RESUMO
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.
Assuntos
Adipogenia , Fármacos Antiobesidade , Iridoides , Animais , Camundongos , Células 3T3-L1 , Adipogenia/efeitos dos fármacos , Fármacos Antiobesidade/farmacologia , Dieta Hiperlipídica , Camundongos Endogâmicos C57BL , Obesidade/metabolismo , PPAR gama/metabolismo , Aumento de Peso , Iridoides/farmacologiaRESUMO
Hydroponic ginseng (HPG) has been known to have various bio-functionalities, including an antioxidant effect. Recently, fermentation by lactic acid bacteria has been studied to enhance bio-functional activities in plants by biologically converting their chemical compounds. HPG roots and shoots were fermented with Leuconostoc mesenteroides KCCM 12010P isolated from kimchi. The total phenolic compounds, antioxidant, anti-inflammatory, and anti-adipogenic effects of these fermented samples were evaluated in comparison with non-fermented samples (control). During 24 h fermentation of HPG roots and shoots, the viable number of cells increased to 7.50 Log colony forming unit (CFU)/mL. Total phenolic and flavonoid contents of the fermented HPG roots increased by 107.19% and 645.59%, respectively, compared to non-fermented HPG roots. The antioxidant activity of fermented HPG, as assessed by 2,2'-azino-bis-3-ethylbenzothiazoline-6-sulfonic acid (ABTS), ß-carotene-linoleic, and ferric reducing antioxidant power (FRAP) assay, was also significantly enhanced. In an anti-inflammatory effect of lipopolysaccharide (LPS)-stimulated RAW 264.7 cells, the nitric oxide content and the expression of inducible nitric oxide synthase (iNOS), tumor necrosis factor-α (TNF-α), interleukin-1ß (IL-1ß), and interleukin-6 (IL-6) decreased when treated with fermented samples. Simultaneously, lipid accumulation in 3T3-L1 adipocyte was reduced when treated with fermented HPG. Fermentation by L. mesenteroides showed improved antioxidant, anti-inflammatory and anti-adipogenic HPG effects. These results show that fermented HPG has potential for applications in the functional food industry.
Assuntos
Adipogenia/efeitos dos fármacos , Anti-Inflamatórios/farmacologia , Antioxidantes/farmacologia , Fermentação , Leuconostoc mesenteroides , Panax/química , Panax/microbiologia , Animais , Anti-Inflamatórios/química , Antioxidantes/química , Flavonoides/química , Concentração de Íons de Hidrogênio , Macrófagos/efeitos dos fármacos , Macrófagos/metabolismo , Camundongos , Óxido Nítrico/metabolismo , Polifenóis , Células RAW 264.7RESUMO
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.
Assuntos
Células 3T3-L1 , Adipócitos , Adipogenia , Alcaloides , Benzodioxóis , Nanopartículas , Piperidinas , Alcamidas Poli-Insaturadas , Amido , Animais , Camundongos , Nanopartículas/química , Alcamidas Poli-Insaturadas/química , Alcamidas Poli-Insaturadas/farmacologia , Benzodioxóis/farmacologia , Benzodioxóis/química , Piperidinas/farmacologia , Piperidinas/química , Adipogenia/efeitos dos fármacos , Alcaloides/química , Alcaloides/farmacologia , Adipócitos/efeitos dos fármacos , Amido/química , Amido/análogos & derivados , Tamanho da Partícula , Liberação Controlada de Fármacos , Diferenciação Celular/efeitos dos fármacosRESUMO
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.
RESUMO
In this study, we investigated the probiotic properties and anti-obesity effects of bacterial strains isolated from homemade kimchi. Lactiplantibacillus plantarum KU15117 was isolated using lactobacilli selective medium. L. plantarum KU15117 did not produce ß-glucuronidase and showed high tolerance to artificial gastric juice and bile salt, acceptable resistance to antibiotics, and high adhesion ability to HT-29 cells. The anti-adipogenic activity of L. plantarum KU15117 at 109 CFU/well was confirmed by the reduction of oil red O staining and intracellular triglyceride level. Additionally, the expression levels of fatty acid synthase, CCAAT/enhance-binding protein-α, and peroxisome proliferator-activated receptor-γ, which are associated with the early stage of adipocyte differentiation, were significantly lower in the probiotic-treated group than in the control group. These results suggest that L. plantarum KU15117 has probiotic properties and anti-obesity effects and could be used as a prophylactic probiotics.
Assuntos
Adipogenia , Probióticos , Células 3T3-L1 , Adipócitos , Animais , Lactobacillaceae , Camundongos , Obesidade/metabolismo , Probióticos/farmacologiaRESUMO
Gentisic acid (GA), a benzoic acid derivative present in various food ingredients, has been shown to have diverse pharmaceutical activities such as anti-carcinogenic, antioxidant, and hepatoprotective effects. In this study, we used a co-culture system to investigate the mechanisms of the anti-inflammatory and anti-adipogenic effects of GA on macrophages and adipocytes, respectively, as well as its effect on obesity-related chronic inflammation. We found that GA effectively suppressed lipopolysaccharide-stimulated inflammatory responses by controlling the production of nitric oxide and pro-inflammatory cytokines and modulating inflammation-related protein pathways. GA treatment also inhibited lipid accumulation in adipocytes by modulating the expression of major adipogenic transcription factors and their upstream protein pathways. Furthermore, in the macrophage-adipocyte co-culture system, GA decreased the production of obesity-related cytokines. These results indicate that GA possesses effective anti-inflammatory and anti-adipogenic activities and may be used in developing treatments for the management of obesity-related chronic inflammatory diseases.
Assuntos
Adipogenia/efeitos dos fármacos , Anti-Inflamatórios/farmacologia , Gentisatos/farmacologia , Células 3T3-L1 , Adipócitos/efeitos dos fármacos , Adipócitos/metabolismo , Animais , Sobrevivência Celular/efeitos dos fármacos , Técnicas de Cocultura , Citocinas/metabolismo , Inflamação/metabolismo , Macrófagos/efeitos dos fármacos , Macrófagos/metabolismo , Camundongos , Proteínas Quinases Ativadas por Mitógeno/metabolismo , NF-kappa B/metabolismo , Óxido Nítrico/metabolismo , Células RAW 264.7 , Transdução de Sinais/efeitos dos fármacosRESUMO
Date seeds are a by-product of the date fruit processing industry with minimal human use; however, they are a rich source of polyphenols with a range of potential biological properties. The current study investigates the cytotoxicity of date seed polyphenols against cancer cell lines, its ability to combat hyperglycemia, its antioxidant potential and its anti-adipogenic effect. The present work aimed to establish the usefulness of date seeds in the food industry as a functional ingredient. The anti-tumour activity of DSE was tested in a panel of cell lines such as MCF-7, MDA-MB-231, Hep-G2, Caco-2, and PC-3 by measuring cell viability and cleaved PARP. Lipid accumulation and effect on the differentiation of 3T3-L1 cells (adipocytes) were tested with date seed extract treatments. The influence of date seed polyphenols on glucose uptake was studied in 3T3-L1 cells and C2C12 cells (muscle cells). The antioxidant activity of the polyphenols from date seed products such as date seed extract (DSE), date seed powder (DSP), and date seeds fortified bread (DSB) was tested following in-vitro digestion to study their stability in the gastrointestinal milieu. DSE treatment resulted in significantly reduced viability in MCF-7 and Hep-G2 cells with 48-h treatments. Glucose uptake increased in the adipocytes with DSE treatments; moreover, it inhibited adipocyte differentiation and lipid accumulation. DSE decreased the expression levels of PPAR-γ, C/EBPα, adiponectin and upregulated GLUT-4, and phospho-AMPK. This study also found that date seed samples retained antioxidant activity in the digestive milieu and concludes that the date seed polyphenols remain active in the digestive milieu and exhibit potential anti-hyperglycemic and anti-adipogenic activity.
RESUMO
BACKGROUND: Endogenously expressed microRNAs (miRNAs) have attracted attention as important regulators in post-transcriptionally controlling gene expression of various physiological processes. As miRNA dysregulation is often associated with various disease patterns, such as obesity, miRNA-27a might therefore be a promising candidate for miRNA mimic replacement therapy by inhibiting adipogenic marker genes. However, application of naked nucleic acids faces some limitations concerning poor enzymatic stability, bio-membrane permeation and cellular uptake. To overcome these obstacles, the development of appropriate drug delivery systems (DDS) for miRNAs is of paramount importance. METHODS: In this work, a triple combination of atomic force microscopy (AFM), brightfield (BF) and fluorescence microscopy was used to trace the cellular adhesion of N-TER peptide-nucleic acid complexes followed by time-dependent uptake studies using confocal laser scanning microscopy (cLSM). To reveal the biological effect of miRNA-27a on adipocyte development after transfection treatment, Oil-Red-O (ORO)- staining was performed to estimate the degree of in lipid droplets accumulated ORO in mature adipocytes by using light microscopy images as well as absorbance measurements. RESULTS: The present findings demonstrated that amphipathic N-TER peptides represent a suitable DDS for miRNAs by promoting non-covalent complexation through electrostatic interactions between both components as well as cellular adhesion of the N-TER peptide - nucleic acid complexes followed by uptake across cell membranes and intracellular release of miRNAs. The anti-adipogenic effect of miRNA-27a in 3T3-L1 cells could be detected in mature adipocytes by reduced lipid droplet formation. CONCLUSION: The present DDS assembled from amphipathic N-TER peptides and miRNAs is capable of inducing the anti-adipogenic effect of miRNA-27a by reducing lipid droplet accumulation in mature adipocytes. With respect to miRNA mimic replacement therapies, this approach might provide new therapeutic strategies to prevent or treat obesity and obesity-related disorders.