Flavopiridol inhibits adipogenesis and improves metabolic homeostasis by ameliorating adipose tissue inflammation in a diet-induced obesity model.

Repositioning of FDA approved/clinical phase drugs has recently opened a new opportunity for rapid approval of drugs, as it shortens the overall process of drug discovery and development. In previous studies, we predicted the possibility of better activity profiles of flavopiridol, the FDA approved orphan drug with better fit value 2.79 using a common feature pharmacophore model for anti-adipogenic compounds (CFMPA). The present study aimed to investigate the effect of flavopiridol on adipocyte differentiation and to determine the underlying mechanism. Flavopiridol inhibited adipocyte differentiation in different cell models like 3T3-L1, C3H10T1/2, and hMSCs at 150 nM. Flavopiridol was around 135 times more potent than its parent molecule rohitukine. The effect was mediated through down-regulation of key transcription factors of adipogenesis i.e. Peroxisome proliferator-activated receptor gamma (PPARγ), CCAAT/enhancer-binding protein alpha (C/EBPα), and their downstream targets, including adipocyte protein -2 (aP2) and fatty acid synthase (FAS). Further, results revealed that flavopiridol arrested the cell cycle in G1/S phase during mitotic clonal expansion by suppressing cell cycle regulatory proteins i.e. Cyclins and CDKs. Flavopiridol inhibited insulin-stimulated signalling in the early phase of adipocyte differentiation by downregulation of AKT/mTOR pathway. In addition, flavopiridol improved mitochondrial function in terms of increased oxygen consumption rate (OCR) in mature adipocytes. In the mouse model of diet-induced obesity, flavopiridol attenuated obesity-associated adipose tissue inflammation and improved serum lipid profile, glucose tolerance as well as insulin sensitivity. In conclusion, the FDA approved drug flavopiridol could be placed as a potential drug candidate for the treatment of cancer and obesity comorbid patients.

New anti-adipogenic triterpenoid saponins from the aerial parts of Glinus oppositifolius.

Glinus oppositifolius L., a member of the Molluginaceae family, has a long-standing history of utilization as both a vegetable and a medicinal agent across numerous countries. This plant possesses a diverse range of pharmacological activities and attracts scientific interest in studying its chemical profile. The present phytochemical investigation of the plant resulted in the isolation of eleven new triterpenoid saponins, accompanied by three known compounds. Their structures were elucidated by intensive spectroscopic analysis, DFT calculations, and comparison with previously reported data. The isolates were evaluated for their anti-adipogenic effect and cytotoxicity against human cancer cell lines, namely, colorectal carcinoma HCT116, hepatoblastoma cell HepG2, breast cancer cell MDA-MB-231, and human lung adenocarcinoma cell A549. Compounds 5, 7, and 13 exhibited a potent inhibitory effect against the differentiation of preadipocyte 3T3-L1. In addition, compound 13 displayed inhibitory effects against the growth of A549 cancer cells.

Development of piperine nanoparticles stabilized by OSA modified starch through wet-media milling technique with enhanced anti-adipogenic effect in 3T3-L1 adipocytes.

Piperine (PIP) has been known for its pharmacological activities with low water solubility and poor dissolution, which limits its nutritional application. The purpose of this research was to enhance PIP stability, dispersibility and biological activity by preparing PIP nanoparticles using the wet-media milling approach combined with nanosuspension solidification methods of spray/freeze drying. Octenyl succinic anhydride (OSA)-modified waxy maize starch was applied as the stabilizer to suppress aggregation of PIP nanoparticles. The particle size, redispersibility, storage stability and in vitro release behavior of PIP nanoparticles were measured. The regulating effect on adipocyte differentiation was evaluated using 3T3-L1 cell model. Results showed that PIP nanoparticles had a reduced particle size of 60 ± 1 nm, increased release rate in the simulated gastric (SGF) and intestinal fluids (SIF) and enhanced inhibition effect on adipogenesis in 3T3-L1 cells compared with free PIP, indicating that PIP-loaded nanoparticles with improved stability and anti-adipogenic property were developed successfully by combining wet-media milling and drying methods.

A human omentum-specific mesothelial-like stromal population inhibits adipogenesis through IGFBP2 secretion.

Adipose tissue plasticity is orchestrated by molecularly and functionally diverse cells within the stromal vascular fraction (SVF). Although several mouse and human adipose SVF cellular subpopulations have by now been identified, we still lack an understanding of the cellular and functional variability of adipose stem and progenitor cell (ASPC) populations across human fat depots. To address this, we performed single-cell and bulk RNA sequencing (RNA-seq) analyses of >30 SVF/Lin- samples across four human adipose depots, revealing two ubiquitous human ASPC (hASPC) subpopulations with distinct proliferative and adipogenic properties but also depot- and BMI-dependent proportions. Furthermore, we identified an omental-specific, high IGFBP2-expressing stromal population that transitions between mesothelial and mesenchymal cell states and inhibits hASPC adipogenesis through IGFBP2 secretion. Our analyses highlight the molecular and cellular uniqueness of different adipose niches, while our discovery of an anti-adipogenic IGFBP2+ omental-specific population provides a new rationale for the biomedically relevant, limited adipogenic capacity of omental hASPCs.

Limonoids isolated from Chisocheton ceramicus Miq. and the antiadipogenic mechanism of action of ceramicine B.

Different types of limonoids have been isolated from plants of the Chisocheton genus, notably from the species Chisocheton ceramicus Miq. which is largely distributed in the Indonesian archipelago and Malaysia region. A variety of natural products have been found in the bark of the tree and characterized as antimicrobial and/or antiproliferative agents. The isolated limonoids include chisomicines A-E, proceranolide, and a few other compounds. A focus is made on a large series of limonoids designated ceramicines A to Z including derivatives with antiparasitic activities, antioxidant, antimelanogenic, and antiproliferative effects and/or acting as regulators of lipogenesis. The lead compound in the series is ceramicine B functioning as a potent inhibitor of lipid droplet accumulation (LDA). Extracts from Chisocheton ceramicus and ceramicines have shown anti-LDA effects, with little or no cytotoxic effects. Ceramicine B is the most active compound functioning as a regulator of lipid storage in cells and tissues. Ceramicine B is a transcriptional repressor of peroxisome proliferator-activated receptor γ (PPARγ) and an inhibitor of phosphorylation of the transcription factor FoxO1, acting via an upstream molecular target. Targeting of glycogen synthase kinase-3ß is proposed, based on the analogy with structurally related limonoids known to target this enzyme, and supported by a molecular docking analysis. The target and pathway implicated in ceramicine B activity are discussed. The analysis shed light on ceramicine B as a natural product precursor for the design of novel compounds capable of reducing LDA in cells and of potential interest for the treatment of obesity, liver diseases, and other pathologies.

Bacoside-A repressed the differentiation and lipid accumulation of 3T3-L1 preadipocytes by modulating the expression of adipogenic genes.

Obesity is one of the more complicated diseases, it can induce numerous life-threatening diseases mainly diabetes mellitus, cardiovascular disease, hypertension, and certain cancers. In this study, we assessed the efficacy of bacoside-A (a dammarane-type triterpenoid saponin derived from the plant Bacopa monniera Linn.) on the adipogenesis of 3T3-L1 preadipocytes. Results of this study illustrated that bacoside-A decreased the differentiation of 3T3-L1 cell, as evidenced by diminution of lipid droplets, which contains triglycerides and other lipids. During the differentiation process, transcription factors, which are mainly participating in adipogenesis such us CCAAT/enhancer-binding protein α (C/EBPα) and C/EBPß, peroxisome proliferator-activated receptor-γ (PPARγ), and sterol regulatory element-binding protein-1c (SREBP-1c), expressions were significantly suppressed by bacoside-A. In addition, bacoside-A showed a potent reduction in genes precise to adipocytes such as lipoprotein lipase (LPL), fatty acid synthase (FAS), adipocyte fatty acid-binding protein (FABP4), and leptin expressions. Further, bacoside-A stimulated the phosphorylation of acetyl CoA carboxylase (ACC) and AMP-activated protein kinase (AMPK). These results demonstrated that bacoside-A has anti-adipogenic effects by regulating the transcription factors involved in adipocyte differentiation. Therefore, bacoside-A might be considered as a potent therapeutic agent for alleviating obesity and hyperlipidemia.

Metabolic Insights into Caffeine's Anti-Adipogenic Effects: An Exploration through Intestinal Microbiota Modulation in Obesity.

Obesity, a chronic condition marked by the excessive accumulation of adipose tissue, not only affects individual well-being but also significantly inflates healthcare costs. The physiological excess of fat manifests as triglyceride (TG) deposition within adipose tissue, with white adipose tissue (WAT) expansion via adipocyte hyperplasia being a key adipogenesis mechanism. As efforts intensify to address this global health crisis, understanding the complex interplay of contributing factors becomes critical for effective public health interventions and improved patient outcomes. In this context, gut microbiota-derived metabolites play an important role in orchestrating obesity modulation. Microbial lipopolysaccharides (LPS), secondary bile acids (BA), short-chain fatty acids (SCFAs), and trimethylamine (TMA) are the main intestinal metabolites in dyslipidemic states. Emerging evidence highlights the microbiota's substantial role in influencing host metabolism and subsequent health outcomes, presenting new avenues for therapeutic strategies, including polyphenol-based manipulations of these microbial populations. Among various agents, caffeine emerges as a potent modulator of metabolic pathways, exhibiting anti-inflammatory, antioxidant, and obesity-mitigating properties. Notably, caffeine's anti-adipogenic potential, attributed to the downregulation of key adipogenesis regulators, has been established. Recent findings further indicate that caffeine's influence on obesity may be mediated through alterations in the gut microbiota and its metabolic byproducts. Therefore, the present review summarizes the anti-adipogenic effect of caffeine in modulating obesity through the intestinal microbiota and its metabolites.

Preventing Adipogenesis and Preserving Mitochondria and GLUT-4 Functions by Extracts and Isolated Compounds of Australian Acacia saligna.

Acacia saligna's secondary metabolites show promise in treating type 2 diabetes mellitus and its related conditions. We previously discovered that methanolic extracts, isolated flavonoids, and cyclitols effectively preserve mitochondria in 3T3-L1 adipocytes. In this current work, quantification of lipid droplet levels with Oil Red O assay showed a noticeable decrease in lipogenesis in 3T3-L1 cells. Methanolic leaf and bark extracts and isolated compounds, (-)-epicatechin 6 and myricitrin 8, reduced cellular lipid levels by 21.15% to 25.28%, respectively. mRNA levels of key regulators of mitochondrial biogenesis, such as adiponectin, PGC-1α, and mtTFA, were increased. Methanolic flower extract (FL-MeOH) and its chemical components, naringenin 1 and D-(+)-pinitol 5a, increased these gene levels from 10% to 29% at the higher dose. Our study found that FL-MeOH slightly reduced pro-inflammatory cytokines TNF-α and IL-6, attributed to two phytochemicals, naringenin-7-O-α-L-arabinofuranoside 2 and D-(+)-pinitol 5a. Western blot analysis also showed that adipocytes treated with MeOH extracts had higher GLUT-4 expression levels than untreated adipocytes. Overall, A. saligna extracts and their isolated compounds demonstrated anti-lipogenesis activity during 3T3-L1 cell differentiation, modulation of transcriptional levels of adiponectin, PGC-1α, and mtTFA, reducing TNF-α and IL-6 mRNA levels, promoting mitochondrial biogenesis, and enhancing GLUT-4 expression.

Antiadipogenic and antiobesogenic effects of pterostilbene in 3T3-L1 preadipocyte models.

Since obesity causes at least 2.8 million death each year and is a major risk factor for many diseases, it is critical to evaluate alternative treatment approaches. In this context, studies on the research of natural product-based therapeutics in the fight against obesity are increasing. In this study, it was aimed to evaluate the antiadipogenic and antiobesogenic efficacy of pterostilbene a natural phenolic compound in 3T3-L1 cells. The mature 3T3-L1 adipocytes were exposed to pterostilbene at different concentrations and half-maximum inhibitory concentrations (IC50) were determined by MTT assay. Oil-Red-O staining was applied to determine lipid accumulation. Phase contrast microscopy, Giemsa, F-actin and DAPI staining were applied to examine the efficacy of pterostilbene on the morphology of 3T3-L1 adipocyte cells. Moreover, expressions of adinopectin and glucose transporter-4 (Glut-4) in relation to insulin resistance were evaluated using immunofluorescent staining and qRT-PCR. Pterostilbene caused no significant cytotoxicity towards preadipocytes at concentrations ≤7.5 -M and the percentage of viable cells remained above about 86% for 24 h, 48 h and 72 h (p > 0.05). Therefore, pterostilbene treatment at 5 and 7.5 -M was used in the subsequent experiments as safe dosages. In addition, it was observed that pterostilbene treatment reduced lipid accumulation in adipocyte differentiation. Adipocytes treated with a dose of 7.5 -M for 14 days showed less intense lipid deposition and a more spindle-like morphology compared to the adipocytes treated with a dose of 5 -M. Especially on the 14th day, actin filaments were filamentous in adipocytes treated with pterostilbene 7.5 -M compared to the adipocytes treated with a dose of 5 -M; the filaments were similarly oriented as in preadipocytes, and chromatin condensation was observed to be quite high. Our data suggests that the pterostilbene supplementation may help weight control and the antiadipogenic and that antiobesogenic activity is mediated in part by reduction of lipid accumulation and induction of Glut-4 and Adiponectin levels.

Sex Hormone-Binding Globulin (SHBG) Maintains Proper Equine Adipose-Derived Stromal Cells (ASCs)' Metabolic Functions and Negatively Regulates their Basal Adipogenic Potential.

BACKGROUND: Sex hormone binding globulin (SHBG) deteriorated expression has been recently strongly correlated to increased level of circulating pro-inflammatory cytokines and insulin resistance, which are typical manifestations of equine metabolic syndrome (EMS). Despite previous reports demonstrated the potential therapeutic application of SHBG for liver-related dysfunctions, whether SHBG might modulate equine adipose-derived stem/stromal cells (EqASCs) metabolic machinery remains unknown. Therefore, we evaluated for the first time the impact of SHBG protein on metabolic changes in ASCs isolated from healthy horses. METHODS: Beforehand, SHBG protein expression has been experimentally lowered using a predesigned siRNA in EqASCs to verify its metabolic implications and potential therapeutic value. Then, apoptosis profile, oxidative stress, mitochondrial network dynamics and basal adipogenic potential have been evaluated using various molecular and analytical techniques. RESULTS: The SHBG knockdown altered the proliferative and metabolic activity of EqASCs, while dampening basal apoptosis via Bax transcript suppression. Furthermore, the cells treated with siRNA were characterized by senescent phenotype, accumulation of reactive oxygen species (ROS), nitric oxide, as well as decreased mitochondrial potential that was shown by mitochondrial membrane depolarization and lower expression of key mitophagy factors: PINK, PARKIN and MFN. The addition of SHBG protein reversed the impaired and senescent phenotype of EMS-like cells that was proven by enhanced proliferative activity, reduced apoptosis resistance, lower ROS accumulation and greater mitochondrial dynamics, which is proposed to be related to a normalization of Bax expression. Crucially, SHBG silencing enhanced the expression of key pro-adipogenic effectors, while decreased the abundance of anti-adipogenic factors namely HIF1-α and FABP4. The addition of exogenous SHBG further depleted the expression of PPARγ and C/EBPα and restored the levels of FABP4 and HIF1-α evoking a strong inhibitory potential toward ASCs adipogenesis. CONCLUSION: Herein, we provide for the first time the evidence that SHBG protein in importantly involved in various key metabolic pathways governing EqASCs functions, and more importantly we showed that SHBG negatively affect the basal adipogenic potential of tested ASCs through a FABP4-dependant pathway, and provide thus new insights for the development of potential anti-obesity therapeutic approach in both animals and humans.

Prebiotic and Anti-Adipogenic Effects of Radish Green Polysaccharide.

Radish (Raphanus sativus L.) greens are consumed as a source of nutrition, and their polysaccharides such as rhamnogalacturonan-I possess certain beneficial properties. This study investigated the prebiotic effects of a radish green polysaccharide (RGP) on gut health and obesity. The prebiotic activity of RGP was evaluated based on the pH changes and short-chain fatty acids (SCFAs) concentration. The results showed that 0.5% RGP had a higher prebiotic activity score than inulin and increased SCFAs production in all five prebiotic strains. Moreover, RGP inhibited fat accumulation in 3T3-L1 adipocytes, indicating its potential to reduce obesity. Overall, these findings suggested that the polysaccharide of radish greens has prebiotic effects and may serve as a beneficial prebiotic for gut health and obesity.

Development and Characterization of Cationic Nanostructured Lipid Carriers as Drug Delivery Systems for miRNA-27a.

Although miRNA-27a has been identified as a promising candidate for miRNA mimic therapy of obesity, its application is limited due to enzymatic degradation and low membrane permeation. To overcome these problems, we developed cationic nanostructured lipid carriers (cNLCs) using high-pressure homogenization and used them as non-viral carriers for the anti-adipogenic miRNA-27a. Cargo-free octadecylamine-containing NLCs and miRNA/cNLC complexes were characterized regarding particle size, size distributions, zeta potential, pH values, particle topography and morphology, and entrapment efficacy. Furthermore, the cytotoxicity and cellular uptake of the miRNA/cNLC complex in the 3T3-L1 cell line were investigated. The investigation of the biological effect of miRNA-27a on adipocyte development and an estimation of the accumulated Oil-Red-O (ORO) dye in lipid droplets in mature adipocytes were assessed with light microscopy and absorbance measurements. The obtained data show that cNLCs represent a suitable DDS for miRNAs, as miRNA/cNLC particles are rapidly formed through non-covalent complexation due to electrostatic interactions between both components. The miRNA-27a/cNLC complex induced an anti-adipogenic effect on miRNA-27a by reducing lipid droplet accumulation in mature adipocytes, indicating that this approach might be used as a new therapeutic strategy for miRNA mimic replacement therapies in the prevention or treatment of obesity and obesity-related disorders.

A new sesquiterpene synthase catalyzing the formation of (R)-ß-bisabolene from medicinal plant Colquhounia coccinea var. mollis and its anti-adipogenic and antibacterial activities.

The sesquiterpene ß-bisabolene possessing R and S configurations is commonly found in plant essential oils with antimicrobial and antioxidant activities. Here, we report the cloning and functional characterization of a (R)-ß-bisabolene synthase gene (CcTPS2) from a Lamiaceae medicinal plant Colquhounia coccinea var. mollis. The biochemical function of CcTPS2 catalyzing the cyclization of farnesyl diphosphate to form a single product (R)-ß-bisabolene was characterized through an engineered Escherichia coli producing diverse polyprenyl diphosphate precursors and in vitro enzyme assay, indicating that CcTPS2 was a high-fidelity (R)-ß-bisabolene synthase. The production of (R)-ß-bisabolene in an engineered E. coli strain harboring the exogenous mevalonate pathway, farnesyl diphosphate synthase and CcTPS1 genes was 17 mg/L under shaking flask conditions. Ultimately, 120 mg of purified (R)-ß-bisabolene was obtained from the engineered E. coli, and its structure was elucidated by detailed spectroscopic analyses (including 1D and 2D NMR, and specific rotation). Four chimeric enzymes were constructed through domain swapping, which altered the product outcome, indicating the region important for substrate and product specificity. In addition, (R)-ß-bisabolene exhibited anti-adipogenic activity in the model organism Caenorhabditis elegans and antibacterial activity selectively against Gram-positive bacteria.

Inhibitory Effects of Loganin on Adipogenesis In Vitro and In Vivo.

Obesity is characterized by the excessive accumulation of mature adipocytes that store surplus energy in the form of lipids. In this study, we investigated the inhibitory effects of loganin on adipogenesis in mouse preadipocyte 3T3-L1 cells and primary cultured adipose-derived stem cells (ADSCs) in vitro and in mice with ovariectomy (OVX)- and high-fat diet (HFD)-induced obesity in vivo. For an in vitro study, loganin was co-incubated during adipogenesis in both 3T3-L1 cells and ADSCs, lipid droplets were evaluated by oil red O staining, and adipogenesis-related factors were assessed by qRT-PCR. For in vivo studies, mouse models of OVX- and HFD-induced obesity were orally administered with loganin, body weight was measured, and hepatic steatosis and development of excessive fat were evaluated by histological analysis. Loganin treatment reduced adipocyte differentiation by accumulating lipid droplets through the downregulation of adipogenesis-related factors, including peroxisome proliferator-activated receptor γ (Pparg), CCAAT/enhancer-binding protein α (Cebpa), perilipin 2 (Plin2), fatty acid synthase (Fasn), and sterol regulatory element binding transcription protein 1 (Srebp1). Loganin administration prevented weight gain in mouse models of obesity induced by OVX and HFD. Further, loganin inhibited metabolic abnormalities, such as hepatic steatosis and adipocyte enlargement, and increased the serum levels of leptin and insulin in both OVX- and HFD-induced obesity models. These results suggest that loganin is a potential candidate for preventing and treating obesity.

Integerrima A-E, phenylethanoid glycosides from the stem of Callicarpa integerrima.

Five new phenylethanoid glycosides integerrima A-E (1-5) were isolated from the stem of Callicarpa integerrima for the first time. Their structures were elucidated by extensive spectroscopic analyses. In addition, cytotoxicity, anti-adipogenic and antioxidant activities were evaluated. All the phenylethanoid glycosides would be nontoxic to the normal human hepatocytes LO-2 and pre-adipocytes 3T3-L1 cell lines, significantly promote the proliferation of normal hepatocytes, thus displaying the potential for hepatoprotective. Integerrima A (1), C (3) and D (4) exhibited selectively moderate cytotoxic activity against the hepatoma cell lines Bel-7402, with the IC50 value at 72.66, 80.43 and 84.88 µmol/L, respectively. Moreover, integerrima D (4) had significant activities on reducing lipid droplet formation, with the inhibition rate of 48.02% on the concentration of 200 µg/mL. Finally, the result of FRAP assays exhibited remarkable antioxidant activity in integerrima E (5), which was close to the positive control ascorbic acid with the concentration of 100 µg/mL.

Anti-pancreatic lipase and anti-adipogenic effects of 5, 7, 3',4',5' -pentamethoxy and 6, 2',4'-trimethoxy flavone - An In vitro study.

In this study, the anti-obesity effects of 5,7,3',4',5-pentamethoxyflavone (PMF) and 6,2',4'-trimethoxyflavone (TMF) were evaluated through two distinct mechanisms of action: inhibition of crude porcine pancreatic lipase (PL), and inhibition of adipogenesis in 3T3-L1 pre-adipocytes. Both flavones show dose dependent, competitive inhibition of PL activity. Molecular docking studies revealed binding of the flavones to the active site of PL. In 3T3-L1 adipocytes, both flavones reduced the accumulation of lipids and triglycerides. PMF and TMF also lowered the expression of adipogenic and lipogenic genes. They both reduced the expression of peroxisome proliferator-activated receptor-gamma (PPAR-γ), CCAAT/enhancer-binding protein α and ß (C/EBP α and ß), sterol regulatory element-binding protein 1 (SREBF 1), fatty acid synthase (FASN), adipocyte binding protein 2 (aP2), and leptin gene. In addition, these flavones enhanced adiponectin mRNA expression, increased lipolysis and enhanced the expression of lipolytic genes: adipose triglycerides lipase (ATGL), hormone sensitive lipase (HSL) and monoglycerides lipase (MAGL) in mature 3T3-L1 adipocytes. Overall, PMF was seen to be a more potent inhibitor of both PL activity and adipogenesis versus TMF. These results suggest that PMF and TMF possess anti-obesity activities and can be further evaluated for their anti-obesity effects.

The activity comparison of six dietary flavonoids identifies that luteolin inhibits 3T3-L1 adipocyte differentiation through reducing ROS generation.

Mitochondrial reactive oxygen species (ROS)generation plays an essential role in the process of adipocyte differentiation and is involved in the development of obesity and associated metabolic diseases. Various dietary flavonoids possess the substantial anti-adipogenic activity. However, it is unclear whether these flavonoids inhibit adipocyte differentiation by reducing ROS generation. In this study, the effects of six common dietary flavonoids on adipocyte differentiation were assessed in 3T3-L1 cells. The flavonoids with the same backbone of 5,7-dihydroxylflavone, including flavones apigenin, chrysin, luteolin and flavonols kaempferol, myricetin, quercetin, dose-dependently inhibited 3T3-L1 adipocyte differentiation, suggesting an associated hierarchy of inhibitory capability: luteolin > quercetin > myricetin > apigenin/kaempferol > chrysin. Meanwhile, six flavonoids were found to inhibit adipogenic gene expression and the early stage of adipocyte differentiation. Among the tested flavonoids, luteolin significantly reduced both intracellular and mitochondrial ROS generation during adipocyte differentiation. Further, luteolin treatment depressed the elevation of H2O2 concentration in the early stage of 3T3-L1 differentiation and reversed the facilitated effects of exogenous H2O2 on 3T3-L1 adipocyte differentiation and ROS generation. Altogether, the activity comparison of six dietary flavonoids identifies that luteolin inhibits 3T3-L1 adipocyte differentiation through reducing ROS generation, elucidating a new mechanism underlying the anti-adipogenic actions of flavonoids.

Effects of the Probiotic Lactiplantibacillus plantarum KU15120 Derived from Korean Homemade Diced-Radish Kimchi Against Oxidation and Adipogenesis.

Intestinal microflora can influence abnormal adipocyte growth. Therefore, this study was aimed to investigate the probiotic properties and antioxidant and antiobesity effects of isolated strains from homemade kimchi. Among the isolated strains, Lactiplantibacillus plantarum KU15120 showed high tolerance to artificial gastric juice and bile salt conditions, high adhesion to HT-29 cells, nonproduction of ß-glucuronidase, nonhemolysis, and acceptable resistance to antibiotics. It showed high antioxidant activity, including DPPH and ABTS radical scavenging and antioxidant activity, as determined by the ß-carotene bleaching assay. Oil red O staining and intracellular triglyceride levels revealed reduced lipid accumulation, which confirmed the anti-adipogenic activity of L. plantarum KU15120. In addition, the expression levels of fatty acid synthase, CCAAT/enhance-binding protein α, and peroxisome proliferator-activated receptor Î³, were significantly lower in the probiotic-treated group than in the control group. These results suggest that L. plantarum KU15120 has probiotic properties, antioxidant, and antiobesity effects and could be used as a therapeutic probiotics.

Bioconverted Fruit Extract of Akebia Quinata Exhibits Anti-Obesity Effects in High-Fat Diet-Induced Obese Rats.

Akebia quinata, commonly called chocolate vine, has various bioactivities, including antioxidant and anti-obesity properties. However, the anti-obesity effects of bioconverted extracts of A. quinate have not been examined. In this study, A. quinata fruit extracts was bioconverted using the enzyme isolated from the soybean paste fungi Aspergillus kawachii. To determine whether the bioconversion process could influence the anti-obesity effects of A. quinata fruit extracts, we employed 3T3-L1 adipocytes and HFD-induced obese rats. We observed that the bioconverted fruit extract of A. quinata (BFE) afforded anti-obesity effects, which were stronger than that for the non-bioconverted fruit extract (FE) of A. quinata. In 3T3-L1 adipocytes, treatment with BFE at concentrations of 20 and 40 µg reduced intracellular lipids by 74.8 (p < 0.05) and 54.9% (p < 0.01), respectively, without inducing cytotoxicity in preadipocytes. Moreover, the oral administration of BFE at the concentration of 300 mg/kg/day significantly reduced body and adipose tissue weights (p < 0.01) in HFD-induced obese rats. Plasma cholesterol values were reduced, whereas HDL was increased in BFE receiving rats. Although FE could exert anti-obesity effects, BFE supplementation induced more robust effects than FE. These results could be attributed to the bioconversion-induced alteration of bioactive compound content within the extract.

Anti-adipogenic activities of pheophorbide a and pyropheophorbide a isolated from wild bitter gourd (Momordica charantia L. var. abbreviata Seringe) in vitro.

BACKGROUND: The wild bitter gourd (WBG) is a commonly consumed vegetable in Asia that has antioxidant and hypoglycemic properties. The present study aimed to investigate the anti-adipogenic activities of isolated compounds from WBG on 8-day differentiated cultures of 3 T3-L1 adipocytes that were then stained with Oil Red O (ORO) or diamidino-2-phenylindole (DAPI). RESULTS: ORO stains of the methanol extracts of de-seeded HM86 cultivar of WBG (WBG-M) and the ethyl acetate fractions (WBG-M-EA) showed anti-adipogenic activities against differentiated adipocytes. Two chlorophyll-degraded compounds, pheophorbide a (1) and pyropheophorbide a (2), were isolated from WBG-M-EA. Treatments with 1 (5, 10, and 20 µmol L-1 ) and 2 (2.5, 5, and 10 µmol L-1 ) showed dose-dependent reductions in lipid accumulations and reduced nuclear DAPI stains in differentiated 3 T3-L1 adipocytes. The concentrations for 50% inhibition against lipid accumulations of 1 and 2, respectively, were 16.05 and 7.04 µmol L-1 . Treatments with 1 and 2 showed enhanced lactate dehydrogenase release in the first 4-day cell mitotic clonal expansions during the differentiating cultural processes, although the effect was less on the non-differentiating cultural processes. Thus, 1 and 2 were more toxic to differentiating adipocytes than to non-differentiated pre-adipocytes, which partly resulted in anti-adipogenic activities with lowered lipid accumulations. CONCLUSION: Both 1 and 2 showed anti-adipogenic activities in cell models. These chlorophyll-degraded compounds commonly exist in several vegetables during storage or edible seaweeds, which will provide resources for further investigations aiming to test anti-obesity in animal studies. © 2022 Society of Chemical Industry.