents were greater than those of other muscles. The comprehensive action of lipid metabolism genes was consistent with that of the IMF content, among which the FAS, H-FABP, PPARγ, and ATGL genes had positive and negative effects on the process of IMF deposition in Taihang black goats.