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1.
Cells ; 10(12)2021 11 27.
Artigo em Inglês | MEDLINE | ID: mdl-34943840

RESUMO

Alcohol consumption and obesity are known risk factors of steatohepatitis. Here, we report that the deficiency of CRAMP (cathelicidin-related antimicrobial peptide-gene name: Camp) is protective against a high-fat diet (HFD) plus acute alcohol (HFDE)-induced liver injury. HFDE markedly induced liver injury and steatosis in WT mice, which were attenuated in Camp-/- mice. Neutrophil infiltration was lessened in the liver of Camp-/- mice. HFDE feeding dramatically increased epididymal white adipose tissue (eWAT) mass and induced adipocyte hypertrophy in WT mice, whereas these effects were attenuated by the deletion of Camp. Furthermore, Camp-/- mice had significantly increased eWAT lipolysis, evidenced by up-regulated expression of lipolytic enzymes, adipose triglyceride lipase (ATGL) and hormone-sensitive lipase (HSL). The depletion of Camp also increased uncoupling protein 1 (UCP1)-dependent thermogenesis in the brown adipose tissue (BAT) of mice. HFDE fed Camp-/- mice had elevated protein levels of fibroblast growth factor 21 (FGF21) in the eWAT, with an increased adiponectin production, which had been shown to alleviate hepatic fat deposition and inflammation. Collectively, we have demonstrated that Camp-/- mice are protected against HFD plus alcohol-induced liver injury and steatosis through FGF21/adiponectin regulation. Targeting CRAMP could be an effective approach for prevention/treatment of high-fat diet plus alcohol consumption-induced steatohepatitis.


Assuntos
Adiponectina/metabolismo , Catelicidinas/deficiência , Dieta Hiperlipídica/efeitos adversos , Etanol/efeitos adversos , Fatores de Crescimento de Fibroblastos/metabolismo , Fígado/lesões , Fígado/metabolismo , Adipócitos/patologia , Tecido Adiposo/patologia , Tecido Adiposo Marrom/patologia , Tecido Adiposo Branco/patologia , Animais , Catelicidinas/metabolismo , Ácidos Graxos/metabolismo , Fígado Gorduroso/complicações , Comportamento Alimentar , Hipertrofia , Inflamação/patologia , Lipólise , Fígado/patologia , Masculino , Camundongos , Ganho de Peso
2.
Poult Sci ; 100(12): 101480, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34700095

RESUMO

Adiponectin (ADPN) is related to fatty acid synthesis and oxidation in mammals. In chickens, the lipid metabolism, structure and sequence of ADPN are different from that in mammals. The aim of this study was to determine the role of ADPN in broilers lipid metabolism by investigating the temporal and spatial expression profiles of ADPN and its receptors, as well as their response to feed restriction. The results showed that the abdominal fat has the highest expression level, followed by the duodenum, glandular stomach, heart, hypothalamus, liver, and skeletal muscle. Broilers have high energy mobilization during their early stage of growth, in which the fat demand in the liver and muscles is high, thus the expression of ADPN and its receptor are also increased. To study the effects of feed restriction on ADPN and lipid metabolism, broilers were fasted for 12 h and refeed for 2 h. The results showed that fasting decreased the concentration of triglyceride (TG) (P < 0.05) and total cholesterol (TCHO) (P < 0.05) in plasma. The mRNA expression of ADPN in the liver (P < 0.05), breast (P < 0.05) and thigh (P < 0.05), and the mRNA expression of ADPNR1 in the liver (P < 0.05) and duodenum (P < 0.05) were significantly increased in the Fasted group. All above phenomena were recovered after refeeding, suggesting that feed restriction may promote the utilization of fatty acids in active metabolism tissues through ADPN, to guarantee the energy homeostasis of the body. However, the AMP-activated protein kinase (AMPK) signaling pathway and hepatic lipid metabolism were not necessary to cause the above changes under this experimental condition.


Assuntos
Galinhas , Receptores de Adiponectina , Adiponectina/genética , Adiponectina/metabolismo , Animais , Galinhas/genética , Galinhas/metabolismo , Metabolismo dos Lipídeos/genética , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Receptores de Adiponectina/genética , Receptores de Adiponectina/metabolismo
3.
Nutrients ; 13(10)2021 Sep 26.
Artigo em Inglês | MEDLINE | ID: mdl-34684387

RESUMO

Eating disorders and obesity are important health problems with a widespread global epidemic. Adiponectin (AdipoQ), the most abundant adipokine in the plasma, plays important roles in the regulation of energy homeostasis, glucose metabolism and lipid metabolism. Plasma adiponectin concentration is negatively associated with obesity and binge eating disorder. There is a growing interest in the appetite regulation function of adiponectin. However, the effect of AdipoQ on feeding behavior is controversial and closely related to nutritional status and food composition. In this review, we summarize the literatures about the discovery, structure, tissue distribution, receptors and regulation of nutritional status, and focus on the biological function of adiponectin in the regulation of food intake in the central and peripheral system.


Assuntos
Adiponectina/metabolismo , Regulação do Apetite , Animais , Jejum/metabolismo , Comportamento Alimentar , Nutrientes/metabolismo , Receptores de Adiponectina/metabolismo
4.
Georgian Med News ; (316-317): 135-141, 2021.
Artigo em Russo | MEDLINE | ID: mdl-34511460

RESUMO

The article discusses modern views on the metabolic characteristics of adipose tissue in patients with non-alcoholic fatty liver disease (NAFLD). An association has been shown between NAFLD and metabolic risk factors such as dyslipidemia, hyperglycemia, and visceral obesity. The analysis of modern literature on adipose tissue as an endocrine organ is carried out. The recently revealed physiological and pathophysiological properties of adipokines are discussed. It has been documented that adiponectin counteracts the effect of angiotensin II on endothelial cells and prevents their apoptosis by increasing the association between eNOS and heat shock protein. Adiponectin can function as a negative regulator of angiogenesis. It inhibits the proliferation and migration of endothelial cells and markedly inhibits the growth of new blood vessels. The ratio of adiponectin to leptin is a biomarker of adipose tissue dysfunction and correlates better and more accurately with insulin resistance than adiponectin or leptin. The researchers concluded that fatty tissue dysfunction caused by low adiponectin levels may contribute to oxidative stress and inflammation. Medications aimed at synthesizing adiponectin will be useful in the treatment of NAFLD, obesity, diabetes, and cardiovascular disease.


Assuntos
Adiponectina/metabolismo , Resistência à Insulina , Hepatopatia Gordurosa não Alcoólica , Tecido Adiposo , Células Endoteliais , Humanos , Leptina
5.
Int J Clin Pract ; 75(11): e14698, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34342920

RESUMO

BACKGROUND AND AIMS: Dehydroepiandrosterone (DHEA) supplementation has been investigated in patients with altered cortisol levels and is proposed to ameliorate the metabolic profile related to adipose tissue. However, further research is warranted and evidence is no compelling for liver safety. Hence, we aimed to meta-analyse the effects of DHEA supplementation on circulating levels of cortisol, liver enzymes, and adipokines. METHODS: We searched literature published in PubMed, Web of Science, Embase and Scopus, until December 2020. We obtained overall results using the generic inverse of variance method with a random-effects model. RESULTS: Through 10 arms, serum cortisol levels decreased significantly after DHEA supplementation [weighted mean difference (WMD): -53.581 nmol/L, 95% confidence interval (CI): -88.2, -18.9, P = .002], without significant heterogeneity (I2  = 36%, P = .117). In contrast, any significance was noted for adiponectin (WMD: -0.045 µg/mL, 95% CI: -0.56, 0.47; P = .865), leptin (WMD: -2.55 µg/mL, 95% CI: -6.2, 1.06; P = .166), aspartate transaminase (AST) (WMD: -3.7 U/L, 95% CI: -10.35, 2.95; P = .276), and alanine aminotransferase (ALT) (WMD: -1.7 U/L, 95% CI: -3.45, 0.06; P = .058). CONCLUSION: DHEA supplementation decreased circulating cortisol but did not alter adiponectin, leptin, AST, and ALT levels. Hence, DHEA supplementation could be considered as an adjunct in the management of hypercortisolaemia and is safe for the liver.


Assuntos
Adiponectina/metabolismo , Leptina/metabolismo , Desidroepiandrosterona/metabolismo , Suplementos Nutricionais , Humanos , Hidrocortisona/metabolismo , Fígado/metabolismo , Ensaios Clínicos Controlados Aleatórios como Assunto
6.
Molecules ; 26(15)2021 Jul 30.
Artigo em Inglês | MEDLINE | ID: mdl-34361783

RESUMO

Amber-the fossilized resin of trees-is rich in terpenoids and rosin acids. The physiological effects, such as antipyretic, sedative, and anti-inflammatory, were used in traditional medicine. This study aims to clarify the physiological effects of amber extract on lipid metabolism in mouse 3T3-L1 cells. Mature adipocytes are used to evaluate the effect of amber extract on lipolysis by measuring the triglyceride content, glucose uptake, glycerol release, and lipolysis-related gene expression. Our results show that the amount of triacylglycerol, which is stored in lipid droplets in mature adipocytes, decreases following 96 h of treatment with different concentrations of amber extract. Amber extract treatment also decreases glucose uptake and increases the release of glycerol from the cells. Moreover, amber extract increases the expression of lipolysis-related genes encoding perilipin and hormone-sensitive lipase (HSL) and promotes the activity of HSL (by increasing HSL phosphorylation). Amber extract treatment also regulates the expression of other adipocytokines in mature adipocytes, such as adiponectin and leptin. Overall, our results indicate that amber extract increases the expression of lipolysis-related genes to induce lipolysis in 3T3-L1 cells, highlighting its potential for treating various obesity-related diseases.


Assuntos
Adipócitos/efeitos dos fármacos , Âmbar/farmacologia , Misturas Complexas/farmacologia , Regulação da Expressão Gênica/efeitos dos fármacos , Hipolipemiantes/farmacologia , Lipólise/efeitos dos fármacos , Células 3T3-L1 , Adipócitos/citologia , Adipócitos/metabolismo , Adiponectina/genética , Adiponectina/metabolismo , Âmbar/química , Animais , Diferenciação Celular , Misturas Complexas/química , Etanol/química , Glucose/metabolismo , Glicerol/metabolismo , Hipolipemiantes/química , Leptina/genética , Leptina/metabolismo , Gotículas Lipídicas/química , Gotículas Lipídicas/efeitos dos fármacos , Gotículas Lipídicas/metabolismo , Camundongos , Perilipina-1/genética , Perilipina-1/metabolismo , Fosforilação/efeitos dos fármacos , Esterol Esterase/genética , Esterol Esterase/metabolismo , Triglicerídeos/metabolismo
7.
Oxid Med Cell Longev ; 2021: 2207125, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34457110

RESUMO

Obesity is increasing worldwide in prepubertal children, reducing the age of onset of associated comorbidities, including type 2 diabetes. Sulfur-containing amino acids, methionine, cysteine, and their derivatives play important roles in the transmethylation and transsulfuration pathways. Dysregulation of these pathways leads to alterations in the cellular methylation patterns and an imbalanced redox state. Therefore, we tested the hypothesis that one-carbon metabolism is already dysregulated in prepubertal children with obesity. Peripheral blood was collected from 64 children, and the plasma metabolites from transmethylation and transsulfuration pathways were quantified by HPLC. The cohort was stratified by BMI z-scores and HOMA-IR indices into healthy lean (HL), healthy obese (HO), and unhealthy obese (UHO). Fasting insulin levels were higher in the HO group compared to the HL, while the UHO had the highest. All groups presented normal fasting glycemia. Furthermore, high-density lipoprotein (HDL) was lower while triglycerides and lactate levels were higher in the UHO compared to HO subjects. S-adenosylhomocysteine (SAH) and total homocysteine levels were increased in the HO group compared to HL. Additionally, glutathione metabolism was also altered. Free cystine and oxidized glutathione (GSSG) were increased in the HO as compared to HL subjects. Importantly, the adipocyte secretory function was already compromised at this young age. Elevated circulating leptin and decreased adiponectin levels were observed in the UHO as compared to the HO subjects. Some of these alterations were concomitant with alterations in the DNA methylation patterns in the obese group, independent of the impaired insulin levels. In conclusion, our study informs on novel and important metabolic alterations in the transmethylation and the transsulfuration pathways in the early stages of obesity. Moreover, the altered secretory function of the adipocyte very early in life may be relevant in identifying early metabolic markers of disease that may inform on the increased risk for specific future comorbidities in this population.


Assuntos
Biomarcadores/análise , Metilação de DNA , Estresse Oxidativo , Obesidade Pediátrica/epidemiologia , Adiponectina/genética , Adiponectina/metabolismo , Estudos de Casos e Controles , Criança , Pré-Escolar , Estudos de Coortes , Feminino , Humanos , Leptina/genética , Leptina/metabolismo , Masculino , Oxirredução , Obesidade Pediátrica/genética , Obesidade Pediátrica/metabolismo , Obesidade Pediátrica/patologia , Estados Unidos/epidemiologia
8.
Nutrients ; 13(8)2021 Jul 27.
Artigo em Inglês | MEDLINE | ID: mdl-34444736

RESUMO

Pomegranate juice (Punica granatum) has been used since ancient times in traditional medicine (Unani Medicine, Ayurveda); its main compounds are anthocyanins and ellagic acid, which have anti-inflammatory, antioxidant, hepatoprotective, and cardiovascular health effects. The objective was to evaluate the effect of pomegranate juice on inflammation, blood pressure, and vascular and physiological markers associated with obesity induced by a high-fat diet in a murine model. The results show that pomegranate juice reduces the concentration of low-density lipoprotein cholesterol (cLDL) 39% and increases the concentration of high-density lipoprotein cholesterol (cHDL) by 27%, leading to a 12%-18% decrease in the risk of cardiovascular diseases (CVD). In addition to reducing blood pressure by 24%, it also had an antiatherogenic effect by decreasing sE-selectin levels by 42%. On the other hand, the juice significantly increased adiponectin levels in adipose tissue, decreased levels of inflammation markers (tumor necrosis factor-α (TNF-α), plasminogen activator inhibitor-1 (PAI-1), interleukin-17A (IL-17A), interleukin-6 (IL-6), interleukin-1ß (IL-1ß)), and inhibited the monocyte chemoattractant protein-1 (MCP-1). Pomegranate juice requires clinical studies to prove its immunoregulatory and therapeutic effects on cardiovascular and atherogenic risks.


Assuntos
Tecido Adiposo/metabolismo , Doenças Cardiovasculares/prevenção & controle , Sucos de Frutas e Vegetais , Fatores de Risco de Doenças Cardíacas , Inflamação , Obesidade/fisiopatologia , Romã (Fruta) , Adiponectina/metabolismo , Tecido Adiposo/imunologia , Animais , Biomarcadores/análise , Pressão Sanguínea , Doenças Cardiovasculares/etiologia , Quimiocina CCL2/antagonistas & inibidores , Citocinas/metabolismo , Dieta Hiperlipídica , Ingestão de Energia , Sucos de Frutas e Vegetais/análise , Lipídeos/sangue , Masculino , Obesidade/complicações , Ratos , Ratos Wistar
9.
Int J Mol Sci ; 22(16)2021 Aug 20.
Artigo em Inglês | MEDLINE | ID: mdl-34445677

RESUMO

Adiponectin is an adipokine associated with the healthy obese phenotype. Adiponectin increases insulin sensitivity and has cardio and vascular protection actions. Studies related to adiponectin, a modulator of the innate and acquired immunity response, have suggested a role of this molecule in asthma. Studies based on various asthma animal models and on the key cells involved in the allergic response have provided important insights about this relation. Some of them indicated protection and others reversed the balance towards negative effects. Many of them described the cellular pathways activated by adiponectin, which are potentially beneficial for asthma prevention or for reduction in the risk of exacerbations. However, conclusive proofs about their efficiency still need to be provided. In this article, we will, briefly, present the general actions of adiponectin and the epidemiological studies supporting the relation with asthma. The main focus of the current review is on the mechanisms of adiponectin and the impact on the pathobiology of asthma. From this perspective, we will provide arguments for and against the positive influence of this molecule in asthma, also indicating the controversies and sketching out the potential directions of research to complete the picture.


Assuntos
Adiponectina/metabolismo , Asma/metabolismo , Asma/fisiopatologia , Adipocinas/metabolismo , Adiponectina/fisiologia , Humanos , Resistência à Insulina/fisiologia , Leptina/metabolismo , Obesidade/metabolismo
10.
Int J Mol Sci ; 22(13)2021 Jun 28.
Artigo em Inglês | MEDLINE | ID: mdl-34203452

RESUMO

Adipokines secreted by hypertrophic visceral adipose tissue (VAT) instigate low-grade inflammation, followed by hyperglycemia (HG)-related metabolic disorders. The latter may develop with the participation of epigenetic modifications. Our aim was to assess how HG influences selected epigenetic modifications and the expression of interleukin 6 (IL-6) and adiponectin (APN; gene symbol ADIPOQ) during the adipogenesis of human visceral preadipocytes (HPA-v). Adipocytes (Ads) were chronically or transiently HG-treated during three stages of adipogenesis (proliferation, differentiation, maturation). We measured adipokine mRNA, protein, proven or predicted microRNA expression (RT-qPCR and ELISA), and enrichment of H3K9/14ac, H3K4me3, and H3K9me3 at gene promoter regions (chromatin immunoprecipitation). In chronic HG, we detected different expression patterns of the studied adipokines at the mRNA and protein levels. Chronic and transient HG-induced changes in miRNA (miR-26a-5p, miR-26b-5p, let-7d-5p, let-7e-5p, miR-365a-3p, miR-146a-5p) were mostly convergent to altered IL-6 transcription. Alterations in histone marks at the IL6 promoter were also in agreement with IL-6 mRNA. The open chromatin marks at the ADIPOQ promoter mostly reflected the APN transcription during NG adipogenesis, while, in the differentiation stage, HG-induced changes in all studied marks were in line with APN mRNA levels. In summary, HG dysregulated adipokine expression, promoting inflammation. Epigenetic changes coexisted with altered expression of adipokines, especially for IL-6; therefore, epigenetic marks induced by transient HG may act as epi-memory in Ads. Such changes in the epigenome and expression of adipokines could be instrumental in the development of inflammation and metabolic deregulation of VAT.


Assuntos
Adipócitos/metabolismo , Adiponectina/metabolismo , Hiperglicemia/metabolismo , Regiões Promotoras Genéticas/genética , Adipogenia/genética , Adipogenia/fisiologia , Adiponectina/genética , Imunoprecipitação da Cromatina , Ensaio de Imunoadsorção Enzimática , Epigênese Genética/genética , Epigênese Genética/fisiologia , Humanos , Hiperglicemia/genética , Interleucina-6/metabolismo
11.
Int J Mol Sci ; 22(14)2021 Jul 06.
Artigo em Inglês | MEDLINE | ID: mdl-34298894

RESUMO

(1) The high-fat diet (HFD) of western countries has dramatic effect on the health of several organs, including the digestive tract, leading to the accumulation of fats that can also trigger a chronic inflammatory process, such as that which occurs in non-alcohol steatohepatitis. The effects of a HFD on the small intestine, the organ involved in the absorption of this class of nutrients, are still poorly investigated. (2) To address this aspect, we administered a combined HFD with sucrose (HFD w/Suc, fat: 58% Kcal) regimen (18 months) to mice and investigated the morphological and molecular changes that occurred in the wall of proximal tract of the small intestine compared to the intestine of mice fed with a standard diet (SD) (fat: 18% Kcal). (3) We found an accumulation of lipid droplets in the mucosa of HFD w/Suc-fed mice that led to a disarrangement of mucosa architecture. Furthermore, we assessed the expression of several key players involved in lipid metabolism and inflammation, such as perilipin, leptin, leptin receptor, PI3K, p-mTOR, p-Akt, and TNF-α. All these molecules were increased in HFD mice compared to the SD group. We also evaluated anti-inflammatory molecules like adiponectin, adiponectin receptor, and PPAR-γ, and observed their significant reduction in the HFD w/Suc group compared to the control. Our data are in line with the knowledge that improper eating habits present a primary harmful assault on the bowel and the entire body's health. (4) These results represent a promising starting point for future studies, helping to better understand the complex and not fully elucidated spectrum of intestinal alterations induced by the overconsumption of fat.


Assuntos
Dieta Hiperlipídica/efeitos adversos , Sacarose na Dieta/administração & dosagem , Sacarose na Dieta/efeitos adversos , Mucosa Intestinal/patologia , Intestino Delgado/patologia , Adiponectina/metabolismo , Animais , Comportamento Alimentar/fisiologia , Mucosa Intestinal/metabolismo , Intestino Delgado/metabolismo , Leptina/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Obesidade/metabolismo , Obesidade/patologia , PPAR gama/metabolismo , Receptores para Leptina/metabolismo
12.
Int J Mol Sci ; 22(14)2021 Jul 16.
Artigo em Inglês | MEDLINE | ID: mdl-34299261

RESUMO

Many approaches have been used in the effective management of type 2 diabetes mellitus. A recent paradigm shift has focused on the role of adipose tissues in the development and treatment of the disease. Brown adipose tissues (BAT) and white adipose tissues (WAT) are the two main types of adipose tissues with beige subsets more recently identified. They play key roles in communication and insulin sensitivity. However, WAT has been shown to contribute significantly to endocrine function. WAT produces hormones and cytokines, collectively called adipocytokines, such as leptin and adiponectin. These adipocytokines have been proven to vary in conditions, such as metabolic dysfunction, type 2 diabetes, or inflammation. The regulation of fat storage, energy metabolism, satiety, and insulin release are all features of adipose tissues. As such, they are indicators that may provide insights on the development of metabolic dysfunction or type 2 diabetes and can be considered routes for therapeutic considerations. The essential roles of adipocytokines vis-a-vis satiety, appetite, regulation of fat storage and energy, glucose tolerance, and insulin release, solidifies adipose tissue role in the development and pathogenesis of diabetes mellitus and the complications associated with the disease.


Assuntos
Tecido Adiposo/metabolismo , Complicações do Diabetes/metabolismo , Diabetes Mellitus/metabolismo , Adipocinas/metabolismo , Adiponectina/metabolismo , Tecido Adiposo Bege/metabolismo , Tecido Adiposo Marrom/metabolismo , Tecido Adiposo Branco/metabolismo , Animais , Metabolismo Energético/fisiologia , Humanos , Insulina/metabolismo , Resistência à Insulina/fisiologia , Leptina/metabolismo , Obesidade/metabolismo
14.
Int J Mol Sci ; 22(13)2021 Jun 24.
Artigo em Inglês | MEDLINE | ID: mdl-34202651

RESUMO

Dieting is a common but often ineffective long-term strategy for preventing weight gain. Similar to humans, adult rats exhibit progressive weight gain. The adipokine leptin regulates appetite and energy expenditure but hyperleptinemia is associated with leptin resistance. Here, we compared the effects of increasing leptin levels in the hypothalamus using gene therapy with conventional caloric restriction on weight gain, food consumption, serum leptin and adiponectin levels, white adipose tissue, marrow adipose tissue, and bone in nine-month-old female Sprague-Dawley rats. Rats (n = 16) were implanted with a cannula in the 3rd ventricle of the hypothalamus and injected with a recombinant adeno-associated virus, encoding the rat gene for leptin (rAAV-Lep), and maintained on standard rat chow for 18 weeks. A second group (n = 15) was calorically-restricted to match the weight of the rAAV-Lep group. Both approaches prevented weight gain, and no differences in bone were detected. However, calorically-restricted rats consumed 15% less food and had lower brown adipose tissue Ucp-1 mRNA expression than rAAV-Lep rats. Additionally, calorically-restricted rats had higher abdominal white adipose tissue mass, higher serum leptin and adiponectin levels, and higher marrow adiposity. Caloric restriction and hypothalamic leptin gene therapy, while equally effective in preventing weight gain, differ in their effects on energy intake, energy expenditure, adipokine levels, and body composition.


Assuntos
Restrição Calórica , Metabolismo Energético , Terapia Genética , Hipotálamo/metabolismo , Leptina/genética , Adipocinas/sangue , Adipocinas/genética , Adipocinas/metabolismo , Adiponectina/genética , Adiponectina/metabolismo , Tecido Adiposo Branco/metabolismo , Adiposidade/genética , Animais , Biomarcadores , Peso Corporal , Medula Óssea/metabolismo , Dependovirus/genética , Ingestão de Energia , Metabolismo Energético/genética , Feminino , Expressão Gênica , Terapia Genética/métodos , Vetores Genéticos , Leptina/metabolismo , Ratos , Transgenes
15.
Cells ; 10(6)2021 06 09.
Artigo em Inglês | MEDLINE | ID: mdl-34207844

RESUMO

Hyperglycemia linked to diabetes results in endothelial dysfunction. In the present work, we comprehensively characterized effects of short-term hyperglycemia induced by administration of an insulin receptor antagonist, the S961 peptide, on endothelium and perivascular adipose tissue (PVAT) in mice. Endothelial function of the thoracic and abdominal aorta in 12-week-old male C57Bl/6Jrj mice treated for two weeks with S961 infusion via osmotic pumps was assessed in vivo using magnetic resonance imaging and ex vivo by detection of nitric oxide (NO) production using electron paramagnetic resonance spectroscopy. Additional methods were used to analyze PVAT, aortic segments and endothelial-specific plasma biomarkers. Systemic disruption of insulin signaling resulted in severe impairment of NO-dependent endothelial function and a loss of vasoprotective function of PVAT affecting the thoracic as well as abdominal parts of the aorta, however a fall in adiponectin expression and decreased uncoupling protein 1-positive area were more pronounced in the thoracic aorta. Results suggest that dysfunctional PVAT contributes to vascular pathology induced by altered insulin signaling in diabetes, in the absence of fat overload and obesity.


Assuntos
Tecido Adiposo , Endotélio Vascular , Hiperglicemia/induzido quimicamente , Receptor de Insulina/antagonistas & inibidores , Adiponectina/metabolismo , Tecido Adiposo/metabolismo , Tecido Adiposo/patologia , Animais , Endotélio Vascular/metabolismo , Endotélio Vascular/patologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Óxido Nítrico/metabolismo , Proteína Desacopladora 1/metabolismo
16.
Cells ; 10(6)2021 06 12.
Artigo em Inglês | MEDLINE | ID: mdl-34204799

RESUMO

Studies of adipose tissue biology have demonstrated that adipose tissue should be considered as both passive, energy-storing tissue and an endocrine organ because of the secretion of adipose-specific factors, called adipokines. Adiponectin is a well-described homeostatic adipokine with metabolic properties. It regulates whole-body energy status through the induction of fatty acid oxidation and glucose uptake. Adiponectin also has anti-inflammatory and antidiabetic properties, making it an interesting subject of biomedical studies. Perivascular adipose tissue (PVAT) is a fat depot that is conterminous to the vascular wall and acts on it in a paracrine manner through adipokine secretion. PVAT-derived adiponectin can act on the vascular wall through endothelial cells and vascular smooth muscle cells. The present review describes adiponectin's structure, receptors, and main signaling pathways. We further discuss recent studies of the extent and nature of crosstalk between PVAT-derived adiponectin and endothelial cells, vascular smooth muscle cells, and atherosclerotic plaques. Furthermore, we argue whether adiponectin and its receptors may be considered putative therapeutic targets.


Assuntos
Adiponectina/metabolismo , Tecido Adiposo/metabolismo , Vasos Sanguíneos/metabolismo , Homeostase/fisiologia , Animais , Aterosclerose/metabolismo , Vasos Sanguíneos/patologia , Células Endoteliais/metabolismo , Humanos , Músculo Liso Vascular/metabolismo
17.
J Immunol ; 207(2): 389-397, 2021 07 15.
Artigo em Inglês | MEDLINE | ID: mdl-34155068

RESUMO

The study aimed to revalidate the influence of WBCs on chronic disease risk factors and to verify which markers are independently involved in WBC level changes in a Korean population. A total of 80 Korean subjects were divided into three groups, according to the WBC count: mild decrease in WBC, normal WBC, and mild increase in WBC. Fasting blood samples for analyzing biochemical parameters and inflammatory markers were obtained from the subjects, and their body fat composition was evaluated by dual energy x-ray absorptiometry and computed tomography. The WBC levels were related to levels of adiponectin, triglyceride, and insulin, which are associated with the risk of chronic diseases. In the mild increase in WBC group, high-sensitivity C-reactive protein (hs-CRP) and TNF-α levels increased, and s.c. fat area at the first lumbar vertebrae and fourth lumbar vertebrae decreased. The WBC count positively correlated with hs-CRP and TNF-α levels and most of the body fat composition data, evaluated by dual energy x-ray absorptiometry and computed tomography. Notably, hs-CRP and TNF-α levels, fat mass, and visceral-to-s.c. fat area ratio at the first lumbar vertebrae were revealed as independent predictors of WBC level change. Finally, the receiver operating characteristic curve analysis showed that the additional use of body fat composition data with the conventional inflammatory markers reliably enhanced the predictive capacity of WBC level changes. Thus, we suggest that by controlling inflammatory markers and body fat composition, WBC levels can be kept within a range that is safe from the risk of chronic diseases.


Assuntos
Tecido Adiposo/metabolismo , Composição Corporal/fisiologia , Leucócitos/metabolismo , Leucócitos/fisiologia , Adiponectina/metabolismo , Adulto , Biomarcadores/metabolismo , Proteína C-Reativa/metabolismo , Doença Crônica , Feminino , Humanos , Inflamação/metabolismo , Inflamação/fisiopatologia , Gordura Intra-Abdominal/metabolismo , Masculino , Pessoa de Meia-Idade , Obesidade , Adulto Jovem
18.
Front Immunol ; 12: 677550, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34084174

RESUMO

Background: Adiponectin is an important immunomodulatory mediator in inflammatory conditions. While we previously showed that adiponectin receptor 1 (AdipoR1) is expressed in murine regulatory T cells (Tregs), its expression in human Tregs remain unknown. Here, we examined the expression of AdipoR1 in human Tregs and whether its ligand, globular adiponectin (gAd) affects the Treg ability to secrete IL-10 and the role of Type 2 (T2) inflammation in such process. Methods: Human Tregs from peripheral blood were analyzed by flow cytometry for AdipoR1, Helios and IL-10 expression. CD4+ T cells enriched from peripheral blood mononuclear cells (PBMCs) were cultured in the presence or the absence of gAd or the chemical adiponectin receptor agonist, AdipoRon, or in a T2 cytokine milieu. Flow cytometry was then used to assess intracellular IL-10, IL-10 secreting cells, FOXP3 and Helios expression, and phosphorylated p38 MAP kinase (MAPK). IL-10 levels in CD4+ T cell supernatants were quantified by ELISA. Results: We found that a subset of human Tregs expressed AdipoR1. Importantly, more Helios- cells expressed AdipoR1 than Helios+ cells. Likewise, there was a higher frequency of IL-10+ cells within Helios- AdipoR1+ Tregs compared to Helios+ AdipoR1+ Tregs. In contrast, the IL-10 mean fluorescence intensity (MFI) was higher in Helios+ AdipoR1+ Tregs compared to Helios-AdipoR1+ Tregs. When human CD4+ T cells were treated with gAd or AdipoRon, a significant increase in IL-10 secretion, FOXP3 expression, and p38 MAPK phosphorylation was observed in Helios- AdipoR1+ Tregs. Interestingly, gAd under T2 cytokine milieu significantly increased the intracellular levels of IL-10, mainly in Helios+ AdipoR1+ Tregs, and IL-10 levels in supernatants of CD4+ T cells. Conclusions: Collectively, our findings suggest that adiponectin/AdipoR1 axis promotes IL-10 release by Tregs, mainly in Helios- Tregs, and the effect was amplified by T2 inflammation in Helios+ Tregs.


Assuntos
Adiponectina/metabolismo , Interleucina-10/metabolismo , Receptores de Adiponectina/metabolismo , Transdução de Sinais/imunologia , Linfócitos T Reguladores/imunologia , Adiponectina/farmacologia , Doadores de Sangue , Células Cultivadas , Fatores de Transcrição Forkhead/metabolismo , Humanos , Fator de Transcrição Ikaros/metabolismo , Inflamação/imunologia , Inflamação/metabolismo , Ligantes , Piperidinas/farmacologia , Receptores de Adiponectina/agonistas , Transdução de Sinais/efeitos dos fármacos , Linfócitos T Reguladores/metabolismo , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismo
19.
Aging (Albany NY) ; 13(11): 15433-15443, 2021 06 07.
Artigo em Inglês | MEDLINE | ID: mdl-34096884

RESUMO

OBJECTIVE: This study aimed to explore the association between the risk of newly diagnosed type 2 diabetes and galectin-3 and adiponectin and to investigate whether their joint action shows a favorable diabetes assessment performance. METHODS: We conducted a community-based study in 135 newly diagnosed patients with type 2 diabetes and 270 age- and sex-matched nondiabetic patients. Odds ratios and 95% confidence intervals were determined using logistic regression analysis. Receiver operating characteristic curve, decision curve analysis and calibration plot were used to explore their efficacy and clinical utility for models. RESULTS: High quartiles of galectin-3/adiponectin (quartile 4 vs 1: OR 2.43 [95% CIs: 1.21-5.00]) showed the strongest correlation with an increased risk of type 2 diabetes in the total population, which was consistent in the older population (age≥50 years old) in adjustment models. The combination + lipids + galectin-3/adiponectin model (AUC = 0.72 [95% CIs: 0.66-0.77]) displayed better diabetes assessment performance than the other two models. CONCLUSIONS: High galectin-3 and low adiponectin levels were associated with the high risk of diabetes, and their joint action was a superior promising factor for evaluating diabetes risk. The diabetes discriminative strength of galectin-3/adiponectin was better in the older population than the younger.


Assuntos
Adiponectina/metabolismo , Diabetes Mellitus Tipo 2/sangue , Galectina 3/sangue , Biomarcadores/sangue , Estudos Transversais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Modelos Biológicos , Razão de Chances , Curva ROC , Fatores de Risco
20.
FASEB J ; 35(7): e21728, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-34110658

RESUMO

Proliferation and differentiation of preadipocytes, and other cell types, is accompanied by an increase in glucose uptake. Previous work showed that a pulse of high glucose was required during the first 3 days of differentiation in vitro, but was not required after that. The specific glucose metabolism pathways required for adipocyte differentiation are unknown. Herein, we used 3T3-L1 adipocytes as a model system to study glucose metabolism and expansion of the adipocyte metabolome during the first 3 days of differentiation. Our primary outcome measures were GLUT4 and adiponectin, key proteins associated with healthy adipocytes. Using complete media with 0 or 5 mM glucose, we distinguished between developmental features that were dependent on the differentiation cocktail of dexamethasone, insulin, and isobutylmethylxanthine alone or the cocktail plus glucose. Cocktail alone was sufficient to activate the capacity for 2-deoxglucose uptake and glycolysis, but was unable to support the expression of GLUT4 and adiponectin in mature adipocytes. In contrast, 5 mM glucose in the media promoted a transient increase in glucose uptake and glycolysis as well as a significant expansion of the adipocyte metabolome and proteome. Using genetic and pharmacologic approaches, we found that the positive effects of 5 mM glucose on adipocyte differentiation were specifically due to increased expression of 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase 3 (PFKFB3), a key regulator of glycolysis and the ancillary glucose metabolic pathways. Our data reveal a critical role for PFKFB3 activity in regulating the cellular metabolic remodeling required for adipocyte differentiation and maturation.


Assuntos
Adipócitos/metabolismo , Glucose/metabolismo , Fosfofrutoquinase-2/metabolismo , Células 3T3-L1 , Adipócitos/efeitos dos fármacos , Adiponectina/metabolismo , Animais , Diferenciação Celular/efeitos dos fármacos , Diferenciação Celular/fisiologia , Linhagem Celular , Dexametasona/farmacologia , Transportador de Glucose Tipo 4/metabolismo , Glicólise/efeitos dos fármacos , Glicólise/fisiologia , Insulina/farmacologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Xantinas/farmacologia
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