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1.
Int J Mol Sci ; 22(24)2021 Dec 16.
Artigo em Inglês | MEDLINE | ID: mdl-34948320

RESUMO

The global burden of obesity has multiplied owing to its rapidly growing prevalence and obesity-related morbidity and mortality. In addition to the classic role of depositing extra energy, adipose tissue actively interferes with the metabolic balance by means of secreting bioactive compounds called adipokines. While most adipokines give rise to inflammatory conditions, the others with anti-inflammatory properties have been the novel focus of attention for the amelioration of cardiometabolic complications. This review compiles the current evidence on the roles of anti-inflammatory adipokines, namely, adiponectin, vaspin, the C1q/TNF-related protein (CTRP) family, secreted frizzled-related protein 5 (SFRP5), and omentin-1 on cardiometabolic health. Further investigations on the mechanism of action and prospective human trials may pave the way to their clinical application as innovative biomarkers and therapeutic targets for cardiovascular and metabolic disorders.


Assuntos
Adipocinas/metabolismo , Anti-Inflamatórios/metabolismo , Doenças Cardiovasculares/metabolismo , Inflamação/metabolismo , Animais , Sistema Cardiovascular/metabolismo , Humanos
2.
Cells ; 10(12)2021 11 28.
Artigo em Inglês | MEDLINE | ID: mdl-34943849

RESUMO

In recent years, there has been a large amount of evidence on the role of microRNA (miRNA) in regulating adipose tissue physiology. Indeed, miRNAs control critical steps in adipocyte differentiation, proliferation and browning, as well as lipolysis, lipogenesis and adipokine secretion. Overnutrition leads to a significant change in the adipocyte miRNOME, resulting in adipose tissue dysfunction. Moreover, via secreted mediators, dysfunctional adipocytes may impair the function of other organs and tissues. However, given their potential to control cell and whole-body energy expenditure, miRNAs also represent critical therapeutic targets for treating obesity and related metabolic complications. This review attempts to integrate present concepts on the role miRNAs play in adipose tissue physiology and obesity-related dysfunction and data from pre-clinical and clinical studies on the diagnostic or therapeutic potential of miRNA in obesity and its related complications.


Assuntos
Tecido Adiposo/metabolismo , Tecido Adiposo/fisiopatologia , MicroRNAs/genética , Adipogenia/genética , Adipocinas/metabolismo , Regulação da Expressão Gênica , Humanos , Resistência à Insulina/genética , MicroRNAs/metabolismo
3.
Int J Mol Sci ; 22(19)2021 Sep 24.
Artigo em Inglês | MEDLINE | ID: mdl-34638645

RESUMO

Leptin has been suggested to play a role in amyotrophic lateral sclerosis (ALS), a fatal progressive neurodegenerative disease. This adipokine has previously been shown to be associated with a lower risk of ALS and to confer a survival advantage in ALS patients. However, the role of leptin in the progression of ALS is unknown. Indeed, our understanding of the mechanisms underlying leptin's effects in the pathogenesis of ALS is very limited, and it is fundamental to determine whether alterations in leptin's actions take place in this neurodegenerative disease. To characterize the association between leptin signaling and the clinical course of ALS, we assessed the mRNA and protein expression profiles of leptin, the long-form of the leptin receptor (Ob-Rb), and leptin-related signaling pathways at two different stages of the disease (onset and end-stage) in TDP-43A315T mice compared to age-matched WT littermates. In addition, at selected time-points, an immunoassay analysis was conducted to characterize plasma levels of total ghrelin, the adipokines resistin and leptin, and metabolic proteins (plasminogen activator inhibitor type 1 (PAI-1), gastric inhibitory peptide (GIP), glucagon-like peptide 1 (GLP-1), insulin and glucagon) in TDP-43A315T mice compared to WT controls. Our results indicate alterations in leptin signaling in the spinal cord and the hypothalamus on the backdrop of TDP-43-induced deficits in mice, providing new evidence about the pathways that could link leptin signaling to ALS.


Assuntos
Esclerose Amiotrófica Lateral/metabolismo , Leptina/metabolismo , Transdução de Sinais/fisiologia , Adipocinas/metabolismo , Animais , Humanos , Masculino , Camundongos , Neurônios Motores/metabolismo , Doenças Neurodegenerativas/metabolismo , Medula Espinal/metabolismo
4.
Int J Mol Sci ; 22(19)2021 Sep 28.
Artigo em Inglês | MEDLINE | ID: mdl-34638803

RESUMO

Adipose tissue releases a large range of bioactive factors called adipokines, many of which are involved in inflammation, glucose homeostasis and lipid metabolism. Under pathological conditions such as obesity, most of the adipokines are upregulated and considered as deleterious, due to their pro-inflammatory, pro-atherosclerotic or pro-diabetic properties, while only a few are downregulated and would be designated as beneficial adipokines, thanks to their counteracting properties against the onset of comorbidities. This review focuses on six adipose-derived lipid-binding proteins that have emerged as key factors in the development of obesity and diabetes: Retinol binding protein 4 (RBP4), Fatty acid binding protein 4 (FABP4), Apolipoprotein D (APOD), Lipocalin-2 (LCN2), Lipocalin-14 (LCN14) and Apolipoprotein M (APOM). These proteins share structural homology and capacity to bind small hydrophobic molecules but display opposite effects on glucose and lipid metabolism. RBP4 and FABP4 are positively associated with metabolic syndrome, while APOD and LCN2 are ubiquitously expressed proteins with deleterious or beneficial effects, depending on their anatomical site of expression. LCN14 and APOM have been recently identified as adipokines associated with healthy metabolism. Recent findings on these lipid-binding proteins exhibiting detrimental or protective roles in human and murine metabolism and their involvement in metabolic diseases are also discussed.


Assuntos
Adipocinas/metabolismo , Tecido Adiposo/metabolismo , Síndrome Metabólica/metabolismo , Animais , Apolipoproteínas D/metabolismo , Apolipoproteínas M/metabolismo , Proteínas de Ligação a Ácido Graxo/metabolismo , Humanos , Lipocalina-2/metabolismo , Síndrome Metabólica/etiologia , Obesidade/metabolismo , Proteínas Plasmáticas de Ligação ao Retinol/metabolismo
5.
Nutrients ; 13(10)2021 Sep 28.
Artigo em Inglês | MEDLINE | ID: mdl-34684432

RESUMO

Overweight and obesity in children and adolescents are overwhelming problems in western countries. Adipocytes, far from being only fat deposits, are capable of endocrine functions, and the endocrine activity of adipose tissue, resumable in adipokines production, seems to be a key modulator of central nervous system function, suggesting the existence of an "adipo-cerebral axis." This connection exerts a key role in children growth and puberty development, and it is exemplified by the leptin-kisspeptin interaction. The aim of this review was to describe recent advances in the knowledge of adipose tissue endocrine functions and their relations with nutrition and growth. The peculiarities of major adipokines are briefly summarized in the first paragraph; leptin and its interaction with kisspeptin are focused on in the second paragraph; the third paragraph deals with the regulation of the GH-IGF axis, with a special focus on the model represented by growth hormone deficiency (GHD); finally, old and new nutritional aspects are described in the last paragraph.


Assuntos
Tecido Adiposo/metabolismo , Córtex Cerebral/metabolismo , Retroalimentação Fisiológica , Obesidade Pediátrica/etiologia , Obesidade Pediátrica/metabolismo , Adipócitos/metabolismo , Adipocinas/metabolismo , Animais , Biomarcadores , Criança , Desenvolvimento Infantil , Fenômenos Fisiológicos da Nutrição Infantil , Pré-Escolar , Suscetibilidade a Doenças , Hormônio do Crescimento/metabolismo , Humanos , Fator de Crescimento Insulin-Like I/metabolismo , Kisspeptinas/metabolismo , Puberdade/genética , Puberdade/metabolismo , Transdução de Sinais
6.
FASEB J ; 35(11): e21910, 2021 11.
Artigo em Inglês | MEDLINE | ID: mdl-34610176

RESUMO

C1q/TNF-related protein (CTRP) family comprises fifteen highly conserved secretory proteins with diverse central and peripheral functions. In zebrafish, mouse, and human, CTRP4 is most highly expressed in the brain. We previously showed that CTRP4 is a metabolically responsive regulator of food intake and energy balance, and mice lacking CTRP4 exhibit sexually dimorphic changes in ingestive behaviors and systemic metabolism. Recent single-cell RNA sequencing also revealed Ctrp4/C1qtnf4 expression in diverse neuronal cell types across distinct anatomical brain regions, hinting at additional roles in the central nervous system not previously characterized. To uncover additional central functions of CTRP4, we subjected Ctrp4 knockout (KO) mice to a battery of behavioral tests. Relative to wild-type (WT) littermates, loss of CTRP4 does not alter exploratory, anxiety-, or depressive-like behaviors, motor function and balance, sensorimotor gating, novel object recognition, and spatial memory. While pain-sensing mechanisms in response to thermal stress and mild shock are intact, both male and female Ctrp4 KO mice have increased sensitivity to pain induced by higher-level shock, suggesting altered nociceptive function. Importantly, CTRP4 deficiency impairs hippocampal-dependent associative learning and memory as assessed by trace fear conditioning paradigm. This deficit is sex-dependent, affects only female mice, and is associated with altered expression of learning and memory genes (Arc, c-fos, and Pde4d) in the hippocampus and cortex. Altogether, our behavioral and gene expression analyses have uncovered novel aspects of the CTRP4 function and provided a physiological context to further investigate its mechanism of action in the central and peripheral nervous system.


Assuntos
Adipocinas/genética , Expressão Gênica , Técnicas de Inativação de Genes/métodos , Aprendizagem em Labirinto , Memória Espacial , Adipocinas/metabolismo , Animais , Ansiedade/genética , Comportamento Animal , Córtex Cerebelar/metabolismo , Feminino , Hipocampo/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Teste de Desempenho do Rota-Rod
7.
Int J Mol Sci ; 22(19)2021 Oct 07.
Artigo em Inglês | MEDLINE | ID: mdl-34639186

RESUMO

Multiple sclerosis (MS), a chronic inflammatory and demyelinating disease of the central nervous system (CNS), is a major clinical and societal problem, which has a tremendous impact on the life of patients and their proxies. Current immunomodulatory and anti-inflammatory therapies prove to be relatively effective; however, they fail to concomitantly stop ongoing neurological deterioration and do not reverse acquired disability. The proportion to which genetic and environmental factors contribute to the etiology of MS is still incompletely understood; however, a recent association between MS etiology and obesity was shown, with obesity greatly increasing the risk of developing MS. An altered balance of adipokines, which are white adipose tissue (WAT) hormones, plays an important role in the low-grade chronic inflammation during obesity by their pervasive modification of local and systemic inflammation. Vice versa, inflammatory factors secreted by immune cells affect adipokine function. To explore the role of adipokines in MS pathology, we will here review the reciprocal effects of adipokines and immune cells and summarize alterations in adipokine levels in MS patient cohorts. Finally, we will discuss proof-of-concept studies demonstrating the therapeutic potential of adipokines to target both neuroinflammation and neurodegeneration processes in MS.


Assuntos
Adipocinas/metabolismo , Inflamação/imunologia , Esclerose Múltipla/imunologia , Esclerose Múltipla/patologia , Animais , Humanos , Esclerose Múltipla/metabolismo
8.
PLoS One ; 16(9): e0257275, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34516574

RESUMO

BACKGROUND: Previous studies showed the possible association between obesity, dietary pattern, and depressive symptoms. Due to the lack of enough data to confirm the association of obesity and depression in the Middle East, here, we aimed to explore the possible mediatory role of adipokines Galectin-3, transforming growth factor-beta (TGF-ß), and endothelial plasminogen activator inhibitor (PAI-1) in the association between low carbohydrate diet (LCD) and depressive symptoms. METHODS: A total of 256 women aged 17-56 years old were grouped based on their LCD score. Depression anxiety stress scales-21 (DASS-21) self-administered questionnaire was used to evaluate the three negative emotional states of stress, depressive symptoms, and anxiety. Body composition and dietary intake were assessed. Enzyme-linked immunosorbent assay (ELISA) was used to measure the serum levels of Galectin-3, TGF-ß, and PAI-1. RESULTS: No significant difference was observed regarding Galectin-3, TGF-ß, and PAI-1 levels between the groups with dissimilar adherence to LCD or the groups with different levels of depressive symptoms (P>0.05). However, there was a negative association between LCD score as a covariant and depressive symptoms as an independent variable (P = 0.02) and remarkably, a regression model linear analysis using Galectin-3, TGF-ß, and PAI-1 as confounding variables indicated the mediatory role of these adipokines in this association (P>0.05). In other words, adipokines eliminated the significance of the relationship between adherence to LCD and depressive symptoms. CONCLUSION: It seems that higher adherence to LCD is probably associated with a lower prevalence of depressive symptoms in obese adults through the mediatory role of adipokines.


Assuntos
Adipocinas/sangue , Depressão/sangue , Dieta com Restrição de Carboidratos , Obesidade/sangue , Sobrepeso/sangue , Adipocinas/metabolismo , Adolescente , Adulto , Antropometria , Transtornos de Ansiedade/sangue , Transtornos de Ansiedade/metabolismo , Composição Corporal/fisiologia , Estudos Transversais , Depressão/metabolismo , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Obesidade/metabolismo , Sobrepeso/metabolismo , Adulto Jovem
9.
J Immunol ; 207(8): 1959-1963, 2021 10 15.
Artigo em Inglês | MEDLINE | ID: mdl-34544802

RESUMO

Previous studies indicate that IL-17A plays an important role in mediating the intestinal microbiota and systemic metabolic functions. However, it is not known where IL-17RA signaling occurs to mediate these effects. To investigate this question, we used intestinal epithelial-specific (Il17ra ΔIEC ) and liver-specific (Il17raΔLiver ) IL-17RA knockout mice as well as littermate control mice. Our results indicate that intestinal IL-17RA signaling helps mediate systemic metabolic functions upon exposure to prolonged high-fat diet. Il17ra ΔIEC mice display impaired glucose metabolism, altered hormone and adipokine levels, increased visceral adiposity, and greater hepatic lipid deposition when compared with their littermate controls. We show that IL-17RA-driven changes in microbiota composition are responsible for regulating systemic glucose metabolism. Altogether, our data elucidate the importance of intestinal IL-17RA signaling in regulating high-fat diet-mediated systemic glucose and lipid metabolism.


Assuntos
Interleucina-17/metabolismo , Mucosa Intestinal/fisiologia , Fígado/fisiologia , Doenças Metabólicas/imunologia , Microbiota/imunologia , Receptores de Interleucina-17/metabolismo , Adipocinas/metabolismo , Animais , Dieta Hiperlipídica , Modelos Animais de Doenças , Glucose/metabolismo , Hormônios/metabolismo , Humanos , Metabolismo dos Lipídeos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Transdução de Sinais
10.
Cells ; 10(9)2021 09 06.
Artigo em Inglês | MEDLINE | ID: mdl-34571976

RESUMO

Type 2 diabetes mellitus is a severe public health issue worldwide. It displays a harmful effect on different organs as the eyes, kidneys and neural cells due to insulin resistance and high blood glucose concentrations. To date, the available treatments for this disorder remain limited. Several reports have correlated obesity with type 2 diabetes. Mainly, dysfunctional adipocytes and the regulation of high secretion of inflammatory cytokines are the crucial links between obesity and insulin resistance. Several clinical and epidemiological studies have also correlated the onset of type 2 diabetes with inflammation, which is now indicated as a new target for type 2 diabetes treatment. Thus, it appears essential to discover new drugs able to inhibit the secretion of proinflammatory adipocytokines in type 2 diabetes. Adipocytes produce inflammatory cytokines in response to inflammation or high glucose levels. Once activated by a specific ligand, CXCR1 and CXCR2 mediate some cytokines' effects by activating an intracellular signal cascade once activated by a specific ligand. Therefore, it is conceivable to hypothesize that a specific antagonist of these receptors may ameliorate type 2 diabetes and glucose metabolism. Herein, differentiated 3T3-L1-adipocytes were subjected to high glucose or inflammatory conditions or the combination of both and then treated with ladarixin, a CXCR1/2 inhibitor. The results obtained point towards the positive regulation by ladarixin on insulin sensitivity, glucose transporters GLUT1 and GLUT4, cytokine proteome profile and lipid metabolism, thus suggesting ladarixin as a potentially helpful treatment in type 2 diabetes mellitus and obesity.


Assuntos
Inflamação/tratamento farmacológico , Resistência à Insulina/fisiologia , Insulina/metabolismo , Receptores de Interleucina-8B/antagonistas & inibidores , Transdução de Sinais/efeitos dos fármacos , Sulfonamidas/farmacologia , Células 3T3-L1 , Adipócitos/efeitos dos fármacos , Adipócitos/metabolismo , Adipocinas/metabolismo , Animais , Linhagem Celular , Citocinas/metabolismo , Diabetes Mellitus Tipo 2/tratamento farmacológico , Diabetes Mellitus Tipo 2/metabolismo , Glucose/metabolismo , Inflamação/metabolismo , Metabolismo dos Lipídeos/efeitos dos fármacos , Camundongos , Células RAW 264.7
11.
Int J Mol Sci ; 22(18)2021 Sep 14.
Artigo em Inglês | MEDLINE | ID: mdl-34576066

RESUMO

Papain is a proteolytic enzyme present in the leaves, fruits, roots, and latex of the Carica papaya (papaya) plant. Although it exhibits a wide range of activities, there are no reports on the anti-obesity effects of papain. This study examined the anti-obesity effect and obesity-involved anti-inflammatory mechanism of papain in in vivo and in vitro models using high-fat diet (HFD)-induced obese mice and 3T3-L1 preadipocytes. Oral administration of papain reduced HFD-induced weight of the body, liver, and adipose tissues of mice. Papain also reduced hepatic lipid accumulation and adipocyte size. Moreover, serum total cholesterol and triglyceride levels were markedly reduced in papain-treated mice. In addition, papain inhibited the differentiation of preadipocytes and oil accumulation in 3T3-L1 preadipocytes and rat primary preadipocytes. Mechanistically, papain significantly downregulated the protein levels of key adipogenesis regulators and reversed the expression of pro-inflammatory cytokines and adipokines in HFD-induced obese mice and 3T3-L1 preadipocytes. Papain also markedly enhanced activation of the AMP-activated protein kinase pathway in both models. Collectively, these results suggest that papain exerts anti-obesity effects in HFD-induced mice and 3T3-L1 preadipocytes by regulating levels of adipogenic factors involved in lipid metabolism and inflammation; thus, it could be useful in the prevention and treatment of obesity.


Assuntos
Proteínas Quinases Ativadas por AMP/metabolismo , Adipócitos/patologia , Dieta Hiperlipídica , Inflamação/patologia , Metabolismo dos Lipídeos/efeitos dos fármacos , Obesidade/metabolismo , Obesidade/patologia , Papaína/farmacologia , Células 3T3-L1 , Adipócitos/efeitos dos fármacos , Adipócitos/metabolismo , Adipogenia/efeitos dos fármacos , Adipocinas/metabolismo , Adiposidade/efeitos dos fármacos , Animais , Biomarcadores/metabolismo , Peso Corporal/efeitos dos fármacos , Ativação Enzimática/efeitos dos fármacos , Fígado Gorduroso/patologia , Proteína Forkhead Box O1/metabolismo , Hipertrofia , Lipídeos/sangue , Fígado/efeitos dos fármacos , Fígado/patologia , Macrófagos/efeitos dos fármacos , Macrófagos/patologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Obesos , Tamanho do Órgão/efeitos dos fármacos , Sirtuína 1/metabolismo
12.
Rev Cardiovasc Med ; 22(3): 799-805, 2021 Sep 24.
Artigo em Inglês | MEDLINE | ID: mdl-34565078

RESUMO

Metabolic Syndrome (MS) remains the leading cause of mortality and morbidity globally. Adipose tissue releases adipokines that play key roles in metabolic and cardio-cerebro-vascular homeostasis. Subfatin, induced after exercise or upon cold exposure in adipose tissue, is a novel secreted protein homologous to Metrn, a neutrophic factor with angiogenic properties. The protein was proved to be of great significance in the browning of white adipose tissue (BWT) and insulin resistance (IR). It affected insulin sensitivity at least via its local autocrine/paracrine action through AMP-activated protein kinase (AMPK) or peroxisome proliferator-activated receptor δ (PPAR-δ) dependent signaling. Subfatin blocked the release of inflammatory mediators, improved intracellular insulin signal transduction and reversed IR. It also improved glucose tolerance and played a key role in metabolism and cardiovascular and cerebrovascular homeostasis. It was reported that the level of serum subfatin was significantly correlated with the occurrence and severity of coronary heart disease, which might be a new target for the treatment of coronary heart disease. In addition, exercise increased the level of subfatin in circulation and adipose tissue, promoted energy consumption, improved glucose and lipid metabolism, increased the heat production of brown fat, and strengthened the anti-inflammatory mechanism. Given its role in metabolic disorders, subfatin is considered as a candidate biomarker of MS. However, the clinical significance of subfatin remains largely unclear. The purpose of this article is to review the research on the effect of subfatin on MS in recent years.


Assuntos
Resistência à Insulina , Síndrome Metabólica , Adipocinas/metabolismo , Tecido Adiposo , Humanos , Metabolismo dos Lipídeos , Síndrome Metabólica/diagnóstico
13.
Biomolecules ; 11(7)2021 07 14.
Artigo em Inglês | MEDLINE | ID: mdl-34356649

RESUMO

Curcumin is a known anti-adipogenic agent for alleviating obesity and related disorders. Comprehensive comparisons of the anti-adipogenic activity of curcumin with other curcuminoids is minimal. This study compared adipogenesis inhibition with curcumin, demethoxycurcumin (DMC), and bisdemethoxycurcumin (BDMC), and their underlying mechanisms. We differentiated 3T3-L1 cells in the presence of curcuminoids, to determine lipid accumulation and triglyceride (TG) production. The expression of adipogenic transcription factors and lipogenic proteins was analyzed by Western blot. A significant reduction in Oil red O (ORO) staining was observed in the cells treated with curcuminoids at 20 µM. Inhibition was increased in the order of curcumin < DMC < BDMC. A similar trend was observed in the detection of intracellular TG. Curcuminoids suppressed differentiation by downregulating the expression of peroxisome proliferator-activated receptor γ (PPARγ) and CCAAT/enhancer-binding protein α (C/EBPα), leading to the downregulation of the lipogenic enzymes acetyl-CoA carboxylase (ACC) and fatty acid synthase (FAS). AMP-activated protein kinase α (AMPKα) phosphorylation was also activated by BDMC. Curcuminoids reduced the release of proinflammatory cytokines and leptin in 3T3-L1 cells in a dose-dependent manner, with BDMC showing the greatest potency. BDMC at 20 µM significantly decreased leptin by 72% compared with differentiated controls. Molecular docking computation indicated that curcuminoids, despite having structural similarity, had different interaction positions to PPARγ, C/EBPα, and ACC. The docking profiles suggested a possible interaction of curcuminoids with C/EBPα and ACC, to directly inhibit their expression.


Assuntos
Adipogenia/efeitos dos fármacos , Diarileptanoides/química , Diarileptanoides/farmacologia , Células 3T3-L1 , Adipócitos/citologia , Adipócitos/efeitos dos fármacos , Adipogenia/fisiologia , Adipocinas/metabolismo , Animais , Diferenciação Celular/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Curcuma/química , Curcumina/análise , Curcumina/farmacologia , Enzimas/metabolismo , Metabolismo dos Lipídeos/efeitos dos fármacos , Camundongos , Simulação de Acoplamento Molecular , PPAR gama/química , PPAR gama/metabolismo , Extratos Vegetais/análise , Extratos Vegetais/farmacologia , Triglicerídeos/metabolismo
14.
Cells ; 10(8)2021 08 20.
Artigo em Inglês | MEDLINE | ID: mdl-34440913

RESUMO

The C1q/TNF-related protein 3 (CTRP3) represents a pleiotropic adipokine reciprocally associated with obesity and type 2 diabetes mellitus and exhibits anti-inflammatory properties in relation to lipopolysaccharides (LPS)-mediated effects in adipocytes, as well as monocytes/macrophages. Here, we focused on the influence of CTRP3 on LPS-mediated effects in endothelial cells in order to expand the understanding of a possible anti-inflammatory function of CTRP3 in a setting of endotoxemia. An organ- and tissue-specific expression analysis by real-time PCR revealed a considerable Ctrp3 expression in various adipose tissue compartments; however, higher levels were detected in the aorta and in abundantly perfused tissues (bone marrow and the thyroid gland). We observed a robust Ctrp3 expression in primary endothelial cells and a transient upregulation in murine endothelial (MyEND) cells by LPS (50 ng/mL). In MyEND cells, CTRP3 inhibited the LPS-induced expression of interleukin (Il)-6 and the tumor necrosis factor (Tnf)-α, and suppressed the LPS-dependent expression of the major endothelial adhesion molecules Vcam-1 and Icam-1. The LPS-induced adhesion of monocytic cells to an endothelial monolayer was antagonized by CTRP3. In C57BL/6J mice with an LPS-induced systemic inflammation, exogenous CTRP3 did not affect circulating levels of TNF-α, ICAM-1, and VCAM-1. In conclusion, we characterized CTRP3 beyond its function as an adipokine in a setting of vascular inflammation. CTRP3 inhibited LPS-induced endothelial expression of adhesion molecules and monocyte cell adhesion, indicating an important vascular anti-inflammatory role for CTRP3 in endotoxemia.


Assuntos
Adipocinas/imunologia , Tecido Adiposo/imunologia , Células Endoteliais/imunologia , Perfilação da Expressão Gênica , Inflamação/imunologia , Adipocinas/genética , Adipocinas/metabolismo , Tecido Adiposo/metabolismo , Animais , Adesão Celular/efeitos dos fármacos , Adesão Celular/genética , Adesão Celular/imunologia , Moléculas de Adesão Celular/genética , Moléculas de Adesão Celular/imunologia , Moléculas de Adesão Celular/metabolismo , Linhagem Celular , Citocinas/genética , Citocinas/imunologia , Citocinas/metabolismo , Células Endoteliais/efeitos dos fármacos , Células Endoteliais/metabolismo , Regulação da Expressão Gênica/efeitos dos fármacos , Regulação da Expressão Gênica/imunologia , Humanos , Inflamação/genética , Inflamação/metabolismo , Lipopolissacarídeos/farmacologia , Masculino , Camundongos Endogâmicos C57BL , Receptor 4 Toll-Like/genética , Receptor 4 Toll-Like/imunologia , Receptor 4 Toll-Like/metabolismo
15.
Sci Rep ; 11(1): 17001, 2021 08 20.
Artigo em Inglês | MEDLINE | ID: mdl-34417537

RESUMO

Osteoarthritis (OA) is a degenerative joint disease characterized by cartilage loss and reduced joint function. OA risk factors are age and obesity. Many adipokines are altered by obesity but also OA although systemic adipokine regulation in OA is not always clear. Therefore, metabolic effects of diet-induced obesity on OA development as well as the influence of obesity and OA progression on systemic vs. local adipokine expression in joints were compared. C57Bl/6-mice fed with HFD (high fat diet) or normal diet prior to destabilization of the medial meniscus (DMM) were sacrificed 4/6/8 weeks after surgery. Sera were evaluated for adiponectin, leptin, visfatin, cytokines. Liver grading and staging for non-alcoholic steatohepatitis (NASH) was performed and crown-like structures (CLS) in adipose tissue measured. OA progression was scored histologically. Adipokine-expressing cells and types were evaluated by immunohistochemistry. Time-dependent changes in DMM-progression were reflected by increased systemic adiponectin levels in DMM especially combined with HFD. While HFD increased serum leptin, DMM reduced systemic leptin significantly. OA scores correlated with bodyweight, leptin and hepatic scoring. Locally, increased numbers of adiponectin- and leptin-producing fibroblasts were observed in damaged menisci but visfatin was not changed. Local adipokine expression was independent from systemic levels, suggesting different mechanisms of action.


Assuntos
Adipocinas/metabolismo , Obesidade/complicações , Obesidade/metabolismo , Osteoartrite do Joelho/complicações , Osteoartrite do Joelho/metabolismo , Adipocinas/biossíntese , Adipocinas/sangue , Animais , Dieta Hiperlipídica , Modelos Animais de Doenças , Masculino , Meniscos Tibiais/patologia , Camundongos , Camundongos Endogâmicos C57BL , Obesidade/sangue , Osteoartrite do Joelho/sangue
16.
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
17.
Int J Mol Sci ; 22(13)2021 Jun 27.
Artigo em Inglês | MEDLINE | ID: mdl-34198988

RESUMO

Secreted frizzled-related protein 5 (SFRP5), an antagonist of the noncanonical WNT pathway, has a controversial role in liver disease. The aim of this study was to analyze the role of SFRP5 and the noncanonical WNT pathway in nonalcoholic fatty liver disease (NAFLD). Plasma SFRP5 levels were determined by ELISA in women with normal weight (NW; n = 20) and morbid obesity (MO; n = 69). Women with MO were subclassified according to hepatic histology into normal liver (NL; n = 28), NAFLD (n = 41) (simple steatosis (SS; n = 24), and nonalcoholic steatohepatitis (NASH; n = 17)). We used RT-qPCR to evaluate the hepatic mRNA expression of SFRP5, WNT5A, and JNK in women with MO. SFRP5 levels were lower in NW than in MO patients who underwent a very low-calorie diet before surgery. Hepatic SFRP5 mRNA expression was higher in SS than in NL or NASH; additionally, patients with hepatic inflammation or ballooning presented lower SFRP5 abundance. WNT5A and JNK expression was enhanced in NAFLD compared with NL. In conclusion, circulating SFRP5 levels depend on the diet, and hepatic SFRP5 seems to have a protective role in the first steps of NAFLD; however, SFRP5 could be deregulated in an advanced stage while WNT5A and JNK are activated, promoting liver damage.


Assuntos
Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Hepatopatia Gordurosa não Alcoólica/metabolismo , Obesidade Mórbida/complicações , Obesidade Mórbida/metabolismo , Proteínas Adaptadoras de Transdução de Sinal/sangue , Adipocinas/metabolismo , Biomarcadores , Índice de Massa Corporal , Suscetibilidade a Doenças , Humanos , Imuno-Histoquímica , Mediadores da Inflamação/metabolismo , MAP Quinase Quinase 4/metabolismo , Hepatopatia Gordurosa não Alcoólica/sangue , Hepatopatia Gordurosa não Alcoólica/etiologia , Hepatopatia Gordurosa não Alcoólica/patologia , RNA Mensageiro/genética , Proteína Wnt-5a/metabolismo
18.
Front Immunol ; 12: 650768, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34248937

RESUMO

The role of adipose tissue (AT) inflammation in obesity and its multiple related-complications is a rapidly expanding area of scientific interest. Within the last 30 years, the role of the adipocyte as an endocrine and immunologic cell has been progressively established. Like the macrophage, the adipocyte is capable of linking the innate and adaptive immune system through the secretion of adipokines and cytokines; exosome release of lipids, hormones, and microRNAs; and contact interaction with other immune cells. Key innate immune cells in AT include adipocytes, macrophages, neutrophils, and innate lymphoid cells type 2 (ILC2s). The role of the innate immune system in promoting adipose tissue inflammation in obesity will be highlighted in this review. T cells and B cells also play important roles in contributing to AT inflammation and are discussed in this series in the chapter on adaptive immunity.


Assuntos
Imunidade Adaptativa/imunologia , Adipócitos/imunologia , Tecido Adiposo/imunologia , Imunidade Inata/imunologia , Obesidade/imunologia , Adipócitos/citologia , Adipócitos/metabolismo , Adipocinas/imunologia , Adipocinas/metabolismo , Tecido Adiposo/citologia , Tecido Adiposo/metabolismo , Citocinas/imunologia , Citocinas/metabolismo , Humanos , Macrófagos/imunologia , Macrófagos/metabolismo , Linfócitos T/imunologia , Linfócitos T/metabolismo
19.
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
20.
Clin Sci (Lond) ; 135(13): 1563-1590, 2021 07 16.
Artigo em Inglês | MEDLINE | ID: mdl-34231841

RESUMO

Despite obesity and diabetes markedly increasing the risk of developing cardiovascular diseases, the molecular and cellular mechanisms that underlie this association remain poorly characterised. In the last 20 years it has become apparent that chronic, low-grade inflammation in obese adipose tissue may contribute to the risk of developing insulin resistance and type 2 diabetes. Furthermore, increased vascular pro-inflammatory signalling is a key event in the development of cardiovascular diseases. Overnutrition exacerbates pro-inflammatory signalling in vascular and adipose tissues, with several mechanisms proposed to mediate this. In this article, we review the molecular and cellular mechanisms by which nutrients are proposed to regulate pro-inflammatory signalling in adipose and vascular tissues. In addition, we examine the potential therapeutic opportunities that these mechanisms provide for suppression of inappropriate inflammation in obesity and vascular disease.


Assuntos
Tecido Adiposo/metabolismo , Doenças Cardiovasculares/metabolismo , Sistema Cardiovascular/metabolismo , Metabolismo Energético , Mediadores da Inflamação/metabolismo , Inflamação/metabolismo , Estado Nutricional , Obesidade/metabolismo , Adipocinas/metabolismo , Tecido Adiposo/efeitos dos fármacos , Tecido Adiposo/imunologia , Tecido Adiposo/fisiopatologia , Animais , Anti-Inflamatórios/uso terapêutico , Doenças Cardiovasculares/imunologia , Doenças Cardiovasculares/fisiopatologia , Doenças Cardiovasculares/prevenção & controle , Sistema Cardiovascular/efeitos dos fármacos , Sistema Cardiovascular/imunologia , Sistema Cardiovascular/fisiopatologia , Metabolismo Energético/efeitos dos fármacos , Humanos , Hipoglicemiantes/uso terapêutico , Inflamação/tratamento farmacológico , Inflamação/imunologia , Inflamação/fisiopatologia , Mediadores da Inflamação/antagonistas & inibidores , Obesidade/tratamento farmacológico , Obesidade/imunologia , Obesidade/fisiopatologia , Estresse Oxidativo , Transdução de Sinais
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