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2.
Life Sci ; 237: 116914, 2019 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-31622606

RESUMO

AIMS: The aim of the presente study was to examine the effects of oral gallic acid (GA) administration on the brown adipose tissue of obese mice fed with high-fat diet. New mechanisms and interactions pathways in thermogenesis were accessed through bioinformatics analyses. MAIN METHODS: Swiss male mice were divided into four groups and fed during 60 days with: standard diet, standard diet combined with gallic acid, high-fat diet and high-fat diet combined with gallic acid. Body weight, food intake, and blood parameters (glucose tolerance test, total-cholesterol, high-density low-c, triglyceride and glucose levels) were evaluated. Brown and subcutaneous white adipose tissue histological analysis were performed. SIRT1 and PGC1-α mRNA expression in the brown adipose tissue were assessed. KEY FINDINGS: Our main findings showed that the gallic acid improved glucose tolerance and metabolic parameters. These results were accompanied by bioinformatics analyses that evidenced SIRT1 as main target in the thermogenesis process, confirmed as increased SIRT1 mRNA expression was evidenced in the brown adipose tissue. SIGNIFICANCE: Together, the data suggest that the gallic acid effect in brown adipose tissue may improve body metabolism, glucose homeostasis and increase thermogenesis.


Assuntos
Tecido Adiposo Marrom/metabolismo , Biologia Computacional/métodos , Dieta Hiperlipídica/efeitos adversos , Ácido Gálico/farmacologia , Metaboloma/efeitos dos fármacos , Obesidade/metabolismo , Sirtuína 1/metabolismo , Tecido Adiposo Marrom/efeitos dos fármacos , Tecido Adiposo Marrom/patologia , Animais , Regulação da Expressão Gênica/efeitos dos fármacos , Masculino , Camundongos , Camundongos Obesos , Obesidade/tratamento farmacológico , Obesidade/etiologia , Sirtuína 1/genética , Termogênese/efeitos dos fármacos
3.
Braz J Med Biol Res ; 52(10): e8491, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31618368

RESUMO

Considering the recognized role of thyroid hormones on the cardiovascular system during health and disease, we hypothesized that type 2 deiodinase (D2) activity, the main activation pathway of thyroxine (T4)-to-triiodothyronine (T3), could be an important site to modulate thyroid hormone status, which would then constitute a possible target for ß-adrenergic blocking agents in a myocardial infarction (MI) model induced by left coronary occlusion in rats. Despite a sustained and dramatic fall in serum T4 concentrations (60-70%), the serum T3 concentration fell only transiently in the first week post-infarction (53%) and returned to control levels at 8 and 12 weeks after surgery compared to the Sham group (P<0.05). Brown adipose tissue (BAT) D2 activity (fmol T4·min-1·mg ptn-1) was significantly increased by approximately 77% in the 8th week and approximately 100% in the 12th week in the MI group compared to that of the Sham group (P<0.05). Beta-blocker treatment (0.5 g/L propranolol given in the drinking water) maintained a low T3 state in MI animals, dampening both BAT D2 activity (44% reduction) and serum T3 (66% reduction in serum T3) compared to that of the non-treated MI group 12 weeks after surgery (P<0.05). Propranolol improved cardiac function (assessed by echocardiogram) in the MI group compared to the non-treated MI group by 40 and 57%, 1 and 12 weeks after treatment, respectively (P<0.05). Our data suggested that the beta-adrenergic pathway may contribute to BAT D2 hyperactivity and T3 normalization after MI in rats. Propranolol treatment maintained low T3 state and improved cardiac function additionally.


Assuntos
Tecido Adiposo Marrom/metabolismo , Antagonistas Adrenérgicos beta/administração & dosagem , Iodeto Peroxidase/metabolismo , Infarto do Miocárdio/metabolismo , Propranolol/administração & dosagem , Tiroxina/sangue , Tri-Iodotironina/sangue , Tecido Adiposo Marrom/efeitos dos fármacos , Animais , Modelos Animais de Doenças , Iodeto Peroxidase/efeitos dos fármacos , Masculino , Ratos , Ratos Wistar , Tiroxina/efeitos dos fármacos , Tri-Iodotironina/efeitos dos fármacos
4.
Chem Biodivers ; 16(10): e1900347, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31532890

RESUMO

Catechins in green tea are well-known to be effective in reducing the risk of obesity. The purpose of this study was to elucidate the effects of catechins present in green tea on adipocyte differentiation and mature adipocyte metabolism. Treatment of 3T3-L1 mouse adipocyte during differentiation adipocytes with (-)-epigallocatechin (EGC) and gallic acid (GA) resulted in dose-dependent inhibition of adipogenesis. Specifically, EGC increased adiponectin and uncoupling protein 1 (UCP1) transcription in mature adipocytes. Transcription levels of adipose triglyceride lipase (ATGL) and hormone-sensitive lipase (HSL) were not significantly impacted by either of the compounds. These results suggest that the EGC is the most effective catechin having anti-obesity activity. Finally, EGC is an attractive candidate component for remodeling obesity.


Assuntos
Tecido Adiposo Marrom/efeitos dos fármacos , Fármacos Antiobesidade/farmacologia , Catequina/análogos & derivados , Células 3T3-L1 , Tecido Adiposo Marrom/metabolismo , Animais , Fármacos Antiobesidade/química , Fármacos Antiobesidade/isolamento & purificação , Catequina/química , Catequina/isolamento & purificação , Catequina/farmacologia , Diferenciação Celular/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Células Cultivadas , Relação Dose-Resposta a Droga , Camundongos , Estrutura Molecular , Relação Estrutura-Atividade , Chá/química
5.
BMC Complement Altern Med ; 19(1): 243, 2019 Sep 05.
Artigo em Inglês | MEDLINE | ID: mdl-31488120

RESUMO

BACKGROUND: Brown adipocytes are known to promote energy expenditure and limit weight gain to combat obesity. Averrhoa bilimbi, locally called belimbing buluh (DBB), is mainly used as an ethnomedicine in the treatment of metabolic disorders including diabetes mellitus, hypertension and obesity. The present study aims to investigate the browning activity on white adipocytes by A. bilimbi leaf extract and to evaluate the potential mechanisms. METHODS: Ethanolic leaf extract of A. bilimbi was exposed to Myf5 lineage precursor cells to stimulate adipocyte differentiation. Protein expressions of brown adipocyte markers were determined through high content screening analysis and validated through western blotting. Mito Stress Test assay was conducted to evaluate the cellular oxygen consumption rate upon A. bilimbi treatment. RESULTS: A. bilimbi ethanolic leaf extract exhibited an adipogenesis effect similar to a PPARgamma agonist. It also demonstrated brown adipocyte differentiation in myoblastic Myf5-positive precursor cells. Expression of UCP1 and PRDM16 were induced. The basal metabolic rate and respiratory capacity of mitochondria were increased upon A. bilimbi treatment. CONCLUSIONS: The findings suggest that Averrhoa bilimbi ethanolic leaf extract induces adipocyte browning through PRDM16 activation and enhances mitochondria activity due to UCP1 up-regulation.


Assuntos
Adipogenia/efeitos dos fármacos , Tecido Adiposo Marrom/efeitos dos fármacos , Averrhoa/química , Obesidade/fisiopatologia , Extratos Vegetais/farmacologia , Células 3T3-L1 , Adipócitos/citologia , Adipócitos/efeitos dos fármacos , Adipócitos/metabolismo , Tecido Adiposo Marrom/citologia , Tecido Adiposo Marrom/metabolismo , Animais , Proteínas de Ligação a DNA/genética , Proteínas de Ligação a DNA/metabolismo , Dieta Hiperlipídica/efeitos adversos , Humanos , Camundongos , Obesidade/tratamento farmacológico , Obesidade/genética , Obesidade/metabolismo , Folhas de Planta/química , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo , Proteína Desacopladora 1/genética , Proteína Desacopladora 1/metabolismo
6.
J Biosci ; 44(4)2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31502571

RESUMO

Brown adipose tissue (BAT) is responsible for adaptive thermogenesis. We previously showed that genetic deficiency of receptor for advanced glycation end products (RAGE) prevented the effects of high-fat diet (HFD). This study was to compare BAT activity in RAGE knock out (Ager-/-, RKO) and wild-type (WT) mice after treated with HFD or LFD. [18F]FDG PET-CT imaging under identical cold-stimulated conditions and mean standard uptake values (SUVmean), ratio of SUViBAT/SUVmuscle (SUVR, muscle as the reference region) and percentage ID/g were used for BAT quantification. The results showed that [18F]FDG uptake (e.g., SUVR) in WT-HFD mice was significantly reduced (three-fold) as compared to that in WT-LFD (1.40 +/- 0.07 and 4.03 +/- 0.38; P = 0.004). In contrast, BAT activity in RKO mice was not significantly affected by HFD, with SUVRRKO-LFD: 2.14 +/- 0.10 and SUVRRKO-LFD: 1.52 +/- 0.13 (P = 0.3). The uptake in WT-LFD was almost double of that in RKO-LFD (P = 0.004); however, there was no significant difference between RKO-HFD and WT-HFD mice (P = 0.3). These results, corroborating our previous findings on the measurement of mRNA transcripts for UCP1 in the BAT, suggest that RAGE may contribute to altered energy expenditure and provide a protective effect against HFD by Ager deletion (Ager -/-).


Assuntos
Tecido Adiposo Marrom/diagnóstico por imagem , Tomografia por Emissão de Pósitrons , Receptor para Produtos Finais de Glicação Avançada/genética , Termogênese/genética , Tecido Adiposo Marrom/metabolismo , Animais , Dieta Hiperlipídica/efeitos adversos , Metabolismo Energético/genética , Camundongos , Camundongos Knockout , Receptor para Produtos Finais de Glicação Avançada/metabolismo , Proteína Desacopladora 1
7.
Nat Commun ; 10(1): 4037, 2019 09 06.
Artigo em Inglês | MEDLINE | ID: mdl-31492869

RESUMO

Increased body weight is a major factor that interferes with smoking cessation. Nicotine, the main bioactive compound in tobacco, has been demonstrated to have an impact on energy balance, since it affects both feeding and energy expenditure at the central level. Among the central actions of nicotine on body weight, much attention has been focused on its effect on brown adipose tissue (BAT) thermogenesis, though its effect on browning of white adipose tissue (WAT) is unclear. Here, we show that nicotine induces the browning of WAT through a central mechanism and that this effect is dependent on the κ opioid receptor (KOR), specifically in the lateral hypothalamic area (LHA). Consistent with these findings, smokers show higher levels of uncoupling protein 1 (UCP1) expression in WAT, which correlates with smoking status. These data demonstrate that central nicotine-induced modulation of WAT browning may be a target against human obesity.


Assuntos
Tecido Adiposo Marrom/efeitos dos fármacos , Hipotálamo/efeitos dos fármacos , Nicotina/farmacologia , Receptores Opioides kappa/metabolismo , Termogênese/efeitos dos fármacos , Tecido Adiposo Marrom/metabolismo , Tecido Adiposo Branco/efeitos dos fármacos , Tecido Adiposo Branco/metabolismo , Adulto , Animais , Peso Corporal/efeitos dos fármacos , Feminino , Estimulantes Ganglionares/administração & dosagem , Estimulantes Ganglionares/farmacologia , Humanos , Hipotálamo/metabolismo , Masculino , Camundongos Knockout , Pessoa de Meia-Idade , Nicotina/administração & dosagem , Ratos Sprague-Dawley , Receptores Opioides kappa/genética , Proteína Desacopladora 1/metabolismo
8.
Biol Pharm Bull ; 42(9): 1554-1561, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31474715

RESUMO

Obesity, which is characterized by an excessive accumulation of body fat, is one of the critical factors causing metabolic syndrome. Many studies have been performed to identify appropriate agents to control obesity, but toxicity remains a problem. Herein, we identified that phenylbutyrate (PBA), which has been used to treat urea cycle disorder with very low toxicity for a long time, efficiently inhibited high fat-induced body weight gain in a diet-induced obesity mouse model (DIO model). PBA treatment decreased body fat mass and increased lean composition. Moreover, PBA increased brown adipose tissue (BAT) activity by increasing glucose uptake, thereby improving glucose tolerance and insulin tolerance. Interestingly, PBA could induce the expression of liver type phosphofructokinase (PFKL), a key enzyme in the glycolytic pathway, and knocking down PFKL dramatically repressed the expression level of Ucp1 as well as those of Prdm16, Cidea, Pgc1α, and Pparγ, which are marker genes for BAT activation. These results strongly suggested that PBA could increase energy expenditure by increasing BAT activity via the induction of PFKL. Taken together, PBA could be used as a therapeutic agent for people with obesity to prevent the development of metabolic syndrome.


Assuntos
Tecido Adiposo Marrom/efeitos dos fármacos , Fármacos Antiobesidade/farmacologia , Dieta Hiperlipídica , Obesidade/prevenção & controle , Fenilbutiratos/farmacologia , Adipócitos/efeitos dos fármacos , Adipócitos/metabolismo , Tecido Adiposo Marrom/diagnóstico por imagem , Tecido Adiposo Marrom/metabolismo , Animais , Modelos Animais de Doenças , Ingestão de Alimentos/efeitos dos fármacos , Fluordesoxiglucose F18 , Glucose/metabolismo , Teste de Tolerância a Glucose , Resistência à Insulina , Masculino , Camundongos Endogâmicos C57BL , Obesidade/metabolismo , Fenilbutiratos/uso terapêutico , Tomografia Computadorizada com Tomografia por Emissão de Pósitrons , Ganho de Peso/efeitos dos fármacos
9.
Mol Cell Biochem ; 461(1-2): 195-204, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31414336

RESUMO

Recent studies on mice with null mutation of the angiotensin type 2 receptor (AT2R) gene have implicated the involvement of AT2R in regulating adipocyte size and obesity, a major risk factor for metabolic syndrome. However, the outcome from these studies remains inconclusive. Therefore, current study was designed to test whether pharmacological activation of AT2R regulates adiposity and lipid metabolism. Male mice (5-weeks old) were pre-treated with vehicle or AT2R agonist (C21, 0.3 mg/kg, i.p., daily, for 4 days) and fed normal diet (ND). Then these animals were subdivided into ND and high-fat diet (HFD) regimen and concomitantly treated with vehicle or C21 through day 14. Vehicle-treated HFD-fed mice demonstrated an increase in epididymal white adipose tissue (eWAT) weight and adipocyte size, which were associated with increased eWAT expression of the lipogenic regulators, fatty acid binding protein and fatty acid synthase, decreased expression of adipose triglyceride lipase and increased expression of hormone-sensitive lipase. Interestingly, C21 pre-treatment altered HFD-induced changes in lipogenic and lipolytic regulators. C21 pre-treatment prevented decrease in expression of uncoupler protein-1 in brown adipose in HFD-fed mice, which was associated with increased core temperature. In addition, C21 pre-treatment ameliorated plasma-free fatty acids, triglycerides, insulin and tumor necrosis factor-α in HFD-fed mice. Ex-vivo study in isolated primary epididymal adipocytes revealed that C21 inhibits long chain fatty acid transporter, via a nitric oxide synthase/guanylate cyclase/protein kinase G-dependent pathway. Collectively, we propose pharmacological activation of AT2R regulates fatty acid metabolism and thermogenesis and prevents HFD-induced adiposity in mice.


Assuntos
Adiposidade , Metabolismo dos Lipídeos , Receptor Tipo 2 de Angiotensina/metabolismo , Adipócitos/citologia , Adipócitos/metabolismo , Adiponectina/sangue , Tecido Adiposo Marrom/metabolismo , Tecido Adiposo Branco/metabolismo , Animais , Temperatura Corporal , Peso Corporal , Tamanho Celular , Ingestão de Energia , Epididimo/anatomia & histologia , Ácidos Graxos/sangue , Insulina/sangue , Masculino , Camundongos Endogâmicos C57BL , Triglicerídeos/sangue , Fator de Necrose Tumoral alfa/sangue , Proteína Desacopladora 1/metabolismo
10.
Food Chem Toxicol ; 133: 110780, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31449894

RESUMO

Dietary Apigenin (AP), a natural flavonoid from plants, could alleviate high-fat diet (HFD) induced obesity and its complication. Nonetheless, the direct correlation between dietary AP and their effects in adipose tissues remained unclear. In this study, male C57BL/6 mice were fed with low-fat diet, HFD with or without 0.04% (w/w) AP for 12 weeks. Dietary AP ameliorated HFD induced body weight gain, glucose intolerance, and insulin resistance. Energy expenditure was increased with no influence on energy intake, which indicated us that AP prevented obesity by enhancing energy export. Interestingly, AP activated lipolysis (ATGL/FOXO1/SIRT1) without higher cycling free fatty acids (FFAs). FFAs were consumed by the upregulation of fatty acid oxidation (AMPK/ACC), thermogenesis, and browning (UCP-1, PGC-1α). Additionally, adipose tissue metabolic inflammation (NF-кB, MAPK) was also reduced by AP. Our study proposed that dietary AP could be explored as a new dietary strategy to combat obesity and related insulin resistance.


Assuntos
Tecido Adiposo Marrom/efeitos dos fármacos , Apigenina/farmacologia , Lipólise/efeitos dos fármacos , Termogênese/efeitos dos fármacos , Tecido Adiposo Marrom/citologia , Tecido Adiposo Marrom/metabolismo , Animais , Dieta Hiperlipídica , Epididimo/citologia , Epididimo/efeitos dos fármacos , Epididimo/metabolismo , Intolerância à Glucose/dietoterapia , Resistência à Insulina , Masculino , Camundongos Endogâmicos C57BL , Gordura Subcutânea/citologia , Gordura Subcutânea/efeitos dos fármacos , Gordura Subcutânea/metabolismo , Ganho de Peso/efeitos dos fármacos
11.
J Agric Food Chem ; 67(36): 10107-10115, 2019 Sep 11.
Artigo em Inglês | MEDLINE | ID: mdl-31434473

RESUMO

We examined the antiobesity effect of a limonoid 7-deacetoxy-7-oxogedunin, named CG-1, purified from the seeds of Carapa guianensis, Meliaceae, known as andiroba in high-fat-diet (HFD)-fed mice. C57BL/6 mice were fed a low-fat diet or an HFD and orally administered CG-1 (20 mg/kg) for 7 weeks. CG-1 lowered the body weight gain and improved the serum triglyceride level and insulin sensitivity in HFD-fed mice. The expression level of the adipogenesis-related genes was lowered by CG-1 in the visceral white adipose tissue (vWAT). The mRNA expression level of the macrophage-related genes decreased in vWAT following the administration of CG-1 to HFD-fed mice. It is noteworthy that CG-1 activated the brown adipose tissue (BAT) with enhanced expression of uncoupling protein 1 and increased the rectal temperature in HFD-fed mice. These results indicate that the limonoid CG-1 decreased body weight gain and ameliorated hypertriglyceridemia and insulin resistance with the activation of BAT in HFD-fed mice.


Assuntos
Tecido Adiposo Marrom/efeitos dos fármacos , Fármacos Antiobesidade/administração & dosagem , Resistência à Insulina , Limoninas/administração & dosagem , Meliaceae/química , Obesidade/tratamento farmacológico , Extratos Vegetais/administração & dosagem , Tecido Adiposo Marrom/metabolismo , Animais , Dieta Hiperlipídica/efeitos adversos , Humanos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Obesidade/genética , Obesidade/metabolismo , Obesidade/fisiopatologia , Sementes/química , Triglicerídeos/sangue , Proteína Desacopladora 1/genética , Proteína Desacopladora 1/metabolismo , Ganho de Peso/efeitos dos fármacos
12.
Int J Mol Sci ; 20(14)2019 Jul 13.
Artigo em Inglês | MEDLINE | ID: mdl-31337027

RESUMO

Brown adipose tissue (BAT) thermogenesis is a conserved mechanism to maintain body temperature in mammals. However, since BAT contribution to energy expenditure can represent a relevant modulator of metabolic homeostasis, many studies have focused on the nervous system and endocrine factors that control the activity of this tissue. There is long-established evidence that the counter-regulatory hormone glucagon negatively influences energy balance, enhances satiety, and increases energy expenditure. Despite compelling evidence showing that glucagon has direct action on BAT thermogenesis, recent findings are questioning this conventional attribute of glucagon action. Glucagon like peptide-1 (GLP-1) is an incretin secreted by the intestinal tract which strongly decreases feeding, and, furthermore, improves metabolic parameters associated with obesity and diabetes. Therefore, GLP-1 receptors (GLP-1-R) have emerged as a promising target in the treatment of metabolic disorders. In this short review, we will summarize the latest evidence in this regard, as well as the current therapeutic glucagon- and GLP-1-based approaches to treating obesity.


Assuntos
Peptídeo 1 Semelhante ao Glucagon/metabolismo , Glucagon/metabolismo , Termogênese , Tecido Adiposo Marrom/efeitos dos fármacos , Tecido Adiposo Marrom/metabolismo , Animais , Metabolismo Energético/efeitos dos fármacos , Humanos , Terapia de Alvo Molecular , Obesidade/tratamento farmacológico , Obesidade/etiologia , Obesidade/metabolismo , Termogênese/efeitos dos fármacos
13.
Food Funct ; 10(8): 4771-4781, 2019 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-31312821

RESUMO

The increased prevalence of obesity significantly affects human health worldwide. Improvement of glycometabolism by dietotherapy/herbal remedy is an effective approach to ameliorate obesity. In this study, high-fat-diet induced obese (DIO) mice were treated with mulberry leaves for 13 weeks. The results showed that mulberry leaves significantly alleviated adiposity of DIO mice including reducing body weight gain, fat accumulation and fasting blood glucose, and improving insulin sensitivity. In addition, mulberry leaves had protective effects on liver and kidneys. The abundant flavonoids, polyphenols and 1-deoxynojirimycin in mulberry leaves were likely responsible for their beneficial effects. Mechanistically, we found that mulberry leaves could alleviate obesity by enhancing brown adipose tissue (BAT) activity partly indicated by elevated thermogenesis and overexpression of uncoupling protein 1 in BAT. Moreover, mulberry leaves significantly increased the Bacteroidetes/Firmicutes ratio and Akkermansia level that were closely associated with obesity development and progression, and decreased the potential proinflammatory Proteobacteria in feces. These findings reveal that the mulberry leaf is an edible plant food with therapeutic potential for obesity and may provide dietotherapy/herbal remedy to the treatment of obesity and its complications.


Assuntos
Tecido Adiposo Marrom/efeitos dos fármacos , Microbioma Gastrointestinal/efeitos dos fármacos , Morus/química , Obesidade/tratamento farmacológico , Extratos Vegetais/administração & dosagem , Tecido Adiposo Marrom/metabolismo , Adiposidade/efeitos dos fármacos , Animais , Bactérias/classificação , Bactérias/efeitos dos fármacos , Bactérias/genética , Bactérias/isolamento & purificação , Dieta Hiperlipídica/efeitos adversos , Humanos , Masculino , Camundongos , Camundongos Obesos , Obesidade/etiologia , Obesidade/metabolismo , Obesidade/microbiologia , Folhas de Planta/química , Proteína Desacopladora 1/genética , Proteína Desacopladora 1/metabolismo
14.
Int J Mol Sci ; 20(13)2019 Jun 28.
Artigo em Inglês | MEDLINE | ID: mdl-31261740

RESUMO

In the presence of dietary lipids, both apolipoprotein A-IV (ApoA-IV) production and brown adipose tissue (BAT) thermogenesis are increased. The effect of dietary lipid-induced AproA-IV on BAT thermogenesis and energy expenditure remains unknown. In the present study, we hypothesized that ApoA-IV knockout (ApoA-IV-KO) mice exhibited decreased BAT thermogenesis to affect energy homeostasis. To test this hypothesis, BAT thermogenesis in wildtype (WT) and ApoA-IV-KO mice fed either a standard low-fat chow diet or a high-fat diet (HFD) was investigated. When fed a chow diet, energy expenditure and food intake were comparable between WT and ApoA-IV-KO mice. After 1 week of HFD consumption, ApoA-IV-KO mice had comparable energy intake but produced lower energy expenditure relative to their WT controls in the dark phase. After an acute feeding of dietary lipids or 1-week HFD feeding, ApoA-IV-KO mice produced lower levels of uncoupling protein 1 (UCP1) and exhibited reduced expression of thermogenic genes in the BAT compared with WT controls. In response to cold exposure, however, ApoA-IV-KO mice had comparable energy expenditure and BAT temperature relative to WT mice. Thus, ApoA-IV-KO mice exhibited reduced diet-induced BAT thermogenesis and energy expenditure.


Assuntos
Tecido Adiposo Marrom/metabolismo , Apolipoproteínas A/genética , Dieta Hiperlipídica , Termogênese , Tecido Adiposo Marrom/fisiologia , Animais , Apolipoproteínas A/deficiência , Gorduras na Dieta/metabolismo , Metabolismo Energético , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Proteína Desacopladora 1/metabolismo
15.
Cells ; 8(7)2019 06 30.
Artigo em Inglês | MEDLINE | ID: mdl-31262098

RESUMO

Obesity is characterized by chronic and low-grade systemic inflammation, an increase of adipose tissue, hypertrophy, and hyperplasia of adipocytes. Adipose tissues can be classified into white, brown, beige and pink adipose tissues, which display different regulatory, morphological and functional characteristics of their adipocyte and immune cells. Brown and white adipocytes can play a key role not only in the control of energy homeostasis, or through the balance between energy storage and expenditure, but also by the modulation of immune and inflammatory responses. Therefore, brown and white adipocytes can orchestrate important immunological crosstalk that may deeply impact the tumor microenvironment and be crucial for cancer establishment and progression. Recent works have indicated that white adipose tissues can undergo a process called browning, in which an inducible brown adipocyte develops. In this review, we depict the mechanisms involved in the differential role of brown, white and pink adipocytes, highlighting their structural, morphological, regulatory and functional characteristics and correlation with cancer predisposition, establishment, and progression. We also discuss the impact of the increased adiposity in the inflammatory and immunological modulation. Moreover, we focused on the plasticity of adipocytes, describing the molecules produced and secreted by those cells, the modulation of the signaling pathways involved in the browning phenomena of white adipose tissue and its impact on inflammation and cancer.


Assuntos
Adiposidade/imunologia , Carcinogênese/imunologia , Inflamação/imunologia , Neoplasias/imunologia , Obesidade/imunologia , Adipócitos Marrons/imunologia , Adipócitos Marrons/metabolismo , Adipócitos Brancos/imunologia , Adipócitos Brancos/metabolismo , Tecido Adiposo Marrom/citologia , Tecido Adiposo Marrom/imunologia , Tecido Adiposo Marrom/metabolismo , Tecido Adiposo Branco/citologia , Tecido Adiposo Branco/imunologia , Tecido Adiposo Branco/metabolismo , Animais , Carcinogênese/patologia , Modelos Animais de Doenças , Progressão da Doença , Metabolismo Energético/imunologia , Humanos , Inflamação/metabolismo , Inflamação/patologia , Neoplasias/metabolismo , Neoplasias/patologia , Obesidade/complicações , Obesidade/metabolismo , Microambiente Tumoral/imunologia
16.
Life Sci ; 232: 116683, 2019 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-31344430

RESUMO

AIMS: Previous work has demonstrated that ketogenic diets promote white fat browning; however, the exact mechanisms underlying this phenomenom have yet to be elucidated. Recently, an in vitro study showed that supraphysiological concentrations of ß-hydroxybutyrate (ßHB) had a strong influence on the induction of adipocyte browning. On the other hand, concentrations in the physiological range, achieved through ketogenic diets and prolonged fasting produce values of 1-3 mM and 4-7 mM, respectively. Herein, we investigated the impact of physiological concentrations of ßHB on metabolism, and the expression of uncoupling protein 1 (UCP1) and other browning markers in adipose tissues. MAIN METHODS: The effects of ßHB on adipocyte browning were investigated in vitro, using primary cultures of isolated visceral and subcutaneous fat cells and cultured 3T3-L1 adipocytes, and in vivo. KEY FINDINGS: It was determined that ßHB failed to induce changes in the oxidative capacity, citrate synthase activity or browning gene expression patterns in isolated adipocytes, and did not exert a permissive effect on ß-adrenergic agonist-induced browning. In addition, 3T3-L1 adipocytes differentiated following ßHB treatment exhibited downregulated Ucp1 expression levels, a result that was recapitulated in the subcutaneous adipose tissue of Wistar rats after ßHB salt treatment. Rats administered ßHB salts also presented reduced brown adipose tissue UCP1 protein expression. SIGNIFICANCE: The mechanisms underlying ketogenic diet-induced browning of adipocytes are not known. The results from the present study indicate that physiological concentrations of ßHB are not responsible for this phenomenon, despite the observed ßHB-mediated downregulation of UCP1 expression.


Assuntos
Ácido 3-Hidroxibutírico/metabolismo , Tecido Adiposo Marrom/metabolismo , Células 3T3-L1 , Animais , Masculino , Camundongos , Ratos , Ratos Wistar , Proteína Desacopladora 1/metabolismo
17.
Nutrients ; 11(6)2019 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-31208033

RESUMO

This study aimed to elucidate the molecular mechanism of Chrysanthemum morifolium Ramat. against obesity and diabetes, by comparing the transcriptional changes in epididymal white adipose tissue (eWAT) with those of the bioactive compound in C. morifolium, luteolin (LU). Male C57BL/6J mice were fed a normal diet, high-fat diet (HFD), and HFD supplemented with 1.5% w/w chrysanthemum leaf ethanol extract (CLE) for 16 weeks. Supplementation with CLE and LU significantly decreased the body weight gain and eWAT weight by stimulating mRNA expressions for thermogenesis and energy expenditure in eWAT via lipid mobilization, which may be linked to the attenuation of dyslipidemia. Furthermore, CLE and LU increased uncoupling protein-1 protein expression in brown adipose tissue, leading to energy expenditure. Of note, CLE and LU supplements enhanced the balance between lipid storage and mobilization in white adipose tissue (WAT), in turn, inhibiting adipocyte inflammation and lipotoxicity of peripheral tissues. Moreover, CLE and LU attenuated hepatic steatosis by suppressing hepatic lipogenesis, thereby ameliorating insulin resistance and dyslipidemia. Our data suggest that CLE helps inhibit obesity and its comorbidities via the complex interplay between liver and WAT in diet-induced obese mice.


Assuntos
Tecido Adiposo Branco/efeitos dos fármacos , Chrysanthemum/química , Suplementos Nutricionais , Etanol/farmacologia , Mobilização Lipídica/efeitos dos fármacos , Doenças Metabólicas/prevenção & controle , Obesidade/prevenção & controle , Fitoterapia , Tecido Adiposo Marrom/metabolismo , Animais , Dieta Hiperlipídica , Metabolismo Energético , Resistência à Insulina , Fígado/metabolismo , Masculino , Doenças Metabólicas/etiologia , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Obesos , Obesidade/etiologia , Extratos Vegetais/farmacologia , Folhas de Planta/química
18.
Int J Mol Sci ; 20(11)2019 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-31159462

RESUMO

Despite tremendous research efforts to identify regulatory factors that control energy metabolism, the prevalence of obesity has been continuously rising, with nearly 40% of US adults being obese. Interactions between secretory factors from adipose tissues and the nervous system innervating adipose tissues play key roles in maintaining energy metabolism and promoting survival in response to metabolic challenges. It is currently accepted that there are three types of adipose tissues, white (WAT), brown (BAT), and beige (BeAT), all of which play essential roles in maintaining energy homeostasis. WAT mainly stores energy under positive energy balance, while it releases fuels under negative energy balance. Thermogenic BAT and BeAT dissipate energy as heat under cold exposure to maintain body temperature. Adipose tissues require neural and endocrine communication with the brain. A number of WAT adipokines and BAT batokines interact with the neural circuits extending from the brain to cooperatively regulate whole-body lipid metabolism and energy homeostasis. We review neuroanatomical, histological, genetic, and pharmacological studies in neuroendocrine regulation of adipose function, including lipid storage and mobilization of WAT, non-shivering thermogenesis of BAT, and browning of BeAT. Recent whole-tissue imaging and transcriptome analysis of differential gene expression in WAT and BAT yield promising findings to better understand the interaction between secretory factors and neural circuits, which represents a novel opportunity to tackle obesity.


Assuntos
Tecido Adiposo/metabolismo , Metabolismo Energético , Sistemas Neurossecretores/metabolismo , Tecido Adiposo/inervação , Tecido Adiposo Bege/metabolismo , Tecido Adiposo Marrom/metabolismo , Tecido Adiposo Branco/metabolismo , Animais , Biomarcadores , Ácidos Graxos/metabolismo , Homeostase , Humanos , Oxirredução , Sistema Nervoso Simpático , Termogênese
19.
PLoS Genet ; 15(6): e1008244, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-31233501

RESUMO

Berardinelli-Seip congenital generalized lipodystrophy is associated with increased bone mass suggesting that fat tissue regulates the skeleton. Because there is little mechanistic information regarding this issue, we generated "fat-free" (FF) mice completely lacking visible visceral, subcutaneous and brown fat. Due to robust osteoblastic activity, trabecular and cortical bone volume is markedly enhanced in these animals. FF mice, like Berardinelli-Seip patients, are diabetic but normalization of glucose tolerance and significant reduction in circulating insulin fails to alter their skeletal phenotype. Importantly, the skeletal phenotype of FF mice is completely rescued by transplantation of adipocyte precursors or white or brown fat depots, indicating that adipocyte derived products regulate bone mass. Confirming such is the case, transplantation of fat derived from adiponectin and leptin double knockout mice, unlike that obtained from their WT counterparts, fails to normalize FF bone. These observations suggest a paucity of leptin and adiponectin may contribute to the increased bone mass of Berardinelli-Seip patients.


Assuntos
Adiponectina/genética , Leptina/genética , Lipodistrofia Generalizada Congênita/genética , Osteosclerose/genética , Adipócitos/metabolismo , Tecido Adiposo Marrom/metabolismo , Animais , Densidade Óssea/genética , Modelos Animais de Doenças , Feminino , Glucose/genética , Glucose/metabolismo , Humanos , Insulina/genética , Gordura Intra-Abdominal/metabolismo , Lipodistrofia Generalizada Congênita/complicações , Lipodistrofia Generalizada Congênita/patologia , Camundongos , Camundongos Knockout , Osteosclerose/etiologia , Osteosclerose/metabolismo , Osteosclerose/patologia , Esqueleto/metabolismo , Esqueleto/patologia , Gordura Subcutânea/metabolismo
20.
Endokrynol Pol ; 70(2): 171-189, 2019.
Artigo em Polonês | MEDLINE | ID: mdl-31070771

RESUMO

Adipose tissue is currently considered not only as an energy store but also as an organ of internal secretion. Numerous adipocytokines regulating a number of human body processes are important in many disease processes, including chronic kidney disease (CKD). Nowadays, the role of zinc α2-glycoprotein (ZAG) is being sought as a potential link between these two organs. ZAG, through its lipolytic effect, contributes to progressive malnutrition in patients undergoing dialysis, and this significantly increases their mortality. It seems that ZAG may be a new potential biomarker of kidney damage, and the specific pharmacotherapy will significantly reduce the progressive process of cachexia.


Assuntos
Tecido Adiposo Marrom/metabolismo , Tecido Adiposo Branco/metabolismo , Desnutrição/metabolismo , Insuficiência Renal Crônica/metabolismo , Proteínas de Plasma Seminal/metabolismo , Biomarcadores/sangue , Humanos , Metabolismo dos Lipídeos , Comunicação Parácrina
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