Objective : In this study, the anti-obesity effect of Fragaria orientalis (FO) on high-fat diet-induced obese mice was investigated. Drug treatment methods are widely used as obesity treatment methods, but research using various natural products is being conducted due to safety concerns. This study aims to evaluate the anti-obesity effect of FO extract, a natural product derived from Mongolia. Methods : C57BL/6 mice were used and divided into three groups, normal diet group, high-fat diet group, and high-fat diet with FO oral treatment group at a dose of 300 mg/kg. Extract was orally provided everyday for 6 weeks. Body Weight and food intake were measured every 2 days and blood lipid profiles and liver function in the sacrificed mice were evaluated. In addition, protein expression in hepatic tissue and histomorphological changes in liver and adipose tissue were observed. Results : Body weight, adipose tissue weight and FER were significantly lower in a high-fat diet with FO treatment than fed only high-fat diet. There was a significant difference between the high-fat diet and the FO-treated high-fat diet mice. As a result of analyzing lipid metabolism-related genes in hepatic tissue, all of p-AMPK, p-ACC, PPAR-α, CPT-1, and UCP-1 showed significant increases, and PPAR-γ also decreased significantly compared to the high-fat diet group. Conclusion : Overall, these results indicate that FO is effectual in improving obesity, suggesting that it can be used as a possible material for anti-obesity agents or functional supplements for weight control.
Obesity is a worldwide epidemic as well as being a major risk factor for diabetes, cardiovascular diseases and several types of cancers. Obesity is mainly due to the overgrowth of adipose tissue arising from an imbalance between energy intake and energy expenditure. Adipose tissue, primarily composed of adipocytes, plays a key role in maintaining whole body energy homeostasis. In view of the treatment of obesity and obesity-related diseases, it is critical to understand the detailed signal transduction mechanisms of adipogenic differentiation. Adipogenic differentiation is tightly regulated by many key signal cascades, including insulin signaling. These signal cascades generally transfer or amplify the signal by using serial tyrosine phosphorylations. Thus, protein tyrosine kinases and protein tyrosine phosphatases are closely related to adipogenic differentiation. Compared to protein tyrosine kinases, protein tyrosine phosphatases have received little attention in adipogenic differentiation. This review aims to highlight the involvement of protein tyrosine phosphatases in adipogenic differentiation and the possibility of protein tyrosine phosphatases as drugs to target obesity.
Resveratrol (RVT) and epigallocatechin gallate (EGCG) individually inhibit adipogenesis in 3T3-L1 adipocytes. The objective was to examine the possibility of interaction between RVT and EGCG, resulting in enhanced inhibition of adipogenesis in 3T3-L1 adipocytes. Preadipocytes were treated with RVT and EGCG individually at 6.25 or $25{\mu}M$ (RVT6.25 or RVT25) and 12.5 or $50{\mu}M$ (EGCG12.5 or EGCG50) and in combination (RVT6.25 + EGCG12.5 and RVT25 + EGCG50). RVT25 as an individual compound decreased lipid accumulation in 3T3-L1 adipocytes by 24%, and RVT25 + EGCG50 further decreased lipid accumulation by 77%. In addition, exposure of 3T3-L1 adipocytes to RVT6.25 + EGCG12.5 and RVT25 + EGCG50 combinations resulted in an enhanced increase of adiponectin release and inhibition of leptin release. Quantitative analysis revealed that the combination of tested materials (RVT6.25 + EGCG12.5 and RVT25 + EGCG50) decreased the expression levels of C/EBP${\alpha}$, PPAR${\gamma}2$, and aP2. These results indicate that the combined treatments with RVT and EGCG produce synergistic effects on inhibiting adipogenesis in 3T3-L1 adipocytes. The overall results suggested that the combining RVT and EGCG might be more capable of exerting antiobesity effects than each individual compound by itself.
Adipocytes are the main constituent of adipose tissue. Understanding the molecular basis of adipogenesis is pivotal to finding the therapeutic targets for treatment of obesity. Melatonin is associated with obesity and its mechanism is currently under intensive investigation. The objective of this study was to investigate the effect of melatonin on adipogenesis in differentiating preadipocytes. 3T3-L1 preadipocytes were cultured in Dulbecco's modified Eagle's medium (DMEM) containing 5% calf serum at 37℃ with 5% CO2 in a humidified incubator. Differentiation was induced using DMEM with 10% fetal bovine serum supplemented with MDI two days after cell confluence (day 0). Cells were treated with 0, 10 and 100 μM melatonin on either day 0 or day 5. 72 hours after each treatment, lipid accumulation was measured by oil red O staining. Proteins were resolved by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) and transferred to membranes. As a result, lipid accumulation decreased with melatonin treatment. ERK pathway, activated when differentiation is induced, also decreased with an increase in melatonin concentration. Furthermore, the expression of key adipogenic factors, C/EBPα, C/EBPβ, and PPARγ, were reduced by melatonin treatment. These results imply that melatonin may inhibit the process of adipogenesis and may have a role as a new anti-obesity agent.
Propyl gallate (PG) used as an additive in various foods has antioxidant and anti-inflammatory effects. Although the functional roles of PG in various cell types are well characterized, it is unknown whether PG has effect on stem cell differentiation. In this study, we demonstrated that PG could inhibit adipogenic differentiation in human adipose tissue-derived mesenchymal stem cells (hAMSCs) by decreasing the accumulation of intracellular lipid droplets. In addition, PG significantly reduced the expression of adipocyte-specific markers including peroxisome proliferator-activated receptor-${\gamma}$ (PPAR-${\gamma}$), CCAAT enhancer binding protein-${\alpha}$ (C/EBP-${\alpha}$), lipoprotein lipase (LPL), and adipocyte fatty acid-binding protein 2 (aP2). PG inhibited adipogenesis in hAMSCs through extracellular regulated kinase (ERK) pathway. Decreased adipogenesis following PG treatment was recovered in response to ERK blocking. Taken together, these results suggest a novel effect of PG on adipocyte differentiation in hAMSCs, supporting a negative role of ERK1/2 pathway in adipogenic differentiation.
Objectives : Ojeok-san (OJS), an oriental herbal formula, has been used in Asian countries including Korea, China and Japan to treat the common cold and illnesses including fatigue and gastrointestinal disorders. The purpose of this study was to examine the anti-obesity effect and molecular mechanism of OJS, on adipogenesis in 3T3-L1 cells. Also, the effects of OJS in obese mice fed a high-fat diet on adiposity were examined.Methods : Preferentially, we analyzed the component of OJS and measured the stability of its component in OJS according to study periods using high performance liquid chromatography (HPLC). In vitro, 3T3-L1 cells were treated with OJS (50 to 200 μg/mL) during differentiation for 8 days. The accumulation of lipid droplets was determined by Oil Red O staining. The expressions of genes related to adipogenesis were measured by RT-PCR and Western blot analyses. For anti-obesty effect in vivo, we experimented for 8 weeks with four group (normal diet (CON), high-fat diet (HF), high-fat diet with OJS (HF+OJS) and high-fat diet with Bang-pung-tong-sung-san (HF+BTS) in comparison group HF+OJS).Results : OJS showed inhibitory activity on adipocyte differentiation at 3T3-L1 preadipocytes without affect cell toxicity as assessed by measuring fat accumulation and adipogenesis. In addition, OJS significantly reduced the expression levels of several adipocyte marker genes including proliferator activated receptor-γ(PPAR-γ) and CCAAT/enhancer-binding protein-α(C/EBP-α). Also OJS-administered mice showed significant inhibitory of body weights and abdominal adipose tissue weights.Conclusions : This study showed that traditional medicine OJS has an anti-obesity effect in vitro and in vivo. Thus, OJS could be developed as a supplement for reduction of body weight gain induced by an obesity.
Purpose: Several studies have proven that EGCG, the primary green tea catechin, and glucosamine-6-phosphate (PGlc) reduce triglyceride contents in 3T3-L1 adipocytes. The objective of this study is to evaluate the combination effect of EGCG and PGlc on decline of accumulated fat in differentiated 3T3-L1 adipocytes. Methods: EGCG and PGlc were administered for 6 day for differentiation of 3T3-L1 adipocytes. Cell viability was measured using the CCK assay kit. In addition, TG accumulation in culture 3T3-L1 adipocytes was investigated by Oil Red O staining. We examined the expres-sion level of several genes and proteins associated with adipogenesis and lipolysis using real-time RT-PCR and Western blot analysis. A flow cytometer Calibar was used to assess the effect of EGCG and PGluco on cell-cycle progression of differentiating 3T3-L1 cells. Results: Intracelluar lipid accumulation was significantly decreased by combination treatment with EGCG $60{\mu}M$ and PGlc $200{\mu}g/m$ compared with control and EGCG treatment alone. In addition, use of combination treatment resulted in directly decreased expression of $PPAR{\gamma}$, $C/EBP{\alpha}$, and SREBP1. In addition, it inhibited adipocyte differentiation and adipogenesis through downstream regulation of adipogenic target genes such as FAS, ACSL1, and LPL, and the inhibitory action of EGCG and PGlc was found to inhibit the mitotic clonal expansion (MCE) process as evidenced by impaired cell cycle entry into S phase and the S to G2/M phase transition of confluent cells and levels of cell cycle regulating proteins such as cyclin A and CDK2. Conclusion: Combination treatment of EGCG and PGlc inhibited adipocyte differentiation through decreased expression of genes related to adipogenesis and adipogenic and cell cycle arrest in early stage of adipocyte differentiation.
Obesity is epidemic worldwide and has reportedly been linked to the progression of several metabolic and cardiovascular diseases. The natural products are decreasing the side effects of medicines used for obesity and also have health benefits dut to their numerous bioactive compounds. In this context, Artemisia scoparia is a widespread plant that has been suggested as possessing various types of bioactivity. In this study, the crude extract from A. scoparia (ASE) was tested for its ability to suppress adipogenesis in mouse 3T3-L1 pre-adipocytes. The molecular pathway by which ASE affects differentiation of 3T3-L1 cells was also investigated. The introduction of ASE to differentiating 3T3-L1 pre-adipocytes resulted in suppressed adipogenesis, as confirmed by decreased intracellular lipid accumulation. The differentiating cells treated with 10 and $100{\mu}g/ml$ of ASE showed 21.9 and 29.0% less lipid accumulation, respectively, than untreated adipocytes. In addition, the results indicated that ASE treatment lowered the expression of the adipogenesis-related factors $PPAR{\gamma}$, $C/EBP{\alpha}$, and SREBP-1c. Furthermore, treating with ASE notably decreased levels of phosphorylated p38, ERK, and JNK in 3T3-L1 adipocytes. These results indicate that ASE exhibits significant anti-adipogenesis activity by downregulating the MAPK and $PPAR{\gamma}$ pathways during the differentiation of 3T3-L1 pre-adipocytes. Therefore, A. scoparia may be a potential source of natural products against obesity.
Kim, Yae-Ji;Cho, Sung-Pil;Lee, Hui-Ju;Hong, Geum-Lan;Kim, Kyung-Hyun;Ryu, Si-Yun;Jung, Ju-Young
Journal of Korean Medicine for Obesity Research
/
v.22
no.1
/
pp.30-37
/
2022
Objectives: Adipogenesis is the process by which pre-adipocytes are differentiated into adipocytes. It also plays an important role in adipocyte formation and lipid accumulation. Ranunculus sceleratus (R. sceleratus) extracts are used for the treatment of various diseases such as hepatitis, jaundice, and tuberous lymphadenitis in oriental medicine. However, its effect on adipogenesis has not yet been studied. In this study, we investigated the effects of R. sceleratus on adipogenesis in 3T3-L1 cells. Methods: Cells were treated with 50, 100, and 200 ㎍/ml of R. sceleratus and cell viability was evaluated. To differentiate the 3T3-L1 preadipocytes, a 3-isobutyl-1-methylxanthine, dexamethasone, and insulin (MDI) solution were used. The accumulation of lipid droplets was determined by Oil Red O staining. The expression levels of adipogenesis-related proteins were also determined. Results: MDI solution differentiated the preadipocytes into adipocytes and accumulation of lipids was observed in the differentiated 3T3-L1 cells. Interestingly, the amount of lipid droplets was reduced after R. sceleratus treatment. In addition, the expression levels of key adipogenic transcription factors, such as CCAAT/enhancer-binding proteins-𝛼 (C/EBP-𝛼) and peroxisome proliferator-activated receptors-𝛾 (PPAR-𝛾) were also reduced after R. sceleratus treatment. Furthermore, R. sceleratus increased AMP-activated kinase (AMPK) phosphorylation and decreased sterol regulatory element-binding protein-1 expression. Conclusions: Our results showed that R. sceleratus reduced preadipocyte differentiation by inhibiting C/EBP-𝛼 and PPAR-𝛾 levels via the AMPK pathway. Therefore, we suggest that R. sceleratus may be potentially used as an anti-adipogenic agent.
Mi Suk Kim;Ji Yun Baek;Ye Jung Choi;Ki Sung Kang;Weon Taek Seo;Ji Hyun Kim;Hyun Young Kim
Journal of Applied Biological Chemistry
/
v.65
no.4
/
pp.313-319
/
2022
Consumption of high fat diet (HFD) induces obesity by accumulating triglycerides and inflammation in the body. In the present study, we investigated the effects of black onion vinegar (BV) on HFD-induced C57BL/6 obese mice model. The HFD-fed obese mice were administered black onion juice (BJ) and BV, respectively, for 6 weeks. The HFD-fed group increased body and organ weights compared with normal control diet-induced group. However, administration of BV significantly reduced body and organ weights compared with HFD-fed group. The BJ- and BV-administered groups improved the serum lipid profiles such as total cholesterol and triglyceride, compared with HFD-fed group. In addition, BV-administered group significantly improved serum high-density lipoprotein cholesterol and low-density lipoprotein cholesterol. The BV-administered mice had increased the number and size of adipose cells in the liver and adipose tissues. The administrations of BJ and BV significantly down-regulated adipogenesis transcription factors and proinflammatory proteins in the liver compared with HFD-fed group. In particular, BV-administered group showed stronger attenuation of adipogenesis-related proteins than the BJ-administered group. Therefore, this study demonstrated that administration of BV attenuated HFD-induced obesity, in particular down-regulation of adipogenesis, and it could be developed as a functional vinegar for anti-obesity.
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