Inhibits Adipocyte Differentiation Research Articles

Citrullus mucosospermus Extract Reduces Weight Gain in Mice Fed a High-Fat Diet.

This study aimed to investigate the therapeutic potential of Citrullus mucosospermus extract (CME) in counteracting adipogenesis and its associated metabolic disturbances in murine models. In vitro experiments utilizing 3T3-L1 preadipocytes revealed that CME potently inhibited adipocyte differentiation, as evidenced by a dose-dependent reduction in lipid droplet formation. Remarkably, CME also attenuated glucose uptake and intracellular triglyceride accumulation in fully differentiated adipocytes, suggesting its ability to modulate metabolic pathways in mature adipose cells. Translating these findings to an in vivo setting, we evaluated the effects of CME in C57BL/6N mice fed a high-fat diet (HFD) for 10 weeks. CME administration, concomitantly with the HFD, resulted in a significant attenuation of body weight gain compared to the HFD control group. Furthermore, CME treatment led to substantial reductions in liver weight, total fat mass, and deposits of visceral and retroperitoneal adipose tissue, underscoring its targeted impact on adipose expansion. Histological analyses revealed the remarkable effects of CME on hepatic steatosis. While the HFD group exhibited severe lipid accumulation within liver lobules, CME dose-dependently mitigated this pathology, with the highest dose virtually abolishing hepatic fat deposition. An examination of adipose tissue revealed a progressive reduction in adipocyte hypertrophy upon CME treatment, culminating in a near-normalization of adipocyte morphology at the highest dose. Notably, CME exhibited potent anti-inflammatory properties, significantly attenuating the upregulation of pro-inflammatory cytokines' mRNA levels (TNF-α, IL-1β and IL-6) in the livers of HFD-fed mice. This suggests a potential mechanism through which CME may exert protective effects against inflammation associated with obesity and fatty liver disease.

Effects of dietary seaweed on obesity-related metabolic status: a systematic review and meta-analysis of randomized controlled trials.

Seaweed is a promising source of anti-obesity agents, including polysaccharides, proteins, polyphenols, carotenoids, and n-3 long-chain polyunsaturated fatty acids. The anti-obesity effects of such compounds may be due to several mechanisms, including inhibition of lipid absorption and metabolism, effect on satiety, and inhibition of adipocyte differentiation. The aim of this study was to assess the evidence from human randomized controlled trials for the effects of seaweed on body-weight status as well as lipid and nonlipid parameters in adults with overweight and obesity. Four databases-Medline, Scopus, Web of Science, and Cochrane Library-were searched from December 2022 to June 2023 using the following key words: Seaweed OR fucoxanthin OR alginates OR fucoidans OR phlorotannin's OR macroalgae OR marine algae AND obesity OR overweight OR BMI OR body mass index. Eleven interventional studies (10 parallel and 1 crossover) were extracted. Meta-analysis showed a significant effect, favoring the intervention group for BMI (body mass index) (standardized mean difference [SMD]: -0.40; 95% CI: -0.65 to -0.16 kg/m2; P = 0.0013) and percentage of fat mass (SMD: -1.48; 95% CI: -2.66% to -0.30%, P = 0.0138). The results were seen when refined or extracted brown seaweed (BMI) or only refined brown seaweed (% fat mass) were administered to participants for at least 8 weeks. Moreover, a significant overall effect of seaweed supplementation on total cholesterol (SMD: -7.72; 95% CI: -12.49 to -2.95 mg/dL; P = 0.0015) and low-density-lipoprotein cholesterol (SMD: -7.33; 95% CI: -11.64 to -3.02 mg/dL; P < 0.001) was noted. Any significant effects of seaweed on glucose metabolism were not shown. Edible seaweed supplementation shows potential for managing obesity and disorders of the blood lipid profile when administered to participants for at least 8 weeks. PROSPERO registration no. CRD42022378484 (www.crd.york.ac.uk/PROSPERO).

Insulin Sensitivity of Adipocytes is Improved by Pomegranate Mesocarp Through Reduced Oxidative Stress and Inflammation

Objective Inflammatory phenomena and increase in oxidative stress in cell physiopathology progression render therapeutic strategies based on nutritional antioxidants necessary. It was thus aimed at assessing the effectiveness of the pomegranate mesocarp extract (PME) on differentiation of preadipocytes to adipocytes in the presence/absence of hydrogen peroxide (H2O2), a model mimicking insulin resistance. Method The effect of PME on lipid accumulation, protein expression of antioxidant, inflammatory and adipogenic biomarkers, reactive oxygen species production, activity of antioxidant enzymes and secretion of IL-6 has been evaluated during the differentiation of preadipocytes to adipocytes, in the presence or absence of H2O2. Results H2O2 reduced the expression of the regulator of insulin sensitivity PPARγ and suppressed adipocyte differentiation. PME counteracted the effect of H2O2. The latter induced a higher level of fat accumulation by promoting the expressions of the adipogenic markers PPARγ, C/EBPα, FABP4 and CD36 as compared to the control and the H2O2-treated differentiating cells. During the progression of adipogenesis, highest increase (p < 0.05) in IL-6 secretion, by 3.16 and 3.85 folds, was observed on day 2 of differentiation in control and H2O2-treated cells, respectively, compared to day 0. PME significantly decreased (p < 0.01) the secretion of the cytokine in addition to suppressing the expression of NFκB. PME also prevented the reduction of superoxide dismutase, catalase and glutathione peroxidase activities that occurred during adipogenesis, by at most 33%, 119% and 42%, respectively. Conclusion These findings indicate that PME efficiently improves insulin sensitivity and can significantly counteract oxidative stress and inflammation.

S-Dihydrodaidzein and 3-(1,3-benzoxazol-2-yl)-benzamide, Two New Potential β-estrogen Receptor Ligands with Anti-adipogenic Activity.

The elucidation of molecular pathways associated with adipogenesis has evidenced the relevance of estrogen and estrogen receptor beta (ERβ). The positive effects of ERβ ligands on adipogenesis, energy expenditure, lipolysis, food intake, and weight loss, make ERβ an attractive target for obesity control. From ligand-based virtual screening, molecular docking, and molecular dynamic simulations, six new likely ERβ ligands (C1 to C6) have been reported with potential for pharmacological obesity treatment. In this study, the effect of molecules C1-C6 on adipogenesis using the murine 3T3-L1 cell line was evaluated. Cell viability was assessed by MTT assays. Lipid accumulation and gene expression were investigated by ORO staining and real-time quantitative RT-PCR experiments, respectively. Cell viability was not significantly affected by C1-C6 at concentrations up to 10 μM. Interestingly, treatment with 10 μM of C1 (S-Dihydrodaidzein) and C2 (3-(1,3-benzoxazol-2-yl)- benzamide) for 72 h inhibited adipocyte differentiation; moreover, ORO staining evidenced a reduced intracellular lipid accumulation (40% at day 7). Consistently, mRNA expression of the adipogenic markers, PPARγ and C/EBPα, was reduced by 50% and 82%, respectively, in the case of C1, and by 83% and 59%, in the case of C2. Altogether, these results show the two new potential β-estrogen receptor ligands, C1 and C2, to exhibit anti-adipogenic activity. They could further be used as lead structures for the development of more efficient drugs for obesity control.

Sesamolin suppresses adipocyte differentiation through Keap1-dependent Nrf2 activation in adipocytes

Sesamolin, a lignan isolated from sesame oils, has been found to possess neuroprotective, anticancer, and free radical scavenging properties. We hypothesized that sesamolin could stimulate the activity of nuclear factor erythroid-derived 2-like 2 (Nrf2) and inhibit adipocyte differentiation of preadipocytes. The objective of this study was to investigate effects of sesamolin on adipocyte differentiation and its underlying molecular mechanisms. In this study, we determined the effects of treatment with 25 to 100 µM sesamolin on adipogenesis in cell culture systems. Sesamolin inhibited lipid accumulation and suppressed the expression of adipocyte markers during adipocyte differentiation of C3H10T1/2, 3T3-L1, and primary preadipocytes. Mechanism studies revealed that sesamolin increased Nrf2 protein expression without inducing its mRNA, leading to an increase in the expression of Nrf2 target genes such as heme oxygenase 1 and NAD(P)H:quinone oxidoreductase 1 (Nqo1) in C3H10T1/2 adipocytes and mouse embryonic fibroblasts. These effects were significantly attenuated in Nrf2 knockout (KO) mouse embryonic fibroblasts, indicating that effects of sesamolin were dependent on Nrf2. In H1299 human lung cancer cells with KO of Kelch like-ECH-associated protein 1 (Keap1), a negative regulator of Nrf2, sesamolin failed to further increase Nrf2 protein expression. However, upon reexpressing Keap1 in Keap1 KO cells, the ability of sesamolin to elevate Nrf2 protein expression was restored, highlighting the crucial role of Keap1 in sesamolin-induced Nrf2 activation. Taken together, these findings show that sesamolin can inhibit adipocyte differentiation through Keap1-mediated Nrf2 activation.

Isoeugenol Inhibits Adipogenesis in 3T3-L1 Preadipocytes with Impaired Mitotic Clonal Expansion.

Isoeugenol (IEG), a natural component of clove oil, possesses antioxidant, anti-inflammatory, and antibacterial properties. However, the effects of IEG on adipogenesis have not yet been elucidated. Here, we showed that IEG blocks adipogenesis in 3T3-L1 cells at an early stage. IEG inhibits lipid accumulation in adipocytes in a concentration-dependent manner and reduces the expression of mature adipocyte-related factors including PPARγ, C/EBPα, and FABP4. IEG treatment at different stages of adipogenesis showed that IEG inhibited adipocyte differentiation by suppressing the early stage, as confirmed by lipid accumulation and adipocyte-related biomarkers. The early stage stimulates growth-arrested preadipocytes to enter mitotic clonal expansion (MCE) and initiates their differentiation into adipocytes by regulating cell cycle-related factors. IEG arrested 3T3-L1 preadipocytes in the G0/G1 phase of the cell cycle and attenuated cell cycle-related factors including cyclinD1, CDK6, CDK2, and cyclinB1 during the MCE stage. Furthermore, IEG suppresses reactive oxygen species (ROS) production during MCE and inhibits ROS-related antioxidant enzymes, including superoxide dismutase1 (SOD1) and catalase. The expression of cell proliferation-related biomarkers, including pAKT and pERK1/2, was attenuated by the IEG treatment of 3T3-L1 preadipocytes. These findings suggest that it is a potential therapeutic agent for the treatment of obesity.

The Impact of FBN1-α5β1 Axis in Fibro/Adipogenic Progenitor Cells (FAPCD9-) on Intramuscular Fat Content in Pigs.

Intramuscular fat (IMF) plays a crucial role in enhancing meat quality, enriching meat flavor, and overall improving palatability. In this study, Single-cell RNA sequencing was employed to analyze the longissimus dorsi (LD) obtained from Guangdong small-ear spotted pigs (GDSS, with high IMF) and Yorkshire pigs (YK, with low IMF). GDSS had significantly more Fibro/Adipogenic Progenitor (FAPs), in which the CD9 negative FAPs (FAPCD9-) having adipogenic potential, as demonstrated by in vitro assays using cells originated from mouse muscle. On the other hand, Yorkshire had more fibro-inflammatory progenitors (FIPs, marked with FAPCD9+), presenting higher expression of the FBN1-Integrin α5β1. FBN1-Integrin α5β1 could inhibit insulin signaling in FAPCD9-, suppressing adipogenic differentiation. Our results demonstrated that fat-type pigs possess a greater number of FAPCD9-, which are the exclusive cells in muscle capable of differentiating into adipocytes. Moreover, lean-type pigs exhibit higher expression of FBN1-Integrin α5β1 axis, which inhibits adipocyte differentiation. These results appropriately explain the observed higher IMF content in fat-type pigs.

Anti-Obesity Effect of Lactobacillus acidophilus DS0079 (YBS1) by Inhibition of Adipocyte Differentiation through Regulation of p38 MAPK/PPARγ Signaling.

Obesity is spawned by an inequality between the portion of energy consumed and the quantity of energy expended. Disease entities such as cardiovascular disease, arteriosclerosis, hypertension, and cancer, which are correlated with obesity, influence society and the economy. Suppression of adipogenesis, the process of white adipocyte generation, remains a promising approach for treating obesity. Oil Red O staining was used to differentiate 3T3-L1 cells for screening 20 distinct Lactobacillus species. Among these, Lactobacillus acidophilus DS0079, referred to as YBS1, was selected for further study. YBS1 therapy decreased 3T3-L1 cell development. Triglyceride accumulation and mRNA expression of the primary adipogenic marker, peroxisome proliferator-activated receptor gamma (PPARγ), including its downstream target genes, adipocyte fatty acid binding protein 4 and adiponectin, were almost eliminated. YBS1 inhibited adipocyte differentiation at the early stage (days 0-2), but no significant difference was noted between the mid-stage (days 2-4) and late-stage (days 4-6) development. YBS1 stimulated the activation of p38 mitogen-activated protein kinase (p38 MAPK) during the early stages of adipogenesis; however, this effect was eliminated by the SB203580 inhibitor. The data showed that YBS1 administration inhibited the initial development of adipocytes via stimulation of the p38 MAPK signaling pathway, which in turn controlled PPARγ expression. In summary, YBS1 has potential efficacy as an anti-obesity supplement and requires further exploration.

Stellera chamaejasme L. extract inhibits adipocyte differentiation through activation of the extracellular signal-regulated kinase pathway.

Stellera chamaejasme L. (SCL) is a perennial herb with demonstrated bioactivities against inflammation and metabolic dysfunction. Adipocyte differentiation is a critical regulator of metabolic homeostasis and a promising target for the treatment of metabolic diseases, so we examined the effects of SCL on adipogenesis. A methanol extract of SCL dose-dependently suppressed intracellular lipid accumulation in adipocyte precursors cultured under differentiation induction conditions and reduced expression of the adipogenic transcription factors PPARγ and C/EBPα as well as the downstream lipogenic genes fatty acid binding protein 4, adiponectin, fatty acid synthase, and stearoyl-CoA desaturase. The extract also promoted precursor cell proliferation and altered expression of the cell cycle regulators cyclin-dependent kinase 4, cyclin E, and cyclin D1. In addition, SCL extract stimulated extracellular signal-regulated kinase (ERK) phosphorylation, while pharmacological inhibition of ERK effectively blocked the inhibitory effects of SCL extract on preadipocyte differentiation. These results suggest that SCL extract contains bioactive compounds that can suppress adipogenesis through modulation of the ERK pathway.

Jun Dimerization Protein 2 (JDP2) Increases p53 Transactivation by Decreasing MDM2.

The AP-1 protein complex primarily consists of several proteins from the c-Fos, c-Jun, activating transcription factor (ATF), and Jun dimerization protein (JDP) families. JDP2 has been shown to interact with the cAMP response element (CRE) site present in many cis-elements of downstream target genes. JDP2 has also demonstrates important roles in cell-cycle regulation, cancer development and progression, inhibition of adipocyte differentiation, and the regulation of antibacterial immunity and bone homeostasis. JDP2 and ATF3 exhibit significant similarity in their C-terminal domains, sharing 60-65% identities. Previous studies have demonstrated that ATF3 is able to influence both the transcriptional activity and p53 stability via a p53-ATF3 interaction. While some studies have shown that JDP2 suppresses p53 transcriptional activity and in turn, p53 represses JDP2 promoter activity, the direct interaction between JDP2 and p53 and the regulatory role of JDP2 in p53 transactivation have not been explored. In the current study, we provide evidence, for the first time, that JDP2 interacts with p53 and regulates p53 transactivation. First, we demonstrated that JDP2 binds to p53 and the C-terminal domain of JDP2 is crucial for the interaction. Second, in p53-null H1299 cells, JDP2 shows a robust increase of p53 transactivation in the presence of p53 using p53 (14X)RE-Luc. Furthermore, JDP2 and ATF3 together additively enhance p53 transactivation in the presence of p53. While JDP2 can increase p53 transactivation in the presence of WT p53, JDP2 fails to enhance transactivation of hotspot mutant p53. Moreover, in CHX chase experiments, we showed that JDP2 slightly enhances p53 stability. Finally, our findings indicate that JDP2 has the ability to reverse MDM2-induced p53 repression, likely due to decreased levels of MDM2 by JDP2. In summary, our results provide evidence that JDP2 directly interacts with p53 and decreases MDM2 levels to enhance p53 transactivation, suggesting that JDP2 is a novel regulator of p53 and MDM2.

PPARγ antagonists induce aromatase transcription in adipose tissue cultures

Aromatase is the rate-limiting enzyme in the biosynthesis of estrogens and a key risk factor for hormone receptor-positive breast cancer. In postmenopausal women, estrogens synthesized in adipose tissue promotes the growth of estrogen receptor positive breast cancers. Activation of peroxisome proliferator-activated receptor gamma (PPARγ) in adipose stromal cells (ASCs) leads to decreased expression of aromatase and differentiation of ASCs into adipocytes. Environmental chemicals can act as antagonists of PPARγ and disrupt its function. This study aimed to test the hypothesis that PPARγ antagonists can promote breast cancer by stimulating aromatase expression in human adipose tissue.Primary cells and explants from human adipose tissue as well as A41hWAT, C3H10T1/2, and H295R cell lines were used to investigate PPARγ antagonist-stimulated effects on adipogenesis, aromatase expression, and estrogen biosynthesis. Selected antagonists inhibited adipocyte differentiation, preventing the adipogenesis-associated downregulation of aromatase. NMR spectroscopy confirmed direct interaction between the potent antagonist DEHPA and PPARγ, inhibiting agonist binding. Short-term exposure of ASCs to PPARγ antagonists upregulated aromatase only in differentiated cells, and a similar effect could be observed in human breast adipose tissue explants. Overexpression of PPARG with or without agonist treatment reduced aromatase expression in ASCs.The data suggest that environmental PPARγ antagonists regulate aromatase expression in adipose tissue through two mechanisms. The first is indirect and involves inhibition of adipogenesis, while the second occurs more acutely.

Brown Algae Dictyopteris divaricata Attenuates Adipogenesis by Modulating Adipocyte Differentiation and Promoting Lipolysis through Heme Oxygenase-1 Activation in 3T3-L1 Cells.

The present study aims to explore the probable anti-adipogenesis effect of Dictyopteris divaricata (D. divaricata) in 3T3-L1 preadipocytes by regulating heme oxygenase-1 (HO-1). The extract of D. divaricata retarded lipid accretion and decreased triglyceride (TG) content in 3T3-L1 adipocytes but increased free glycerol levels. Treatment with the extract inhibited lipogenesis by inhibiting protein expressions of fatty acid synthase (FAS) and lipoprotein lipase (LPL), whereas lipolysis increased by activating phosphorylation of hormone-sensitive lipase (p-HSL) and AMP-activated protein kinase (p-AMPK). The extract inhibited adipocyte differentiation of 3T3-L1 preadipocytes through down-regulating adipogenic transcription factors, including peroxisome proliferator-activated receptor gamma (PPARγ) and CCAAT/enhancer-binding protein α (C/EBPα), and sterol regulatory element-binding protein 1 (SREBP1). This is attributed to the triggering of Wnt/β-catenin signaling. In addition, this study found that treatment with the extract activated HO-1 expression. Pharmacological approaches revealed that treatment with Zinc Protoporphyrin (ZnPP), an HO-1 inhibitor, resulted in an increase in lipid accumulation and a decrease in free glycerol levels. Finally, three adipogenic transcription factors, such as PPARγ, C/EBPα, and SREBP1, restored their expression in the presence of ZnPP. Analysis of chemical constituents revealed that the extract of D. divaricata is rich in 1,4-benzenediol, 7-tetradecenal, fucosterol, and n-hexadecanoic acid, which are known to have multiple pharmacological properties.

Effect of YC-1102 on the Improvement of Obesity in High-Fat Diet-Induced Obese Mice.

Obesity is one of the major risk factors for metabolic diseases worldwide. This study examined the effects of YC-1102, an extract derived from the roots of Rosa multiflora, on 3T3-L1 preadipocytes and high-fat diet (HFD)-induced obese mice. In vivo experiments involved the oral administration of YC-1102 (100, 150, and 200 mg/kg body weight) daily to mice for eight weeks. YC-1102 was found to downregulate the expressions of PPARγ and C/EBPα during adipogenesis, inhibiting adipocyte differentiation and upregulating the expression of PGC-1α for energy metabolism to enhance mitochondrial biogenesis and fatty acid oxidation. It has been shown that daily administration of YC-1102 to mice receiving a HFD prevented an increase in body weight and the accumulation of body fat. YC-1102 administration also reduced TG, TC, and LDL cholesterol levels, as well as glucose and leptin levels, and increased adiponectin levels, thus effectively inhibiting the metabolism of lipids. YC-1102-treated mice showed significant reductions in the mRNA expression of PPARγ and C/EBPα. The levels of PGC-1α involved in energy metabolism increased significantly in the YC-1102-treated mice when compared to the HFD-treated mice. According to the findings of this study, YC-1102 has a dual mechanism that reduces transcription factors that promote the differentiation of adipocytes and increases transcription factors that promote energy consumption.

Crocus sativus tepals extract suppresses subcutaneous adipose tissue hypertrophy and improves systemic insulin sensitivity in mice on high-fat diet.

Obesity is a pressing problem worldwide for which standard therapeutic strategies have limited effectiveness. The use of natural products seems to be a promising approach to alleviate obesity and its associated complications. The tepals of Crocus sativus (Cr) plant, usually wasted in saffron production, are an unexplored source of bioactive compounds. Our aim was to elucidate the mechanisms of Cr tepals extract in obesity by investigating its effects on adipocyte differentiation, visceral adipose tissue (VAT) and subcutaneous adipose tissue (SAT) hypertrophy, and lipid metabolism in an animal model of diet-induced obesity. To this end, mouse 3T3-F442A preadipocytes were treated with Cr tepals extract and the expression of adipocyte differentiation genes was determined. Caloric intake, body mass, triglycerides, systemic insulin sensitivity, histology, insulin signaling, and lipid metabolism in VAT and SAT were analyzed in mice fed a 60% fat diet for 14 weeks and treated orally with Cr tepals extract during the last 5 weeks of the diet. We demonstrated for the first time that Cr tepals extract inhibits adipocyte differentiation in vitro. The animal model confirmed that oral treatment with Cr tepals extract results in weight loss, improved systemic insulin sensitivity, lower triglycerides, and improved lipid peroxidation. The suppressive effect of Cr tepals extract on adipocyte hypertrophy and inflammation was observed only in SAT, which, together with preserved SAT insulin signaling, most likely contributed to improved systemic insulin sensitivity. Our results suggest the functionality of SAT as a possible target for the treatment of obesity and its complications.

Sophoridine Counteracts Obesity via Src-Mediated Inhibition of VEGFR Expression and PI3K/AKT Phosphorylation.

Sophoridine (SRP) is a natural quinolizidine alkaloid found in many traditional Chinese herbs, though its effect on adipose tissue is unclear. We improved serum lipid levels by administering SRP by gavage in high-fat diet (HFD)-fed C57BL/6 mice. After 11 weeks, SRP supplementation significantly reduced body weight gain and improved glucose homeostasis, while reducing subcutaneous fat and liver weight. SRP also inhibited cell proliferation and differentiation of 3T3-L1 cells. Proteomics analysis revealed that SRP inhibits adipocyte differentiation by interacting with Src, thereby suppressing vascular endothelial growth factor receptor 2 (VEGFR2) expression and PI3K/AKT phosphorylation. This study provides an empirical basis for the treatment of obesity with small molecules.

Conjugated Linoleic Acid Reduces Lipid Accumulation via Down-regulation Expression of Lipogenic Genes and Up-regulation of Apoptotic Genes in Grass Carp (Ctenopharyngodon idella) Adipocyte In Vitro.

The relationship between conjugated linoleic acid (CLA) and lipogenesis has been extensively studied in mammals and some cell lines, but it is relatively rare in fish, and the potential mechanism of action of CLA reducing fat mass remains unclear. The established primary culture model for studying lipogenesis in grass carp (Ctenopharyngodon idella) preadipocytes was used in the present study, and the objective was to explore the effects of CLA on intracellular lipid and TG content, fatty acid composition, and mRNA levels of adipogenesis transcription factors, lipase, and apoptosis genes in grass carp adipocytes in vitro. The results showed that CLA reduced the size of adipocyte and lipid droplet and decreased the content of intracellular lipid and TG, which was accompanied by a significant down-regulation of mRNA abundance in transcriptional regulators including peroxisome proliferator-activated receptor (PPAR) γ, CCAAT/enhancer-binding protein (C/EBP) α, sterol regulatory element-binding protein (SREBP) 1c, lipase genes including fatty acid synthase (FAS), acetyl-CoA carboxylase (ACC), lipoprotein lipase (LPL). Meanwhile, it decreased the content of saturated fatty acids (SFAs) and n - 6 polyunsaturated fatty acid (n-6 PUFA) and increased the content of monounsaturated fatty acid (MUFA) and n - 3 polyunsaturated fatty acid (n-3 PUFA) in primary grass carp adipocyte. In addition, CLA induced adipocyte apoptosis through downregulated anti-apoptotic gene B-cell CLL/lymphoma 2 (Bcl-2) mRNA level and up-regulated pro-apoptotic genes tumor necrosis factor-α (TNF-α), Bcl-2-associated X protein (Bax), Caspase-3, and Caspase-9 mRNA level in a dose-dependent manner. These findings suggest that CLA can act on grass carp adipocytes through various pathways, including decreasing adipocyte size, altering fatty acid composition, inhibiting adipocyte differentiation, promoting adipocyte apoptosis, and ultimately decreasing lipid accumulation.

전사인자 발현 조절을 통한 황금/아티초코 복합추출물의 지방분화 억제 효과

In this study, we investigated cytotoxicity, inhibition of adipocyte differentiation, lipolysis, and expression of obesity-related transcription factors inhibition of the Scutellaria baicalensis Georgi/Cynara scolymus L. mixture extract (SCME)to evaluate its use as an anti-obesity natural material. As a result, cell viability for 3T3-L1 cells did not affect cell growth up to a concentration of 500 μg/ml in all samples. Adipocyte differentiation and fat accumulation inhibited in a concentration-dependent manner by Scutellaria baicalensis Georgi extract (SGE) and Cynara scolymus L. leaf extract (CLLE) treatment. In the case of adipocyte differentiation, SCME suppressed more than the SGE and CLLE at a concentration of 500 μg/ml. The amount of accumulated fat was also lower in SCME (32.2%) than in AGE and CLLE (47.7~41.0%). Lipolytic efficacy was reduced by 48.2% compared to the control when SCME was treated at a concentration of 500 μg/ml. Expressions of PPAR-γ, aP2, and ADIPOQ were also decreased in a concentration-dependent manner by SCME, and were decreased by 19.7%, 42.0%, and 12.7% at a concentration of 1,000 μg/ml, respectively. As a result of the above, it is judged that SCME exhibits effects of suppressing adipocyte differentiation and fat accumulation and lipolysis by regulating the expression of transcription factors related to adipocyte differentiation and fat accumulation. In order to utilize SCME as an anti-obesity material, Future study is necessary to conduct preclinical experiments in the future.

BMP8B Activates Both SMAD2/3 and NF-κB Signals to Inhibit the Differentiation of 3T3-L1 Preadipocytes into Mature Adipocytes.

Bone morphogenetic protein 8B (BMP8B) has been found to regulate the thermogenesis of brown adipose tissue (BAT) and the browning process of white adipose tissue (WAT). However, there is no available information regarding the role of BMP8B in the process of adipocyte differentiation. Here, we showed that BMP8B down-regulates transcriptional regulators PPARγ and C/EBPα, thereby impeding the differentiation of 3T3-L1 preadipocytes into fully mature adipocytes. BMP8B increased the phosphorylation levels of SMAD2/3, and TP0427736 HCl (SMAD2/3 inhibitor) significantly reduced the ability of BMP8B to inhibit adipocyte differentiation, suggesting that BMP8B repressed adipocyte differentiation through the SMAD2/3 pathway. Moreover, the knockdown of BMP I receptor ALK4 significantly reduced the inhibitory effect of BMP8B on adipogenesis, indicating that BMP8B triggers SMAD2/3 signaling to suppress adipogenesis via ALK4. In addition, BMP8B activated the NF-κB signal, which has been demonstrated to impede PPARγ expression. Collectively, our data demonstrated that BMP8B activates both SMAD2/3 and NF-κB signals to inhibit adipocyte differentiation. We provide previously unidentified insight into BMP8B-mediated adipogenesis.

Effects of Cinnamon (Cinnamomum zeylanicum) Extract on Adipocyte Differentiation in 3T3-L1 Cells and Lipid Accumulation in Mice Fed a High-Fat Diet.

Flavonoids and phenolic acid are two of the rich polyphenols found in cinnamon (Cinnamomum zeylanicum). The effects of cinnamon extract on the inhibition of adipocyte differentiation in 3T3-L1 fibroblast cells and prohibitory lipid accumulation in male mice fed a high-fat diet were examined. Upon treating 3T3-L1 cells with cinnamon for 3 days, the cinnamon inhibited lipid accumulation and increased gene expression levels, such as those of adiponectin and leptin. In in vivo experiments, mice were randomized into four groups after a one-week acclimation period, as follows: normal diet, normal diet + 1% cinnamon extract, high-fat diet, and high-fat diet + 1% cinnamon extract. After 14 weeks of supplementation, we found that cinnamon extract increased the expression of lipolysis-related proteins, such as AMPK, p-ACC, and CPT-1, and reduced the expression of lipid-synthesis-related proteins, such as SREBP-1c and FAS, in liver tissue. Our results show that cinnamon extract may exhibit anti-obesity effects via the inhibition of lipid synthesis and adipogenesis and the induction of lipolysis in both 3T3-L1 fibroblast cells and mice fed a high-fat diet. Accordingly, cinnamon extract may have potential anti-obesity effects.

(E)-3-(4-(tert-Butyl)Phenyl)-N-Isobutyl-2-Methylacrylamide Suppresses Adipogenesis in High-Fat-Fed Mice

Obesity is caused by excessive adipogenesis and leads to metabolic diseases such as diabetes, hypertension, and degenerative arthritis. Therefore, there is an ever-increasing need to identify new anti-obesity compounds. In this study, the anti-obesity effects of (E)-3-(4-(tert-butyl)phenyl)-N-isobutyl-2-methylacrylamide (BPIMA) were evaluated using pre-adipocytes and a high-fat-fed C57BL/6J mouse model. As the results, BPIMA effectively inhibited adipocyte differentiation (64.3% at 40 μM) without exhibiting any cytotoxicity. Additionally, BPIMA decreased the protein levels of PPARγ, FAS, C/EBP, and SREBP in 3T3-L1 cells in a concentration-dependent manner. In C57BL/6J mice, a significant decrease in body weight, adipose tissue, and fatty liver was observed in the BPIMA-treated high-fat group compared to that observed in the vehicle-treated high-fat group; the serum levels of total cholesterol and glucose also significantly decreased in the BPIMA-treated high-fat group. Moreover, the weight and fat level of liver and serum AST, ALT activity in the BPIMA-treated high-fat group were similar to low fat diet-control group. These findings show that BPIMA may be a potential anti-obesity compound.