• Ocean and Polar Research
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• v.44 no.1
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• pp.29-38
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• 2022

Halophytes are plants that live in harsh environments in coastal regions and are known for their diverse chemical compositions. Limonium tetragonum, a halophyte endemic to Korean shores, is known for its bioactive compounds and is utilized in folk medicine. In this study L. tetragonum extract (LHE) was used to determine and evaluate its anti-osteoporotic properties. Pre-adipocyte and pre-osteoblasts were induced to differentiate along with LHE treatment, and their differentiation was evaluated using differentiation markers. LHE treatment decreased lipid accumulation in 3T3-L1 preadipocytes during adipogenesis. Results indicated that the LHE treatment also decreased the levels of key adipogenic transcription factors: PPARγ, SREBP1c, and C/EBPα. Enhancing osteoblastogenesis by LHE treatment was confirmed in osteoblastogenesis-induced MC3T3-E1 pre-osteoblasts. Cells treated with LHE resulted in increased calcification and alkaline phosphatase (ALP) activity compared with osteoblasts without LHE treatment. Pro-osteogenic and anti-adipogenic effects were also confirmed in D1 murine mesenchymal stromal cells which are capable of differentiation into both adipocytes and osteoblasts. LHE hindered adipogenesis and enhanced osteoblastogenesis in D1 MSCs in a similar fashion. In conclusion, L. tetragonum is believed to possess the potential to be utilized as a nutraceutical ingredient against osteoporotic conditions.

• Journal of Life Science
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• v.21 no.9
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• pp.1346-1353
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• 2011

Sophora tonkinensis Gapnep has been used as a traditional herbal medicine in oriental regions since ancient times. In this study, the effect and mechanism of the MeOH extract of Sophora tonkinensis Gapnep (STME) on adipocite differentiation and adipogenesis in 3T3-L1 preadipocites were investigated. Treatment with STME in the concentration range of 0-200 ${\mu}g$/ml significantly inhibited the differentiation of 3T3-L1 preadipocites in a dose-dependent manner, as determined by a decrease in intracellular lipid droplets and lipid contents measured by Oil Red O staining. In association with the inhibitory effect of lipid accumulation, the expressions of the proteins concerned with adipogenesis in 3T3-L1 preadipocites were also investigated. Treatment with STME reduced the expressions of peroxisome proliferator-activated receptor ${\gamma}$ (PPAR${\gamma}$), cytidine-cytidine-adenosine-adenosine-thymine (CCAAT)/enhancer-binding proteins ${\alpha}$ and ${\beta}$ (C/EBP${\alpha}$ and C/EBP${\beta}$) and sterol regulatory element binding protein (SREBP), which are adipocyte specific markers. In flow cytometry analysis, the inhibitory effect of differentiation was caused by G1 arrest and following mitotic clonal expansion cease. Therefore, we also investigated the alteration of G1 phase arrest-related proteins. As a result, the expression of p21 protein was significantly increased, while the expressions of Cdk2, E2F-1 and phospho-Rb were reduced in a dose-dependent manner in STME treated 3T3-L1 cells. According to these results, STME might inhibit differentiation through G1 arrest in 3T3-L1 preadipocytes adipogenesis, and further studies, which are in progress, have to be completed to identify the active compounds.

• Journal of Microbiology and Biotechnology
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• v.30 no.1
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• pp.21-30
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• 2020

Natural products are widely used due to their various biological activities which include anti-inflammatory, antioxidant, and anti-obesity effects. In this study, we determined the antioxidative and anti-obesity effects of Polygonum cuspidatum 50% ethanol extract (PEE). The antioxidative effect of PEE was evaluated using its radical scavenging activity, total phenolic content, and reducing power. The anti-obesity effect of PEE was investigated using 3T3-L1 adipocytes. The antioxidative activity of PEE was progressively increased in various concentrations, mainly due to the presence of phenolic compounds. PEE also alleviated lipid accumulation on 3T3-L1 adipocytes and downregulated the mRNA and protein production of adipogenesis-related (SREBP-1c, PPARγ, C/EBPα) and lipogenesis-related (aP2, FAS, ACC) markers. Furthermore, we found that the inhibitory effect on lipid accumulation via PEE was caused by the alleviation of NF-κB, p38 MAPK, ERK1/2, and JNK at the protein level. Taken together, our results imply that PEE is a potential antioxidant that can prevent obesity-associated disorders.

• Journal of Life Science
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• v.32 no.12
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• pp.979-988
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• 2022

Halophytes have been reported to possess a variety of physiological activities, such as anti-cancer, anti-oxidant, anti-diabetes, anti-inflammatory, and anti-obesity. Studies on the roots of the halophyte Rosa rugosa, in particular, have shown a variety of physiological activities and are known to be effective for nursing diabetic complications in traditional Korean medicine. In this study, the effect of R. rugosa on adipogenesis was investigated in 3T3-L1 pre-adipocytes treated with crude extract and solvent fractions (H₂O, n-BuOH, 85% aq. MeOH, and n-Hex) obtained from R. rugosa roots. Treatment with extract and the solvent fractions inhibited the formation of intracellular lipid droplets in differentiated 3T3-L1 adipocytes compared to the untreated group. In particular, n-BuOH and 85% aq. MeOH fractions effectively decreased the expression of adipogenic transcription factors: peroxisome proliferator activated receptor-γ (PPARγ), CCAAT/enhancer-binding protein α (C/EBPα), and sterol regulatory element-binding protein 1c (SREBP1c) in both mRNA and protein levels. In conclusion, these results suggest that R. rugosa contains anti-adipogenic molecules that can be utilized as a nutraceutical against obesity. Further refining of n-BuOH and 85% aq. MeOH fractions and analysis of their action mechanisms could yield potential therapeutic agents with anti-adipogenic effects.

• Food Science of Animal Resources
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• v.39 no.2
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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).

• Animal Bioscience
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• v.37 no.7
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• pp.1156-1167
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• 2024

Objective: MicroRNAs (miRNAs) are endogenous non-coding RNAs that can play a role in the post-transcriptional regulation of mammalian preadipocyte differentiation. However, the precise functional mechanism of its regulation of fat metabolism is not fully understood. Methods: We identified bta-miR-365-3p, which specifically targets the 3' untranslated region (3'UTR) of the FK506-binding protein 5 (FKBP5), and verified its mechanisms for regulating expression and involvement in adipogenesis. Results: In this study, we found that the overexpression of bta-miR-365-3p significantly decreased the lipid accumulation and triglyceride content in the adipocytes. Compared to inhibiting bta-miR-36 5-3p group, overexpression of bta-miR-365-3p can inhibit the expression of adipocyte differentiation-related genes C/EBPα and PPARγ. The dual-luciferase reporter system further validated the targeting relationship between bta-miR-365-3p and FKBP5. FKBP5 mRNA and protein expression were detected by quantitative real-time polymerase chain reaction and Western blot. Overexpression of bta-miR-365-3p significantly down-regulated FKBP5 expression, while inhibition of bta-miR-365-3p showed the opposite, indicating that bta-miR-365-3p negatively regulates FKBP5. Adenosine 5'-monophosphate (AMP)-activated protein kinase/mammalian target of rapamycin (AMPK/mTOR) signaling pathway is closely related to the regulation of cell growth and is involved in the development of bovine adipocytes. In this study, overexpression of bta-miR-365-3p significantly inhibited mRNA and protein expression of AMPK, mTOR, and SREBP1 genes, while the inhibition of bta-miR-365-3p expression was contrary to these results. Overexpression of FKBP5 significantly upregulated AMPK, mTOR, and SREBP1 gene expression, while inhibition of FKBP5 expression was contrary to the above experimental results. Conclusion: In conclusion, these results indicate that bta-miR-365-3p may be involved in the AMPK/mTOR signaling pathway in regulating Yanbian yellow cattle preadipocytes differentiation by targeting the FKBP5 gene.

• Food Science and Preservation
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• v.22 no.1
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• pp.27-35
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• 2015

Anti-obese effects of mulberry (Morus alba L.) root bark was investigated in vitro by measuring its inhibitory effect against 3T3-L1 preadipocyte differentiation and digestive enzymes such as ${\alpha}$-amylase, ${\alpha}$-glucosidase and pancreatic lipase. Ethanol extract of mulberry root bark (MRE) showed the potent inhibitory activities on ${\alpha}$-amylase, ${\alpha}$-glucosidase and pancreatic lipase with $IC_{50}$ values of $7.86{\pm}0.36$, $0.12{\pm}0.03$ and $7.93{\pm}0.11mg/mL$, respectively. Furthermore, MRE significantly suppressed cellular lipid accumulation in 3T3-L1 cells in a dose-dependent manner. To elucidate the mechanism of MRE, we performed qRT-PCR and Western blotting for the expression of genes related with adipogenesis and lipogenesis. Treatment of MRE markedly suppressed the protein expression of $PPAR{\gamma}$, $C/EBP{\alpha}$ and SREBP-1c, as well as FAS and ACC, which are the key transcription factors and metabolic enzymes in adipogenesis and lipogenesis. In addition, qRT-PCR analysis indicated that the anti-adipogenesis effect of MRE might be due to its inhibition at transcription levels. These results demonstrate that MRE can effectively suppress adipocyte differentiation and inhibit key enzymes related to obesity. Our findings suggest that mulberry root bark may have a potential benefit in preventing obesity.

• The Korean Journal of Physiology and Pharmacology
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• v.22 no.1
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• pp.23-33
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• 2018

Cushing's syndrome (CS) is a collection of symptoms caused by prolonged exposure to excess cortisol. Chronically elevated glucocorticoid (GC) levels contribute to hepatic steatosis. We hypothesized that histone deacetylase inhibitors (HDACi) could attenuate hepatic steatosis through glucocorticoid receptor (GR) acetylation in experimental CS. To induce CS, we administered adrenocorticotropic hormone (ACTH; 40 ng/kg/day) to Sprague-Dawley rats by subcutaneous infusion with osmotic mini-pumps. We administered the HDACi, sodium valproate (VPA; 0.71% w/v), in the drinking water. Treatment with the HDACi decreased steatosis and the expression of lipogenic genes in the livers of CS rats. The enrichment of GR at the promoters of the lipogenic genes, such as acetyl-CoA carboxylase (Acc), fatty acid synthase (Fasn), and sterol regulatory element binding protein 1c (Srebp1c), was markedly decreased by VPA. Pan-HDACi and an HDAC class I-specific inhibitor, but not an HDAC class II a-specific inhibitor, attenuated dexamethasone (DEX)-induced lipogenesis in HepG2 cells. The transcriptional activity of Fasn was decreased by pretreatment with VPA. In addition, pretreatment with VPA decreased DEX-induced binding of GR to the glucocorticoid response element (GRE). Treatment with VPA increased the acetylation of GR in ACTH-infused rats and DEX-induced HepG2 cells. Taken together, these results indicate that HDAC inhibition attenuates hepatic steatosis through GR acetylation in experimental CS.

• Journal of Microbiology and Biotechnology
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• v.31 no.7
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• pp.1011-1021
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• 2021

The root bark of Ulmus davidiana var. japonica (Japanese elm) is used in Korea and other East Asian countries as a traditional herbal remedy to treat a variety of inflammatory diseases and ailments such as edema, gastric cancer and mastitis. For this study, we investigated the lipid metabolism and anti-obesity efficacy of ethyl alcohol extract of Ulmus davidiana var. japonica root bark (UDE). First, HPLC was performed to quantify the level of (+)-catechin, the active ingredient of UDE. In the following experiments, cultured 3T3-L1 pre-adipocytes and high-fat diet (HFD)-fed murine model were studied for anti-obesity efficacy by testing the lipid metabolism effects of UDE and (+)-catechin. In the test using 3T3-L1 pre-adipocytes, treatment with UDE inhibited adipocyte differentiation and significantly reduced the production of adipogenic genes and transcription factors PPARγ, C/EBPα and SREBP-1c. HFD-fed, obese mice were administered with UDE (200 mg/kg per day) and (+)-catechin (30 mg/kg per day) by oral gavage for 4 weeks. Weight gain, epididymal and abdominal adipose tissue mass were significantly reduced, and a change in adipocyte size was observed in the UDE and (+)-catechin treatment groups compared to the untreated control group (^***p < 0.001). Significantly lower total cholesterol and triglyceride levels were detected in UDE-treated HFD mice compared to the control, revealing the efficacy of UDE. In addition, it was found that lipid accumulation in hepatocytes was also significantly reduced after administration of UDE. These results suggest that UDE has significant anti-obesity and lipid metabolism effects through inhibition of adipocyte differentiation and adipogenesis.

• Molecules and Cells
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• v.44 no.2
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• pp.116-125
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• 2021

Cardiovascular diseases (CVDs) are the most common cause of death in patients with nonalcoholic fatty liver disease (NAFLD) and dyslipidemia is considered at least partially responsible for the increased CVD risk in NAFLD patients. The aim of the present study is to understand how hepatic de novo lipogenesis influences hepatic cholesterol content as well as its effects on the plasma lipid levels. Hepatic lipogenesis was induced in mice by feeding a fat-free/high-sucrose (FF/HS) diet and the metabolic pathways associated with cholesterol were then analyzed. Both liver triglyceride and cholesterol contents were significantly increased in mice fed an FF/HS diet. Activation of fatty acid synthesis driven by the activation of sterol regulatory element binding protein (SREBP)-1c resulted in the increased liver triglycerides. The augmented cholesterol content in the liver could not be explained by an increased cholesterol synthesis, which was decreased by the FF/HS diet. HMG-CoA reductase protein level was decreased in mice fed an FF/HS diet. We found that the liver retained more cholesterol through a reduced excretion of bile acids, a reduced fecal cholesterol excretion, and an increased cholesterol uptake from plasma lipoproteins. Very low-density lipoproteintriglyceride and -cholesterol secretion were increased in mice fed an FF/HS diet, which led to hypertriglyceridemia and hypercholesterolemia in Ldlr-/- mice, a model that exhibits a more human like lipoprotein profile. These findings suggest that dietary cholesterol intake and cholesterol synthesis rates cannot only explain the hypercholesterolemia associated with NAFLD, and that the control of fatty acid synthesis should be considered for the management of dyslipidemia.