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1.
Plast Reconstr Surg ; 146(2): 309-320, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32740581

RESUMO

BACKGROUND: Adipose-derived stem cells are considered as candidate cells for regenerative plastic surgery. Measures to influence cellular properties and thereby direct their regenerative potential remain elusive. Hyperbaric oxygen therapy-the exposure to 100% oxygen at an increased atmospheric pressure-has been propagated as a noninvasive treatment for a multitude of indications and presents a potential option to condition cells for tissue-engineering purposes. The present study evaluates the effect of hyperbaric oxygen therapy on human adipose-derived stem cells. METHODS: Human adipose-derived stem cells from healthy donors were treated with hyperbaric oxygen therapy at 2 and 3 atm. Viability before and after each hyperbaric oxygen therapy, proliferation, expression of surface markers and protein contents of transforming growth factor (TGF)-ß, tumor necrosis factor-α, hepatocyte growth factor, and epithelial growth factor in the supernatants of treated adipose-derived stem cells were measured. Lastly, adipogenic, osteogenic, and chondrogenic differentiation with and without use of differentiation-inducing media (i.e., autodifferentiation) was examined. RESULTS: Hyperbaric oxygen therapy with 3 atm increased viability, proliferation, and CD34 expression and reduced the CD31/CD34/CD45 adipose-derived stem cell subset and endothelial progenitor cell population. TGF-ß levels were significantly decreased after two hyperbaric oxygen therapy sessions in the 2-atm group and decreased after three hyperbaric oxygen therapy sessions in the 3-atm group. Hepatocyte growth factor secretion remained unaltered in all groups. Although the osteogenic and chondrogenic differentiation were not influenced, adipogenic differentiation and autodifferentiation were significantly enhanced, with osteogenic autodifferentiation significantly alleviated by hyperbaric oxygen therapy with 3 atm. CONCLUSION: Hyperbaric oxygen therapy with 3 atm increases viability and proliferation of adipose-derived stem cells, alters marker expression and subpopulations, decreases TGF-ß secretion, and skews adipose-derived stem cells toward adipogenic differentiation. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, V.


Assuntos
Adipogenia/efeitos dos fármacos , Diferenciação Celular/efeitos dos fármacos , Engenharia Celular/métodos , Células-Tronco Mesenquimais/efeitos dos fármacos , Oxigênio/administração & dosagem , Tecido Adiposo/citologia , Adulto , Biomarcadores/metabolismo , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Células Cultivadas , Citocinas/metabolismo , Feminino , Humanos , Peptídeos e Proteínas de Sinalização Intercelular/metabolismo , Masculino , Células-Tronco Mesenquimais/fisiologia , Pessoa de Meia-Idade , Pressão , Cultura Primária de Células/métodos
2.
Cell Prolif ; 53(8): e12871, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32597546

RESUMO

OBJECTIVES: Osteonecrosis of the femoral head (ONFH), largely caused by alcohol abuse, is a refractory bone disease characterized by the impaired capacity of osteogenic differentiation of bone mesenchymal stem cells (BMSCs), as well as the disordered adipocyte accumulation. Chrysophanic acid (CPA) is a natural anthraquinone which has lipid regulation and bone protection capacity. The aim of this study was to reveal the potential function of CPA and the underlying mechanisms for the alcohol-induced ONFH. MATERIALS AND METHODS: The effects of alcohol and CPA on BMSCs were investigated by cell proliferation, induced differentiation assays and immunofluorescent staining. Meanwhile, the function of PI3K/AKT and AMPK pathway was investigated in the process of osteogenic and adipogenic differentiation, respectively. Furthermore, we established the rat model of alcohol-induced ONFH to reveal the pharmacotherapeutic effect of CPA in vivo using radiographical and histopathological methods. RESULTS: In vitro, alcohol significantly inhibited the proliferation and osteogenic differentiation of BMSCs but stimulated the adipogenic differentiation. However, CPA could counteract the anti-osteogenesis of alcohol partly via PI3K/AKT pathway and retard the promotion of alcohol-induced adipogenesis via AMPK pathway. In vivo, radiographical and histopathological findings showed that CPA could alleviate alcohol-induced ONFH and substantially restore the bone volume. CONCLUSIONS: We demonstrated that CPA ameliorated alcohol-induced ONFH possibly via regulating the differentiation tendency of BMSCs. Hence, CPA may become a beneficial herb extract to alleviate alcohol-induced ONFH.


Assuntos
Antraquinonas/farmacologia , Proliferação de Células/efeitos dos fármacos , Cabeça do Fêmur/patologia , Células-Tronco Mesenquimais/efeitos dos fármacos , Osteogênese/efeitos dos fármacos , Osteonecrose/patologia , Adipogenia/efeitos dos fármacos , Animais , Diferenciação Celular/efeitos dos fármacos , Cabeça do Fêmur/efeitos dos fármacos , Células-Tronco Mesenquimais/citologia , Ratos Sprague-Dawley
3.
PLoS One ; 15(6): e0234641, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32574164

RESUMO

Chondrocytes, comparable to many cells from the connective tissue, dedifferentiate and end up in a similar fibroblastoid cell type, marked by the loss of the specific expression pattern. Here, chondrocytes isolated from osteoarthritic (OA) patients were investigated. The OA chondrocytes used in this work were not affected by the loss of specific gene expression upon cell culture. The mRNA levels of known cartilage markers, such as SOX5, SOX6, SOX9, aggrecan and proteoglycan 4, remained unchanged. Since chondrocytes from OA and healthy tissue show different DNA methylation patterns, the underlying mechanisms of cartilage marker maintenance were investigated with a focus on the epigenetic modification by DNA methylation. The treatment of dedifferentiated chondrocytes with the DNA methyltransferase inhibitor 5-aza-2´-deoxycytidine (5-aza-dC) displayed no considerable impact on the maintenance of marker gene expression observed in the dedifferentiated state, while the chondrogenic differentiation capacity was compromised. On the other hand, the pre-cultivation with 5-aza-dC improved the osteogenesis and adipogenesis of OA chondrocytes. Contradictory to these effects, the DNA methylation levels were not reduced after treatment for four weeks with 1 µM 5-aza-dC. In conclusion, 5-aza-dC affects the differentiation capacity of OA chondrocytes, while the global DNA methylation level remains stable. Furthermore, dedifferentiated chondrocytes isolated from late-stage OA patients represent a reliable cell source for in vitro studies and disease models without the need for additional alterations.


Assuntos
Condrócitos/patologia , Decitabina/farmacologia , Osteoartrite/patologia , Adipogenia/efeitos dos fármacos , Adipogenia/genética , Biomarcadores/metabolismo , Cartilagem Articular/efeitos dos fármacos , Cartilagem Articular/metabolismo , Proliferação de Células/efeitos dos fármacos , Proliferação de Células/genética , Forma Celular/efeitos dos fármacos , Forma Celular/genética , Células Cultivadas , Condrócitos/efeitos dos fármacos , Condrócitos/metabolismo , Colágeno Tipo II/metabolismo , DNA (Citosina-5-)-Metiltransferases/metabolismo , Metilação de DNA/efeitos dos fármacos , Metilação de DNA/genética , Matriz Extracelular/efeitos dos fármacos , Matriz Extracelular/metabolismo , Regulação da Expressão Gênica/efeitos dos fármacos , Humanos , Osteoartrite/genética , Osteogênese/efeitos dos fármacos , Osteogênese/genética
4.
Hum Cell ; 33(3): 502-511, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32447572

RESUMO

Antipsychotic-induced weight gain is a well-established but poorly understood clinical phenomenon. New mechanistic insights into how antipsychotics modulate adipose physiology are sorely needed, in hopes of either devising a therapeutic intervention to ameliorate weight gain or contributing to improved design of future agents. In this study, we have hypothesized that the weight gain-associated tricyclic antipsychotics clozapine and chlorpromazine directly impact adipose tissue by potentiating adipogenic differentiation of preadipocytes. Utilizing a well-established in vitro model system (3T3-L1 preadipocyte cell line), we demonstrate that, when applied specifically during induction of adipogenic differentiation, both clozapine and chlorpromazine significantly potentiate in vitro adipogenesis, observed as morphological changes and increased intracellular lipid accumulation. These persistent effects, observed at endpoints well after the end of antipsychotic exposure, are accompanied by increased transcript- and protein-level expression of the mature adipocyte marker perilipin-1, as indicated by RT-qPCR and Western blotting, but not by further upregulation of pro-adipogenic transcription factors versus positive controls. Our findings point to a possible physiological mechanism of antipsychotic-induced hyperplasia, with potentiated expression of mature adipocyte markers enhancing the differentiation and maturation of preadipocytes.


Assuntos
Adipócitos/citologia , Adipogenia/efeitos dos fármacos , Adipogenia/genética , Antidepressivos Tricíclicos/efeitos adversos , Diferenciação Celular/efeitos dos fármacos , Diferenciação Celular/genética , Expressão Gênica/efeitos dos fármacos , Expressão Gênica/genética , Células Cultivadas , Humanos , Ganho de Peso/efeitos dos fármacos
5.
Arch Biochem Biophys ; 686: 108365, 2020 06 15.
Artigo em Inglês | MEDLINE | ID: mdl-32315651

RESUMO

Pelargonidin is a natural compound that exists widely in fruits, and exerts antioxidant, anti-atherosclerotic, anti-inflammatory, anti-hyperglycemic, and anti-diabetic activities. However, there have not been any studies concerning its anti-obesity potential to date. Therefore, we evaluated the anti-obesity potential of pelargonidin via inhibition of adipogenesis in 3T3-L1 cells. The cellular oil droplet content was decreased to 68.14%, 56.75%, and 48.39% and triglyceride accumulation decreased to 74.53%, 61.54%, and 47.86% after incubation with 5 µM, 10 µM, and 20 µM pelargonidin, respectively, when compared with DMSO group. Furthermore, pelargonidin treatment led to decrease in glucose consumption. Western blot assay illustrated that the expression of PPAR-γ was suppressed to 63.25%, 47.52%, and 21.23% after incubation with 5 µM, 10 µM, and 20 µM pelargonidin when compared with DMSO group. Then, we measured the expression of some target proteins of PPAR-γ, and found that pelargonidin decreased the expressions of HMGCR, LPL, Glut4, and A-FABP. Besides, the result of Luciferase Reporter Assay indicated that pelargonidin inhibited PPAR-γ transcription activity. These results indicated that pelargonidin exerts anti-adipogenic activity in 3T3-L1 cells through inhibition of PPAR-γ signaling pathway, and pelargonidin could be used as a potential anti-obesity agent.


Assuntos
Adipogenia/efeitos dos fármacos , Antocianinas/farmacologia , Fármacos Antiobesidade/farmacologia , PPAR gama/metabolismo , Células 3T3-L1 , Animais , Antocianinas/metabolismo , Fármacos Antiobesidade/metabolismo , Regulação para Baixo/efeitos dos fármacos , Proteínas de Ligação a Ácido Graxo/genética , Proteínas de Ligação a Ácido Graxo/metabolismo , Regulação da Expressão Gênica/efeitos dos fármacos , Glucose/metabolismo , Transportador de Glucose Tipo 4/genética , Transportador de Glucose Tipo 4/metabolismo , Lipase Lipoproteica/genética , Lipase Lipoproteica/metabolismo , Camundongos , Triglicerídeos/genética , Triglicerídeos/metabolismo
6.
Clin Sci (Lond) ; 134(7): 827-851, 2020 04 17.
Artigo em Inglês | MEDLINE | ID: mdl-32271386

RESUMO

Major shifts in human lifestyle and dietary habits toward sedentary behavior and refined food intake triggered steep increase in the incidence of metabolic disorders including obesity and Type 2 diabetes. Patients with metabolic disease are at a high risk of cardiovascular complications ranging from microvascular dysfunction to cardiometabolic syndromes including heart failure. Despite significant advances in the standards of care for obese and diabetic patients, current therapeutic approaches are not always successful in averting the accompanying cardiovascular deterioration. There is a strong relationship between adipose inflammation seen in metabolic disorders and detrimental changes in cardiovascular structure and function. The particular importance of epicardial and perivascular adipose pools emerged as main modulators of the physiology or pathology of heart and blood vessels. Here, we review the peculiarities of these two fat depots in terms of their origin, function, and pathological changes during metabolic deterioration. We highlight the rationale for pharmacological targeting of the perivascular and epicardial adipose tissue or associated signaling pathways as potential disease modifying approaches in cardiometabolic syndromes.


Assuntos
Adipocinas/antagonistas & inibidores , Tecido Adiposo/efeitos dos fármacos , Anti-Inflamatórios/uso terapêutico , Vasos Sanguíneos/efeitos dos fármacos , Doenças Cardiovasculares/tratamento farmacológico , Mediadores da Inflamação/antagonistas & inibidores , Inflamação/tratamento farmacológico , Pericárdio/efeitos dos fármacos , Adipogenia/efeitos dos fármacos , Adipocinas/metabolismo , Tecido Adiposo/metabolismo , Tecido Adiposo/patologia , Tecido Adiposo/fisiopatologia , Adiposidade/efeitos dos fármacos , Animais , Vasos Sanguíneos/metabolismo , Vasos Sanguíneos/patologia , Vasos Sanguíneos/fisiopatologia , Doenças Cardiovasculares/metabolismo , Doenças Cardiovasculares/patologia , Doenças Cardiovasculares/fisiopatologia , Metabolismo Energético/efeitos dos fármacos , Humanos , Inflamação/metabolismo , Inflamação/patologia , Inflamação/fisiopatologia , Mediadores da Inflamação/metabolismo , Terapia de Alvo Molecular , Pericárdio/metabolismo , Pericárdio/patologia , Pericárdio/fisiopatologia , Transdução de Sinais
7.
Invest Ophthalmol Vis Sci ; 61(3): 39, 2020 03 09.
Artigo em Inglês | MEDLINE | ID: mdl-32196098

RESUMO

Purpose: Inflammation, hyaluronan production, and adipogenesis are the main pathological events leading to Graves' orbitopathy (GO). Guggulsterone (GS), a phytosterol found in the resin of the guggul plant, is a well-known treatment for several inflammatory disorders, such as arthritis, obesity, and hyperlipidemia. Here we investigated the effects of GS treatment on GO pathology. Methods: Using primary cultures of orbital fibroblasts from GO patients and non-GO controls, we examined the effects of GS on hyaluronan production and the production of proinflammatory cytokines induced by interleukin (IL)-1ß, using real-time reverse transcription-polymerase chain reaction analysis, western blots, and enzyme-linked immunosorbent assays. Further, adipogenic differentiation was evaluated by quantification of Oil Red O staining and assessment of protein levels of peroxisome proliferator activator gamma (PPARγ), CCAAT-enhancer-binding proteins (C/EBP) α and ß, and sterol regulatory element-binding protein-1 (SREBP-1). Results: Treatment with noncytotoxic concentrations of GS resulted in the dose-dependent inhibition of IL-1ß-induced inflammatory cytokines, including IL-6, IL-8, MCP-1, and COX-2, at both mRNA and protein levels. The hyaluronan level was also significantly suppressed by GS. Moreover, GS significantly decreased the formation of lipid droplets and expression of PPARγ, C/EBP α/ß, and SREBP-1 in a dose-dependent manner. GS pretreatment attenuated the phosphorylation of nuclear factor-kappa B induced by IL-1ß. Conclusions: Our data show significant inhibitory effects of GS on inflammation, production of hyaluronan, and adipogenesis in orbital fibroblasts. To our knowledge, this is the first in vitro preclinical evidence of the therapeutic effect of GS in GO.


Assuntos
Fibroblastos/efeitos dos fármacos , Oftalmopatia de Graves/tratamento farmacológico , Órbita/efeitos dos fármacos , Pregnenodionas/uso terapêutico , Adipogenia/efeitos dos fármacos , Adulto , Idoso , Western Blotting , Proteína alfa Estimuladora de Ligação a CCAAT/metabolismo , Proteína beta Intensificadora de Ligação a CCAAT/metabolismo , Diferenciação Celular , Células Cultivadas , Commiphora/química , Citocinas/metabolismo , Relação Dose-Resposta a Droga , Ensaio de Imunoadsorção Enzimática , Feminino , Fibroblastos/metabolismo , Oftalmopatia de Graves/metabolismo , Humanos , Ácido Hialurônico/metabolismo , Masculino , Pessoa de Meia-Idade , Órbita/metabolismo , PPAR gama/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Reação em Cadeia da Polimerase em Tempo Real , Proteína de Ligação a Elemento Regulador de Esterol 1/metabolismo , Adulto Jovem
8.
J Med Food ; 23(3): 266-272, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-32191574

RESUMO

Mulberry (Morus alba L.) fruits have long been used in traditional medicine and as edible berries in many countries. This study investigated the antiadipogenic effect of high hydrostatic pressure mulberry fruit extract (MFE) during 3T3-L1 adipocyte differentiation. MFE decreased lipid and triglyceride accumulation and glycerol-3-phosphate dehydrogenase activity. The mRNA expression levels of genes related to adipogenesis, such as the adipocyte protein 2, proliferator-activated receptor-γ, and CCAAT/enhancer binding protein-α, were suppressed by MFE. They also reduced microRNA (miR)-21 and miR-143 expression, which are involved in adipogenesis. In contrast, adenosine monophosphate-activated protein kinase (AMPK) activity was increased by MFE. These results suggested that MFE may suppress adipogenesis through modulating miR-21/143 expression and AMPK activity in 3T3-L1 adipocytes, which may be useful as antiobesity food agents.


Assuntos
Proteínas Quinases Ativadas por AMP/metabolismo , Adipócitos/citologia , Adipogenia/efeitos dos fármacos , MicroRNAs/genética , Morus/química , Extratos Vegetais/farmacologia , Células 3T3-L1 , Proteínas Quinases Ativadas por AMP/genética , Adipócitos/efeitos dos fármacos , Adipócitos/metabolismo , Animais , Fármacos Antiobesidade/química , Fármacos Antiobesidade/farmacologia , Proteína alfa Estimuladora de Ligação a CCAAT/genética , Proteína alfa Estimuladora de Ligação a CCAAT/metabolismo , Regulação para Baixo/efeitos dos fármacos , Frutas/química , Humanos , Camundongos , MicroRNAs/metabolismo , Obesidade/genética , Obesidade/metabolismo , PPAR gama/metabolismo , Extratos Vegetais/química , Triglicerídeos/metabolismo
9.
J Med Food ; 23(3): 250-257, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-32191575

RESUMO

Obesity is a world-wide health concern with increasing mortality and morbidity rates. Development of novel therapeutic agents for obesity from phytochemicals may lead to the effective prevention and control of obesity and obesity-related complications. 6-acetyl-2,2-dimethylchroman-4-one (1) was isolated from a dietary plant, Artemisia princeps. The antiobesity effect of compound 1 was determined in human bone marrow-derived mesenchymal stromal cells (hBM-MSCs) induced to differentiate into adipocytes. Treatment with compound 1 resulted in decreased lipid accumulation and expression of key adipogenic markers, proliferator-activated receptor-γ, CCAAT/enhancer-binding protein-α, and sterol regulatory element-binding transcription factor 1. It was also shown that compound 1 downregulated the adipogenesis-induced p38 and JNK MAPK activation, while upregulating adipogenesis inhibitory ß-catenin-dependent Wnt10b pathway. Compound 1 was also able to stimulate adenosine monophosphate-activated protein kinase phosphorylation, which was suggested to be the underlying mechanism that resulted in inhibition of adipogenesis in hBM-MSCs. In conclusion, 6-acetyl-2,2-dimethylchroman-4-one was identified as a bioactive constituent of A. princeps that exerts antiobesity properties via suppressing adipocyte formation.


Assuntos
Proteínas Quinases Ativadas por AMP/metabolismo , Adipócitos/citologia , Adipogenia/efeitos dos fármacos , Artemisia/química , Medicamentos de Ervas Chinesas/farmacologia , Células-Tronco Mesenquimais/citologia , Obesidade/fisiopatologia , Proteínas Quinases Ativadas por AMP/genética , Adipócitos/metabolismo , Células da Medula Óssea/citologia , Células da Medula Óssea/efeitos dos fármacos , Células da Medula Óssea/metabolismo , Proteína alfa Estimuladora de Ligação a CCAAT/genética , Proteína alfa Estimuladora de Ligação a CCAAT/metabolismo , Diferenciação Celular/efeitos dos fármacos , Medicamentos de Ervas Chinesas/química , Humanos , Células-Tronco Mesenquimais/efeitos dos fármacos , Células-Tronco Mesenquimais/metabolismo , Obesidade/tratamento farmacológico , Obesidade/genética , Obesidade/metabolismo , PPAR gama/genética , PPAR gama/metabolismo , Transdução de Sinais/efeitos dos fármacos
10.
Chem Biol Interact ; 318: 108978, 2020 Feb 25.
Artigo em Inglês | MEDLINE | ID: mdl-32044341

RESUMO

2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) accumulates in human body, probably influencing adipocyte differentiation and causing various toxic effects, including wasting syndrome. Recently, orientin, a phenolic compound abundant in natural health products, has been shown to have antioxidant properties. We investigated the protective effects of orientin against TCDD-induced adipocyte dysfunction and its underlying mechanisms. In this study, orientin suppressed TCDD-induced loss of lipid accumulation. Orientin inhibited TCDD-driven decreases in the levels of peroxisome proliferator-activated receptor γ and adiponectin. Orientin also reduced TCDD-induced prostaglandin E2, and cytosolic phospholipase A2α levels, and increased TCDD-inhibited peroxisome proliferator-activated receptor gamma coactivator 1-alpha levels in 3T3-L1 adipocytes. TCDD reduced the levels of insulin receptor substrate 1 and glucose transporter 4, and decreased insulin-stimulated glucose uptake activity; however, orientin diminished these TCDD-induced effects. These results suggest that orientin may have beneficial effects on the prevention of TCDD-induced wasting syndrome and type II diabetes mellitus accompanied by insulin resistance.


Assuntos
Adipócitos/efeitos dos fármacos , Adipogenia/efeitos dos fármacos , Flavonoides/farmacologia , Glucosídeos/farmacologia , Insulina/metabolismo , Dibenzodioxinas Policloradas/toxicidade , Transdução de Sinais/efeitos dos fármacos , Células 3T3-L1 , Animais , Dinoprostona , Regulação da Expressão Gênica/efeitos dos fármacos , Glucose/metabolismo , Camundongos
11.
BMC Complement Med Ther ; 20(1): 33, 2020 Feb 05.
Artigo em Inglês | MEDLINE | ID: mdl-32024512

RESUMO

BACKGROUND: Obesity is a major public health concern worldwide. A sedentary life and a nutritional transition to processed foods and high-calorie diets are contributing factors to obesity. The demand for nutraceutical foods, such as herbal weight-loss products, which offer the potential to counteract obesity, has consequently increased. We hypothesised that Opuntia cladodes consumption could assist weight management in an obesity prevention context. METHODS: This study was designed to explore the anti-adipogenic effects of lyophilised Opuntia cladode powders (OCP) in an in vitro cellular model for adipocyte differentiation and an in vivo high-fat-diet (HFD)-induced obesity rat model. Two OCP were tested, one from wild species O. streptacantha and the second from the most known species O. ficus-indica. RESULTS: Pre-adipocytes 3 T3-F442A were treated by OCP during the differentiation process by insulin. OCP treatment impaired the differentiation in adipocytes, as supported by the decreased triglyceride content and a low glucose uptake, which remained comparable to that observed in undifferentiated controls, suggesting that an anti-adipogenic effect was exerted by OCP. Sprague-Dawley rats were fed with a normal or HFD, supplemented or not with OCP for 8 weeks. OCP treatment slightly reduced body weight gain, liver and abdominal fat weights, improved some obesity-related metabolic parameters and increased triglyceride excretion in the faeces. Taken together, these results showed that OCP might contribute to reduce adipogenesis and fat storage in a HFD context, notably by promoting the faecal excretion of fats. CONCLUSIONS: Opuntia cladodes may be used as a dietary supplement or potential therapeutic agent in diet-based therapies for weight management to prevent obesity.


Assuntos
Adipócitos/efeitos dos fármacos , Adipogenia/efeitos dos fármacos , Suplementos Nutricionais , Fezes/química , Obesidade/tratamento farmacológico , Opuntia , Animais , Peso Corporal/efeitos dos fármacos , Diferenciação Celular/efeitos dos fármacos , Dieta Hiperlipídica , Glucose/metabolismo , Masculino , México , Pós , Ratos , Ratos Sprague-Dawley , Triglicerídeos/metabolismo
12.
Endocrinology ; 161(3)2020 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-32067051

RESUMO

The incidence of obesity has reached an all-time high, and this increase is observed worldwide. There is a growing need to understand all the factors that contribute to obesity to effectively treat and prevent it and associated comorbidities. The obesogen hypothesis proposes that there are chemicals in our environment termed obesogens that can affect individual susceptibility to obesity and thus help explain the recent large increases in obesity. This review discusses current advances in our understanding of how obesogens act to affect health and obesity susceptibility. Newly discovered obesogens and potential obesogens are discussed, together with future directions for research that may help to reduce the impact of these pervasive chemicals.


Assuntos
Adipogenia/efeitos dos fármacos , Poluentes Ambientais/efeitos adversos , Obesidade/induzido quimicamente , Animais , Feminino , Humanos , Gravidez , Efeitos Tardios da Exposição Pré-Natal
13.
J Med Food ; 23(3): 273-280, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-32023417

RESUMO

Young persimmon fruit (YPF) has recently been reported to have a regulatory effect on lipid metabolism. The aim of this study was to investigate whether the YPF aqueous extract (YPFE) exert an antiobesity effect by modulating lipid metabolism in the white adipose tissue (WAT) of obese C57BLKS/J db/db mice. YPFE (100 or 200 mg/kg body weight/day) or distilled water as a vehicle was orally administered by gavage to 12-week-old obese male db/db mice for 3 weeks (n = 7 for each group). YPFE administration significantly reduced body weight and WAT size. Furthermore, YPFE considerably reduced triglyceride and cholesterol concentrations in serum and WAT. Obese vehicle treated mice exhibited an enhanced protein expression of adipogenic and lipogenic genes. However, this increased expression was alleviated in the YPFE-fed groups, resulting in inhibition of adipogenesis and downregulation of fatty acid synthesis. In addition, there was an increase in the level of transcription factors associated with fatty acid oxidation in the YPFE-treated group. In obese mice, the expression of proteins associated with cholesterol metabolism was augmented. YPFE did not affect cholesterol synthesis, but cholesterol efflux-related proteins were significantly upregulated. YPF exerts beneficial effects on obesity by inhibiting adipogenesis and reducing lipid synthesis and accumulation by regulation of lipid-related transcription factors in the WAT of obese mice.


Assuntos
Tecido Adiposo Branco/efeitos dos fármacos , Fármacos Antiobesidade/administração & dosagem , Diospyros/química , Metabolismo dos Lipídeos/efeitos dos fármacos , Obesidade/tratamento farmacológico , Adipogenia/efeitos dos fármacos , Tecido Adiposo Branco/metabolismo , Animais , Colesterol/sangue , Frutas/química , Humanos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Obesos , Obesidade/sangue , Obesidade/fisiopatologia
14.
Artigo em Inglês | MEDLINE | ID: mdl-31904421

RESUMO

Obesity is characterized by uncontrolled expansion of adipose tissue mass, resulting in adipocyte hypertrophy (increased adipocyte size) and hyperplasia (increased number of adipocytes). The number of adipose cells is directly related to adipocyte differentiation process from stromal vascular cells to mature adipocytes. It is known that epigenetic factors influence adipose differentiation program. However, how specific epigenome modifiers affect white adipocyte differentiation and metabolic phenotype is still matter of research. Here, we provide evidence that class I histone deacetylases (HDACs) are involved both in the differentiation of adipocytes and in determining the metabolic features of these cells. We demonstrate that inhibition of class I HDACs from the very first stage of differentiation amplifies the differentiation process and imprints cells toward a highly oxidative phenotype. These effects are related to the capacity of the inhibitor to modulate H3K27 acetylation on enhancer regions regulating Pparg and Ucp1 genes. These epigenomic modifications result in improved white adipocyte functionality and metabolism and induce browning. Collectively, our results show that modulation of class I HDAC activity regulates the metabolic phenotype of white adipocytes via epigenetic imprinting on a key histone mark.


Assuntos
Adipócitos Marrons/efeitos dos fármacos , Adipogenia/efeitos dos fármacos , Epigênese Genética/efeitos dos fármacos , Inibidores de Histona Desacetilases/farmacologia , Histona Desacetilases/metabolismo , Adipócitos Marrons/citologia , Adipócitos Marrons/metabolismo , Adipócitos Brancos/citologia , Adipócitos Brancos/efeitos dos fármacos , Adipócitos Brancos/metabolismo , Animais , Linhagem Celular , Histona Desacetilases/genética , Humanos , Camundongos , Obesidade/tratamento farmacológico , Obesidade/genética , Obesidade/metabolismo , Estresse Oxidativo/efeitos dos fármacos
15.
Int J Mol Med ; 45(2): 589-596, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31894306

RESUMO

Acer okamotoanum is reported to have various antioxidant, anti­inflammatory and beneficial immune system effects. The anti­adipocyte differentiation effects and mechanisms of the ethyl acetate (EtOAc) fraction of an A. okamotoanum extraction was investigated in 3T3­L1 adipocyte cells. Treatment with differentiation inducers increased the level of triglycerides (TGs) in 3T3­L1 adipocyte cells compared with an untreated control. However, the EtOAc fraction of A. okamotoanum significantly decreased TGs. Treatment with 1, 2.5 and 5 µg/ml showed weak activity, but TG production was inhibited at 10 µg/ml compared with the control. In addition, A. okamotoanum caused a significant downregulation of proteins related to adipogenesis, such as γ­cytidine­cytidine­adenosine­adenosine­thymidine/enhancer binding protein­α, ­ß and peroxisome proliferator­activated receptor­Î³, compared with the untreated control. Furthermore, A. okamotoanum significantly upregulated lipolysis related protein, hormone­sensitive lipase and the phosphorylation of adenosine monophosphate­activated protein kinase (AMPK). Therefore, these results indicate that A. okamotoanum suppressed adipogenesis and increased lipolysis and the activation of AMPK, suggesting a protective role in adipocyte differentiation.


Assuntos
Acer , Adipogenia/efeitos dos fármacos , Ativadores de Enzimas/farmacologia , Lipólise/efeitos dos fármacos , Extratos Vegetais/farmacologia , Células 3T3-L1 , Acer/química , Animais , Ativadores de Enzimas/química , Camundongos , Extratos Vegetais/química , Proteínas Quinases/metabolismo
16.
FASEB J ; 34(1): 898-911, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31914598

RESUMO

Adipogenesis, a critical process that converts adipocyte precursors into adipocytes, is considered a potential therapeutic target for the treatment of obesity. Ezetimibe, a drug approved by the United States Food and Drug Administration, is used for the treatment of hypercholesterolemia. Recently, it was reported to ameliorate high fat diet-induced dyslipidemia in mice and reduce lipid accumulation in hepatocytes through the activation of AMPK. However, the anti-adipogenic effects of ezetimibe and the underlying molecular mechanism have not yet been elucidated. Here, we found that ezetimibe reduced lipid accumulation via activating AMPK during the early phase of adipogenesis. We also observed that ezetimibe inhibited peroxisome proliferator-activated receptor γ, which is a major transcription factor of adipogenesis. Furthermore, ezetimibe-mediated AMPK activation reduced lipid accumulation by inhibiting mTORC1 signaling, leading to the downregulation of lipogenesis-related genes. Mitotic clonal expansion, required for adipogenesis, accelerates cell cycle progression and cell proliferation. We additionally observed that ezetimibe prevented the progression of mitotic clonal expansion by arresting the cell cycle at the G0/G1 phase, which was followed by the inhibition of cell proliferation. Collectively, ezetimibe-mediated inhibition of adipogenesis is dependent on the AMPK-mTORC1 pathway. Thus, we suggest that ezetimibe might be a promising drug for the treatment of obesity.


Assuntos
Proteínas Quinases Ativadas por AMP/metabolismo , Adipogenia/efeitos dos fármacos , Ezetimiba/farmacologia , Metabolismo dos Lipídeos , Alvo Mecanístico do Complexo 1 de Rapamicina/metabolismo , Células 3T3-L1 , Animais , Compostos Azo , Proliferação de Células , Ativação Enzimática , Regulação da Expressão Gênica , Camundongos , PPAR gama/metabolismo , RNA Interferente Pequeno/metabolismo , Transdução de Sinais
17.
Int J Mol Sci ; 21(2)2020 Jan 10.
Artigo em Inglês | MEDLINE | ID: mdl-31936890

RESUMO

Ergosterol peroxide is a natural compound of the steroid family found in many fungi, and it possesses antioxidant, anti-inflammatory, anticancer and antiviral activities. The anti-obesity activity of several edible and medicinal mushrooms has been reported, but the effect of mushroom-derived ergosterol peroxide on obesity has not been studied. Therefore, we analyzed the effect of ergosterol peroxide on the inhibition of triglyceride synthesis at protein and mRNA levels and differentiation of 3T3-L1 adipocytes. Ergosterol peroxide inhibited lipid droplet synthesis of differentiated 3T3-L1 cells, expression of peroxisome proliferator-activated receptor gamma (PPARγ) and CCAT/enhancer-binding protein alpha (C/EBPα), the major transcription factors of differentiation, and also the expression of sterol regulatory element-binding protein-1c (SREBP-1c), which promotes the activity of PPARγ, resulting in inhibition of differentiation. It further inhibited the expression of fatty acid synthase (FAS), fatty acid translocase (FAT), and acetyl-coenzyme A carboxylase (ACC), which are lipogenic factors. In addition, it inhibited the phosphorylation of mitogen-activated protein kinases (MAPKs) involved in cell proliferation and activation of early differentiation transcription factors in the mitotic clonal expansion (MCE) stage. As a result, ergosterol peroxide significantly inhibited the synthesis of triglycerides and differentiation of 3T3-L1 cells, and is, therefore, a possibile prophylactic and therapeutic agent for obesity and related metabolic diseases.


Assuntos
Adipócitos/metabolismo , Fármacos Antiobesidade/farmacologia , Diferenciação Celular/efeitos dos fármacos , Ergosterol/análogos & derivados , Metabolismo dos Lipídeos/efeitos dos fármacos , Reishi/química , Células 3T3-L1/efeitos dos fármacos , Adipogenia/efeitos dos fármacos , Adipocinas , Animais , Fármacos Antiobesidade/uso terapêutico , Proteína alfa Estimuladora de Ligação a CCAAT/metabolismo , Sobrevivência Celular/efeitos dos fármacos , Regulação para Baixo/efeitos dos fármacos , Ergosterol/química , Ergosterol/farmacologia , Ergosterol/uso terapêutico , Lipogênese/efeitos dos fármacos , Camundongos , PPAR gama/metabolismo , Fosforilação/efeitos dos fármacos , Proteína de Ligação a Elemento Regulador de Esterol 1/metabolismo , Triglicerídeos
18.
Food Funct ; 11(1): 297-304, 2020 Jan 29.
Artigo em Inglês | MEDLINE | ID: mdl-31915782

RESUMO

In recent years, the conversion of white adipocytes to brown-like adipocytes by pharmacological and dietary compounds has gained attention as an effective strategy to fight obesity. Strawberry bioactive compounds present several biological activities including antioxidant, anti-inflammatory, anti-cancer, anti-atherosclerotic and antiadipogenic properties. However, to the best of our knowledge, the possible role of strawberry bioactive compounds in white adipose tissue (WAT) browning has never been explored. Our results demonstrated that a strawberry methanolic extract (SE) significantly reduced 3T3-L1 pre-adipocytes differentiation, and down-regulated the mRNA expression of the adipogenic transcription factors CCAAT/enhancer-binding protein (C/REB- α) and peroxisome proliferation-activated receptor (PPAR-γ). It also down-regulated the mRNA expression of resistin and angiotensinogen, two genes considered as markers of white adipocytes, while increased the mRNA expression of pyruvate dehydrogenase lipoamide kinase isozyme 4 (PDK4) and uncoupling protein 1 (UCP1) which, conversely, are brown adipocyte-specific markers. Likewise, SE stimulated AMP-activated protein kinase (AMPKα), sirtuin 1 (Sirt1) and the peroxisome proliferator activated receptor gamma coactivator 1-alpha (PGC-1α), suggesting a possible increase in mitochondrial biogenesis. It also stimulated oxygen consumption rate and uncoupled respiration. Taken together, all these results suggest that SE induces brown fat-like phenotype in 3T3-L1 cells and may have potential therapeutic implications for treatment and/or prevention of obesity.


Assuntos
Adipócitos Marrons/citologia , Adipócitos Brancos/efeitos dos fármacos , Adipogenia/efeitos dos fármacos , Fragaria/química , Extratos Vegetais/farmacologia , Células 3T3-L1 , Proteínas Quinases Ativadas por AMP/metabolismo , Adipócitos Brancos/citologia , Animais , Proteína alfa Estimuladora de Ligação a CCAAT/metabolismo , Diferenciação Celular , Metanol , Camundongos , PPAR gama/metabolismo , Quinase Piruvato Desidrogenase (Transferência de Acetil)/metabolismo , Sirtuína 1/metabolismo , Fatores de Transcrição/metabolismo , Proteína Desacopladora 1/metabolismo
19.
J Sci Food Agric ; 100(6): 2389-2398, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-31916584

RESUMO

BACKGROUND: Promoting brown and beige adipogenesis contributes to adaptive thermogenesis, which provides a defense against obesity and related disorders. Apple polyphenols (APs) play a significant role in treating variety of metabolic diseases. This study was conducted to determine the effects of APs on the development of brown and beige adipocytes and thermogenesis and investigate whether these effects are mediated by adenosine monophosphate-activated protein kinase (AMPK). High-fat diet (HFD)-induced obese mice and differentiated 3T3-L1 adipocytes were subjected to APs treatment. The thermogenic program and associated regulatory factors, and the involvement of AMPKα was assessed. RESULTS: Dietary APs supplementation reduced adiposity and improved insulin sensitivity in HFD-induced obese mice. Moreover, APs increased the oxygen consumption and heat production and decreased respiratory exchange ratio, which were accompanied by the upregulation of thermogenic genes expression and the activation of AMPKα in brown fat and inguinal white fat. Further, APs treatment directly increased expression of brown adipogenic markers and induced phosphorylation of AMPKα in differentiated 3T3-L1 adipocytes, whereas the beneficial effects of APs were reversed by AMPK inhibition. CONCLUSION: Our results provide new insights into the function of APs in regulating brown/beige adipogenesis and adaptive thermogenesis and suggest the potential application of APs in the prevention and therapeutics of obesity and associated metabolic diseases. © 2020 Society of Chemical Industry.


Assuntos
Proteínas Quinases Ativadas por AMP/efeitos dos fármacos , Adipogenia/efeitos dos fármacos , Polifenóis/farmacologia , Termogênese/efeitos dos fármacos , Células 3T3-L1 , Adipócitos Bege/efeitos dos fármacos , Adipócitos Bege/metabolismo , Tecido Adiposo Marrom/efeitos dos fármacos , Tecido Adiposo Marrom/metabolismo , Animais , Diferenciação Celular , Dieta , Dieta Hiperlipídica/efeitos adversos , Suplementos Nutricionais , Resistência à Insulina , Masculino , Malus/química , Camundongos , Camundongos Endogâmicos C57BL
20.
Int J Mol Sci ; 21(2)2020 Jan 09.
Artigo em Inglês | MEDLINE | ID: mdl-31936485

RESUMO

Understanding of adipogenesis is important to find remedies for obesity and related disorders. In addition, it is also critical in bone disorders because there is a reciprocal relationship between adipogenesis and osteogenesis in bone micro-environment. Oxysterols are pro-osteogenic and anti-adipogenic molecules via hedgehog activation in pluripotent bone marrow stomal cells. However, no study has evaluated the role of specific oxysterols in C3H10T1/2 cells, which are a good cell model for studying osteogenesis and adipogenesis in bone-marrows. Thus, we investigated the effects of specific oxysterols on adipogenesis and expression of adipogenic transcripts in C3H10T1/2 cells. Treatment of cells with DMITro significantly induced mRNA expression of Pparγ. This induction was significantly inhibited by 25-HC. The expression of C/cepα, Fabp4 and Lpl was also inhibited by 25-HC. To determine the mechanism by which 25-HC inhibits adipogenesis, the effects of the hedgehog signalling pathway inhibitor, cyclopamine and CUR61414, were evaluated. Treatment of C3H10T1/2 cells with DMITro + cyclopamine or DMITro + CUR61414 for 96h did not modulate adipocyte differentiation; cyclopamine and CUR61414 did not reverse the inhibitory effects of 25-HC, suggesting that the canonical hedgehog signalling may not play a role in the anti-adipogenic effects of 25-HC in C3H10T1/2 cells. In addition, LXR agonist did not inhibit adipogenesis, but 25-HC strongly inhibits adipogenesis of C3H10T1/2 cells. Our observations showed that 25-HC was the most potent oxysterol in inhibiting adipogenesis and the expression of key adipogenic transcripts in C3H10T1/2 cells among the tested oxysterols, suggesting its potential application in providing an intervention in osteoporosis and obesity. We also report that the inhibitory effects of 25-HC on adipogenic differentiation in C3H10T1/2 cells are not mediated by hedgehog signaling and LXR.


Assuntos
Adipogenia/efeitos dos fármacos , Hidroxicolesteróis/farmacologia , Células-Tronco Pluripotentes/citologia , Adipogenia/genética , Animais , Benzoatos/farmacologia , Benzilaminas/farmacologia , Linhagem Celular , Regulação da Expressão Gênica/efeitos dos fármacos , Proteínas Hedgehog/genética , Proteínas Hedgehog/metabolismo , Metabolismo dos Lipídeos/efeitos dos fármacos , Receptores X do Fígado/agonistas , Receptores X do Fígado/metabolismo , Camundongos , Oxisteróis/farmacologia , Células-Tronco Pluripotentes/efeitos dos fármacos , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Transdução de Sinais/efeitos dos fármacos , Células Estromais/citologia , Células Estromais/efeitos dos fármacos , Fatores de Tempo
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