Adipogenesis refers to the process of formation of adipose tissue. It is a multistep process starting with clonal expansion of mesenchymal cells and the Differentiation of these mesenchymal cells into Pre-Adipocytes and finally into mature Adipocytes .
Many phytochemicals and herbal extracts show Inhibitory effects on Adipogenesis in cell models and mouse models. However, lack of clinical evidence and epidemiological data to support their roles in Inhibiting Adipogenesis hindered their development to become an Anti-Obesity therapeutic agent. Furthermore, many of these phytochemicals have low bioavailability. Chemical structural modification or targeted delivery system may help to increase their Anti-Adipogenesis or Anti-Obesity efficacies. Nevertheless, many of these phytochemicals are abundantly found in our daily food, or they are the herbs for cooking or seasoning. For example, resveratrol is rich in red wine and grapes; genistein is rich in soy; quercetin in apples and onions, and curcumin is a well-known component of the cook seasoning. Therefore, a healthy diet can definitely help us to increase the uptake of these phytochemicals in our daily life. Moreover, combination of phytochemicals or herbal extracts may act synergistically to Inhibit Adipogenesis .
Indeed, Obesity is not simply an excess accumulation of white Adipose Tissue but is usually associated with insulin resistance and an increased production of metabolic hormones coupled with chronic low-grade state of Inflammation . To effectively Reduce Obesity , a holistic strategy with the consumption of phytochemicals or herbal extracts can be designed not only to Reduce Adipose Tissue Mass , but also increase thermogenic energy expenditure, improve insulin sensitivity, Reduce plasma lipids which can help to Reduce the Obesity -associated dyslipidemia and other comorbid conditions.
Obesity is a global health problem characterized as an increase in the Mass of Adipose Tissue . Adipogenesis is one of the key pathways that increases the Mass of Adipose Tissue , by which preAdipocyte s mature into Adipocytes through cell Differentiation . Peroxisome proliferator-activated receptor γ (PPARγ ), the chief regulator of Adipogenesis , has been acutely investigated as a molecular target for natural products in the development of anti-Obesity treatments. In this review, the regulation of PPARγ expression by natural products through Inhibition of CCAAT/enhancer-binding protein β (C/EBPβ) and the farnesoid X receptor (FXR), increased expression of GATA-2 and GATA-3 and activation of the Wnt/β-catenin pathway were analyzed. Furthermore, the regulation of PPARγ transcriptional activity associated with natural products through the antagonism of PPARγ and activation of Sirtuin 1 (Sirt1) and AMP-activated protein kinase (AMPK) were discussed. Lastly, regulation of mitogen-activated protein kinase (MAPK) by natural products, which might regulate both PPARγ expression and PPARγ transcriptional activity, was summarized. Understanding the role natural products play, as well as the mechanisms behind their regulation of PPARγ activity is critical for future research into their therapeutic potential for fighting Obesity .
Obesity has become a global epidemic in both developed and developing countries, and it is a significant risk factor for various diseases such as Diabetes , cancer, heart disease, and hypertension. In the present study, the effect of naturally occurring Antioxidants (Flavonoids and Phenolic Acids ) on the Inhibition of Adipogenesis in 3T3-L1 Adipocytes was investigated. The results showed that o-coumaric acid and rutin had the highest Inhibition on intracellular triglyceride (61.3 and 83.0%, respectively) among 15 Phenolic Acids and 6 Flavonoids tested. However, the oil red o stained material (OROSM) showed that cell number in 3T3-L1 Adipocytes was not influenced by those compounds. For glycerol-3-phosphate dehydrogenase (GPDH) activity, the data indicated that o-coumaric acid and rutin had the highest Inhibition on GPDH activity (54.2 and 66.8%, respectively) among the compounds tested. o-Coumaric acid and rutin also Inhibited the expression of PPARγ , C/EBPα and leptin and then up-regulated expression of adiponectin at the protein level. Some naturally occurring Antioxidants efficiently suppressed Adipogenesis in 3T3-L1 Adipocytes . These results suggest that o-coumaric acid and rutin targeted for Adipocyte functions could be effective in improving the symptoms of Metabolic Syndrome.
The anti-lipidaemic and anti-inflammatory effects of açai Polyphenols in 3T3-L1 mouse Adipocytes were investigated. Pre-Adipocytes were differentiated with and without açai-Polyphenols at concentrations of 2.5, 5 and 10 µg gallic acid equivalents (GAE)/mL. Results showed that açai Polyphenols Reduce the accumulation of intracellular lipids in differentiated Adipocytes in a dose-dependent manner and downregulated PPARγ 2. The gene-expression of Adipogenic transcription factors C/EBPα , C/ebpβ, Klf5 and Srebp1c was decreased. This was accompanied by a reduction of Adipogenic genes, including aP2, LPL, FATP1 and FAS, leptin and total PAI and an increase of adiponectin. Additionally, açai Polyphenols protected cells against the production of ROS and decreased the expression of mRNA and protein levels of pro-inflammatory cytokines when 3T3-L1 cells were challenged with TNF-α. Thus, these results indicate that açai Polyphenols may be useful in the prevention of Adipogenesis , oxidative stress and Inflammation .
Açai seed extract (ASE) exerts antiobesogenic effects.•ASE regulates lipogenic signaling pathways.•ASE is promising functional food ingredient for the management of Obesity .
Body Adiposity is an important risk factor for the development of chronic non-transmissible diseases. Studies on the process of Adipogenesis from ScienceDirect’s AI-generated Topic PagesAdipogenesis have been extensively performed in vivo and in vitro models to describe the molecular and cellular bases ofAdipose Tissue development and the effect of natural products in this process. The açai seed extract (ASE) has been evidenced as a potential regulator of bodyMass . In our work high-fat diet–fed mice treated with ASE (300 mg/Kg/d) (HFD-ASE) showed a lower adipose index (−32.63%, p < 0.001) than the high-fat diet–fed mice group (HFD) and theAdipocytes from the HFD group were considerably enlarged (p < 0.001) compared to those in the control group (CG) and HFD-ASE group (+175% and +123%, respectively). We also evaluated the effects of ASE on the modulation ofAdipogenesis in3T3-L1 cells. ASE exposure (25 and 100 μg/mL) led to a decrease of 26.6 (p < 0.05) in proliferation and alsoInhibitedpre-Adipocyte Differentiation through the decreasing expression (p < 0.05) of transcription factors andAdipogenic proteins such as PPARɣ, SREBP-1, and FAS. These results show that the ASEReduce Adipogenesis and suppress lipid accumulation in the in vivo model and in3T3-L1 Adipocytesand reinforce ASE as a potential strategy to modulateAdipogenesis .
The genus Acer contains several species with various bioactivities including antioxidant, antitumor and anti-inflammatory properties. However, Acer okamotoanum Nakai, one species within this genus has not been fully studied yet. Therefore, in this study, we investigated the Anti-Adipogenic activities of leaf extract from A. okamotoanum Nakai (LEAO) on 3T3-L1 preadipocytes . Adipogenesis is one of the cell Differentiation processes, which converts preadipocytes into mature Adipocytes . Nowadays, Inhibition of Adipogenesis is considered as an effective strategy in the field of Anti-Obesity research. In this study, we observed that LEAO decreased the accumulation of lipid droplets during Adipogenesis and down-regulated the expression of key Adipogenic transcription factors such as peroxisome proliferator-activated receptor γ (PPAR γ) and CCAAT/enhancer binding protein α (C/EBP α). In addition, LEAO inactivated PI3K/Akt signaling and its downstream factors that promote Adipogenesis by inducing the expression of PPAR γ. LEAO also activated β-catenin signaling, which prevents the Adipogenic program by suppressing the expression of PPAR γ. Therefore, we found that treatment with LEAO is effective for attenuating Adipogenesis in 3T3-L1 cells . Consequently, these findings suggest that LEAO has the potential to be used as a therapeutic agent for preventing Obesity .
The present study investigated the AntiObesity effect of Achyranthes bidentata Blume root water extract in a 3T3-L1 Adipocyte Differentiation model and rats fed with a high-fat diet. To investigate the effect of Achyranthes bidentata Blume on Adipogenesis in vitro, differentiating 3T3-L1 cells in Adipocyte -induction media were treated every two days with Achyranthes bidentata Blume at various concentrations (1 to 25 μg/mL) for eight days. We found that Achyranthes bidentata Blume root Inhibited 3T3-L1 Adipocyte Differentiation without affecting cell viability, and Western blot analysis revealed that phospho-Akt expression was markedly decreased, whereas there was no significant change in perilipin expression. Furthermore, administration of Achyranthes bidentataBlume root (0.5 g/kg body weight for six weeks) to rats fed with a high-fat diet significantly Reduced body Weight Gain without affecting food intake, and the level of triglyceride was significantly decreased when compared to those in rats fed with only a high-fat diet. These results suggest that Achyranthes bidentata Blume root water extract could have a beneficial effect on Inhibition of Adipogenesis and controlling body weight in rats fed with a high-fat diet.
Acorn (Quercus acutissima CARR.) is a nut from the Fagaceae family that has been used in traditional medicine for many years. However, shells from acorns are regarded as a by-product and are mostly discarded. Anti-Adipogenic activities of acorn shells were investigated using 3T3-L1 cells and methanol shell extracts (AE-M). AE-M demonstrated Cu2+-chelation activities and anti-oxidant activities via reduction of oxidative stress levels induced using AAPH. Six days after Adipocyte Differentiation , 50 and 100 μg/mL AE-M completely suppressed 3T3-L1 Adipogenesis and the Anti-Adipogenic effect was stronger than for the positive control 50 μM quercetin. Treatment with AE-M in 3T3-L1 cells Reduced mRNA expression levels of Adipogenic genes. AE-M-Inhibition was found in Pre-Adipogenic , early, and intermediate stages of Adipogenesis in 3T3-L1 cells . The Wnt/β-catenin signaling pathway is required for AE-M-Inhibition of 3T3-L1 Adipogenesis .
Adenanthin, a natural ent-kaurane diterpenoid extracted from the herb Isodon adenantha, has been reported to increase intracellular reactive oxygen species in leukemic and hepatocellular carcinoma cells. However, the function and mechanism of the compound in Adipogenesis and the development of Obesity is still unknown. In this study, we demonstrated that adenanthin Inhibited Adipogenesis of 3T3-L1 and mouse embryonic fibroblasts, and the underlying mechanism included two processes: a delayed mitotic clonal expansion via G0/G1 cell cycle arrest by Inhibiting the RB-E2F1 signaling pathway and a Reduced C/EBPβ signaling by Inhibiting the expression and activity of C/EBPβ during mitotic clonal expansion. Furthermore, adenanthin significantly Reduced the growing body weight and Adipose Tissue Mass during high-fat diet-inducing Obesity of mice, indicating the beneficial effects of adenanthin as a potential agent for prevention of Obesity .
In this work, we showed that adenanthin functioned its Anti-Adipogenic effect by increasing the intracellular ROS level during MCE and then affected two processes: (1) Inhibited the RB-E2F1 signaling pathway and results in a G0/G1 cell cycle arrest during MCE at the early stage of Adipocyte Differentiation ; (2) Reduced C/EBPβ transcriptional activity by Inhibiting the expression and activity of C/EBPβ during MCE. These results were in line with the Inhibitory effect of adenanthin on HFD-induced development of Obesity in mice.
ROS, oxygen-derived small molecules, react readily with various chemical structures including proteins, lipids, sugars, and nucleic acids [36]. In recent years, there has been an accumulating understanding of ROS as signaling molecules [37]. Most research groups now believe that a regulated basal level of ROS is necessary and advantageous for maintenance of cell functions, such as proliferation, Differentiation , and survival [38,39]. Increasing evidence has indicated that ROS plays a key role for Adipogenesis , but whether the increased ROS is positive or negative for Adipogenesis is still controversial. Some studies demonstrate that ROS promotes Adipocytes to differentiate [22,23], however, other studies show that ROS is indicated to Inhibit Adipocyte Differentiation by reducing the DNA-binding activity of C/EBPβ [24] and suppressing MCE [25]. Consistent with these findings [24,25], in our case, increased ROS Inhibited Adipogenesis , which was rescued by treatment of cells with adenanthin supplemented with H2O2 cleaner NAC (Figure 4). Furthermore, we exogenously treated cells with various doses of H2O2 (50 to 1200 μM) and found that lower doses (100, 200, and 400 μM) of H2O2 promoted 3T3-L1 Differentiation , whereas higher doses (800, 1000, and 1200 μM) of H2O2Inhibited 3T3-L1 Differentiation (Supplementary Figure S1a–c), implying that “positive” or “negative” roles of H2O2 relies on its level as previous report [26].
It is well known that Adipogenesis occurs in several stages and involves a cascade of transcription factors [40]. Our results showed that adenanthin functions in MCE (Figure 3 and Figure 4). When it was induced to Differentiation , growth-arrested 3T3-L1 preadipocytes synchronously re-enter the cell cycle and undergo MCE followed by expression of genes that produce the Adipocyte phenotype. MCE is a prerequisite for Differentiation of 3T3-L1 preadipocytes into Adipocytes [16]. Therefore, cell cycle regulation at the early stage of Adipogenesis has been considered as a strategy for modulating Adipogenesis [41]. Recently, many natural products have been reported to be Anti-Obesity agents that can Inhibit MCE of 3T3-L1 Adipocytes [41,42,43]. In our work, we found that adenanthin could attenuate cell cycle progression through a G0/G1 arrest during MCE by decreasing protein levels of the phosphorylation of RB, E2F1, Cyclin B1, and Cdk1 and modestly increased protein levels of P21 and P18 (Figure 3 and Figure 4d–f). As the cells cross the G1/S checkpoint, C/EBPβ acquires DNA-binding activity. Coincident with the acquisition of DNA-binding activity, C/EBPβ binds to centromeres through consensus C/EBP-binding sites in centromeric satellite DNA [15,20]. Consistent with a previous study [43], our results showed that adenanthin Inhibits the expression and activity of C/EBPβ during MCE (Figure 4b,c).
Finally, our results demonstrated that adenanthin Reduced the growing body weight and Adipose Tissue Mass during the early stage of induction of Obesity (Figure 5a–d). Moreover, to evaluate the safety of adenanthin, the serum of HFD fed mice after a 30-day exposure to adenanthin was collected and serum aspartate amino transferase (AST), alamine amino transferase (ALT), and creatinine levels between vehicle and adenanthin-treated mice were evaluated, and the results were not significantly changed (Supplementary Table S1). Whether adenanthin is active during the late stage of Obesity or has an Anti-Obesity effect is still unknown. In the future, we can monitor the activity of adenanthin during different stages of HFD-induced Obesity .
In summary, adenanthin, a natural ent-kaurane diterpenoid isolated from the herb Isodon adenantha in 1987 [27], was able to Inhibit Adipogenesis of 3T3-L1 and mouse embryonic fibroblasts (MEFs) through regulation of ROS and significantly Reduced the growing body weight and Adipose Tissue Mass during HFD-induced development of Obesity in mice, revealing adenanthin may be a potential agent for prevention of Obesity .
The AMP-activated protein kinase (AMPK) activator, 5-aminoimidazole-4-carboxamide ribonucleoside (AICAR), has been found to Inhibit the Differentiation of 3T3-L1 Adipocytes , if added at an early phase of Differentiation . AICAR blocks the expression of the late Adipogenic markers, fatty acid synthase and acetyl-CoA carboxylase, and of the transcription factors, C/EBPα and PPARγ . It also Inhibits early clonal expansion of Pre-Adipocytes , prevents the fall in C/EBPβ expression during the intermediate stage of Differentiation and Inhibits the late phase expression of CHOP-10, an antagonist of C/EBPβ. These data suggest a possible Inhibitory role for AMPK in the process of adipose Differentiation and suggest that AMPK might be a target to block Adipogenesis .
Obesity is one of the principal causative factors involved in the development of Metabolic Syndrome . AMP-activated protein kinase (AMPK) is an energy sensor that regulates cellular metabolism. The role of AMP-activated protein kinase in Adipocyte Differentiation is not completely understood, therefore, we examined the effect of 5-aminoimidazole-4-carboxamide-1-β-D-ribofuranoside (AICAR), a pharmacological activator of AMP-activated protein kinase (AMPK) on Adipocyte Differentiation in 3T3L1 cells and in a mouse D iet induced o besity (DIO) model.
Methods
To examine the effect of AICAR on Adipocyte Differentiation in 3T3L1 cells and in a mouse Diet i nduced o besity (DIO) model, 3T3L1 cells were differentiatied in the presence or absence of different concentration of AICAR and neutral lipid content and expression of various Adipocyte -specific transcription factors were examined. In vivo study, treated and untreated mice with AICAR (0.1–0.5 mg/g body weight) were fed high-fat diet (60% kcal% fat) to induce DIO and several parameters were studied.
Results
AICAR blocked Adipogenic conversion in 3T3L1 cells along with significant decrease in the neutral lipid content by downregulating several Adipocyte -specific transcription factors including peroxisome proliferators-activated receptor γ (PPARγ ), C/EBPα and ADD1/SREBP1, which are critical for Adipogenesis in vitro. Moreover, intraperitoneal administration of AICAR (0.5 mg g/body weight) to mice fed with high-fat diet (60% kcal% fat) to induce DIO, significantly blocked the body Weight Gain and total content of epididymal fat in these mice over a period of 6 weeks. AICAR treatment also restored normal adipokine levels and resulted in significant improvement in glucose tolerance and insulin sensitivity. The reduction in Adipose Tissue content in AICAR treated DIO mice was due to reduction in lipid accumulation in the pre-existing Adipocytes . However, no change was observed in the expression of PPARγ , C/EBPα and ADD1/SREBP1 transcription factors in vivo though PGC1α expression was significantly induced.
Conclusion
Our study demonstrates that AICAR treatment significantly attenuates adipoctye Differentiation in vitro. However, its administration restricted the body weight, epididymal fat content and normalized metabolic alteration mediated by diet induced Obesity in mice. Increase in phosphorylation of ACC and AMPKα during Adipocyte Differentiation and AMPK activity in epididymal Adipose Tissue in DIO mice raises doubts about the involvement of AMPK in this process.
This paper describes effects of several sulfur-containing compounds from garlic on the cell viability, apoptosis and Adipogenesis in 3T3-L1 Adipocytes . In both preadipocytes and mature Adipocytes , 100 and 200 microM ajoene significantly decreased cell viability and increased apoptosis. The effect on apoptosis was further confirmed with Hoechst staining. In contrast, diallyl sulfide, diallyl disulfide, diallyl trisulfide, deoxyalliin, and allyl methyl sulfide had no significant effect on cell viability or apoptosis in either preadipocytes or mature Adipocytes . In maturing preadipocytes ajoene significantly decreased lipid accumulation in a dose-dependent manner and these results were further confirmed by a decrease in lipid droplet number and lipid content through Oil Red O staining. There was no significant change in lipid accumulation in maturing preadipocytes treated with other garlic derivatives. Thus, despite the same source of origin, garlic, ajoene was the only one with potent effects on cell viability, apoptosis and Adipogenesis in 3T3-L1 Adipocytes .
Anti-Adipogenic and AntiDiabetic activities of Allium hookeri root water extracts (ARW) were assessed. Oil Red O staining showed that treatment with ARW caused a dose-dependent reduction in lipid accumulation. ARW was also involved in Adipocyte Lipolysis via LPL activity, and in the concentration of glycerol in a culture medium. On the basis of the concentration of adipokines following ARW treatment, ARW appeared to Inhibit expression of PPAR-γ, to Reduce concentrations of leptin and resistin, to increase the concentration of adiponectin, and to Inhibit lipid accumulation. ARW modulated adipokine expression associated with insulin resistance and sensitivity. 3T3-L1 Adipocytes treated with ARW showed increased GLUT-4 expression with increased glucose uptake into Adipocytes . ARW showed effectiveness for improvement of Diabetic conditions.
Allium hookeri (AH) is widely consumed as a herbal medicine. It possesses biological activity against metabolic diseases. The objective of this study was to investigate effects of AH root water extract (AHR) on Adipogenesis in 3T3-L1 cells and in high-fat diet (HFD)-induced obese mice. AHR Inhibited lipid accumulation during Adipocyte Differentiation by downregulation of gene expression, such as hormone sensitive lipase (HSL), lipoprotein lipase (LPL) and an Adipogenic gene, CCAAT/enhancer binding protein-α in 3T3-L1 preadipocytes . Oral administration of AHR significantly suppressed body Weight Gain , Adipose Tissue weight, serum leptin levels, and Adipocyte cell size in HFD-induced obese mice. Moreover, AHR significantly decreased hepatic mRNA expression levels of cholesterol synthesis genes, such as 3-hydroxy-3-methylglutaryl CoA reductase, sterol regulatory element-binding transcription factor (SREBP)-2, and low-density lipoprotein receptor, as well as fatty acid synthesis genes, such as SREBP-1c and fatty acid synthase. Serum triglyceride levels were also lowered by AHR, likely as a result of the upregulating gene involved in fatty acid β-oxidation, carnitine palmitoyltransferase 1a, in the liver. AHR treatment activated gene expression of peroxisome proliferator-activated receptor-γ, which might have promoted HSL and LPL-medicated Lipolysis , thereby reducing white Adipose Tissue weight. In conclusion, AHR treatment can improve metabolic alterations induced by HFD in mice by modifying expression levels of genes involved in Adipogenesis , lipogenesis, and Lipolysis in the white Adipose Tissue and liver. View Full-Text
Allium hookeri has been widely cultivated and used as a vegetable and medicine in Asia, but its Anti-Obesity effects have not been previously reported. In this study, the effects of a leaf extract of A. hookeri on Obesity were investigated by administering a high-fat diet (HFD) to mice. Male Institute of Cancer Research mice (n = 32; 5 weeks old) were randomly divided into four groups: normal-diet group, HFD group, HFD containing 200 mg/kg/day A. hookeri leaf extract (HFD-A1), and HFD containing 400 mg/kg/day A. hookeri leaf extract (HFD-A2). A. hookeri leaf extract was orally administered daily for 4 weeks. We found that the body Weight Gain and organ tissue weights of mice in the HFD-A1 and HFD-A2 groups were significantly lower compared with those of mice in the HFD group. Administration of A. hookeri leaf extract also significantly decreased the size of the epididymal Adipose Tissue (AT). Serum levels of triglyceride (TG), total cholesterol, low-density lipoprotein cholesterol, and the atherogenic index were significantly lower in the HFD-A1 and HFD-A2 groups than in the HFD group. The TG and total cholesterol levels in the hepatic, epididymal, and mesenteric ATs of the HFD-A2 group were significantly lower than the levels in the HFD group. In addition, mRNA levels of liver fatty acid synthase and lipoprotein lipase were decreased in the A. hookeri leaf extract groups compared with those of the HFD group. These results demonstrate that intake of A. hookeri leaf may have beneficial effects for suppressing Obesity -related disease.
•Andrographolide attenuates ERK and GSK3β-dependent C/EBPβ activation.
•Andrographolide arrests 3 T3-L1 Adipocytes at G0/G1 phase.
Andrographolide,a diterpenoid, is the most abundant terpenoid in Andrographis paniculata, a popular Chinese herbal medicine. Andrographolide displays diverse biological activities including hypoglycemia, hypolipidemia, anti-Inflammation , and anti-tumorigenesis. Recent evidence indicates that andrographolide displays Anti-Obesity property by Inhibiting lipogenic gene expression, however, the underlying mechanisms remain to be elucidated. In this study, the effects of andrographolide on transcription factor cascade and mitotic clonal expansion in 3T3-L1 Preadipocyte Differentiation into Adipocyte were determined. Andrographolide dose-dependently (0–15 μM) Inhibited CCAAT/enhancer-binding protein α (C/EBPα ) and C/EBPβ mRNA and protein expression as well as peroxisome proliferator-activated receptor γ (PPARγ ) protein level during the Adipogenesis of 3T3-L1 cells . Concomitantly, fatty acid synthase and stearoyl-CoA desaturase expression and lipid accumulation were attenuated by andrographolide. Oil-red O staining further showed that the first 48 h after the initiation of Differentiation was critical for andrographolide Inhibition of Adipocyte formation. Andrographolide Inhibited the phosphorylation of PKA and the activation of cAMP response element-binding protein (CREB) in response to a Differentiation cocktail, which led to attenuated C/EBPβ expression. In addition, ERK and GSK3β-dependent C/EBPβ phosphorylation was attenuated by andrographolide. Moreover, andrographolide suppressed cyclin A, cyclin E, and CDK2 expression and impaired the progression of mitotic clonal expansion (MCE) by arresting the cell cycle at the Go/G1 phase. Taken together, these results indicate that andrographolide has a potent Anti-Obesity action by Inhibiting PKA-CREB-mediated C/EBPβ expression as well as C/EBPβ transcriptional activity, which halts MCE progression and attenuates C/EBPα and PPARγ expression.
Obesity is defined as the accumulation of excess Adipose Tissue resulting from various metabolic disorders. Adipocyte dysfunction is strongly associated with the development of Obesity and insulin resistance. Metabolic Syndrome is characterized by a group of metabolic risk factors in one person. Abdominal Obesity and Adipocyte dysfunction play an important role in the development of this syndrome. Anthocyanins are used as a food coloring, and they are widely distributed in human diets including berries, suggesting that large amounts of Anthocyanins are ingested from plant-based foods. This study shows that Anthocyanins have a significant potency of AntiObesity and ameliorate Adipocyte function in in vitro and in vivo systems and also that they have important implications for preventing Metabolic Syndrome .
Anthocyanins have been shown to suppress body weight and fat Mass in animal studies. However, the effect of Anthocyanins on the process of lipid accumulation during Adipocyte Differentiation is not fully understood and the lipogenic transcription factors regulated by Anthocyanins have not been identified. We investigated the effects of Anthocyanins on lipogenesis pathways during Adipocyte Differentiation in 3T3-L1 cells . Anthocyanins Reduced triglyceride (TG) accumulation in a dose-dependent manner during Adipocyte Differentiation . Accumulation of TG was rapidly reversed by anthocyanin withdrawal. Anthocyanins markedly Reduced gene and protein expression levels of lipogenic transcription factors such as liver X receptor α, sterol regulatory element-binding protein-1c, peroxisome proliferators-activated receptor-γ, and CCAAT enhancer-binding protein-α. In addition, the target gene and protein expression of these lipogenic transcription factors such as fatty acid synthase, stearoyl-CoA desaturase-1, and acetyl-CoA carboxylase α were markedly suppressed by Anthocyanins . Thus, Anthocyanins suppress lipid accumulation in Adipocytes due to broad Inhibition of the transcription factors regulating lipogenesis. This may partially explain the mechanism by which Anthocyanins exert their Anti-Obesity effect.
Antofine (ANTF) is a phenanthroindolizidine alkaloid isolated from the root of Cynanchum paniculatum Kitagawa (Asclepiadaceae), which is used as an herbal remedy for pain and Inflammation . ANTF also possesses antiviral and antitumorigenic activities. In this study, we investigated the role of ANTF in Adipogenesis . Chronic ABTF administration suppressed Adipocyte Differentiation and marker expression in a dose-dependent manner. Furthermore, acute administration of ANTF at early stages of Differentiation process Inhibited lipid droplet formation and Adipogenic gene expression. ANTF Treatment decreased expression of PPARγ protein, a master transcription factor in the regulation of Adipocyte Differentiation , leading to a suppression of aP2 promoter activity. These results suggest that ANTF exerts potent Anti-Adipogenic effects via direct suppression of PPARγ protein expression, with consequent downregulation of Adipogenic gene expression.
•Antrodia cinnamomea (AC) has been used as a natural dietary supplement for health promotion.
•AC prevents high fat diet-induced Obesity in vivo.
•AC Inhibits Adipogenesis and mitotic clonal expansion in vitro.
•AC has potential applications to treat Obesity , insulin resistance and hepatic steatosis.
This study examined the Anti-Obesity and Anti-Adipogenic effects of Antrodia cinnamomea. Oral administration of aqueous extract of A. cinnamomea (ACW) significantly Reduced high-fat diet-induced body Weight Gain and relative perirenal and mesenteric fat weight in C57BL/6J mice. Administration of ACW significantly Reduced serum insulin, leptin, aspartate aminotransferase levels, HOMA-IR index, and hepatic cholesterol and triacylglycerol levels. Next, investigation of whether ACW and its polysaccharides (PS) and non-polysaccharides (NPS) subfractions possess Anti-Adipogenic action was conducted. Evidence showed that ACW, PS and NPS significantly Inhibited lipid deposits in 3T3-L1 Adipocytes . Both ACW and NPS significantly Inhibited mitotic clonal expansion process of Adipocyte Differentiation . ACW and NPS also significantly decreased the expressions of PPARγ , C/EBPα , aP2 and FAS genes, while PS markedly Inhibited PPARγ and aP2 gene expression. Our data indicated that ACW Inhibits Preadipocyte Differentiation and Adipogenesis . These results suggested that ACW may have therapeutic potential for Obesity and related metabolic disorders.
Apigetrin, a flavonoid found in many plant leaves and seeds, has been known to possess antimutagenic, anti-cancer, antioxidant and anti-inflammatory properties. Here, we are investigating the effect of the apigetrin on Adipocytes Differentiation in 3T3-L1 Adipocytes , and elucidating the mechanism of its action.
Methods
Lipids accumulation was measured by Oil Red O staining and cell cycle was analyzed by flow cytometry. The antioxidant effect of apigetrin was evaluated against hydrogen peroxide. The expression of various genes, involved in Adipogenesis and Inflammation , was studied by real-time PCR.
Results
Our results showed that apigterin treatment Inhibited significantly lipid accumulation without effect on cell viability at 100 μM, and it exerted the Anti-Adipogenic effect during the early stages of Differentiation . Flow cytometry analysis showed that apigenin-7-O-glucoside (Ap7G) Inhibited cell proliferation during mitotic clonal expansion and caused cell cycle delay. Quantitative PCR analysis revealed that the mRNA levels of C/EBP-α, PPAR-γ, SREBP-1c and FAS were suppressed after apigetrin treatment at 100 μM. Moreover, the mRNA level of pro-inflammatory genes (TNF-α and IL-6) were suppressed after apigterin treatment, at high concentration Preadipocyte cells.
Conclusion
Taken together, these results indicated that apigenin-7-O-glucoside Inhibits Adipogenesis of 3T3-L1 preadipocytes at early stage of Adipogenesis .
Although arctigenin (ARC) has been reported to have some pharmacological effects such as anti‐Inflammation , anti‐cancer, and antioxidant, there have been no reports on the anti‐Obesity effect of ARC. The aim of this study is to investigate whether ARC has an anti‐Obesity effect and mediates the AMP‐activated protein kinase (AMPK) pathway. We investigated the anti‐Adipogenic effect of ARC using 3T3‐L1 pre‐Adipocytes and human Adipose Tissue ‐derived mesenchymal stem cells (hAMSCs). In high‐fat diet (HFD)‐induced obese mice, whether ARC can Inhibit Weight Gain was investigated. We found that ARC Reduced Weight Gain , fat pad weight, and triglycerides in HFD‐induced obese mice. ARC also Inhibited the expression of peroxisome proliferator‐activated receptor gamma (PPARγ ) and CCAAT/enhancer‐binding protein alpha (C/EBPα ) in in vitro and in vivo. Furthermore, ARC induced the AMPK activation resulting in down‐modulation of Adipogenesis ‐related factors including PPARγ , C/EBPα , fatty acid synthase, Adipocyte fatty acid‐binding protein, and lipoprotein lipase. This study demonstrates that ARC can Reduce key Adipogenic factors by activating the AMPK in vitro and in vivo and suggests a therapeutic implication of ARC for Obesity treatment.
The purpose of this study was to examine the effects and associated mechanisms of arctiin, a lignan compound found in burdock, on Adipogenesis in 3T3-L1 cells . Also, the effects of arctiin supplementation in obese mice fed a high-fat diet on Adiposity were examined.
MATERIALS/METHODS
3T3-L1 cells were treated with arctiin (12.5 to 100 µM) during Differentiation for 8 days. The accumulation of lipid droplets was determined by Oil Red O staining and intracellular triglyceride contents. The expressions of genes related to Adipogenesis were measured by real-time RT-PCR and Western blot analyses. For in vivo study, C57BL/6J mice were first fed either a control diet (CON) or high-fat diet (HF) to induce Obesity , and then fed CON, HF, or HF with 500 mg/kg BW arctiin (HF + AC) for four weeks.
RESULTS
Arctiin treatment to 3T3-L1 Pre-Adipocytes markedly decreased Adipogenesis in a dose-dependent manner. The arctiin treatment significantly decreased the protein levels of the key Adipogenic regulators PPARγ and C/EBPα , and also significantly Inhibited the expression of SREBP-1c, fatty acid synthase, fatty acid-binding protein and lipoprotein lipase. Also, arctiin greatly increased the phosphorylation of AMP-activated protein kinase (AMPK) and its downstream target phosphorylated-acetyl CoA carboxylase. Furthermore, administration of arctiin significantly decreased the body weight in obese mice fed with the high-fat diet. The epididymal, perirenal or total visceral Adipose Tissue weights of mice were all significantly lower in the HF + AC than in the HF. Arctiin administration also decreased the sizes of lipid droplets in the epididymal Adipose Tissue .
CONCLUSIONS
Arctiin Inhibited Adipogenesis in 3T3-L1 Adipocytes through the Inhibition of PPARγ and C/EBPα and the activation of AMPK signaling pathways. These findings suggest that arctiin has a potential benefit in preventing Obesity .
Aristolochia manshuriensis Kom (AMK) is a traditional medicinal herb used for the treatment of arthritis, rheumatism, hepatitis, and Anti-Obesity . Because of nephrotoxicity and carcinogenicity of AMK, there are no pharmacological reports on Anti-Obesity potential of AMK. Here, we showed AMK has an Inhibitory effect on Adipocyte Differentiation of 3T3-L1 cells along with significantly decrease in the lipid accumulation by downregulating several Adipocyte -specific transcription factors including peroxisome proliferation-activity receptor γ (PPAR-γ), CCAAT/enhancer binding protein α (C/EBP-α) and C/EBP-β, which are critical for Adipogenesis in vitro. AMK also markedly activated the extracellular signal-regulated protein kinase 1/2 (ERK1/2) pathway including Ras, Raf1, and mitogen-activated protein kinase kinase 1 (MEK1), and significantly suppressed Akt pathway by Inhibition of phosphoinositide-dependent kinase 1 (PDK1). Aristolochic acid (AA) and ethyl acetate (EtOAc) fraction of AMK with AA were significantly Inhibited TG accumulation, and regulated two pathway (ERK1/2 and Akt) during Adipocyte Differentiation , and was not due to its cytotoxicity. These two pathways were upstream of PPAR-γ and C/EBPα in the Adipogenesis . In addition, gene expressions of secreting factors such as fatty acid synthase (FAS), adiponectin, lipopreotein lipase (LPL), and aP2 were significantly Inhibited by treatment of AMK during Adipogenesis . We used the high-fat diet (HFD)-induced Obesity mouse model to determine the Inhibitory effects of AMK on Obesity . Oral administration of AMK (62.5 mg/kg/day) significantly decreased the fat tissue weight, total cholesterol (TC), and low density lipoprotein-cholesterol (LDL-C) concentration in the blood. The results of this study suggested that AMK Inhibited lipid accumulation by the down-regulation of the major transcription factors of the adipogensis pathway including PPAR-γ and C/EBP-α through regulation of Akt pathway and ERK 1/2 pathway in 3T3-L1 Adipocytes and HFD-induced Obesity mice, and AA may be main act in Inhibitory effects of AMK during Adipocyte Differentiation .
Aristolochia manshuriensis Kom is a traditional medicinal herb used for treatment of arthritis, rheumatism, hepatitis. Its extract Inhibited Adipocyte Differentiation by regulating ERK1/2 and Akt pathway. Besides, expressions of FAS, LPL and aP2 were significantly Reduced by the extract treatment during Adipogenesis
