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1.
Cardiovasc Pathol ; 49: 107259, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32692664

RESUMO

Perivascular adipose tissue (PVAT) is a fat tissue deposit that encircles the vasculature. PVAT is traditionally known to protect the vasculature from external stimuli that could cause biological stress. In addition to the protective role of PVAT, it secretes certain biologically active substances known as adipokines that induce paracrine effects on proximate blood vessels. These adipokines influence vascular tones. There are different types of PVAT and they are phenotypically and functionally distinct. These are the white and brown PVATs. Under certain conditions, white PVAT could undergo phenotypic switch to attain a brown PVAT-like phenotype. This type of PVAT is referred to as Beige PVAT. The morphology of adipose tissue is influenced by species, age, and sex. These factors play significant roles in adipose tissue mass, functionality, paracrine activity, and predisposition to vascular diseases. The difficulty that is currently experienced in extrapolating animal models to human physiology could be traceable to these factors. Up till now, the involvement of PVAT in the development of vascular pathology is still not well understood. Brown and white PVAT contribute differently to vascular pathology. Thus, the PVAT could be a therapeutic target in curbing certain vascular diseases. In this review, knowledge would be updated on the multifaceted involvement of PVAT in vascular pathology and also explore its vascular therapeutic potential.


Assuntos
Tecido Adiposo Bege/patologia , Tecido Adiposo Marrom/patologia , Tecido Adiposo Branco/patologia , Artérias/patologia , Doenças Vasculares/patologia , Adipocinas/metabolismo , Tecido Adiposo Bege/efeitos dos fármacos , Tecido Adiposo Bege/metabolismo , Tecido Adiposo Bege/fisiopatologia , Tecido Adiposo Marrom/efeitos dos fármacos , Tecido Adiposo Marrom/metabolismo , Tecido Adiposo Marrom/fisiopatologia , Tecido Adiposo Branco/efeitos dos fármacos , Tecido Adiposo Branco/metabolismo , Tecido Adiposo Branco/fisiopatologia , Adiposidade , Animais , Artérias/efeitos dos fármacos , Artérias/metabolismo , Artérias/fisiopatologia , Fármacos Cardiovasculares/uso terapêutico , Hemodinâmica , Humanos , Mediadores da Inflamação/metabolismo , Comunicação Parácrina , Transdução de Sinais , Doenças Vasculares/tratamento farmacológico , Doenças Vasculares/metabolismo , Doenças Vasculares/fisiopatologia
2.
Am J Physiol Endocrinol Metab ; 319(2): E354-E362, 2020 08 01.
Artigo em Inglês | MEDLINE | ID: mdl-32603260

RESUMO

Browning of white adipose tissue (WAT) has been shown to reduce obesity and obesity-related complications, suggesting that factors that promote WAT browning may have applications in the development of therapeutic strategies for treating obesity. Here, we show that ablation of spinophilin (SPL), a ubiquitously expressed, multidomain scaffolding protein, increases metabolism and improves energy balance. Male and female SPL knockout (KO) and wild-type (WT) littermate controls were fed a chow diet or a high-fat diet (HFD). Body weight, hepatic steatosis, glucose and insulin tolerance, physical activity, and expression of browning genes in adipose tissues were measured and compared. Male SPL knockout (KO) mice fed a chow diet were significantly leaner, had lower body weights, and exhibited better glucose tolerance and insulin sensitivity than wild-type (WT) littermate controls. When fed an HFD, SPL KO mice were protected from increased body fat, weight gain, hepatic steatosis, hyperinsulinemia, and insulin resistance. Physical activity of SPL KO mice was markedly increased compared with WT controls. Furthermore, expression of the brown adipocyte marker, uncoupling protein-1 (UCP-1), and the mitochondrial activity markers, cd137 and c-idea, were significantly increased in visceral WAT (vWAT) of SPL KO mice, suggesting that SPL knockout protected the mice from HFD-induced obesity and its metabolic complications, at least in part, by promoting the browning of white adipocytes in vWAT. Our data identify a critical role of SPL in regulating glucose homeostasis, obesity, and adipocyte browning. These results suggest SPL may serve as a drug target for obesity and diabetes.


Assuntos
Dieta Hiperlipídica/efeitos adversos , Resistência à Insulina/fisiologia , Proteínas dos Microfilamentos/deficiência , Proteínas do Tecido Nervoso/deficiência , Obesidade/prevenção & controle , Adiponectina/sangue , Tecido Adiposo Marrom/fisiopatologia , Tecido Adiposo Branco/fisiopatologia , Animais , Metabolismo Energético , Fígado Gorduroso/fisiopatologia , Fígado Gorduroso/prevenção & controle , Feminino , Leptina/sangue , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Proteínas dos Microfilamentos/fisiologia , Proteínas do Tecido Nervoso/fisiologia , Obesidade/etiologia , Obesidade/fisiopatologia , Esforço Físico/fisiologia
3.
PLoS One ; 15(5): e0232400, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32384084

RESUMO

Metabolic parameters ranging from circulating nutrient levels and substrate utilization to energy expenditure and thermogenesis are temporally modulated by the circadian timing system. During critical embryonic developmental periods, maternal over-nutrition could alter key elements in different tissues associated with the generation of circadian rhythmicity, compromising normal rhythmicity development. To address this issue, we determine whether maternal over-nutrition leads to alterations in the development of circadian rhythmicity at physiological and behavioral levels in the offspring. For this, female rabbits were fed a standard diet (SD) or high-fat and carbohydrate diet (HFCD) before mating and during gestation. Core body temperature and gross locomotor activity were continuously recorded in newborn rabbits, daily measurements of body weight and the amount of milk ingested was carried out. At the end of lactation, tissue samples, including brown adipose tissue (BAT) and white adipose tissue (WAT), were obtained for determining the expression of uncoupling protein-1 (UCP1) and cell death-inducing DNA fragmentation factor-like effector A (CIDEA) genes. HFCD pups exhibited conspicuous differences in the development of the daily rhythm of temperature and locomotor activity compared to the SD pups, including a significant increase in the daily mean core temperature, changes in the time when temperature or activity remains above the average, shifts in the acrophase, decrease in the duration and intensity of the anticipatory rise previous to nursing, and changes in frequency of the rhythms. HFCD pups exhibited a significant increase in BAT thermogenesis markers, and a decrease of these markers in WAT, indicating more heat generation by brown adipocytes and alterations in the browning process. These results indicate that maternal over-nutrition alters offspring homeostatic and chronostatic regulation at the physiological and behavioral levels. Further studies are needed to determine whether these alterations are associated with the changes in the organization of the circadian system of the progeny.


Assuntos
Regulação da Temperatura Corporal/fisiologia , Ritmo Circadiano/fisiologia , Lactação/fisiologia , Locomoção/fisiologia , Tecido Adiposo Marrom/fisiopatologia , Tecido Adiposo Branco/fisiopatologia , Animais , Proteínas Reguladoras de Apoptose/genética , Regulação da Temperatura Corporal/genética , Ritmo Circadiano/genética , Modelos Animais de Doenças , Feminino , Expressão Gênica , Lactação/genética , Locomoção/genética , Fenômenos Fisiológicos da Nutrição Materna , Hipernutrição/complicações , Hipernutrição/genética , Hipernutrição/fisiopatologia , Gravidez , Complicações na Gravidez/genética , Complicações na Gravidez/fisiopatologia , Coelhos , Proteína Desacopladora 1/genética
4.
J Med Food ; 23(3): 233-241, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-32191577

RESUMO

Eriocitrin (EC) is an abundant flavonoid in lemons, which is known as a strong antioxidant agent. This study investigated the biological and molecular mechanisms underlying the anti-obesity effect of EC in high-fat diet (HFD)-fed obese mice. C57BL/6N mice were fed an HFD (40 kcal% fat) with or without 0.005% (w/w) EC for 16 weeks. Dietary EC improved adiposity by increasing adipocyte fatty acid (FA) oxidation, energy expenditure, and mRNA expression of thermogenesis-related genes in brown adipose tissue (BAT) and skeletal muscle, whereas it also decreased lipogenesis-related gene expression in white adipose tissue. In addition to adiposity, EC prevented hepatic steatosis by diminishing lipogenesis while enhancing FA oxidation in the liver and fecal lipid excretion, which was linked to attenuation of hyperlipidemia. Moreover, EC improved insulin sensitivity by decreasing hepatic gluconeogenesis and proinflammatory responses. These findings indicate that EC may protect against diet-induced adiposity and related metabolic disorders by controlling thermogenesis of BAT and skeletal muscle, FA oxidation, lipogenesis, fecal lipid excretion, glucose utilization, and gluconeogenesis.


Assuntos
Adiposidade/efeitos dos fármacos , Flavanonas/administração & dosagem , Obesidade/tratamento farmacológico , Extratos Vegetais/administração & dosagem , Tecido Adiposo Marrom/efeitos dos fármacos , Tecido Adiposo Marrom/metabolismo , Tecido Adiposo Marrom/fisiopatologia , Animais , Citrus/química , Dieta Hiperlipídica , Lipogênese/efeitos dos fármacos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Obesos , Músculo Esquelético/efeitos dos fármacos , Músculo Esquelético/metabolismo , Músculo Esquelético/fisiopatologia , Obesidade/etiologia , Obesidade/metabolismo , Obesidade/fisiopatologia , Fitoterapia , Termogênese/efeitos dos fármacos
5.
Chin J Nat Med ; 18(2): 90-102, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-32172952

RESUMO

With the occurrence of aging process, decreased neuron dopamine, disrupted brown adipose tissue (BAT) remodeling and decreased butyrate level all reflect a weak host healthy in certain degree. Nevertheless, the signs of mid-adult gut microbiota, and its association with host healthy are not well understood. In current study, we deemed to illustrate the associations of age, neuron dopamine, BAT remodeling, butyrate and gut microbiota with the aid of traditional herbal formula Kang Shuai Lao Pian (KSLP), which is known for its anti-aging effect. Here, ELISA was performed to detect the production of brain dopamine, the mass of inguinal white adipose tissue versus interscapular brown adipose tissue (iWAT/iBAT) was calculated and considered as a sign of BAT remodeling, 16S rRNA gene sequencing was used to the detection of gut microbiota profiling and gas chromatography was used to measure the butyrate level in mice feces. Our results indicated mid-adult mice already present distinctive gut microbiota profiling compared with young mice, concomitant with which are the lower brain dopamine level and disrupted brown adipose remodeling. KSLP treatment improved the host healthy and regulated gut microbiota with enriched Firmicutes at the expense of Bacteroidetes, particularly increased the relative abundance of bacteria functionally related to dopamine and butyrate productions, which suggest KSLP treatment constructs a healthier gut environment. In conclusion, modulation of gut microbiota and butyrate may connectively regulate dopamine production and BAT remodeling through gut-brain axis and gut-metabolism axis.


Assuntos
Tecido Adiposo Marrom/efeitos dos fármacos , Butiratos/metabolismo , Dopamina/metabolismo , Medicamentos de Ervas Chinesas/farmacologia , Microbioma Gastrointestinal/efeitos dos fármacos , Tecido Adiposo Marrom/fisiopatologia , Fatores Etários , Animais , Ceco/microbiologia , Fezes/microbiologia , Feminino , Camundongos
6.
Nutr Metab Cardiovasc Dis ; 30(4): 616-624, 2020 04 12.
Artigo em Inglês | MEDLINE | ID: mdl-32127340

RESUMO

BACKGROUND AND AIMS: Several studies have shown that glucagon-like peptide-1 (GLP-1) analogues can affect resting energy expenditure, and preclinical studies suggest that they may activate brown adipose tissue (BAT). The aim of the present study was to investigate the effect of treatment with liraglutide on energy metabolism and BAT fat fraction in patients with type 2 diabetes. METHODS AND RESULTS: In a 26-week double-blind, placebo-controlled trial, 50 patients with type 2 diabetes were randomized to treatment with liraglutide (1.8 mg/day) or placebo added to standard care. At baseline and after treatment for 4, 12 and 26 weeks, we assessed resting energy expenditure (REE) by indirect calorimetry. Furthermore, at baseline and after 26 weeks, we determined the fat fraction in the supraclavicular BAT depot using chemical-shift water-fat MRI at 3T. Liraglutide reduced REE after 4 weeks, which persisted after 12 weeks and tended to be present after 26 weeks (week 26 vs baseline: liraglutide -52 ± 128 kcal/day; P = 0.071, placebo +44 ± 144 kcal/day; P = 0.153, between group P = 0.057). Treatment with liraglutide for 26 weeks did not decrease the fat fraction in supraclavicular BAT (-0.4 ± 1.7%; P = 0.447) compared to placebo (-0.4 ± 1.4%; P = 0.420; between group P = 0.911). CONCLUSION: Treatment with liraglutide decreases REE in the first 12 weeks and tends to decrease this after 26 weeks without affecting the fat fraction in the supraclavicular BAT depot. These findings suggest reduction in energy intake rather than an increase in REE to contribute to the liraglutide-induced weight loss. TRIAL REGISTRY NUMBER: NCT01761318.


Assuntos
Tecido Adiposo Marrom/efeitos dos fármacos , Adiposidade/efeitos dos fármacos , Diabetes Mellitus Tipo 2/tratamento farmacológico , Metabolismo Energético/efeitos dos fármacos , Hipoglicemiantes/uso terapêutico , Incretinas/uso terapêutico , Liraglutida/uso terapêutico , Perda de Peso/efeitos dos fármacos , Tecido Adiposo Marrom/metabolismo , Tecido Adiposo Marrom/fisiopatologia , Idoso , Diabetes Mellitus Tipo 2/diagnóstico , Diabetes Mellitus Tipo 2/metabolismo , Diabetes Mellitus Tipo 2/fisiopatologia , Método Duplo-Cego , Feminino , Humanos , Hipoglicemiantes/efeitos adversos , Incretinas/efeitos adversos , Liraglutida/efeitos adversos , Masculino , Pessoa de Meia-Idade , Países Baixos , Estudos Prospectivos , Fatores de Tempo , Resultado do Tratamento
7.
Nutrients ; 12(2)2020 Jan 24.
Artigo em Inglês | MEDLINE | ID: mdl-31991562

RESUMO

Obesity is a serious metabolic syndrome characterized by high levels of cholesterol, lipids in the blood, and intracellular fat accumulation in adipose tissues. It is known that the suppression of adipogenic protein expression is an effective approach for the treatment of obesity, and regulates fatty acid storage and transportation in adipose tissues. The 60% ethanol extract of Grateloupia elliptica (GEE), a red seaweed from Jeju Island in Korea, was shown to exert anti-adipogenic activity in 3T3-L1 cells and in mice with high-fat diet (HFD)-induced obesity. GEE inhibited intracellular lipid accumulation in 3T3-L1 cells, and significantly reduced expression of adipogenic proteins. In vivo experiments indicated a significant reduction in body weight, as well as white adipose tissue (WAT) weight, including fatty liver, serum triglycerides, total cholesterol, and leptin contents. The expression of the adipogenic proteins, SREBP-1 and PPAR-γ, was significantly decreased by GEE, and the expression of the metabolic regulator protein was increased in WAT. The potential of GEE was shown in WAT, with the downregulation of PPAR-γ and C/EBP-α mRNA; in contrast, in brown adipose tissue (BAT), the thermogenic proteins were increased. Collectively, these research findings suggest the potential of GEE as an effective candidate for the treatment of obesity-related issues via functional foods or pharmaceutical agents.


Assuntos
Adipogenia/efeitos dos fármacos , Tecido Adiposo Marrom/efeitos dos fármacos , Tecido Adiposo Branco/efeitos dos fármacos , Fármacos Antiobesidade/farmacologia , Obesidade/tratamento farmacológico , Extratos Vegetais/farmacologia , Rodófitas , Alga Marinha , Termogênese/efeitos dos fármacos , Células 3T3-L1 , Tecido Adiposo Marrom/metabolismo , Tecido Adiposo Marrom/fisiopatologia , Tecido Adiposo Branco/metabolismo , Tecido Adiposo Branco/fisiopatologia , Adiposidade/efeitos dos fármacos , Animais , Fármacos Antiobesidade/isolamento & purificação , Proteínas Estimuladoras de Ligação a CCAAT/metabolismo , Dieta Hiperlipídica , Modelos Animais de Doenças , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Obesidade/metabolismo , Obesidade/fisiopatologia , PPAR gama/metabolismo , Extratos Vegetais/isolamento & purificação , Rodófitas/química , Alga Marinha/química , Transdução de Sinais , Proteína de Ligação a Elemento Regulador de Esterol 1/metabolismo
8.
Eur J Endocrinol ; 181(5): 473-480, 2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-31491743

RESUMO

Objective: To evaluate whether brown adipose tissue (BAT) activity is altered in women with polycystic ovary syndrome (PCOS), and whether BAT activity correlates with plasma levels of irisin, a myokine that can induce BAT formation. Design: We performed a cross-sectional study including women with PCOS (n = 45) and a healthy control group (n = 25) matched by age and body mass index (BMI). Methods: BAT activity was measured using 18F-FDG positron emission tomography-computed tomography (PET-CT) and plasma irisin levels were measured by a validated enzyme immunoassay. Results: Total BAT activity was significantly reduced in women with PCOS (maximal standardized uptake value (SUVmax): median 7.4 g/mL, interquartile range 0.9-15.4) compared to controls (median 13.0 g/mL, interquartile range 4.7-18.4, P = 0.047). However, this difference was no longer significant after adjustment for waist circumference, a surrogate marker of central adiposity. In the PCOS group, BAT activity correlated negatively with BMI (Spearman's r = -0.630, P = 0.000) and waist circumference (r = -0.592, P = 0.000) but not with plasma irisin levels. Conclusions: BAT activity was reduced in women with PCOS possibly due to increased central adiposity. In PCOS women, BAT activity did not correlate with plasma irisin levels.


Assuntos
Tecido Adiposo Marrom/fisiopatologia , Síndrome do Ovário Policístico/fisiopatologia , Tecido Adiposo Marrom/diagnóstico por imagem , Adiposidade , Adolescente , Adulto , Índice de Massa Corporal , Estudos Transversais , Feminino , Fibronectinas/sangue , Fluordesoxiglucose F18 , Humanos , Estilo de Vida , Pessoa de Meia-Idade , Síndrome do Ovário Policístico/diagnóstico por imagem , Tomografia por Emissão de Pósitrons , Resultado do Tratamento , Circunferência da Cintura , Adulto Jovem
9.
Nutrients ; 11(7)2019 Jul 23.
Artigo em Inglês | MEDLINE | ID: mdl-31340540

RESUMO

Selenium, an essential trace element known mainly for its antioxidant properties, is critical for proper brain function and regulation of energy metabolism. Whole-body knockout of the selenium recycling enzyme, selenocysteine lyase (Scly), increases susceptibility to metabolic syndrome and diet-induced obesity in mice. Scly knockout mice also have decreased selenoprotein expression levels in the hypothalamus, a key regulator of energy homeostasis. This study investigated the role of selenium in whole-body metabolism regulation using a mouse model with hypothalamic knockout of Scly. Agouti-related peptide (Agrp) promoter-driven Scly knockout resulted in reduced weight gain and adiposity while on a high-fat diet (HFD). Scly-Agrp knockout mice had reduced Agrp expression in the hypothalamus, as measured by Western blot and immunohistochemistry (IHC). IHC also revealed that while control mice developed HFD-induced leptin resistance in the arcuate nucleus, Scly-Agrp knockout mice maintained leptin sensitivity. Brown adipose tissue from Scly-Agrp knockout mice had reduced lipid deposition and increased expression of the thermogenic marker uncoupled protein-1. This study sheds light on the important role of selenium utilization in energy homeostasis, provides new information on the interplay between the central nervous system and whole-body metabolism, and may help identify key targets of interest for therapeutic treatment of metabolic disorders.


Assuntos
Proteína Relacionada com Agouti/metabolismo , Dieta Hiperlipídica , Hipotálamo/enzimologia , Leptina/metabolismo , Liases/deficiência , Neurônios/metabolismo , Obesidade/prevenção & controle , Tecido Adiposo Marrom/enzimologia , Tecido Adiposo Marrom/fisiopatologia , Adiposidade , Animais , Modelos Animais de Doenças , Feminino , Técnicas de Inativação de Genes , Hipotálamo/fisiopatologia , Liases/genética , Masculino , Camundongos Endogâmicos C57BL , Camundongos Knockout , Obesidade/enzimologia , Obesidade/genética , Obesidade/fisiopatologia , Transdução de Sinais , Proteína Desacopladora 1/metabolismo , Ganho de Peso
10.
J Agric Food Chem ; 67(25): 7073-7081, 2019 Jun 26.
Artigo em Inglês | MEDLINE | ID: mdl-31240927

RESUMO

Obesity has been demonstrated as a disruptor of female fertility. Our previous study showed the antiobesity effects of calcium on HFD-fed male mice. However, the role of calcium in alleviating reproductive dysfunction of HFD-fed female mice remains unclear. Here, we found that HFD led to estrus cycle irregularity (longer cycle duration and shorter estrus period) and subfertility (longer conception time, lower fertility index, and less implantations) in mice. However, the HFD-induced reproductive abnormality was alleviated by calcium supplementation. Additionally, calcium supplementation enhanced activation/thermogenesis of BAT and browning of WAT in HFD-fed mice. Consequently, the abnormality of energy metabolism and glucose homeostasis induced by HFD were improved by calcium supplementation, with elevated metabolic rates and core temperature. In conclusion, these data showed that calcium supplementation alleviated HFD-induced estrous cycle irregularity and subfertility associated with concomitantly enhanced BAT thermogenesis and WAT browning, suggesting the potential application of calcium in improving obesity-related reproductive disorders.


Assuntos
Tecido Adiposo Marrom/fisiopatologia , Tecido Adiposo Branco/fisiopatologia , Cálcio/administração & dosagem , Ciclo Estral/efeitos dos fármacos , Doenças dos Genitais Femininos/tratamento farmacológico , Infertilidade/tratamento farmacológico , Obesidade/complicações , Termogênese/efeitos dos fármacos , Tecido Adiposo Marrom/efeitos dos fármacos , Tecido Adiposo Branco/efeitos dos fármacos , Animais , Dieta Hiperlipídica/efeitos adversos , Suplementos Nutricionais/análise , Metabolismo Energético/efeitos dos fármacos , Feminino , Doenças dos Genitais Femininos/etiologia , Doenças dos Genitais Femininos/metabolismo , Doenças dos Genitais Femininos/fisiopatologia , Humanos , Infertilidade/etiologia , Infertilidade/metabolismo , Infertilidade/fisiopatologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL
11.
Nutr Metab Cardiovasc Dis ; 29(6): 633-638, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-30956026

RESUMO

BACKGROUND AND AIMS: Sunlight exposure is associated with a number of health benefits including protecting us from autoimmunity, cardiovascular disease, obesity and diabetes. Animal studies have confirmed that ultraviolet (UV)-B radiation, independently of vitamin D, can limit diet-induced obesity, metabolic syndrome and atherosclerosis. The aim of this study is to investigate whether exposure to the UV radiation contained in sunlight impacts on these disease parameters. METHODS AND RESULTS: We have trialled an intervention with solar UV in obese and atherosclerosis-prone mice. We have discovered that solar-simulated UV can significantly limit diet-induced obesity and reduce atheroma development in mice fed a diet high in sugar and fat. The optimal regime for this benefit was exposure once a week to solar UV equivalent to approximately 30 min of summer sun. Exposure to this optimal dose of solar UV also led to a significant increase in liver triglycerides which may protect the liver from damage. CONCLUSION: Our results show that the UV contained in sunlight has the potential to prevent and treat chronic disease at sites distant from irradiated skin. A major health challenge going forward will be to harness the power of the sun safely, without risking an increase in skin cancers.


Assuntos
Tecido Adiposo Marrom/efeitos da radiação , Aterosclerose/prevenção & controle , Dieta Hiperlipídica , Fígado/efeitos da radiação , Obesidade/prevenção & controle , Triglicerídeos/metabolismo , Terapia Ultravioleta , Ganho de Peso/efeitos da radiação , Tecido Adiposo Marrom/metabolismo , Tecido Adiposo Marrom/fisiopatologia , Adiposidade/efeitos da radiação , Animais , Aterosclerose/genética , Aterosclerose/metabolismo , Aterosclerose/patologia , Modelos Animais de Doenças , Fígado/metabolismo , Masculino , Camundongos Endogâmicos C57BL , Camundongos Knockout para ApoE , Obesidade/etiologia , Obesidade/metabolismo , Obesidade/fisiopatologia , Proteína Desacopladora 1/metabolismo
12.
Am J Pathol ; 189(5): 1041-1052, 2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-30790561

RESUMO

Missense mutations in the gasdermin-A3 (Gsdma3) gene are associated with skin inflammation and hair loss in mice. However, the physiological function of Gsdma3 remains unclear. Herein, we reported that mice carrying the Gsdma3 Y344H mutation that encodes a presumptive activated form of Gsdma3 show increased heat production along with lower body fat percentages. Detailed analysis indicated that this metabolic phenotype is mediated by serum IL-6-induced up-regulation of thermogenesis in brown adipose tissue. The mutant form of Gsdma3 promotes the expression of IL-6 in the epidermis in a c-Jun N-terminal kinase (JNK) signaling-dependent manner. The higher whole-body heat production in alopecia and excoriation mice could be suppressed by an IL-6 receptor/GP130 inhibitor. Our results uncovered Gsdma3/IL-6-dependent cross talk between the skin and brown adipose tissue.


Assuntos
Tecido Adiposo Marrom/fisiopatologia , Alopecia/fisiopatologia , Interleucina-6/metabolismo , Proteínas/metabolismo , Fator de Transcrição STAT3/metabolismo , Dermatopatias/fisiopatologia , Termogênese , Animais , Regulação da Temperatura Corporal , Interleucina-6/genética , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Mutação , Fenótipo , Proteínas/genética , Fator de Transcrição STAT3/genética , Transdução de Sinais
13.
FASEB J ; 33(4): 5425-5439, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-30759346

RESUMO

Brown adipose tissue (BAT) is an exclusive tissue of nonshivering thermogenesis. It is fueled by lipids and glucose and involved in energy and metabolic homeostasis. Intrauterine exposure to hyperglycemia during gestational diabetes mellitus may result in abnormal fetal development and metabolic phenotypes in adulthood. However, whether intrauterine hyperglycemia influences the development of BAT is unknown. In this study, mouse embryos were exposed to the intrauterine hyperglycemia environment by injecting streptozocin into pregnant mice at 1 d post coitum (dpc). The structure of BAT was examined by hematoxylin and eosin staining and immunohistochemical analysis. The glucose uptake in BAT was measured in vivo by [18F]-fluoro-2-deoxyglucose-micro-positron emission tomography. The gene expression in BAT was determined by real-time PCR, and the 5'-C-phosphate-G-3' site-specific methylation was quantitatively analyzed. Intrauterine hyperglycemia exposure resulted in the impaired structure of BAT and decreased glucose uptake function in BAT in adulthood. The expressions of the genes involved in thermogenesis and mitochondrial respiratory chain in BAT, such as Ucp1, Cox5b, and Elovl3, were down-regulated by intrauterine hyperglycemia exposure at 18.5 dpc and at 16 wk of age. Furthermore, higher methylation levels of Ucp1, Cox5b, and Elovl3 were found in offspring of mothers with streptozotocin-induced diabetes. Our results provide the evidence for enduring inhibitory effects of intrauterine hyperglycemia on BAT development in offspring. Intrauterine hyperglycemia is associated with increased DNA methylation of the BAT specific genes in offspring, which support an epigenetic involvement.-Yu, D.-Q., Lv, P.-P., Yan, Y.-S., Xu, G.-X., Sadhukhan, A., Dong, S., Shen, Y., Ren, J., Zhang, X.-Y., Feng, C., Huang, Y.-T., Tian, S., Zhou, Y., Cai, Y.-T., Ming, Z.-H., Ding, G.-L., Zhu, H., Sheng, J.-Z., Jin, M., Huang, H.-F. Intrauterine exposure to hyperglycemia retards the development of brown adipose tissue.


Assuntos
Tecido Adiposo Marrom/fisiopatologia , Hiperglicemia/fisiopatologia , Útero/fisiopatologia , Tecido Adiposo Marrom/metabolismo , Animais , Metilação de DNA/fisiologia , Diabetes Mellitus Experimental/metabolismo , Diabetes Mellitus Experimental/fisiopatologia , Diabetes Gestacional/induzido quimicamente , Diabetes Gestacional/metabolismo , Diabetes Gestacional/fisiopatologia , Transporte de Elétrons/fisiologia , Feminino , Expressão Gênica/fisiologia , Glucose/metabolismo , Hiperglicemia/metabolismo , Camundongos , Camundongos Endogâmicos ICR , Gravidez , Estreptozocina/farmacologia , Termogênese/fisiologia , Útero/metabolismo
14.
Clin Endocrinol (Oxf) ; 90(3): 425-432, 2019 03.
Artigo em Inglês | MEDLINE | ID: mdl-30548504

RESUMO

OBJECTIVE: Polycystic ovary syndrome (PCOS) is associated with increased obesity with a greater propensity to weight gain and a lack of sustainable lifestyle interventions. Altered brown adipose tissue (BAT) thermogenesis is a potential contributor to obesity in PCOS. BAT activity and modulation have not been studied in PCOS. This observational study explored BAT thermogenesis and its associations in women with and without PCOS. PARTICIPANTS AND METHODS: Cutaneous temperature was recorded from supraclavicular (indicator of BAT activity) and upper arm regions using dataloggers (SubCue, Calgary, Canada) in a cross-sectional substudy, nested within a randomized control trial, of community-recruited premenopausal women with (n = 47, Rotterdam diagnostic criteria) and without (n = 11) PCOS. RESULTS: Complete temperature data were available in 44 PCOS (mean age: 30.0 ± 6.2, mean BMI: 29.3 ± 5.5) and 11 non-PCOS (mean age: 33.0 ± 7.0, mean BMI: 25 ± 3) women. Women with PCOS had lower supraclavicular skin temperature compared to controls overall (33.9 ± 0.7 vs 34.5 ± 1, P < 0.05) and during sleep (34.5 ± 0.6 vs 35.2 ± 0.9, P < 0.001). In the PCOS group, supraclavicular skin temperature overall and over sleep and waking hours correlated inversely with testosterone (r = -0.41 P < 0.05, r = -0.485 P < 0.01 and r = -0.450 P < 0.01 respectively). Testosterone levels explained approximately 15%, 30% and 20% of the variability in supraclavicular skin temperature overall and over sleep and waking hours in women with PCOS, respectively. CONCLUSION: Women with PCOS have lower BAT activity compared to controls. BAT thermogenesis is negatively associated with androgen levels in PCOS.


Assuntos
Tecido Adiposo Marrom/fisiopatologia , Síndrome do Ovário Policístico/fisiopatologia , Termogênese , Adulto , Estudos de Casos e Controles , Feminino , Humanos , Síndrome do Ovário Policístico/sangue , Temperatura Cutânea , Testosterona/sangue , Adulto Jovem
15.
Ann Surg ; 269(3): 554-563, 2019 03.
Artigo em Inglês | MEDLINE | ID: mdl-28817438

RESUMO

OBJECTIVE: The aim of this study was to uncover the mediators and mechanistic events that facilitate the browning of white adipose tissue (WAT) in response to burns. BACKGROUND: In hypermetabolic patients (eg, burns, cancer), the browning of WAT has presented substantial clinical challenges related to cachexia, atherosclerosis, and poor clinical outcomes. Browning of the adipose tissue has recently been found to induce and sustain hypermetabolism. Although browning appears central in trauma-, burn-, or cancer-induced hypermetabolic catabolism, the mediators are essentially unknown. METHODS: WAT and blood samples were collected from patients admitted to the Ross Tilley Burn Centre at Sunnybrook Hospital. Wild type, CCR2 KO, and interleukin (IL)-6 KO male mice were purchased from Jax laboratories and subjected to a 30% total body surface area burn injury. WAT and serum collected were analyzed for browning markers, macrophages, and metabolic state via histology, gene expression, and mitochondrial respiration. RESULTS: In the present study, we show that burn-induced browning is associated with an increased macrophage infiltration, with a greater type 2 macrophage profile in the fat of burn patients. Similar to our clinical findings in burn patients, both an increase in macrophage recruitment and a type 2 macrophage profile were also observed in post burn mice. Genetic loss of the chemokine CCR2 responsible for macrophage migration to the adipose impairs burn-induced browning. Mechanistically, we show that macrophages recruited to burn-stressed subcutaneous WAT (sWAT) undergo alternative activation to induce tyrosine hydroxylase expression and catecholamine production mediated by IL-6, factors required for browning of sWAT. CONCLUSION: Together, our findings uncover macrophages as the key instigators and missing link in trauma-induced browning.


Assuntos
Tecido Adiposo Marrom/fisiopatologia , Tecido Adiposo Branco/fisiopatologia , Queimaduras/fisiopatologia , Ativação de Macrófagos/fisiologia , Adulto , Animais , Biomarcadores/sangue , Queimaduras/sangue , Queimaduras/imunologia , Estudos de Casos e Controles , Feminino , Citometria de Fluxo , Humanos , Imuno-Histoquímica , Interleucina-6/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Pessoa de Meia-Idade , Reação em Cadeia da Polimerase
16.
Aging (Albany NY) ; 10(10): 2709-2722, 2018 10 18.
Artigo em Inglês | MEDLINE | ID: mdl-30334813

RESUMO

Ames dwarf (Prop1df) mice possess a loss-of-function mutation that results in deficiency of growth hormone, prolactin, and thyroid-stimulating hormone, as well as exceptional longevity. Work in other laboratories suggests that increased respiration and lipid utilization are important for maximizing mammalian longevity. Interestingly, these phenotypes are observed in Ames dwarf mice. We recently demonstrated that Ames dwarf mice have hyperactive brown adipose tissue (BAT), and hypothesized that this may in part be due to their increased surface to mass ratio leading to increased heat loss and an increased demand for thermogenesis. Here, we used increased environmental temperature (eT) to interrogate this hypothesis. We found that increased eT diminished BAT activity in Ames dwarf mice, and led to the normalization of both VO2 and respiratory quotient between dwarf and normal mice, as well as partial normalization (i.e. impairment) of glucose homeostasis in Ames dwarf mice housed at an increased eT. Together, these data suggest that an increased demand for thermogenesis is partially responsible for the improved energy metabolism and glucose homeostasis which are observed in Ames dwarf mice.


Assuntos
Tecido Adiposo Marrom/metabolismo , Nanismo/metabolismo , Metabolismo Energético , Ambiente Controlado , Glucose/metabolismo , Calefação , Tecido Adiposo Marrom/fisiopatologia , Adiposidade , Animais , Nanismo/genética , Nanismo/fisiopatologia , Metabolismo Energético/genética , Predisposição Genética para Doença , Proteínas de Homeodomínio/genética , Homeostase , Mutação com Perda de Função , Masculino , Camundongos Mutantes , Fenótipo , Termogênese
17.
Nutrients ; 10(9)2018 Aug 25.
Artigo em Inglês | MEDLINE | ID: mdl-30149637

RESUMO

Obesity results from the body having either high energy intake or low energy expenditure. Based on this energy equation, scientists have focused on increasing energy expenditure to prevent abnormal fat accumulation. Activating the human thermogenic system that regulates body temperature, particularly non-shivering thermogenesis in either brown or white adipose tissue, has been suggested as a promising solution to increase energy expenditure. Together with the increasing interest in understanding the mechanism by which plant-derived dietary compounds prevent obesity, flavonoids were recently shown to have the potential to regulate non-shivering thermogenesis. In this article, we review the latest research on flavonoid derivatives that increase energy expenditure through non-shivering thermogenesis.


Assuntos
Tecido Adiposo Marrom/efeitos dos fármacos , Tecido Adiposo Branco/efeitos dos fármacos , Fármacos Antiobesidade/farmacologia , Metabolismo Energético/efeitos dos fármacos , Flavonoides/farmacologia , Obesidade/tratamento farmacológico , Termogênese/efeitos dos fármacos , Tecido Adiposo Marrom/metabolismo , Tecido Adiposo Marrom/fisiopatologia , Tecido Adiposo Branco/metabolismo , Tecido Adiposo Branco/fisiopatologia , Adiposidade/efeitos dos fármacos , Animais , Humanos , Obesidade/metabolismo , Obesidade/fisiopatologia
18.
Prog Cardiovasc Dis ; 61(2): 232-245, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29981351

RESUMO

Human brown adipose tissue (BAT) was re-discovered in 2009 by several independent groups, who showed that it is present and active in adults, as judged from the profound uptake of the glucose analogue radiotracer 18F-fluorodeoxyglucose in positron-emission tomography and computed tomography scan analysis after cold exposure. A potential clinical implication of activating BAT relates to its high metabolic activity and its potential role in stimulating energy expenditure (i.e. resting energy expenditure, meal-induced thermogenesis, and cold-induced thermogenesis), which makes it an attractive target to reduce adiposity. Moreover, due to its ability to oxidise glucose and lipids, BAT activation may also potentially exert beneficial metabolic and cardiovascular effects through reducing glucose and lipid levels, respectively. This review describes the potential role of human BAT in the prevention and treatment of obesity, metabolism, and cardiovascular disease focusing on its impact on energy expenditure and management of body fat accumulation as well as on glucose and lipid metabolism. This article also summarises the strategies that are currently being studied to activate human BAT.


Assuntos
Tecido Adiposo Marrom/metabolismo , Doenças Cardiovasculares/metabolismo , Metabolismo Energético , Obesidade/metabolismo , Termogênese , Tecido Adiposo Marrom/fisiopatologia , Adiposidade , Doenças Cardiovasculares/epidemiologia , Doenças Cardiovasculares/fisiopatologia , Doenças Cardiovasculares/terapia , Glucose/metabolismo , Humanos , Metabolismo dos Lipídeos , Obesidade/epidemiologia , Obesidade/fisiopatologia , Obesidade/terapia , Fatores de Risco
19.
Cardiovasc Drugs Ther ; 32(5): 531-539, 2018 10.
Artigo em Inglês | MEDLINE | ID: mdl-30022354

RESUMO

PURPOSE: Arterial stiffness is an inevitable consequence of the aging process and is considered an early stage in the development of cardiovascular diseases. The perivascular adipose tissue (PVAT) is a distinct functional integral layer of the vasculature actively involved in blood pressure regulation and atherosclerosis development via PVAT-derived paracrine/autocrine factors. However, there is little knowledge regarding the relationship between PVAT and arterial stiffness. METHODS: Using unique mice lacking PVAT, high-fat diet-induced obesity, and in mice overexpressing brown adipocyte selective mitoNEET, we investigated the relationship between PVAT and arterial stiffness in mice. RESULTS: We found that lack of PVAT enhanced arterial stiffness in aging mice. High-fat diet feeding of aging C57BL/6J wild-type mice significantly induced hypertrophic PVAT and enhanced arterial stiffness. Furthermore, the expression of mitoNEET, a mitochondrial membrane protein related to energy expenditure, was significantly increased by pioglitazone treatment, while reduced in the hypertrophic PVAT induced by high-fat diet. Overexpression of mitoNEET in PVAT reduced the expression of inflammatory genes and was associated with lower pulse wave velocity in aging mice. CONCLUSIONS: These data indicate that local PVAT homeostasis especially inflammation in PVAT is associated with arterial stiffness development. Pioglitazone-induced mitoNEET in PVAT prevents PVAT inflammation and is negatively associated with arterial stiffness. These findings provide new experimental insight into the roles of pioglitazone on PVAT in arterial stiffness and indicate that PVAT might be a target to treat or prevent cardiovascular disease.


Assuntos
Tecido Adiposo Marrom/metabolismo , Envelhecimento/metabolismo , Doenças Cardiovasculares/metabolismo , Proteínas de Ligação ao Ferro/metabolismo , Proteínas de Membrana/metabolismo , Obesidade/metabolismo , Rigidez Vascular , Tecido Adiposo Marrom/efeitos dos fármacos , Tecido Adiposo Marrom/fisiopatologia , Adiposidade , Fatores Etários , Envelhecimento/genética , Animais , Doenças Cardiovasculares/genética , Doenças Cardiovasculares/fisiopatologia , Doenças Cardiovasculares/prevenção & controle , Dieta Hiperlipídica , Modelos Animais de Doenças , Masculino , Camundongos Endogâmicos C57BL , Camundongos Knockout para ApoE , Obesidade/genética , Obesidade/fisiopatologia , PPAR gama/deficiência , PPAR gama/genética , Pioglitazona/farmacologia , Transdução de Sinais , Rigidez Vascular/efeitos dos fármacos
20.
Arterioscler Thromb Vasc Biol ; 38(8): 1738-1747, 2018 08.
Artigo em Inglês | MEDLINE | ID: mdl-29954752

RESUMO

Objective- Perivascular adipose tissue (PVAT) contributes to vascular homeostasis by producing paracrine factors. Previously, we reported that selective deletion of PPARγ (peroxisome proliferator-activated receptor γ) in vascular smooth muscle cells resulted in concurrent loss of PVAT and enhanced atherosclerosis in mice. To address the causal relationship between loss of PVAT and atherosclerosis, we used BA-PPARγ-KO (brown adipocyte-specific PPARγ knockout) mice. Approach and Results- Deletion of PPARγ in brown adipocytes did not affect PPARγ in white adipocytes or vascular smooth muscle cells or PPARα and PPARδ expression in brown adipocytes. However, development of PVAT and interscapular brown adipose tissue was remarkably impaired, associated with reduced expression of genes encoding lipogenic enzymes in the BA-PPARγ-KO mice. Thermogenesis in brown adipose tissue was significantly impaired with reduced expression of thermogenesis genes in brown adipose tissue and compensatory increase in subcutaneous and gonadal white adipose tissues. Remarkably, basal expression of inflammatory genes and macrophage infiltration in PVAT and brown adipose tissue were significantly increased in the BA-PPARγ-KO mice. BA-PPARγ-KO mice were crossbred with ApoE KO (apolipoprotein E knockout) mice to investigate the development of atherosclerosis. Flow cytometry analysis confirmed increased systemic and PVAT inflammation. Consequently, atherosclerotic lesions were significantly increased in mice with impaired PVAT development, thus indicating that the lack of normal PVAT is sufficient to drive increased atherosclerosis. Conclusions- PPARγ is required for functional PVAT development. PPARγ deficiency in PVAT, while still expressed in vascular smooth muscle cell, enhances atherosclerosis and results in vascular and systemic inflammation, providing new insights on the specific roles of PVAT in atherosclerosis and cardiovascular disease at large.


Assuntos
Adipócitos Marrons/metabolismo , Adipogenia , Tecido Adiposo Marrom/metabolismo , Tecido Adiposo Branco/metabolismo , Doenças da Aorta/metabolismo , Aterosclerose/metabolismo , PPAR gama/deficiência , Adipócitos Marrons/patologia , Tecido Adiposo Marrom/patologia , Tecido Adiposo Marrom/fisiopatologia , Tecido Adiposo Branco/patologia , Tecido Adiposo Branco/fisiopatologia , Adiposidade , Animais , Doenças da Aorta/genética , Doenças da Aorta/patologia , Doenças da Aorta/fisiopatologia , Aterosclerose/genética , Aterosclerose/patologia , Aterosclerose/fisiopatologia , Modelos Animais de Doenças , Feminino , Regulação da Expressão Gênica , Mediadores da Inflamação/metabolismo , Lipogênese/genética , Masculino , Camundongos Endogâmicos C57BL , Camundongos Knockout para ApoE , PPAR gama/genética , Placa Aterosclerótica , Transdução de Sinais , Termogênese
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