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1.
Mol Nutr Food Res ; 68(5): e2300539, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38332573

RESUMO

SCOPE: The rosehip (Rosa canina) is a perennial shrub with a reddish pseudofruit that has demonstrated antidiabetic, antiatherosclerotic, and antiobesogenic effects in rodent models but there is low information about the molecular mechanisms underlying these effects on the onset and progression of diet-induced obesity. METHODS AND RESULTS: Four-week-old C57BL/6J male mice are subjected to a high-fat diet (HFD)-supplemented or not with R. canina flesh for 18 weeks. The results indicated that the R. canina flesh exerts a preventive effect on HFD-induced obesity with a significant reduction in body-weight gain and an improvement of hyperglycemia and insulin resistance caused by a HFD. At the tissue level, subcutaneous white adipose tissue exhibits a higher number of smaller adipocytes, with decreased lipogenesis. On its side, the liver shows a significant decrease in lipid droplet content and in the expression of genes related to lipogenesis, fatty acid oxidation, and glucose metabolism. Finally, the data suggest that most of these effects agree with the presence of a putative Perosxisome proliferator-activated receptor gamma (PPARγ) antagonist in the R. canina flesh. CONCLUSIONS: R. canina flesh dietary supplementation slows down the steatotic effect of a HFD at least in part through the regulation of the transcriptional activity of PPARγ.


Assuntos
Fármacos Antiobesidade , Rosa , Animais , Camundongos , Dieta Hiperlipídica/efeitos adversos , PPAR gama/metabolismo , Rosa/metabolismo , Extratos Vegetais/farmacologia , Extratos Vegetais/metabolismo , Camundongos Endogâmicos C57BL , Obesidade/etiologia , Fármacos Antiobesidade/farmacologia , Fármacos Antiobesidade/metabolismo , Fígado/metabolismo
2.
Nutrients ; 15(24)2023 Dec 14.
Artigo em Inglês | MEDLINE | ID: mdl-38140369

RESUMO

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.


Assuntos
Fármacos Antiobesidade , Cinnamomum zeylanicum , Masculino , Animais , Camundongos , Células 3T3-L1 , Fármacos Antiobesidade/farmacologia , Fármacos Antiobesidade/metabolismo , Dieta Hiperlipídica/efeitos adversos , Adipócitos , Obesidade/etiologia , Obesidade/genética , Adipogenia , Extratos Vegetais/farmacologia , Extratos Vegetais/metabolismo , Lipídeos/farmacologia , Camundongos Endogâmicos C57BL , PPAR gama/metabolismo
3.
Ther Deliv ; 14(11): 675-687, 2023 11.
Artigo em Inglês | MEDLINE | ID: mdl-38018449

RESUMO

Aim: Obesity is a chronic pathology of epidemic proportions. Mature adipocytes from a 3T3-L1 cell line were used as in vitro obesity model to test different bioactive compounds. We aim to evaluate cassis (Ribes nigrum) extract antioxidant activity and its antiadipogenic effect on mature adipocytes. Results: We produced an extract by using enzyme that combines cellulase and pectinase; we obtained high yield of the bioactive compound anthocyanin. Extract showed high antioxidant capacity. We conducted in vitro assays by adding the extract to adipocytes culture medium. Extract reduced intracellular levels of triglyceride by 62% and cholesterol by 32%. Conclusion: Enzymatic extract's high antioxidant activity was likely attributable to its high concentration of anthocyanin. This extract inhibits lipid accumulation in adipocytes.


Obesity is a disease all over the world. By 2030, nearly 20% of adults are predicted to be obese. The consumption of processed foods is related to obesity in some countries such as Argentina. More natural food is needed. There are many different anti-obesity medicines but there is no good one to lose weight. We took extracts from cassis fruits and tested whether they could decrease fats like cholesterol within fat cells. We found that these extracts could successfully reduce the fat levels in the cells. Our results indicate that natural compounds like cassis fruit extract may be helpful in preventing future obesity epidemics.


Assuntos
Fármacos Antiobesidade , Ribes , Triglicerídeos/metabolismo , Triglicerídeos/farmacologia , Antocianinas/farmacologia , Adipogenia , Fármacos Antiobesidade/metabolismo , Fármacos Antiobesidade/farmacologia , Antioxidantes/farmacologia , Antioxidantes/metabolismo , Extratos Vegetais/farmacologia , Adipócitos/metabolismo , Obesidade/metabolismo , Colesterol
4.
J Med Food ; 25(7): 732-740, 2022 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-35723631

RESUMO

Obesity is one of the most common diseases caused by an imbalance in the intake and expenditure of energy, and it is associated with various metabolic complications. This study aimed at investigating the anti-obesity effects and mechanisms of porcine collagen peptide (PCP) using 3T3-L1 preadipocytes and high-fat diet (HFD)-fed mice. The PCP treatment significantly inhibited the adipocyte differentiation and attenuated the mRNA expression of transcription factors (CCAAT/enhancer-binding protein alpha [C/EBPα] and peroxisome proliferator-activated receptor gamma [PPARγ]) and the lipogenic gene (fatty acid synthase [FAS]) expression in 3T3-L1 preadipocytes. In the in vivo study, HFD-fed mice were fed low- (1.5 g/kg body weight/day) and high- (4.5 g/kg body weight/day) PCP for 12 weeks and compared with the normal diet-fed group and HFD-fed control group. The PCP-fed groups showed significantly lower body weight gain, white fat weight gain, serum triglycerides, and adipocyte size compared with the HFD-fed group. The changes in body fat were associated with the upregulation of adiponectin and the downregulation of leptin, C/EBPα, PPARγ, and FAS. These results suggest that PCP has the potential to reduce obesity by suppressing adipogenesis and could be applied as a functional food material.


Assuntos
Adipogenia , Fármacos Antiobesidade , Células 3T3-L1 , Adipócitos , Animais , Fármacos Antiobesidade/metabolismo , Fármacos Antiobesidade/farmacologia , Peso Corporal , Proteína alfa Estimuladora de Ligação a CCAAT/genética , Proteína alfa Estimuladora de Ligação a CCAAT/metabolismo , Colágeno/metabolismo , Dieta Hiperlipídica/efeitos adversos , Ácido Graxo Sintases/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Obesidade/metabolismo , PPAR gama/genética , PPAR gama/metabolismo , Peptídeos/farmacologia , Suínos , Aumento de Peso
5.
Nutrients ; 14(4)2022 Feb 18.
Artigo em Inglês | MEDLINE | ID: mdl-35215514

RESUMO

Polymethoxyflavones (PMFs) are flavonoids exclusively found in certain citrus fruits and have been reported to be beneficial to human health. Most studies have been conducted with PMFs isolated from citrus peels, while there is no study on PMFs isolated from leaves. In this study, we prepared a PMF-rich fraction (PRF) from the leaves of Citrus sunki Hort ex. Tanaka (Jinkyool) and investigated whether the PRF could improve metabolic decline in obese mice induced by a high-fat diet (HFD) for 5 weeks. The HFD-induced obese mice were assigned into HFD, OR (HFD + orlistat at 15.6 mg/kg of body weight/day), and PRF (HFD + 50, 100, and 200 mg/kg of body weight/day) groups. Orlistat and PRF were orally administered for 5 weeks. At the end of the experiment, the serum biochemical parameters, histology, and gene expression profiles in the tissues of each group were analyzed. The body weight gain of the obese mice was significantly reduced after orlistat and PRF administration for 5 weeks. PRF effectively improved HFD-induced insulin resistance and dyslipidemia. Histological analysis in the liver demonstrated that PRF decreased adipocyte size and potentially improved the liver function, as it inhibited the incidence of fatty liver. PRF activated AMP-activated protein kinase (AMPK), acetyl-CoA carboxylase (ACC), and hormone-sensitive lipase (HSL) in HFD-induced obese mice. Moreover, liver transcriptome analysis revealed that PRF administration enriched genes mainly related to fatty-acid metabolism and immune responses. Overall, these results suggest that the PRF exerted an anti-obesity effect via the modulation of lipid metabolism.


Assuntos
Fármacos Antiobesidade , Citrus , Animais , Fármacos Antiobesidade/metabolismo , Dieta Hiperlipídica/efeitos adversos , Fígado/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Obesos , Extratos Vegetais/metabolismo , Extratos Vegetais/farmacologia , Folhas de Planta/química
6.
Rev Cardiovasc Med ; 22(4): 1279-1293, 2021 Dec 22.
Artigo em Inglês | MEDLINE | ID: mdl-34957770

RESUMO

Medicinal plants have been used as an alternative medicine for obesity prevention, and Asian countries, which are major habitats of various medicinal plant species, have traditionally used these medicines for centuries. Obesity is a global health problem caused by excessive fat accumulation linked to abnormal lipid metabolism, such as adipogenesis, lipogenesis, and lipolysis. Accordingly, the effects of medicinal plants on obesity-related mechanisms and biomarkers have been evaluated in various experimental studies. For example, adipogenesis and lipogenesis are regulated by several transcription factors, such as peroxisome proliferator-activated receptor gamma, CCAAT/enhancer binding protein alpha, and fatty acid synthase. Moreover, activation of the adenosine monophosphate-activated protein kinase pathway is accompanied by promotion of lipolysis. However, few reports have consolidated studies of the effects of various Asian medicinal plants on obesity and related mechanisms. Therefore, in this review, we examined the associations of medicinal plants originating from Asian countries with obesity and discussed the related mechanisms and biomarkers from in vitro and in vivo studies.


Assuntos
Fármacos Antiobesidade , Plantas Medicinais , Células 3T3-L1 , Adipócitos/metabolismo , Animais , Fármacos Antiobesidade/efeitos adversos , Fármacos Antiobesidade/metabolismo , Humanos , Camundongos , Obesidade/tratamento farmacológico , Obesidade/epidemiologia , Extratos Vegetais/efeitos adversos
7.
Molecules ; 25(21)2020 Oct 26.
Artigo em Inglês | MEDLINE | ID: mdl-33114490

RESUMO

The naturopathic treatment of obesity is a matter of keen interest to develop efficient natural pharmacological routes for disease management with low or negligible toxicity and side effects. For this purpose, optimized ultrasonicated hydroethanolic extracts of Taraxacum officinale were evaluated for antiobesity attributes. The 2,2-diphenyl-1-picrylhydrazyl method was adopted to evaluate antioxidant potential. Porcine pancreatic lipase inhibitory assay was conducted to assess the in vitro antiobesity property. Ultra-high performance chromatography equipped with a mass spectrometer was utilized to profile the secondary metabolites in the most potent extract. The 60% ethanolic extract exhibited highest extract yield (25.05 ± 0.07%), total phenolic contents (123.42 ± 0.007 mg GAE/g DE), total flavonoid contents (55.81 ± 0.004 RE/g DE), DPPH-radical-scavenging activity (IC50 = 81.05 ± 0.96 µg/mL) and pancreatic lipase inhibitory properties (IC50 = 146.49 ± 4.24 µg/mL). The targeted metabolite fingerprinting highlighted the presence of high-value secondary metabolites. Molecular-binding energies computed by docking tool revealed the possible contribution towards pancreatic lipase inhibitory properties of secondary metabolites including myricetin, isomangiferin, icariside B4, kaempferol and luteolin derivatives when compared to the standard drug orlistat. In vivo investigations revealed a positive impact on the lipid profile and obesity biomarkers of obese mice. The study presents Taraxacum officinale as a potent source of functional bioactive ingredients to impart new insights into the existing pool of knowledge of naturopathic approaches towards obesity management.


Assuntos
Fármacos Antiobesidade/farmacologia , Metabolômica , Simulação de Acoplamento Molecular , Obesidade/tratamento farmacológico , Extratos Vegetais/farmacologia , Taraxacum/química , Animais , Fármacos Antiobesidade/metabolismo , Fármacos Antiobesidade/uso terapêutico , Peso Corporal/efeitos dos fármacos , Cromatografia Líquida de Alta Pressão , Etanol/química , Lipase/antagonistas & inibidores , Lipase/química , Lipase/metabolismo , Camundongos , Obesidade/metabolismo , Pâncreas/enzimologia , Extratos Vegetais/metabolismo , Extratos Vegetais/uso terapêutico , Conformação Proteica , Espectrometria de Massas em Tandem
8.
J Nutr Biochem ; 84: 108458, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32738734

RESUMO

Obesity is characterised by excessive accumulation of fat in white adipose tissue (WAT) which is compartmentalised into two anatomically and functionally diverse depots - visceral and subcutaneous. Advice to substitute essential polyunsaturated fatty acids (PUFAs) for saturated fatty acids is a cornerstone of various obesity management strategies. Despite an array of reports on the role of essential PUFAs on obesity, there still exists a lacuna on their mode of action in distinct depots i.e. visceral (VWAT) and subcutaneous (SWAT). The present study aimed to evaluate the effect of fish oil and corn oil on VWAT and SWAT in high-fat-diet-induced rodent model of obesity. Fish oil (FO) supplementation positively ameliorated the effects of HFD by regulating the anthropometrical and serum lipid parameters. FO led to an overall reduction in fat mass in both depots while specifically inducing beiging of adipocytes in SWAT as indicated by increased UCP1 and PGC1α. We also observed an upregulation of AMPKα and ACC1/2 phosphorylation on FO supplementation in SWAT suggesting a role of AMPK-PGC1α-UCP1 axis in beiging of adipose tissue. On the other hand, corn oil supplementation did not show any improvements in adipose tissue metabolism in both the depots of adipose tissue. The results were analysed using one-way ANOVA followed by Tukey's test in Graphpad Prism 5.0. Combined together our results suggest that n-3 PUFAs exert their anti-obesity effect by regulating adipokine secretion and inducing beiging of SWAT, hence increasing energy expenditure via thermogenic upregulation.


Assuntos
Fármacos Antiobesidade/farmacologia , Óleo de Milho/farmacologia , Dieta Hiperlipídica/efeitos adversos , Ácidos Graxos Ômega-3/farmacologia , Óleos de Peixe/farmacologia , Obesidade/metabolismo , Tecido Adiposo Marrom/efeitos dos fármacos , Tecido Adiposo Marrom/metabolismo , Tecido Adiposo Branco/efeitos dos fármacos , Tecido Adiposo Branco/metabolismo , Animais , Fármacos Antiobesidade/metabolismo , Óleo de Milho/metabolismo , Suplementos Nutricionais , Metabolismo Energético/efeitos dos fármacos , Ácidos Graxos Ômega-3/metabolismo , Óleos de Peixe/metabolismo , Gordura Intra-Abdominal/efeitos dos fármacos , Gordura Intra-Abdominal/metabolismo , Masculino , Obesidade/etiologia , Obesidade/prevenção & controle , Ratos Wistar , Gordura Subcutânea/efeitos dos fármacos , Gordura Subcutânea/metabolismo
9.
Arch Biochem Biophys ; 686: 108364, 2020 06 15.
Artigo em Inglês | MEDLINE | ID: mdl-32315653

RESUMO

Fucoxanthin (Fx), a major carotenoid found in brown seaweed, is known to show a unique and wide variety of biological activities. Upon absorption, Fx is metabolized to fucoxanthinol and amarouciaxanthin, and these metabolites mainly accumulate in visceral white adipose tissue (WAT). As seen in other carotenoids, Fx can quench singlet oxygen and scavenge a wide range of free radicals. The antioxidant activity is related to the neuroprotective, photoprotective, and hepatoprotective effects of Fx. Fx is also reported to show anti-cancer activity through the regulation of several biomolecules and signaling pathways that are involved in either cell cycle arrest, apoptosis, or metastasis suppression. Among the biological activities of Fx, anti-obesity is the most well-studied and most promising effect. This effect is primarily based on the upregulation of thermogenesis by uncoupling protein 1 expression and the increase in the metabolic rate induced by mitochondrial activation. In addition, Fx shows anti-diabetic effects by improving insulin resistance and promoting glucose utilization in skeletal muscle.


Assuntos
Suplementos Nutricionais/análise , Alga Marinha/química , Xantofilas/química , Xantofilas/metabolismo , Tecido Adiposo Branco/efeitos dos fármacos , Tecido Adiposo Branco/metabolismo , Animais , Fármacos Antiobesidade/química , Fármacos Antiobesidade/metabolismo , Antioxidantes/química , Antioxidantes/metabolismo , Descoberta de Drogas , Radicais Livres/metabolismo , Regulação da Expressão Gênica/efeitos dos fármacos , Humanos , Hipoglicemiantes/química , Hipoglicemiantes/metabolismo , Resistência à Insulina , Fígado/metabolismo , Estrutura Molecular , Fármacos Neuroprotetores/química , Fármacos Neuroprotetores/metabolismo , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Receptores Depuradores/metabolismo , Oxigênio Singlete/metabolismo , Proteína Desacopladora 1/química , Proteína Desacopladora 1/metabolismo , Xantofilas/efeitos adversos , beta Caroteno/análogos & derivados , beta Caroteno/química
10.
J Sci Food Agric ; 100(3): 897-903, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31588996

RESUMO

Tea polyphenols (TP) are the main components in tea. Studies in vitro have shown they have significant biological activity; however, the results are inconsistent with experiments in vivo. For the low bioavailability, most TP are thought to remain in the gut and metabolized by intestinal bacteria. In the gut, the unabsorbed TP are metabolized to a variety of derivative products by intestinal flora, which may accumulate to exert beneficial effects. Numerous studies have shown that TP can inhibit obesity and its related metabolism disorders effectively. Meanwhile, it has demonstrated that TP and their derivatives may modulate intestinal micro-ecology. The understanding of the interaction between TP and intestinal microbiota will allow us to better evaluate the contribution of microbial metabolites of TP to anti-obesity activity. This review showed implications for the use of TP as functional food with potential therapeutic utility against obesity by modulating intestinal microbiota, contributing to the improvement of human health. © 2019 Society of Chemical Industry.


Assuntos
Fármacos Antiobesidade/metabolismo , Obesidade/metabolismo , Obesidade/microbiologia , Polifenóis/metabolismo , Chá/metabolismo , Animais , Fármacos Antiobesidade/análise , Camellia sinensis/química , Camellia sinensis/metabolismo , Microbioma Gastrointestinal , Humanos , Polifenóis/análise , Chá/química
11.
Biomed Environ Sci ; 32(8): 578-591, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31488234

RESUMO

OBJECTIVE: We aimed to explore how fermented barley extracts with Lactobacillus plantarum dy-1 (LFBE) affected the browning in adipocytes and obese rats. METHODS: In vitro, 3T3-L1 cells were induced by LFBE, raw barley extraction (RBE) and polyphenol compounds (PC) from LFBE to evaluate the adipocyte differentiation. In vivo, obese SD rats induced by high fat diet (HFD) were randomly divided into three groups treated with oral gavage: (a) normal control diet with distilled water, (b) HFD with distilled water, (c) HFD with 800 mg LFBE/kg body weight (bw). RESULTS: In vitro, LFBE and the PC in the extraction significantly inhibited adipogenesis and potentiated browning of 3T3-L1 preadipocytes, rather than RBE. In vivo, we observed remarkable decreases in the body weight, serum lipid levels, white adipose tissue (WAT) weights and cell sizes of brown adipose tissues (BAT) in the LFBE group after 10 weeks. LFBE group could gain more mass of interscapular BAT (IBAT) and promote the dehydrogenase activity in the mitochondria. And LFBE may potentiate process of the IBAT thermogenesis and epididymis adipose tissue (EAT) browning via activating the uncoupling protein 1 (UCP1)-dependent mechanism to suppress the obesity. CONCLUSION: These results demonstrated that LFBE decreased obesity partly by increasing the BAT mass and the energy expenditure by activating BAT thermogenesis and WAT browning in a UCP1-dependent mechanism.


Assuntos
Adipócitos/efeitos dos fármacos , Fármacos Antiobesidade/metabolismo , Lactobacillus plantarum/química , Obesidade/tratamento farmacológico , Probióticos/metabolismo , Proteína Desacopladora 1/metabolismo , Células 3T3 , Adipócitos/fisiologia , Tecido Adiposo Marrom/efeitos dos fármacos , Tecido Adiposo Marrom/fisiologia , Tecido Adiposo Branco/efeitos dos fármacos , Tecido Adiposo Branco/fisiologia , Ração Animal/análise , Animais , Fármacos Antiobesidade/administração & dosagem , Diferenciação Celular/efeitos dos fármacos , Dieta , Fermentação , Hordeum/química , Masculino , Camundongos , Obesidade/genética , Extratos Vegetais/química , Probióticos/administração & dosagem , Distribuição Aleatória , Ratos , Ratos Sprague-Dawley , Proteína Desacopladora 1/genética
12.
Food Funct ; 10(6): 3502-3513, 2019 Jun 19.
Artigo em Inglês | MEDLINE | ID: mdl-31143917

RESUMO

Obesity is a chronic metabolic disorder that is associated with higher risks of developing diabetes and cardiovascular disease. Chinese dark tea is a fermented beverage with many biological effects and could be considered for the management of obesity. This study is aimed to assess the possible anti-obesity properties of instant dark tea (IDT) and instant pu-erh tea (PET) in high fat diet (HFD)-fed mice. Male C57BL/6 mice were divided into 5 groups. They received low-fat diet (LFD), HFD, HFD supplemented with drinking IDT infusion (5 mg mL-1), PET infusion (5 mg mL-1) or water for 8 weeks. The results showed IDT exhibited better inhibitory effect than PET on body weight gain and visceral fat weights. IDT also improved the serum high-density lipoprotein cholesterol (HDL-C) level, but decreased the low-density lipoprotein cholesterol (LDL-C) and leptin levels more effectively than PET. Both IDT and PET lowered the levels of aspartate aminotransferase (AST) and alanine aminotransferase (ALT) in the plasma and significantly increased the ratio of albumin to globin (A/G) in the serum compared to the control group. IDT treatment reduced the malondialdehyde (MDA) level in the liver. Histomorphology evidenced that the liver tissue architecture was well preserved by IDT administration. Moreover, IDT regulated the expression of obesity-related genes more effectively than PET. Overall, the present findings have provided the proof of concept that dietary IDT could provide a safer and cost-effective option for people with HFD-induced obesity.


Assuntos
Fármacos Antiobesidade/metabolismo , Obesidade/dietoterapia , Extratos Vegetais/metabolismo , Alanina Transaminase/metabolismo , Animais , Camellia sinensis/química , Camellia sinensis/metabolismo , LDL-Colesterol/metabolismo , Dieta Hiperlipídica/efeitos adversos , Alimentos Fermentados/análise , Humanos , Gordura Intra-Abdominal/metabolismo , Leptina/metabolismo , Fígado/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Obesidade/etiologia , Obesidade/metabolismo , Chá/metabolismo
13.
J Med Food ; 22(3): 264-270, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30672719

RESUMO

The anti-obesity effects of fermented Castanea crenata inner shell extract (FCCE) were investigated using high-fat diet (HFD)-induced obese mice. In the FCCE intake groups, body weight gain and adipocyte area were significantly reduced, especially body weight gain in the 250 mg/kg FCCE group (G4) decreased by 37%, respectively, compared with negative control group (G2, HFD group). After oral administration of the FCCE, the increase of serum low-density lipoprotein (LDL)-cholesterol induced by HFD was suppressed significantly, as well as the level of aspartate aminotransferase, and alanine aminotransferase, which are markers of hepatitis induced by obesity. Serum leptin in G4 group was significantly decreased to less than that of G2 group. Also, in G4 and 500 mg/kg FCCE group (G5), enzymes-related lipogenesis, citrate synthase, and ATP citrate lyase were decreased, whereas the level of enoyl-CoA hydratase used for ß-oxidation was significantly increased in comparison with normal diet group. Furthermore, the FCCE stimulated the expression of lipolytic regulators, especially AMP-activated protein kinase. In conclusion, we suggest that the FCCE may ameliorate in diet-induced obesity by regulating lipid metabolism.


Assuntos
Fármacos Antiobesidade/administração & dosagem , Fagaceae/metabolismo , Obesidade/tratamento farmacológico , Extratos Vegetais/administração & dosagem , Proteínas Quinases Ativadas por AMP/metabolismo , ATP Citrato (pro-S)-Liase/metabolismo , Animais , Fármacos Antiobesidade/metabolismo , LDL-Colesterol/metabolismo , Dieta Hiperlipídica/efeitos adversos , Fagaceae/química , Fagaceae/microbiologia , Humanos , Leptina/sangue , Lipogênese/efeitos dos fármacos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Obesos , Obesidade/metabolismo , Obesidade/fisiopatologia , Extratos Vegetais/metabolismo , Saccharomyces cerevisiae/metabolismo , Triglicerídeos/metabolismo
14.
J Med Chem ; 61(24): 11144-11157, 2018 12 27.
Artigo em Inglês | MEDLINE | ID: mdl-30525586

RESUMO

Celastrol is a natural pentacyclic triterpene used in traditional Chinese medicine with significant weight-lowering effects. Celastrol-administered mice at 100 µg/kg decrease food consumption and body weight via a leptin-dependent mechanism, yet its molecular targets in this pathway remain elusive. Here, we demonstrate in vivo that celastrol-induced weight loss is largely mediated by the inhibition of leptin negative regulators protein tyrosine phosphatase (PTP) 1B (PTP1B) and T-cell PTP (TCPTP) in the arcuate nucleus (ARC) of the hypothalamus. We show in vitro that celastrol binds reversibly and inhibits noncompetitively PTP1B and TCPTP. NMR data map the binding site to an allosteric site in the catalytic domain that is in proximity of the active site. By using a panel of PTPs implicated in hypothalamic leptin signaling, we show that celastrol additionally inhibited PTEN and SHP2 but had no activity toward other phosphatases of the PTP family. These results suggest that PTP1B and TCPTP in the ARC are essential for celastrol's weight lowering effects in adult obese mice.


Assuntos
Fármacos Antiobesidade/farmacologia , Obesidade/tratamento farmacológico , Proteína Tirosina Fosfatase não Receptora Tipo 1/antagonistas & inibidores , Proteína Tirosina Fosfatase não Receptora Tipo 2/antagonistas & inibidores , Triterpenos/farmacologia , Sítio Alostérico , Animais , Fármacos Antiobesidade/metabolismo , Domínio Catalítico , Dieta Hiperlipídica/efeitos adversos , Hipotálamo/efeitos dos fármacos , Hipotálamo/metabolismo , Espectroscopia de Ressonância Magnética , Masculino , Camundongos Transgênicos , Obesidade/etiologia , Triterpenos Pentacíclicos , Proteína Tirosina Fosfatase não Receptora Tipo 1/química , Proteína Tirosina Fosfatase não Receptora Tipo 1/genética , Proteína Tirosina Fosfatase não Receptora Tipo 1/metabolismo , Proteína Tirosina Fosfatase não Receptora Tipo 2/química , Proteína Tirosina Fosfatase não Receptora Tipo 2/genética , Proteína Tirosina Fosfatase não Receptora Tipo 2/metabolismo , Relação Estrutura-Atividade , Triterpenos/química , Triterpenos/metabolismo , Redução de Peso/efeitos dos fármacos
15.
J Nutr Sci Vitaminol (Tokyo) ; 64(5): 347-356, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30381625

RESUMO

Marine carotenoids have been reported to prevent and alleviate lifestyle-related diseases including diabetes and obesity. We previously reported that siphonaxanthin, a green algal carotenoid, effectively suppresses adipogenesis in 3T3-L1 cells and prevents lipid accumulation in mesenteric adipose tissue of KK-Ay mice. Thus, we expect that dietary siphonaxanthin-rich marine green algae may effectively prevent obesity. Here, we assessed the effect of dietary siphonaxanthin-rich green algae (Codium cylindricum) on the development of diet-induced obesity in C57BL/6J mice. The mice were fed a low-fat diet (LF; 7% fat, w/w), a high-fat diet (HF; 35% fat, w/w), or a high-fat diet supplemented with 1% or 5% green algal powder (1GA or 5GA) for 78 d. Our results showed that weights of body and perirenal white adipose tissue (WAT) in the 5GA group were significantly lower than that in the HF group. The mesenteric and total WAT, as well as plasma and hepatic cholesterol concentrations tended to be lower in both the 1GA and 5GA groups compared to the HF group. Dietary green algal powder reduced the expression of lipogenesis-related genes and enhanced the expression of energy expenditure-related genes in the mesenteric WAT. Siphonaxanthin accumulated in the mesenteric WAT may contribute to the prevention of adiposity in mesenteric WAT. Furthermore, the reduction in the weight of WAT was attributed to the inhibitory effect on fat absorption of dietary fiber contained in the green algae. Overall, these results indicated that siphonaxanthin-rich green algae may be beneficial for the prevention of obesity and regulation of lipid metabolism.


Assuntos
Tecido Adiposo Branco/metabolismo , Peso Corporal/efeitos dos fármacos , Clorófitas/química , Dieta Hiperlipídica , Metabolismo dos Lipídeos/efeitos dos fármacos , Obesidade/tratamento farmacológico , Xantofilas/uso terapêutico , Adiposidade , Animais , Fármacos Antiobesidade/metabolismo , Fármacos Antiobesidade/farmacologia , Fármacos Antiobesidade/uso terapêutico , Colesterol/sangue , Colesterol/metabolismo , Fibras na Dieta/farmacologia , Fibras na Dieta/uso terapêutico , Suplementos Nutricionais , Metabolismo Energético/genética , Expressão Gênica , Absorção Intestinal/efeitos dos fármacos , Gordura Intra-Abdominal/efeitos dos fármacos , Gordura Intra-Abdominal/metabolismo , Metabolismo dos Lipídeos/genética , Fígado/efeitos dos fármacos , Fígado/metabolismo , Masculino , Mesentério/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Obesos , Obesidade/etiologia , Xantofilas/metabolismo , Xantofilas/farmacologia
16.
J Med Food ; 21(11): 1113-1119, 2018 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-30457472

RESUMO

Black-fruited chokeberries (Aronia melanocarpa), growing mainly in the Central and Eastern European countries, have health benefits due to the high concentrations of polyphenolic compounds. However, a strong bitter taste of chokeberries limits its usage as functional food. We hypothesized that the fermented A. melanocarpa with a reduced bitter taste would improve insulin sensitivity and/or ameliorate weight gain induced by high-fat diet (HFD) in male C57BL/6J mice. The mice were administered with HFD together with the 100 mg/kg of natural A. melanocarpa (T1) or the fermented A. melanocarpa (T2) for 8 weeks. The treatment with T2 (100 mg/kg body weight, p.o.) markedly attenuated the weight gain and the increase in serum triglyceride level induced by HFD. The T2-treated group had better glucose tolerance and higher insulin sensitivity as measured by oral glucose tolerance test and intraperitoneal insulin tolerance test in comparison to the T1-treated group. Phytochemical analysis revealed that the main constituents of T2 were cyanidin-3-xyloside and 1-(3',4'-dihydroxycinnamoyl)cyclopenta-2,3-diol, and the content of cyanidin glycosides (3-glucoside, 3-xyloside) was significantly reduced during the fermentation process. From the above results, we postulated that antiobesity effect of black chokeberry was not closely correlated with the cyanidin content. Fermented chokeberry might be a viable dietary supplement rich in bioactive compounds useful in preventing obesity.


Assuntos
Acetobacter/metabolismo , Fármacos Antiobesidade/metabolismo , Alimentos Fermentados/análise , Obesidade/dietoterapia , Photinia/microbiologia , Extratos Vegetais/metabolismo , Saccharomyces/metabolismo , Animais , Antocianinas/administração & dosagem , Antocianinas/química , Antocianinas/metabolismo , Fármacos Antiobesidade/química , Dieta Hiperlipídica/efeitos adversos , Fermentação , Alimentos Fermentados/microbiologia , Frutas/química , Frutas/metabolismo , Frutas/microbiologia , Humanos , Insulina/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Obesos , Obesidade/etiologia , Obesidade/metabolismo , Photinia/química , Photinia/metabolismo , Extratos Vegetais/química
17.
J Med Food ; 21(9): 927-934, 2018 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-30183503

RESUMO

Dietary chitosan is known for its antiobesity effects by combining with bile acid and lipid droplets. When the chitosan structure is broken into short chains, the fat-binding capacity increases. The aim of this study was to compare long-chain chitosan (LC) with short-chain chitosan (SC) for their antiobesity effects in high-fat diet (HFD)-induced obese C57BL/6J mice for 12 weeks. The body weights of mice in both chitosan groups were decreased, especially in the SC group compared with the LC group. Total white adipose tissue and visceral fat weights were also decreased in mice of the SC group more than those of the HFD group. Moreover, SC supplementation lowered plasma triglyceride (TG) and cholesterol levels, whereas LC only lowered plasma free fatty acid level. Fecal lipids were increased in mice of both LC and SC groups, and hepatic TG and cholesterol levels were decreased in both groups. SC lowered phosphatidate phosphohydrolase activity and elevated ß-oxidation in the liver. Furthermore, SC decreased the expression of the hepatic lipid-regulating genes, including fatty acid synthase, peroxisome proliferator-activated receptor (PPAR)γ1, and PPARγ2; and increased the expression of carnitine palmitoyl transferase 1α and peroxisome proliferator-activated receptor γ coactivator (PGC)1α genes. In conclusion, we demonstrated that long-term supplementation of SC can ameliorate body weight and lipid levels by increasing lipid excretion and regulating lipid metabolism, including some enzyme activities and gene expression levels, in HFD-induced obese mice.


Assuntos
Fármacos Antiobesidade/metabolismo , Quitosana/metabolismo , Obesidade/dietoterapia , Tecido Adiposo/efeitos dos fármacos , Tecido Adiposo/metabolismo , Animais , Fármacos Antiobesidade/química , Peso Corporal/efeitos dos fármacos , Quitosana/química , Dieta Hiperlipídica/efeitos adversos , Feminino , Humanos , Metabolismo dos Lipídeos/efeitos dos fármacos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Obesos , Obesidade/genética , Obesidade/metabolismo , Obesidade/fisiopatologia , Coativador 1-alfa do Receptor gama Ativado por Proliferador de Peroxissomo/genética , Coativador 1-alfa do Receptor gama Ativado por Proliferador de Peroxissomo/metabolismo , Receptores Ativados por Proliferador de Peroxissomo/genética , Receptores Ativados por Proliferador de Peroxissomo/metabolismo , Triglicerídeos/metabolismo
18.
J Physiol Biochem ; 74(4): 647-654, 2018 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-30232707

RESUMO

To fight against metabolic disorders such as insulin resistance, new alimentary behaviors are developed. For instance, hyperproteined, gluten-free, or collagen-enriched diets could be preconized in order to reduce the consequences of obesity. In this aim, this study evaluates the potential effects of warm sea fish collagen peptides (Naticol®) on representative metabolic and inflammatory parameters. For that, male C57Bl6/J mice fed with either a chow- (CD) or high-fat diet (HFD) were submitted or not to specific collagen peptides in drinking water (4 g/kg bw/d) for 20 weeks. Weight, body composition, glucose tolerance, and insulin sensitivity were followed up. Effects of fish collagen peptides on various blood parameters reflecting the metabolism status were also measured (free fatty acids, triglycerides, cholesterol, hormones) together with adipocyte inflammation. Results showed that HFD-fed mice supplemented by fish collagen peptides exhibited a significant lower increase in body weight as soon as the twelfth week of treatment whereas no effect of the peptide was observed in CD fed mice. In line with this result, a weaker increase in fat mass in HFD-fed mice supplemented with Naticol® at both 9 and 18 weeks of treatment was also observed. In spite of this resistance to obesity promoted by fish collagen peptides treatment, no difference in glucose tolerance was found between groups whereas mice treated with Naticol® exhibited a lower basal glycemia. Also, even if no effect of the treatment on adipocyte lipolysis was found, a decrease of inflammatory cytokines was retrieved in collagen-supplemented group arguing for a potential better insulin sensitivity. Altogether, these results need to be completed but are the first describing a benefic role of warm sea fish collagen peptides in a context of metabolic disease paving the route for a potential utilization in human obesity-associated disorders.


Assuntos
Fármacos Antiobesidade/uso terapêutico , Colágeno/uso terapêutico , Suplementos Nutricionais , Proteínas de Peixes da Dieta/uso terapêutico , Resistência à Insulina , Obesidade/terapia , Fragmentos de Peptídeos/uso terapêutico , Tecido Adiposo/imunologia , Tecido Adiposo/metabolismo , Animais , Anti-Inflamatórios não Esteroides/efeitos adversos , Anti-Inflamatórios não Esteroides/química , Anti-Inflamatórios não Esteroides/metabolismo , Anti-Inflamatórios não Esteroides/uso terapêutico , Fármacos Antiobesidade/efeitos adversos , Fármacos Antiobesidade/química , Fármacos Antiobesidade/metabolismo , Apelina/agonistas , Apelina/genética , Apelina/metabolismo , Colágeno/efeitos adversos , Colágeno/química , Colágeno/metabolismo , Citocinas/antagonistas & inibidores , Citocinas/genética , Citocinas/metabolismo , Dieta Hiperlipídica/efeitos adversos , Suplementos Nutricionais/efeitos adversos , Proteínas de Peixes da Dieta/efeitos adversos , Proteínas de Peixes da Dieta/química , Proteínas de Peixes da Dieta/metabolismo , Regulação da Expressão Gênica , Intolerância à Glucose/etiologia , Intolerância à Glucose/imunologia , Intolerância à Glucose/prevenção & controle , Lipólise , Masculino , Camundongos Endogâmicos C57BL , Obesidade/etiologia , Obesidade/metabolismo , Obesidade/fisiopatologia , Paniculite/etiologia , Paniculite/imunologia , Paniculite/prevenção & controle , Fragmentos de Peptídeos/efeitos adversos , Fragmentos de Peptídeos/química , Fragmentos de Peptídeos/metabolismo , Aumento de Peso
19.
Food Funct ; 9(10): 5260-5272, 2018 Oct 17.
Artigo em Inglês | MEDLINE | ID: mdl-30238111

RESUMO

This study aimed to investigate the effects of supplementation with bacterial cellulose (BC), konjac glucomannan (KGM) and combined BC/KGM fiber on high-fat (HF)-diet-induced obesity in C57BL/6J mice. The results showed that combined supplementation with BC/KGM in HF-fed mice was more efficient in reducing body weight, lowing serum lipid profiles and suppressing insulin resistance than single supplementation with BC or KGM. Moreover, supplementation with combined BC/KGM fiber more efficiently alleviated HF-diet-induced liver injury by decreasing hepatic steatosis in comparison with supplementation with BC or KGM alone. Furthermore, supplementation with combined BC/KGM fiber in HF-fed mice had a more positive effect on obesity-associated hepatic inflammation by reducing levels of TNF-α and IL-6 and suppressing the protein expression of Nrf-2/ARE in comparison with supplementation with BC or KGM alone. Consumption of these dietary fibers, especially mixed BC/KGM, resulted in an improved antioxidant defense system and reduced lipid peroxidation in the liver by increasing the activity of antioxidant enzymes and reducing the formation of MDA in the liver. Moreover, supplementation with these fibers regulated the levels of leptin and adiponectin and inhibited the protein expression of PPARγ by reducing the size of cells in the adipose tissue of HF diet-fed mice. Therefore, fiber supplementation (especially with combined BC/KGM) efficiently inhibited HF-induced obesity in mice by reducing insulin resistance, liver injury and inflammation, enhancing the antioxidant defense system and regulating the secretion of adipocytokines and adipogenesis-associated proteins.


Assuntos
Amorphophallus/química , Fármacos Antiobesidade/metabolismo , Celulose/metabolismo , Mananas/metabolismo , Obesidade/dietoterapia , Extratos Vegetais/metabolismo , Polissacarídeos Bacterianos/metabolismo , Adipogenia , Adipocinas/metabolismo , Tecido Adiposo/metabolismo , Amorphophallus/metabolismo , Animais , Dieta Hiperlipídica/efeitos adversos , Gluconacetobacter/química , Gluconacetobacter/metabolismo , Humanos , Interleucina-6/genética , Interleucina-6/metabolismo , Peroxidação de Lipídeos , Fígado/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Fator 2 Relacionado a NF-E2/genética , Fator 2 Relacionado a NF-E2/metabolismo , Obesidade/genética , Obesidade/metabolismo , Obesidade/fisiopatologia , PPAR gama/genética , PPAR gama/metabolismo , Triglicerídeos/metabolismo
20.
Molecules ; 23(8)2018 Jul 28.
Artigo em Inglês | MEDLINE | ID: mdl-30060551

RESUMO

BACKGROUND: The use of resveratrol as a dietary supplement is limited because it is easily oxidized and, after oral ingestion, it is metabolized into enterocytes and hepatocytes. Thus, new formulations are needed in order to improve its oral bioavailability. OBJECTIVE: The objective of this study was to develop and characterize a gastro-resistant formulation of resveratrol for oral administration as a dietary supplement. METHOD: Resveratrol was encapsulated in Eudragit-coated pectin-alginate microparticles. RESULTS: The microparticle size was about 1450 µm, with an encapsulation efficiency of 41.72% ± 1.92%. The dissolution assay conducted, as specified in the European Pharmacopoeia for delayed-release dosage forms, revealed that our microparticles were gastro-resistant, because the resveratrol percentage released from microparticles in acid medium was less than 10%. In addition, the high-performance liquid chromatographic (HPLC) method developed for resveratrol content quantification in the microparticles was validated according to International Council for Harmonisation (ICH) Q2 (R1) guidelines. Finally, the biological activity of resveratrol was investigated in 3T3-L1 mature adipocytes, concluding that the encapsulation process does not affect the activity of resveratrol. CONCLUSION: In summary, the gastro-resistant microparticles developed could represent a suitable method of including resveratrol in dietary supplements and in functional foods used in obesity therapy.


Assuntos
Alginatos/química , Fármacos Antiobesidade/farmacologia , Preparações de Ação Retardada , Pectinas/química , Estilbenos/farmacologia , Triglicerídeos/antagonistas & inibidores , Células 3T3-L1 , Adipócitos/citologia , Adipócitos/efeitos dos fármacos , Adipócitos/metabolismo , Animais , Fármacos Antiobesidade/metabolismo , Materiais Biomiméticos/química , Materiais Biomiméticos/farmacologia , Cápsulas , Diferenciação Celular , Suplementos Nutricionais/análise , Composição de Medicamentos/métodos , Liberação Controlada de Fármacos/efeitos dos fármacos , Suco Gástrico/química , Ácido Glucurônico/química , Ácidos Hexurônicos/química , Humanos , Concentração de Íons de Hidrogênio , Cinética , Camundongos , Tamanho da Partícula , Ácidos Polimetacrílicos/química , Resveratrol , Estilbenos/metabolismo , Triglicerídeos/biossíntese
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