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1.
Int J Mol Sci ; 22(10)2021 May 19.
Artigo em Inglês | MEDLINE | ID: mdl-34069744

RESUMO

Bisphenol A (BPA) is an endocrine-disrupting chemical used in the production of plastics, and is linked to developmental, reproductive, and metabolic disorders including obesity. Manufacturers have begun using 'BPA-free' alternatives instead of BPA in many consumer products. However, these alternatives have had much less testing and oversight, yet they are already being mass-produced and used across industries from plastics to food-contact coatings. Here, we used human female adipose-derived stem cells (hASCs), a type of adult mesenchymal stem cell, to compare the effects of BPA and BPA alternatives on adipogenesis or fat cell development in vitro. We focused on two commonly used BPA replacements, bisphenol AF (BPAF) and tetramethyl bisphenol F (TMBPF; monomer of the new valPure V70 food-contact coating). Human ASCs were differentiated into adipocytes using chemically defined media in the presence of control differentiation media with and without 17ß-estradiol (E2; 10 µM), or with increasing doses of BPA (0, 0.1 and 1 µM), BPAF (0, 0.1, 1 and 10 nM), or TMBPF (0, 0.01 and 0.1 µM). After differentiation, the cells were stained and imaged to visualize and quantify the accumulation of lipid vacuoles and number of developing fat cells. Treated cells were also examined for cell viability and apoptosis (programmed cell death) using the respective cellular assays. Similar to E2, BPA at 0.1 µM and BPAF at 0.1 nM, significantly increased adipogenesis and lipid production by 20% compared to control differentiated cells (based on total lipid vacuole number to cell number ratios), whereas higher levels of BPA and BPAF significantly decreased adipogenesis (p < 0.005). All tested doses of TMBPF significantly reduced adipogenesis and lipid production by 30-40%, likely at least partially through toxic effects on stem cells, as viable cell numbers decreased and apoptosis levels increased throughout differentiation. These findings indicate that low, environmentally-relevant doses of BPA, BPAF, and TMBPF have significant effects on fat cell development and lipid accumulation, with TMBPF having non-estrogenic, anti-adipogenic effects. These and other recent results may provide a potential cellular mechanism between exposure to bisphenols and human obesity, and underscore the likely impact of these chemicals on fat development in vivo.


Assuntos
Adipócitos/metabolismo , Adipogenia/efeitos dos fármacos , Células-Tronco Mesenquimais/efeitos dos fármacos , Adipócitos/efeitos dos fármacos , Adipogenia/fisiologia , Tecido Adiposo/efeitos dos fármacos , Células-Tronco Adultas/efeitos dos fármacos , Apoptose/efeitos dos fármacos , Compostos Benzidrílicos/efeitos adversos , Diferenciação Celular/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Disruptores Endócrinos/toxicidade , Estradiol/farmacologia , Feminino , Humanos , Obesidade/metabolismo , Fenóis/efeitos adversos , Células-Tronco/efeitos dos fármacos
2.
Life Sci ; 278: 119586, 2021 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-33957171

RESUMO

AIMS: The reduction in androgens serum concentration is a physiological condition that accompanies age advancement but can also occur because of prostate cancer and gender affirming treatment or pathological conditions such as functional hypogonadism. However, androgen deficiency is related to a higher risk of developing metabolic disorders such as obesity and type 2 diabetes mellitus (T2DM). Considering that glucagon-like peptide 1 (GLP1) analogs are increasingly used in the treatment of T2DM, we investigated if liraglutide could also attenuate the metabolic changes caused by orchiectomy in rats. MAIN METHODS: Wistar rats were orchiectomized (ORC), and subdivided in four groups: sham saline, sham liraglutide, ORC saline, and ORC liraglutide. After sixty days, metabolic parameters were evaluated in blood, muscle, liver, brown (BAT) and white adipose tissue (WAT) visceral depots. Glucose utilization, oxidation, and conversion to lipids by de novo lipogenesis, and basal and adrenaline-stimulated lipolysis were evaluated in BAT and WAT depots. KEY FINDINGS: Orchiectomy increased triglyceridemia, BAT and rtWAT weight, and lipolysis and reduced glucose utilization. Liraglutide treatment reversed these effects. SIGNIFICANCE: These results indicate that liraglutide improves triglyceridemia and glucose metabolism in WAT depots, which suggests that it may be a promising therapeutic strategy to handle disruptions in energy metabolism caused by androgen deficiency.


Assuntos
Tecido Adiposo/efeitos dos fármacos , Liraglutida/farmacologia , Orquiectomia/efeitos adversos , Tecido Adiposo/metabolismo , Tecido Adiposo Branco/metabolismo , Animais , Peso Corporal , Diabetes Mellitus Tipo 2/metabolismo , Metabolismo Energético/efeitos dos fármacos , Glucose/metabolismo , Metabolismo dos Lipídeos/efeitos dos fármacos , Lipólise , Masculino , Obesidade/metabolismo , Tamanho do Órgão , Oxigênio/metabolismo , Ratos , Ratos Wistar , Triglicerídeos/metabolismo , Ganho de Peso
3.
Front Immunol ; 12: 608875, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33968013

RESUMO

Adipose tissue is now recognized as an active organ with an important homeostatic function in glucose and lipid metabolism and the development of insulin resistance. The present research investigates the role of lipid mediators and lipid profiling for controlling inflammation and the metabolic normal function of white adipose tissue from rats suffering from diet-induced prediabetes. Additionally, the contribution to the adipose lipidome induced by the consumption of marine ω-3 PUFAs as potential regulators of inflammation is addressed. For that, the effects on the inflammatory response triggered by high-fat high-sucrose (HFHS) diets were studied in male Sprague-Dawley rats. Using SPE-LC-MS/MS-based metabolo-lipidomics, a range of eicosanoids, docosanoids and specialized pro-resolving mediators (SPMs) were measured in white adipose tissue. The inflammatory response occurring in prediabetic adipose tissue was associated with the decomposition of ARA epoxides to ARA-dihydroxides, the reduction of oxo-derivatives and the formation of prostaglandins (PGs). In an attempt to control the inflammatory response initiated, LOX and non-enzymatic oxidation shifted toward the production of the less pro-inflammatory EPA and DHA metabolites rather than the high pro-inflammatory ARA hydroxides. Additionally, the change in LOX activity induced the production of intermediate hydroxides precursors of SPMs as protectins (PDs), resolvins (Rvs) and maresins (MaRs). This compensatory mechanism to achieve the restoration of tissue homeostasis was significantly strengthened through supplementation with fish oils. Increasing proportions of ω-3 PUFAs in adipose tissue significantly stimulated the formation of DHA-epoxides by cytochrome P450, the production of non-enzymatic EPA-metabolites and prompted the activity of 12LOX. Finally, protectin PDX was significantly reduced in the adipose tissue of prediabetic rats and highly enhanced through ω-3 PUFAs supplementation. Taken together, these actively coordinated modifications constitute key mechanisms to restore adipose tissue homeostasis with an important role of lipid mediators. This compensatory mechanism is reinforced through the supplementation of the diet with fish oils with high and balanced contents of EPA and DHA. The study highlights new insides on the targets for effective treatment of incipient diet-induced diabetes and the mechanism underlying the potential anti-inflammatory action of marine lipids.


Assuntos
Tecido Adiposo/efeitos dos fármacos , Tecido Adiposo/metabolismo , Óleos de Peixe/administração & dosagem , Homeostase/efeitos dos fármacos , Metabolismo dos Lipídeos/efeitos dos fármacos , Lipidômica , Redes e Vias Metabólicas/efeitos dos fármacos , Animais , Biomarcadores , Cromatografia Líquida , Dieta , Mediadores da Inflamação , Lipidômica/métodos , Masculino , Ratos , Espectrometria de Massas em Tandem
4.
Molecules ; 26(9)2021 Apr 30.
Artigo em Inglês | MEDLINE | ID: mdl-33946279

RESUMO

Various natural products (NPs) have been used to treat obesity and related diseases. However, the best way to fight obesity is preventive, with accurate body weight management through exercise, diet, or bioactive NPs to avoid obesity development. We demonstrated that green tea extract (GTE) is an anti-obesity NP using a zebrafish obesity model. Based on a hypothesis that GTE can prevent obesity, the objective of this study was to assess GTE's ability to attenuate obesity development. Juvenile zebrafish were pretreated with GTE for seven days before obesity induction via a high-fat diet; adult zebrafish were pretreated with GTE for two weeks before obesity induction by overfeeding. As a preventive intervention, GTE significantly decreased visceral adipose tissue accumulation in juveniles and ameliorated visceral adiposity and plasma triglyceride levels in adult zebrafish obesity models. RNA sequencing analysis was performed using liver tissues from adult obese zebrafish, with or without GTE administration, to investigate the underlying molecular mechanism. Transcriptome analysis revealed that preventive GTE treatment affects several pathways associated with anti-obesity regulation, including activation of STAT and downregulation of CEBP signaling pathways. In conclusion, GTE could be used as a preventive agent against obesity.


Assuntos
Extratos Vegetais/farmacologia , Chá/química , Tecido Adiposo/efeitos dos fármacos , Tecido Adiposo/metabolismo , Animais , Biomarcadores , Gordura Intra-Abdominal/efeitos dos fármacos , Gordura Intra-Abdominal/metabolismo , Metabolismo dos Lipídeos/efeitos dos fármacos , Obesidade/tratamento farmacológico , Obesidade/metabolismo , Tamanho do Órgão/efeitos dos fármacos , Extratos Vegetais/química , Transdução de Sinais/efeitos dos fármacos , Peixe-Zebra
5.
Food Funct ; 12(8): 3572-3585, 2021 Apr 26.
Artigo em Inglês | MEDLINE | ID: mdl-33900346

RESUMO

Type 2 diabetic mellitus (T2DM) is a complicated metabolic disorder that is now considered as a major global public health problem. Fucoidan exhibits diverse biological activities, especially prevention of metabolic diseases. In this regard, we herein aimed to reveal the beneficial effect of Sargassum fusiforme fucoidan (SFF) on high-fat diet (HFD) and streptozotocin (STZ) induced T2DM mice. We noted that on the one hand, SFF significantly decreased fasting blood glucose, diet and water intake, and hyperlipidemia, while on the other hand, it improved glucose tolerance. Furthermore, SFF reduced epididymal fat deposition, attenuated the pathological changes in heart and liver tissues, and decreased oxidative stress in diabetic mice. To explore the underlying mechanisms of these ameliorative effects, the gut microbiota was analyzed. Notably, SFF highly enriched benign microbes including Bacteroides, Faecalibacterium and Blautia, as well as increased levels of (R)-carnitine and choline in the colon of diabetic mice. This may be a potential mechanism for alleviating T2DM, thus implying the benefits of SFF as an adjuvant agent for T2DM treatment. Taken together, this study demonstrated a promising application of fucoidan as one of the adjuvant agents for the management of T2DM in the future.


Assuntos
Diabetes Mellitus Experimental/tratamento farmacológico , Diabetes Mellitus Tipo 2/tratamento farmacológico , Microbioma Gastrointestinal/efeitos dos fármacos , Intestinos/efeitos dos fármacos , Polissacarídeos/uso terapêutico , Sargassum/química , Tecido Adiposo/efeitos dos fármacos , Tecido Adiposo/patologia , Animais , Glicemia/análise , Diabetes Mellitus Experimental/sangue , Diabetes Mellitus Experimental/patologia , Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/patologia , Dieta Hiperlipídica , Hiperlipidemias/tratamento farmacológico , Hipoglicemiantes/farmacologia , Fígado/patologia , Masculino , Camundongos , Camundongos Endogâmicos ICR , Miocárdio/patologia , Estresse Oxidativo/efeitos dos fármacos , Polissacarídeos/farmacologia
6.
Nutrients ; 13(4)2021 Mar 30.
Artigo em Inglês | MEDLINE | ID: mdl-33808251

RESUMO

Excessive fat consumption leads to the development of ectopic adipose tissues, affecting the organs they surround. Peripancreatic adipose tissue is implicated in glucose homeostasis regulation and can be impaired in obesity. High palm oil consumption's effects on health are still debated. We hypothesised that crude and refined palm oil high-fat feeding may have contrasting effects on peripancreatic adipocyte hypertrophy, inflammation and lipid oxidation compound production in obese rats. In Wistar rats, morphological changes, inflammation and isoprostanoid production following oxidative stress were assessed in peripancreatic adipose tissue after 12 weeks of diets enriched in crude or refined palm oil or lard (56% energy from fat in each case) versus a standard chow diet (11% energy from fat). Epididymal white and periaortic brown adipose tissues were also included in the study. A refined palm oil diet disturbed glucose homeostasis and promoted lipid deposition in periaortic locations, as well as adipocyte hypertrophy, macrophage infiltration and isoprostanoid (5-F2c-isoprostane and 7(RS)-ST-Δ8-11-dihomo-isofuran) production in peripancreatic adipose tissue. Crude palm oil induced a lower impact on adipose deposits than its refined form and lard. Our results show that the antioxidant composition of crude palm oil may have a protective effect on ectopic adipose tissues under the condition of excessive fat intake.


Assuntos
Tecido Adiposo/efeitos dos fármacos , Gorduras na Dieta/administração & dosagem , Inflamação/induzido quimicamente , Óleo de Palmeira/administração & dosagem , Tecido Adiposo/patologia , Animais , Glicemia , Peso Corporal , Dieta Hiperlipídica/efeitos adversos , Glucose/metabolismo , Lipídeos/sangue , Macrófagos/efeitos dos fármacos , Macrófagos/fisiologia , Masculino , Ratos , Ratos Wistar
7.
Int J Biol Macromol ; 182: 879-898, 2021 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-33857511

RESUMO

High-fat (HF) diets cause obesity, gut microbial dysbiosis and associated disorders and inflammatory bowel disease (IBD) due to increased intestinal permeability, which is an important reason for chronic inflammation and oxidative stress. This study was to investigate the effects and mechanism by which walnut green husk polysaccharides (WGHP) prevents obesity, oxidative stress, inflammation, liver and colon damage in HF diet induced rats. We found that WGHP alleviated HF-induced abnormal weight gain, disordered lipid metabolism, inflammation, oxidative stress, colonic tissue injury and up-regulate the expression level of colonic tight junction protein in the rats. Besides, the administration of WGHP promoted browning of iWAT and thermogenesis in BAT of HF-fed rats, and improved gut microbiota dysbiosis by increasing the bacterial diversity and reducing the relative abundance of potential pathogenic bacteria in the colon of the rats. Furthermore, WGHP consumption not only increased the SCFAs content but also improved the relative abundance of Prevotellaceae and Allobaculum in the gut of rats. Our results suggest that the protective effect of WGHP on metabolic inflammation caused by HF may be due to the regulation of gut microbiota and SCFAs.


Assuntos
Fármacos Antiobesidade/uso terapêutico , Antioxidantes/uso terapêutico , Juglans/química , Hepatopatia Gordurosa não Alcoólica/prevenção & controle , Obesidade/prevenção & controle , Polissacarídeos/uso terapêutico , Tecido Adiposo/efeitos dos fármacos , Tecido Adiposo/metabolismo , Animais , Fármacos Antiobesidade/química , Fármacos Antiobesidade/farmacologia , Antioxidantes/química , Antioxidantes/farmacologia , Colo/efeitos dos fármacos , Colo/metabolismo , Colo/microbiologia , Dieta Hiperlipídica , Ácidos Graxos Voláteis/metabolismo , Microbioma Gastrointestinal , Fígado/efeitos dos fármacos , Fígado/metabolismo , Masculino , Hepatopatia Gordurosa não Alcoólica/tratamento farmacológico , Hepatopatia Gordurosa não Alcoólica/etiologia , Obesidade/tratamento farmacológico , Obesidade/etiologia , Polissacarídeos/química , Polissacarídeos/farmacologia , Ratos , Ratos Sprague-Dawley
8.
FASEB J ; 35(5): e21596, 2021 05.
Artigo em Inglês | MEDLINE | ID: mdl-33871073

RESUMO

Severe burns remain a leading cause of death and disability worldwide. Despite advances in patient care, the excessive and uncontrolled hypermetabolic stress response induced by this trauma inevitably affects every organ system causing substantial morbidity and mortality. Recent evidence suggests interleukin-6 (IL-6) is a major culprit underlying post-burn hypermetabolism. Indeed, genetic deletion of IL-6 alleviates various complications associated with poor clinical outcomes including the adverse remodeling of adipose tissue, cachexia and hepatic steatosis. Thus, pharmacological blockade of IL-6 may be a more favorable treatment option to fully restore metabolic function after injury. To test this, we investigated the safety and effectiveness of blocking IL-6 for post-burn hypermetabolism using a validated anti-IL-6 monoclonal antibody (mAb) in our experimental murine model. Here, we show daily anti-IL-6 mAb administration protects against burn-induced weight loss (P < .0001) without any adverse effect on mortality. At the organ level, post-burn treatment with the IL-6 blocker suppressed the thermogenic activation of adipose tissue (P < .01) and its associated wasting (P < .05). The reduction of browning-induced lipolysis (P < .0001) indirectly decreased hepatic lipotoxicity (P < .01) which improved liver dysfunction (P < .05). Importantly, the beneficial effects of this anti-IL-6 agent extended to the skin, reflected by the decrease in excessive collagen deposition (P < .001) and genes involved in pathologic fibrosis and scarring (P < .05). Together, our results indicate that post-burn IL-6 blockade leads to significant improvements in systemic hypermetabolism by inhibiting pathological alterations in key immunometabolic organs. These findings support the therapeutic potential of anti-IL-6 interventions to improve care, quality of life, and survival in burned patients.


Assuntos
Tecido Adiposo/efeitos dos fármacos , Anticorpos Monoclonais/farmacologia , Queimaduras/complicações , Fibrose/tratamento farmacológico , Interleucina-6/antagonistas & inibidores , Doenças Metabólicas/tratamento farmacológico , Animais , Fibrose/etiologia , Fibrose/patologia , Lipólise , Masculino , Doenças Metabólicas/etiologia , Doenças Metabólicas/patologia , Camundongos , Camundongos Endogâmicos C57BL
9.
J Food Sci ; 86(5): 2103-2117, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33864648

RESUMO

Soyasaponins are triterpenoid glycosides found in soybean. We investigated whether soyasaponin ameliorates lipid metabolism and its possible mechanisms. In C57BL/6J mice fed a high-fat diet (HFD), soyasaponin (SAP) was orally administered for 9 weeks. Additionally, we evaluated the effect of soyasapogenols on 3T3-L1 adipocytes. In HFD-fed mice, the SAP significantly reduced body weight by 7% and relative adipose tissue weight by 35%. X-ray computed tomography demonstrated that the SAP reduced visceral and subcutaneous adipose tissue weights during week 3 of feeding. The SAP reduced sterol regulatory element-binding protein-1c (SREBP-1c) mRNA levels by 32% in the epididymal adipose tissue, significantly decreasing the triacylglycerol (TAG) content by 37% and SREBP-1c and fatty acid synthase mRNA levels by 52% and 61%, respectively, in the liver. In 3T3-L1 adipocytes, soyasapogenol B significantly decreased lipid droplets. The SAP containing soyasaponin A and B as conjugates demonstrate anti-obesity effects by suppressing adipocyte differentiation and lipogenesis, with a preventive effect on hepatic TAG accumulation by suppressing lipogenesis. PRACTICAL APPLICATION: Soyasaponin is one of the oleanane triterpenoids in soybeans. We have demonstrated that soyasaponin potently reduces body weight and white adipose tissue weight, and hepatic triacylglycerol accumulation in high-fat diet-fed mice. Thus, soyasaponin is a beneficial compound to prevent obesity and fatty liver.


Assuntos
Adipogenia , Fármacos Antiobesidade/farmacologia , Dieta Hiperlipídica/efeitos adversos , Lipogênese , Obesidade/prevenção & controle , Ácido Oleanólico/análogos & derivados , Saponinas/farmacologia , Triglicerídeos/metabolismo , Células 3T3-L1 , Tecido Adiposo/efeitos dos fármacos , Tecido Adiposo/metabolismo , Animais , Diferenciação Celular , Metabolismo dos Lipídeos , Fígado/efeitos dos fármacos , Fígado/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Obesidade/etiologia , Obesidade/metabolismo , Obesidade/patologia , Ácido Oleanólico/farmacologia
10.
Phytomedicine ; 86: 153557, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-33852976

RESUMO

BACKGROUND: Pine nut oil (PNO), a standardized and well-defined extract of Pinus koraiensis (Korean pine), has beneficial effects on wound healing, inflammatory diseases, and cancer. However, the explanation for the mechanism by which PNO reduces body fat remains uncertain. We performed a protein-protein interaction network (PPIN) analysis to explore the genes associated with pinolenic acid using the MEDILINE database from PubChem and PubMed. It was concluded through the PPIN analysis that PNO was involved in a neutral lipid biosynthetic process. PURPOSE: This study evaluated the effects of PNO predicted by the network analysis of fat accumulation in chronic obesity mouse models established by feeding a high fat diet (HFD) to C57BL/6J mice and explored potential mechanisms. METHODS: HFD mice were fed only HFD or HFD with PNO at 822 and 1644 mg/kg. After an oral administration of 7 weeks, several body weight and body fat-related parameters were examined, including the following: adipose weight, adipocyte size, serum lipid profiles, adipocyte expression of PPAR-γ, sterol regulatory element binding protein (SREBP)-1c, lipoprotein lipase (LPL) and leptin. RESULTS: We showed that oral administration of PNO to HFD mice reduces body fat weight, fat in tissue, white adipose tissue weight, and adipocyte size. The serum cholesterol was improved in the HFD mice treated with PNO. Additionally, PNO has significantly attenuated the HFD-induced changes in the adipose tissue expression of PPAR-γ, SREBP-1c, LPL, and leptin. CONCLUSIONS: The findings from this study based on the PPIN analysis suggest that PNO has potential as drug to reduce body fat through fat regulatory mechanisms by PPAR-γ and SREBP-1c.


Assuntos
Nozes/química , Óleos Vegetais/química , Mapas de Interação de Proteínas , Adipócitos/efeitos dos fármacos , Tecido Adiposo/efeitos dos fármacos , Tecido Adiposo Branco/efeitos dos fármacos , Animais , Fármacos Antiobesidade/farmacologia , Dieta Hiperlipídica , Leptina/sangue , Ácidos Linolênicos , Lipogênese/efeitos dos fármacos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Obesidade/tratamento farmacológico , PPAR gama/metabolismo , Proteína de Ligação a Elemento Regulador de Esterol 1/metabolismo
11.
Molecules ; 26(7)2021 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-33915783

RESUMO

Obesity has recently emerged as a public health issue facing developing countries in the world. It is caused by the accumulation of fat in adipose, characterized by insulin resistance, excessive lipid accumulation, inflammation, and oxidative stress, leading to an increase in adipokine levels. Herein, we investigated the capacity of a bioactive polyphenolic compound (ferulic acid (FA)) to control adipocyte dysfunction in 3T3-L1 adipocytes (in vitro). Key adipocyte differentiation markers, glycerol content, lipolysis-associated mRNA, and proteins were measured in experimental adipocytes. FA-treated adipocytes exhibited downregulated key adipocyte differentiation factors peroxisome proliferator-activated receptor-γ (PPAR-γ), CCAT enhancer binding-proteins-α (C/EBP-α) and its downstream targets in a time-dependent manner. The FA-treated 3T3-L1 adipocytes showed an increased release of glycerol content compared with non-treated adipocytes. Also, FA treatment significantly up-regulated the lipolysis-related factors, including p-HSL, and p-perilipin, and down-regulated ApoD, Sema3C, Cxcl12, Sfrp2, p-stearoyl-CoA desaturase 1 (SCD1), adiponectin, and Grk5. Also, the FA treatment showed significantly down-regulated adipokines leptin, chemerin, and irisin than the non-treated cells. The present findings indicated that FA showed significant anti-adipogenic and lipogenic activities by regulating key adipocyte factors and enzyme, enhanced lipolysis by HSL/perilipin cascade. FA is considered a potent molecule to prevent obesity and its associated metabolic changes in the future.


Assuntos
Adipócitos/efeitos dos fármacos , Adipócitos/metabolismo , Ácidos Cumáricos/farmacologia , Homeostase/efeitos dos fármacos , Células 3T3-L1 , Tecido Adiposo/efeitos dos fármacos , Tecido Adiposo/metabolismo , Animais , Biomarcadores , Diferenciação Celular/efeitos dos fármacos , Metabolismo dos Lipídeos/efeitos dos fármacos , Lipogênese/efeitos dos fármacos , Camundongos
12.
Nutrients ; 13(3)2021 Mar 09.
Artigo em Inglês | MEDLINE | ID: mdl-33803343

RESUMO

Oxidative stress and dysregulated adipocytokine secretion accompanying hypertrophied adipose tissue induce chronic inflammation, which leads to vascular endothelial dysfunction. The present study investigated the ability of anthocyanin (ACN) and non-anthocyanin polyphenol (PP) fractions from lingonberry fruit to mitigate adipose tissue hypertrophy and endothelial dysfunction using 3T3-L1 adipocytes and human umbilical vein endothelial cells (HUVECs). This study showed that the PP fraction decreased intracellular ROS generation in hypertrophied adipocytes by enhancing antioxidant enzyme expression (SOD2) and inhibiting oxidant enzyme expression (NOX4, iNOS). Moreover, PP and ACN fractions reduced triglyceride content in adipocytes accompanied by downregulation of the expression of lipogenic genes such as aP2, FAS, and DAGT1. Treatment with both fractions modulated the mRNA expression and protein secretion of key adipokines in hypertrophied adipocytes. Expression and secretion of leptin and adiponectin were, respectively, down- and upregulated. Furthermore, PP and ACN fractions alleviated the inflammatory response in TNF-α-induced HUVECs by inhibiting the expression of pro-inflammatory genes (IL-6, IL-1ß) and adhesion molecules (VCAM-1, ICAM-1, SELE). The obtained results suggest that consuming polyphenol-rich lingonberry fruit may help prevent and treat obesity and endothelial dysfunction due to their antioxidant and anti-inflammatory actions.


Assuntos
Adipócitos/efeitos dos fármacos , Endotélio Vascular/efeitos dos fármacos , Extratos Vegetais/farmacologia , Polifenóis/farmacologia , Vaccinium vitis-Idaea/química , Células 3T3-L1 , Adipocinas/metabolismo , Tecido Adiposo/efeitos dos fármacos , Animais , Antocianinas/farmacologia , Antioxidantes/farmacologia , Frutas , Células Endoteliais da Veia Umbilical Humana/efeitos dos fármacos , Humanos , Hipertrofia , Camundongos , Obesidade/tratamento farmacológico , Espécies Reativas de Oxigênio/metabolismo
13.
Int J Mol Sci ; 22(5)2021 Mar 03.
Artigo em Inglês | MEDLINE | ID: mdl-33802611

RESUMO

The objective of this work has been to characterize the estrogenic activity of bisphenol-A (BPA) and the adverse effects on the endocannabinoid system (ECS) in modulating germ cell progression. Male offspring exposed to BPA during the foetal-perinatal period at doses below the no-observed-adverse-effect-level were used to investigate the exposure effects in adulthood. Results showed that BPA accumulates specifically in epididymal fat rather than in abdominal fat and targets testicular expression of 3ß-hydroxysteroid dehydrogenase and cytochrome P450 aromatase, thus promoting sustained increase of estrogens and a decrease of testosterone. The exposure to BPA affects the expression levels of some ECS components, namely type-1 (CB1) and type-2 cannabinoid (CB2) receptor and monoacylglycerol-lipase (MAGL). Furthermore, it affects the temporal progression of germ cells reported to be responsive to ECS and promotes epithelial germ cell exfoliation. In particular, it increases the germ cell content (i.e., spermatogonia while reducing spermatocytes and spermatids), accelerates progression of spermatocytes and spermatids, promotes epithelial detachment of round and condensed spermatids and interferes with expression of cell-cell junction genes (i.e., zonula occcludens protein-1, vimentin and ß-catenin). Altogether, our study provides evidence that early exposure to BPA produces in adulthood sustained and site-specific BPA accumulation in epididymal fat, becoming a risk factor for the reproductive endocrine pathways associated to ECS.


Assuntos
Tecido Adiposo/efeitos dos fármacos , Compostos Benzidrílicos/efeitos adversos , Compostos Benzidrílicos/metabolismo , Endocanabinoides/metabolismo , Epididimo/efeitos dos fármacos , Estrogênios/metabolismo , Células Germinativas/efeitos dos fármacos , Fenóis/efeitos adversos , Fenóis/metabolismo , Tecido Adiposo/metabolismo , Animais , Sistema Endócrino/efeitos dos fármacos , Sistema Endócrino/metabolismo , Epididimo/metabolismo , Epitélio/efeitos dos fármacos , Epitélio/metabolismo , Células Germinativas/metabolismo , Junções Intercelulares/efeitos dos fármacos , Junções Intercelulares/metabolismo , Masculino , Camundongos , Fatores de Risco , Testosterona/metabolismo
14.
Molecules ; 26(7)2021 Apr 06.
Artigo em Inglês | MEDLINE | ID: mdl-33917607

RESUMO

ß-sitosterol (SIT), the most abundant bioactive component of vegetable oil and other plants, is a highly potent antidiabetic drug. Our previous studies show that SIT controls hyperglycemia and insulin resistance by activating insulin receptor and glucose transporter 4 (GLUT-4) in the adipocytes of obesity induced type 2 diabetic rats. The current research was undertaken to investigate if SIT could also exert its antidiabetic effects by circumventing adipocyte induced inflammation, a key driving factor for insulin resistance in obese individuals. Effective dose of SIT (20 mg/kg b.wt) was administered orally for 30 days to high fat diet and sucrose induced type-2 diabetic rats. Metformin, the conventionally used antidiabetic drug was used as a positive control. Interestingly, SIT treatment restores the elevated serum levels of proinflammatory cytokines including leptin, resistin, tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) to normalcy and increases anti-inflammatory adipocytokines including adiponectin in type 2 diabetic rats. Furthermore, SIT decreases sterol regulatory element binding protein-1c (SREBP-1c) and enhances Peroxisome Proliferator-activated receptor-γ (PPAR-γ) gene expression in adipocytes of diabetic rats. The gene and protein expression of c-Jun-N-terminal kinase-1 (JNK1), inhibitor of nuclear factor kappa-B kinase subunit beta (IKKß) and nuclear factor kappa B (NF-κB) were also significantly attenuated in SIT treated groups. More importantly, SIT acts very effectively as metformin to circumvent inflammation and insulin resistance in diabetic rats. Our results clearly show that SIT inhibits obesity induced insulin resistance by ameliorating the inflammatory events in the adipose tissue through the downregulation of IKKß/NF-κB and c-Jun-N-terminal kinase (JNK) signaling pathway.


Assuntos
Adipócitos/metabolismo , Diabetes Mellitus Tipo 2/complicações , Regulação para Baixo , Quinase I-kappa B/metabolismo , Inflamação/tratamento farmacológico , Resistência à Insulina , Obesidade/complicações , Sitosteroides/uso terapêutico , Adipócitos/efeitos dos fármacos , Adipocinas/sangue , Tecido Adiposo/efeitos dos fármacos , Tecido Adiposo/metabolismo , Tecido Adiposo/patologia , Animais , Peso Corporal/efeitos dos fármacos , Citocinas/sangue , Citocinas/genética , Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/metabolismo , Diabetes Mellitus Tipo 2/patologia , Dieta Hiperlipídica , Regulação para Baixo/efeitos dos fármacos , Comportamento Alimentar , Inflamação/sangue , Inflamação/metabolismo , Inflamação/patologia , Mediadores da Inflamação/metabolismo , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Masculino , Simulação de Acoplamento Molecular , NF-kappa B/metabolismo , Obesidade/sangue , PPAR gama/genética , PPAR gama/metabolismo , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Ratos , Sitosteroides/farmacologia , Proteína de Ligação a Elemento Regulador de Esterol 1/metabolismo , Sacarose , Regulação para Cima/efeitos dos fármacos , Regulação para Cima/genética
15.
Molecules ; 26(6)2021 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-33804179

RESUMO

Amomum tsao-ko Crevost et Lemaire (Zingiberaceae) is a medicinal herb found in Southeast Asia that is used for the treatment of malaria, abdominal pain, dyspepsia, etc. The aim of this study was to investigate the effect of an ethanol extract of Amomum tsao-ko (EAT) on obesity and hyperlipidemia in C57BL/6 mice fed a high-carbohydrate diet (HCD). First, the mice were divided into five groups (n = 6/group) as follows: normal diet, HCD, and HCD+EAT (100, 200, and 400 mg/kg/day), which were orally administered with EAT daily for 84 days. Using microcomputed tomography (micro-CT) analysis, we found that EAT inhibited not only body-weight gain, but also visceral fat and subcutaneous fat accumulation. Histological analysis confirmed that EAT decreased the size of fat tissues. EAT consistently improved various indices, including plasma levels of total cholesterol (TC), triglyceride (TG), low-density lipoprotein, high-density lipoprotein, atherogenic index, and cardiac risk factors, which are related to dyslipidemia-a major risk factor for heart disease. The contents of TC and TG, as well as the lipid droplets of HCD-induced hepatic accumulation in the liver tissue, were suppressed by EAT. Taken together, these findings suggest the possibility of developing EAT as a therapeutic agent for improving HCD-induced obesity and hyperlipidemia.


Assuntos
Amomum/química , Carboidratos/efeitos adversos , Dislipidemias/tratamento farmacológico , Obesidade/tratamento farmacológico , Plantas Medicinais/química , Zingiberaceae/química , Tecido Adiposo/efeitos dos fármacos , Animais , Dieta/efeitos adversos , Dislipidemias/metabolismo , Lipoproteínas LDL/metabolismo , Fígado/efeitos dos fármacos , Fígado/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Obesidade/metabolismo , Extratos Vegetais/química , Extratos Vegetais/farmacologia , Triglicerídeos/metabolismo
16.
Food Funct ; 12(6): 2378-2388, 2021 Mar 21.
Artigo em Inglês | MEDLINE | ID: mdl-33645609

RESUMO

It is well known that fat dysfunction is the main driver of development of metabolic disorders. Changes in diet and lifestyle are particularly important to reverse the current global rise in obesity-related metabolic disorders. Seaweed has been consumed for thousands of years, and it is rich in bioactive compounds, especially unique polyphenols. The aim of the present review is to summarize the effects of different seaweed polyphenols on fat function in metabolic disorders and the related mechanisms. Seaweed polyphenols activate white adipose tissue to "brown" or "beige" adipose tissue to enhance energy consumption. In addition, the amelioration of fat factor imbalance and inflammatory response is also considered as an important reason for the regulation of lipid function with seaweed polyphenols. The present review provides an important basis for using seaweed polyphenols as potential dietary supplements to prevent metabolic disorders.


Assuntos
Tecido Adiposo , Doenças Metabólicas/metabolismo , Feófitas/química , Alga Marinha/química , Taninos , Tecido Adiposo/efeitos dos fármacos , Tecido Adiposo/metabolismo , Animais , Humanos , Camundongos , Compostos Fitoquímicos , Polifenóis
17.
Nutrients ; 13(3)2021 Feb 26.
Artigo em Inglês | MEDLINE | ID: mdl-33652910

RESUMO

This study investigated the effect of decaffeinated green tea extract (dGTE), with or without antioxidant nutrients, on fat oxidation, body composition and cardio-metabolic health measures in overweight individuals engaged in regular exercise. Twenty-seven participants (20 females, 7 males; body mass: 77.5 ± 10.5 kg; body mass index: 27.4 ± 3.0 kg·m2; peak oxygen uptake (O2peak): 30.2 ± 5.8 mL·kg-1·min-1) were randomly assigned, in a double-blinded manner, either: dGTE (400 mg·d-1 (-)-epigallocatechin-3-gallate (EGCG), n = 9); a novel dGTE+ (400 mg·d-1 EGCG, quercetin (50 mg·d-1) and α-lipoic acid (LA, 150 mg·d-1), n = 9); or placebo (PL, n = 9) for 8 weeks, whilst maintaining standardised, aerobic exercise. Fat oxidation ('FATMAX' and steady state exercise protocols), body composition, cardio-metabolic and blood measures (serum glucose, insulin, leptin, adiponectin, glycerol, free fatty acids, total cholesterol, high [HDL-c] and low-density lipoprotein cholesterol [LDL-c], triglycerides, liver enzymes and bilirubin) were assessed at baseline, week 4 and 8. Following 8 weeks of dGTE+, maximal fat oxidation (MFO) significantly improved from 154.4 ± 20.6 to 224.6 ± 23.2 mg·min-1 (p = 0.009), along with a 22.5% increase in the exercise intensity at which fat oxidation was deemed negligible (FATMIN; 67.6 ± 3.6%O2peak, p = 0.003). Steady state exercise substrate utilisation also improved for dGTE+ only, with respiratory exchange ratio reducing from 0.94 ± 0.01 at week 4, to 0.89 ± 0.01 at week 8 (p = 0.004). This corresponded with a significant increase in the contribution of fat to energy expenditure for dGTE+ from 21.0 ± 4.1% at week 4, to 34.6 ± 4.7% at week 8 (p = 0.006). LDL-c was also lower (normalised fold change of -0.09 ± 0.06) for dGTE+ by week 8 (p = 0.038). No other significant effects were found in any group. Eight weeks of dGTE+ improved MFO and substrate utilisation during exercise, and lowered LDL-c. However, body composition and cardio-metabolic markers in healthy, overweight individuals who maintained regular physical activity were largely unaffected by dGTE.


Assuntos
Tecido Adiposo/efeitos dos fármacos , Antioxidantes/administração & dosagem , Sobrepeso/terapia , Extratos Vegetais/administração & dosagem , Chá , Adiponectina/sangue , Adulto , Bilirrubina/sangue , Glicemia/efeitos dos fármacos , Composição Corporal/efeitos dos fármacos , Índice de Massa Corporal , Fatores de Risco Cardiometabólico , Colesterol/sangue , Método Duplo-Cego , Metabolismo Energético/efeitos dos fármacos , Enzimas/sangue , Exercício Físico/fisiologia , Ácidos Graxos não Esterificados/sangue , Feminino , Glicerol/sangue , Humanos , Insulina/sangue , Leptina/sangue , Masculino , Pessoa de Meia-Idade , Sobrepeso/fisiopatologia , Oxirredução/efeitos dos fármacos , Consumo de Oxigênio/efeitos dos fármacos
18.
Biochem Pharmacol ; 186: 114491, 2021 04.
Artigo em Inglês | MEDLINE | ID: mdl-33647265

RESUMO

Diabetic nephropathy is a major health challenge with considerable economic burden and significant impact on patients' quality of life. Despite recent advances in diabetic patient care, current clinical practice guidelines fall short of halting the progression of diabetic nephropathy to end-stage renal disease. Moreover, prior literature reported manifestations of renal dysfunction in early stages of metabolic impairment prior to the development of hyperglycemia indicating the involvement of alternative pathological mechanisms apart from those typically triggered by high blood glucose. Here, we extend our prior research work implicating localized inflammation in specific adipose depots in initiating cardiovascular dysfunction in early stages of metabolic impairment. Non-obese prediabetic rats showed elevated glomerular filtration rates and mild proteinuria in absence of hyperglycemia, hypertension, and signs of systemic inflammation. Isolated perfused kidneys from these rats showed impaired renovascular endothelial feedback in response to vasopressors and increased flow. While endothelium dependent dilation remained functional, renovascular relaxation in prediabetic rats was not mediated by nitric oxide and prostaglandins as in control tissues, but rather an upregulation of the function of epoxy eicosatrienoic acids was observed. This was coupled with signs of peri-renal adipose tissue (PRAT) inflammation and renal structural damage. A two-week treatment with non-hypoglycemic doses of metformin or pioglitazone, shown previously to ameliorate adipose inflammation, not only reversed PRAT inflammation in prediabetic rats, but also reversed the observed functional, renovascular, and structural renal abnormalities. The present results suggest that peri-renal adipose inflammation triggers renal dysfunction early in the course of metabolic disease.


Assuntos
Tecido Adiposo/metabolismo , Nefropatias Diabéticas/metabolismo , Modelos Animais de Doenças , Hipoglicemiantes/uso terapêutico , Rim/metabolismo , Estado Pré-Diabético/metabolismo , Tecido Adiposo/efeitos dos fármacos , Animais , Nefropatias Diabéticas/tratamento farmacológico , Nefropatias Diabéticas/etiologia , Ingestão de Energia/fisiologia , Hipoglicemiantes/farmacologia , Inflamação/tratamento farmacológico , Inflamação/etiologia , Inflamação/metabolismo , Rim/efeitos dos fármacos , Masculino , Obesidade , Estado Pré-Diabético/tratamento farmacológico , Ratos , Ratos Sprague-Dawley
19.
Nutrients ; 13(2)2021 Feb 16.
Artigo em Inglês | MEDLINE | ID: mdl-33669347

RESUMO

7,8-Dihydroxyflavone (DHF) is a naturally occurring flavonoid that has been reported to protect against a variety of pathologies. Chronic administration of DHF prevents high-fat diet (HFD)-induced obesity in female, but not male, mice. However, the mechanisms underlying this sexual dimorphism have not been elucidated. We have discovered that oral DHF supplementation significantly attenuates fat mass, hepatic lipid accumulation, and adipose tissue inflammation in female mice. In contrast, male mice were not protected from adiposity, and had a paradoxical worsening of hepatic lipid accumulation and adipose tissue inflammation upon DHF supplementation. Consistent with these sexually dimorphic effects on body weight and metabolic health, 7,8-DHF induced early and stable remodeling of the female intestinal microbiome. DHF supplementation significantly increased gut microbial diversity, and suppressed potentially detrimental bacteria, particularly Desulfovibrionaceae, which are pro-inflammatory and positively associated with obesity and inflammation. Changes in the female gut microbiome preceded alterations in body weights, and in silico analyses indicated that these early microbial changes were highly predictive of subsequent weight gain in female mice. While some alterations in the intestinal microbiome were also observed in male DHF-supplemented mice, these changes were distinct from those in females and, importantly, were not predictive of subsequent body weight changes in male animals. The temporality of microbial changes preceding alterations in body weight in female mice suggests a role for the gut microbiome in mediating the sexually dimorphic effects of DHF on body weight. Given the significant clinical interest in this flavonoid across a wide range of pathologies, further elucidation of these sexually dimorphic effects will aid the development of effective clinical therapies.


Assuntos
Flavonas/farmacologia , Microbioma Gastrointestinal/efeitos dos fármacos , Adipocinas/metabolismo , Tecido Adiposo/efeitos dos fármacos , Animais , Dieta Hiperlipídica/efeitos adversos , Fezes/microbiologia , Feminino , Inflamação/metabolismo , Metabolismo dos Lipídeos/efeitos dos fármacos , Fígado/química , Fígado/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Obesidade/induzido quimicamente , Fatores Sexuais , Ganho de Peso/efeitos dos fármacos
20.
Life Sci ; 274: 119312, 2021 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-33667521

RESUMO

AIMS: Piperine, the major pharmacological ingredient of pepper, can delay the procession of "obesity to diabetes". However, the underlying mechanism remains unclear. This study aims to investigate whether piperine protects against ß-cell dysfunction by inhibiting macrophage accumulation and M1-like polarization. MATERIALS AND METHODS: Pre-diabetic model was induced by feeding 60% high-fat diet (HFD) in C57BL/6C mice, piperine (15 or 30 mg/kg/day) and rosiglitazone (4 mg/kg/day) were given orally for 8 weeks. Oral glucose tolerance test (OGTT), insulin tolerance test (ITT), fasting blood glucose (FBG), total cholesterol (TC) and triglyceride (TG) were used to assay the disorder of glycolipid metabolism. Serum levels of cytokines and insulin were measured by Elisa. Hyperglycemic clamp assay was carried out to evaluate ß-cell function. RT-PCR, immunofluorescence and western blot were used to detect the expression of biomarkers associated with macrophage polarization and ß-cell dedifferentiation. KEY FINDINGS: Piperine protected against ß-cell dysfunction, indicated by the improvement of hyperinsulinemia, OGTT and increased glucose infusion rate (GIR). Piperine dramatically reduced the serum levels of lipopolysaccharide (LPS), interleukin-1ß (IL-1ß) and Galectin-3 (Gal-3), suppressed the expression of M1-like cytokines (CD11c, IL-1ß and Gal-3) in epididymal adipose tissues and islets. Furthermore, piperine partially reversed the down-regulation of Pdx1, inhibited the up-regulation of ALDH1A3 in ß-cell, and these effects were closely related to the mTOR/S6/4E-BP1 signal pathway. SIGNIFICANCE: Piperine markedly ameliorates the dedifferentiation and dysfunction of ß-cell by inhibiting the accumulation and M1-like polarization of macrophages in visceral adipose tissues and islets.


Assuntos
Tecido Adiposo/efeitos dos fármacos , Alcaloides/farmacologia , Benzodioxóis/farmacologia , Inibidores das Enzimas do Citocromo P-450/farmacologia , Inflamação/tratamento farmacológico , Células Secretoras de Insulina/efeitos dos fármacos , Macrófagos/efeitos dos fármacos , Obesidade/complicações , Piperidinas/farmacologia , Alcamidas Poli-Insaturadas/farmacologia , Tecido Adiposo/imunologia , Tecido Adiposo/patologia , Animais , Inflamação/etiologia , Inflamação/patologia , Células Secretoras de Insulina/imunologia , Células Secretoras de Insulina/patologia , Ativação de Macrófagos/efeitos dos fármacos , Macrófagos/imunologia , Macrófagos/patologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Obesos
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