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1.
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
2.
Diabetes ; 70(6): 1303-1316, 2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-34162682

RESUMO

Adiponectin is an adipokine that exerts insulin-sensitizing and anti-inflammatory roles in insulin target tissues including liver. While the insulin-sensitizing function of adiponectin has been extensively investigated, the precise mechanism by which adiponectin alleviates diet-induced hepatic inflammation remains elusive. Here, we report that hepatocyte-specific knockout (KO) of the adaptor protein APPL2 enhanced adiponectin sensitivity and prevented mice from developing high-fat diet-induced inflammation, insulin resistance, and glucose intolerance, although it caused fatty liver. The improved anti-inflammatory and insulin-sensitizing effects in the APPL2 hepatocyte-specific KO mice were largely reversed by knocking out adiponectin. Mechanistically, hepatocyte APPL2 deficiency enhances adiponectin signaling in the liver, which blocks TNF-α-stimulated MCP-1 expression via inhibiting the mTORC1 signaling pathway, leading to reduced macrophage infiltration and thus reduced inflammation in the liver. With results taken together, our study uncovers a mechanism underlying the anti-inflammatory role of adiponectin in the liver and reveals the hepatic APPL2-mTORC1-MCP-1 axis as a potential target for treating overnutrition-induced inflammation in the liver.


Assuntos
Proteínas Adaptadoras de Transdução de Sinal/fisiologia , Adiponectina/fisiologia , Hepatite/genética , Proteínas Adaptadoras de Transdução de Sinal/genética , Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Animais , Movimento Celular/genética , Quimiocina CCL2/genética , Quimiocina CCL2/metabolismo , Dieta Hiperlipídica/efeitos adversos , Regulação para Baixo/genética , Fígado Gorduroso/genética , Fígado Gorduroso/metabolismo , Fígado Gorduroso/patologia , Hepatite/imunologia , Hepatite/metabolismo , Hepatite/patologia , Hepatócitos/metabolismo , Inflamação/genética , Inflamação/imunologia , Inflamação/metabolismo , Inflamação/patologia , Resistência à Insulina/genética , Fígado/imunologia , Fígado/metabolismo , Fígado/patologia , Macrófagos/fisiologia , Masculino , Camundongos , Camundongos Knockout
3.
Nutrients ; 13(4)2021 Apr 02.
Artigo em Inglês | MEDLINE | ID: mdl-33918360

RESUMO

Adiponectin (a protein consisting of 244 amino acids and characterized by a molecular weight of 28 kDa) is a cytokine that is secreted from adipose tissues (adipokine). Available evidence suggests that adiponectin is involved in a variety of physiological functions, molecular and cellular events, including lipid metabolism, energy regulation, immune response and inflammation, and insulin sensitivity. It has a protective effect on neurons and neural stem cells. Adiponectin levels have been reported to be negatively correlated with cancer, cardiovascular disease, and diabetes, and shown to be affected (i.e., significantly increased) by proper healthy nutrition. The present review comprehensively overviews the role of adiponectin in a range of diseases, showing that it can be used as a biomarker for diagnosing these disorders as well as a target for monitoring the effectiveness of preventive and treatment interventions.


Assuntos
Adiponectina/fisiologia , Tecido Adiposo/metabolismo , Estado Nutricional/fisiologia , Doença de Alzheimer/metabolismo , Animais , Biomarcadores/metabolismo , Doenças Cardiovasculares/metabolismo , Diabetes Mellitus/metabolismo , Metabolismo Energético/fisiologia , Humanos , Imunidade/fisiologia , Inflamação , Resistência à Insulina/fisiologia , Metabolismo dos Lipídeos/fisiologia , Neoplasias/metabolismo , Fatores de Proteção
4.
Clin Exp Metastasis ; 38(2): 119-138, 2021 04.
Artigo em Inglês | MEDLINE | ID: mdl-33591548

RESUMO

Cancer is a complex disease, with various pre-existing health ailments enhancing its pathology. In cancer, the extracellular environment contains various intrinsic physiological factors whose levels are altered with aging and pre-existing conditions. In obesity, the tumor microenvironment and metastases are enriched with factors that are both derived locally, and from other physiological compartments. Similarly, in obesity, the cancer cell environment both at the site of origin and at the secondary site i.e., metastatic niche, contains significantly more phenotypically-altered adipocytes than that of un-obese cancer patients. Indeed, obesity has been linked with cancer progression, metastasis, and therapy resistance. Adipocytes not only interact with tumor cells, but also with adjacent stromal cells at primary and metastatic sites. This review emphasizes the importance of bidirectional interactions between adipocytes and breast tumor cells in breast cancer progression and its bone metastases. This paper not only chronicles the role of various adipocyte-derived factors in tumor growth, but also describes the significance of adipocyte-derived bone metastatic factors in the development of bone metastasis of breast cancer. It provides a molecular view of the interplay between the adipocytes and tumor cells involved in breast cancer bone metastasis. However, more research is needed to determine if targeting cancer-associated adipocytes holds promise as a potential therapeutic approach for breast cancer bone metastasis treatment. Interplay between adipocytes and breast cancer cells at primary cancer site and metastatic bone microenvironment. AMSC Adipose-derived mesenchymal stem cell, CAA Cancer associated adipocytes, CAF Cancer associated fibroblast, BMSC Bone marrow derived mesenchymal stem cell, BMA Bone marrow adipocyte.


Assuntos
Adiposidade/fisiologia , Neoplasias Ósseas/secundário , Neoplasias da Mama/patologia , Adiponectina/fisiologia , Estrogênios/fisiologia , Feminino , Humanos , Lipólise , Células-Tronco Mesenquimais/fisiologia , Ligante RANK/fisiologia , Fator de Crescimento Transformador beta/fisiologia , Microambiente Tumoral/fisiologia
5.
Int J Mol Sci ; 21(21)2020 Nov 04.
Artigo em Inglês | MEDLINE | ID: mdl-33158216

RESUMO

Rheumatoid arthritis (RA) is a systemic chronic inflammatory autoimmune joint disease, characterized by progressive articular damage and joint dysfunction. One of the symptoms of this disease is persistent inflammatory infiltration of the synovial membrane, the principle site of inflammation in RA. In the affected conditions, the cells of the synovial membrane, fibroblast-like synoviocytes and macrophage-like synovial cells, produce enzymes degrading cartilage and underlining bone tissue, as well as cytokines increasing the infiltration of immune cells. In patients with RA, higher levels of adiponectin are measured in the serum and synovial fluid. Adiponectin, a secretory product that is mainly white adipose tissue, is a multifunctional protein with dual anti-inflammatory and pro-inflammatory properties. Several studies underline the fact that adiponectin can play an important pro-inflammatory role in the pathophysiology of RA via stimulating the secretion of inflammatory mediators. This narrative review is devoted to the presentation of recent knowledge on the role played by one of the adipokines produced by adipose tissue-adiponectin-in the pathogenesis of rheumatoid arthritis.


Assuntos
Adiponectina/fisiologia , Artrite Reumatoide/etiologia , Adipocinas/fisiologia , Adiponectina/metabolismo , Tecido Adiposo/metabolismo , Tecido Adiposo/fisiologia , Artrite Reumatoide/metabolismo , Artrite Reumatoide/patologia , Artrite Reumatoide/fisiopatologia , Humanos , Inflamação/metabolismo , Inflamação/patologia , Inflamação/fisiopatologia , Mediadores da Inflamação/fisiologia , Membrana Sinovial/metabolismo , Membrana Sinovial/patologia , Sinoviócitos/patologia , Sinoviócitos/fisiologia
6.
Endocr Regul ; 54(3): 157-159, 2020 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-32857714

RESUMO

Adiponectin is a hormone secreted by adipose tissue, exerting many positive effects in the human body. Its action has been widely studied, placing it into the metabolic health beneficial products of the adipose tissue. Nevertheless, adiponectin has been shown to exert some extra beneficial non metabolic actions, as well. Adiponectin levels can be related to reduced incidence of cancer in obese patients. Moreover, adiponectin has been shown to be implicated in the positive fertility outcomes of women. Some new studies have also indicated that adiponectin has a potential effect in the control of appetite, which raises a question, whether adiponectin could be accredited to be useful in the endocrine evaluation of obesity. Could these additional non-metabolic actions prove its helpfulness?


Assuntos
Adiponectina/fisiologia , Fármacos Antiobesidade/uso terapêutico , Hormônios/uso terapêutico , Obesidade/tratamento farmacológico , Adiponectina/farmacologia , Adiponectina/uso terapêutico , Fármacos Antiobesidade/farmacologia , Biomarcadores/análise , Depressão/diagnóstico , Depressão/tratamento farmacológico , Sistema Endócrino/efeitos dos fármacos , Sistema Endócrino/fisiologia , Fármacos para a Fertilidade/farmacologia , Fármacos para a Fertilidade/uso terapêutico , Antagonistas de Hormônios/farmacologia , Antagonistas de Hormônios/uso terapêutico , Hormônios/farmacologia , Humanos , Resistência à Insulina , Neoplasias/complicações , Neoplasias/diagnóstico , Neoplasias/terapia , Obesidade/etiologia , Transdução de Sinais/efeitos dos fármacos
7.
Ann Biol Clin (Paris) ; 78(3): 243-252, 2020 06 01.
Artigo em Francês | MEDLINE | ID: mdl-32540813

RESUMO

Adiponectin is a major adipokine involved in energy homeostasis that exerts insulin-sensitizing properties. The level of adiponectin is reduced in situations of insulin resistance and is negatively associated with several pathophysiological situations including abdominal obesity, metabolic syndrome, steatosis and non-alcoholic steatohepatitis, type 2 diabetes, some cancers and cognitive diseases. These aspects are discussed in this review.


Assuntos
Adiponectina/fisiologia , Animais , Transtornos Cognitivos/etiologia , Transtornos Cognitivos/metabolismo , Transtornos Cognitivos/patologia , Diabetes Mellitus Tipo 2/etiologia , Diabetes Mellitus Tipo 2/metabolismo , Diabetes Mellitus Tipo 2/patologia , Fígado Gorduroso/etiologia , Fígado Gorduroso/metabolismo , Humanos , Insulina/metabolismo , Resistência à Insulina/fisiologia , Síndrome Metabólica/etiologia , Síndrome Metabólica/metabolismo , Síndrome Metabólica/patologia , Neoplasias/etiologia , Neoplasias/metabolismo , Neoplasias/patologia , Obesidade/metabolismo , Obesidade/patologia , Obesidade/fisiopatologia
9.
Ann Biol Clin (Paris) ; 78(3): 253-260, 2020 06 01.
Artigo em Francês | MEDLINE | ID: mdl-32420888

RESUMO

Elevated circulating leptin levels have been associated with an increased cardiovascular risk in humans. However, recent meta-analyses show that certain epidemiological studies did not find this association, suggesting distinct effects of leptin depending on the pathophysiological context. Studies performed in mice deficient in leptin or in leptin receptors are often contradictory, showing both protective and deleterious effects of leptin. These effects appear to vary depending on the genetic background of the animal and the doses of leptin administered, making interpretation of the results difficult. In humans, elevated adiponectinemia is associated with a favourable cardiovascular risk profile. Adiponectin exerts protective effects at all stages of development of atherosclerotic plaque. However, our knowledge of the pathophysiological mechanisms involved in these protective effects has been established from cellular models, which do not necessarily reproduce the pathology in all its complexity. In addition, mouse models have a very different lipoprotein metabolism from humans, which does not always allow extrapolation of results to humans. Finally, epidemiological studies evaluating adiponectin as a marker of cardiovascular risk show paradoxical results since a high serum adiponectin concentration has not been associated with a reduction in the number of cardiovascular events but with an increase of cardiovascular and all causes mortality in healthy subjects and coronary patients. These observations illustrate the paradox of adipokines actions and show the complexity to use these biomarkers in cardiovascular diseases. Resistance to the action of these adipokines is one of the hypotheses put forward to explain these discrepancies.


Assuntos
Adiponectina/farmacologia , Sistema Cardiovascular/efeitos dos fármacos , Leptina/farmacologia , Adiponectina/fisiologia , Animais , Biomarcadores/sangue , Cardiotônicos/farmacologia , Doenças Cardiovasculares/sangue , Doenças Cardiovasculares/diagnóstico , Doenças Cardiovasculares/etiologia , Sistema Cardiovascular/fisiopatologia , Humanos , Leptina/fisiologia , Camundongos , Fatores de Risco
10.
Ann Biol Clin (Paris) ; 78(3): 261-264, 2020 06 01.
Artigo em Francês | MEDLINE | ID: mdl-32420889

RESUMO

Leptin and adiponectin are two adipokines currently used as biomarkers for diagnostic orientation and phenotyping in syndromes of lipodystrophy and severe insulin resistance. The level of these biomarkers also has an impact on the therapeutic management of the patients. These aspects, as well as our experience as a reference center, are described in this brief overview.


Assuntos
Adiponectina/fisiologia , Resistência à Insulina , Leptina/fisiologia , Lipodistrofia/diagnóstico , Síndrome Metabólica/diagnóstico , Adiponectina/sangue , Biomarcadores/análise , Biomarcadores/sangue , Humanos , Resistência à Insulina/fisiologia , Leptina/sangue , Lipodistrofia/patologia , Lipodistrofia/terapia , Síndrome Metabólica/terapia , Fenótipo , Índice de Gravidade de Doença
11.
Artigo em Inglês | MEDLINE | ID: mdl-32194507

RESUMO

Adiponectin (APN) is a multi-functional adipokine which sensitizes the insulin signals, stimulates mitochondria biogenesis, and suppresses inflammation. By virtue of these beneficial properties, APN may protect against metabolic syndrome, including obesity and type II diabetes mellitus. Since these diseases are associated with hypoadiponectinemia, it is suggested that loss of function of APN might be involved. In contrast, despite beneficial properties for cardiovascular cells, APN is detrimental in circulatory diseases, including chronic heart failure (CHF) and chronic kidney disease (CKD). Notably, such an APN paradox might also be applicable to neurodegeneration. Although APN is neuroprotective in various experimental systems, APN was shown to be associated with the severity of amyloid accumulation and cognitive decline in a recent prospective cohort study in elderly. Furthermore, Alzheimer's disease (AD) was associated with hyperadiponectinemia in many studies. Moreover, APN was sequestered by phospho-tau into the neurofibrillary tangle in the postmortem AD brains. These results collectively indicate that APN might increase the risk of AD. In this context, the objective of the present study is to elucidate the mechanism of the APN paradox in AD. Hypothetically, APN might be involved in the stimulation of the amyloidogenic evolvability in reproductive stage, which may later manifest as AD by the antagonistic pleiotropy mechanism during aging. Given the accumulating evidence that AD and CHF are mechanistically overlapped, it is further proposed that the APN paradox of AD might be converged with those of other diseases, such as CHF and CKD.


Assuntos
Adiponectina/fisiologia , Doença de Alzheimer/etiologia , Proteínas Amiloidogênicas/metabolismo , Degeneração Neural/metabolismo , Degeneração Neural/prevenção & controle , Adiponectina/farmacologia , Envelhecimento/fisiologia , Doença de Alzheimer/epidemiologia , Doença de Alzheimer/metabolismo , Doença de Alzheimer/prevenção & controle , Animais , Encéfalo/efeitos dos fármacos , Encéfalo/metabolismo , Encéfalo/patologia , Disfunção Cognitiva/metabolismo , Disfunção Cognitiva/patologia , Disfunção Cognitiva/prevenção & controle , Modelos Animais de Doenças , Progressão da Doença , Humanos , Camundongos , Degeneração Neural/patologia , Neurônios/efeitos dos fármacos , Neurônios/fisiologia , Neuroproteção/efeitos dos fármacos
12.
Obes Rev ; 21(5): e13004, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-32067339

RESUMO

This review describes the multifaceted effects of adiponectin on breast cancer cell signalling, tumour metabolism, and microenvironment. It is largely documented that low adiponectin levels are associated with an increased risk of breast cancer. However, it needs to be still clarified what are the extents of the decrease of local/intra-tumoural adiponectin concentrations, which promote breast tumour malignancy. Most of the anti-proliferative and pro-apoptotic effects induced by adiponectin have been obtained in breast cancer cells not expressing estrogen receptor alpha (ERα). Here, we will highlight recent findings demonstrating the mechanistic effects through which adiponectin is able to fuel genomic and non-genomic estrogen signalling, inhibiting LKB1/AMPK/mTOR/S6K pathway and switching energy balance. Therefore, it emerges that the reduced adiponectin levels in patients with obesity work to sustain tumour growth and progression in ERα-positive breast cancer cells. All this may contribute to remove the misleading paradigm that adiponectin univocally inhibits breast cancer cell growth and progression independently on ERα status. The latter concept, here clearly provided by pre-clinical studies, may have translational relevance adopting adiponectin as a potential therapeutic tool. Indeed, the interfering role of ERα on adiponectin action addresses how a separate assessment of adiponectin treatment needs to be considered in novel therapeutic strategies for ERα-positive and ERα-negative breast cancer.


Assuntos
Adiponectina/fisiologia , Neoplasias da Mama/fisiopatologia , Receptor alfa de Estrogênio/fisiologia , Adiponectina/administração & dosagem , Adiponectina/deficiência , Neoplasias da Mama/etiologia , Neoplasias da Mama/patologia , Proliferação de Células , Receptor alfa de Estrogênio/análise , Receptor alfa de Estrogênio/genética , Feminino , Humanos , Sistema Imunitário , Obesidade/complicações , Obesidade/fisiopatologia , Fatores de Risco , Transdução de Sinais
13.
Reproduction ; 159(3): 227-239, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-32023207

RESUMO

Preimplantation embryos are sensitive to maternal hormones affecting embryonic signal transduction and metabolic functions. We examined whether adiponectin, the most abundantly secreted adipokine, can influence glucose transport in mouse embryonic cells. In mouse blastocysts full-length adiponectin stimulated glucose uptake, while no effect of globular adiponectin was found. Full-length adiponectin stimulated translocation of GLUT8 glucose transporter to the cell membrane; we did not detect significant changes in the intracellular localization of GLUT4 glucose transporter in adiponectin-treated blastocysts. To study adiponectin signaling in detail, we used embryoid bodies formed from mouse embryonic carcinoma cell (ECC) line P19. We confirmed the expression of adiponectin receptors in these cells. Similar to mouse blastocysts, full-length adiponectin, but not globular adiponectin, stimulated glucose uptake in ECC P19 embryoid bodies. Moreover, full-length adiponectin stimulated AMPK and p38 MAPK phosphorylation. These results indicate that besides AMPK, p38 MAPK is a potential target of adiponectin in mouse embryonic cells. AMPK inhibitor did not influence the adiponectin-stimulated p38 MAPK phosphorylation, indicating independent action of these two signaling pathways. In mouse embryos adiponectin acts as a hormonal regulator of glucose uptake, which becomes especially important in phases with reduced levels of circulating insulin. Our results suggest that adiponectin maintains the glucose supply for early embryos under hypoinsulinaemic conditions, for example, in mothers suffering from type 1 diabetes mellitus.


Assuntos
Adiponectina/fisiologia , Blastocisto/metabolismo , Proteínas Facilitadoras de Transporte de Glucose/metabolismo , Transportador de Glucose Tipo 4/metabolismo , Glucose/metabolismo , Animais , Linhagem Celular Tumoral , Corpos Embrioides/metabolismo , Feminino , Sistema de Sinalização das MAP Quinases , Camundongos , Receptores de Adiponectina/metabolismo
14.
Clin Exp Rheumatol ; 38(1): 11-18, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31025923

RESUMO

OBJECTIVES: Rheumatoid arthritis (RA) is characterised by the overproduction of autoantibodies such as rheumatoid factor (RF) and anti-cyclic citrullinated peptide (anti-CCP) antibody. T follicular helper (Tfh) cells are a specialised Th subset that provides signals to B cells, promoting the secretion of antibodies. Our previous studies showed that the frequency of circulating Tfh cells were markedly increased in RA patients and positively correlated with disease activity and the levels of anti-CCP autoantibody. Adiponectin (AD) is an adipokine secreted mainly by adipocytes. Our previous work has demonstrated that AD is highly expressed in the inflamed synovial joint tissue and correlates closely with progressive bone erosion in RA patients. However, it remains unknown whether AD aggravates the severity of RA via modulating Tfh cells. This study aims to investigate whether AD exerts effect on Tfh cells in RA. METHODS: CD4+ T cells were purified from peripheral blood mononuclear cells (PBMCs) of healthy controls (HC), and adiponectin receptor 1 (AdipoR1) expression on the surface of CD4+CXCR5+PD-1+ (Tfh) cells was detected by flow cytometry. Purified HC CD4+ T cells were cultured with different concentration fetal bovine serun (FBS) in the presence or absence of AD. The percentages of Tfh cells were analysed by flow cytometry. RA or osteoarthritis (OA) fibroblast-like synoviocytes (FLSs) were stimulated with AD for 72h and then co-cultured with HC CD4+ T cells through cell-to-cell contact or in a transwell system. The percentages of Tfh cells were analysed by flow cytometry and the levels of soluble factors such as interleukin-(IL)-6, IL-21, IL-12 and IFNγ in the supernatants were determined by Human Magnetic Bead Panel or Enzyme linked immunosorbent assay (ELISA). Then anti-IL-6 antibody and/or anti-IL-21 antibody was added to the co-culture system, and the percentages of Tfh cells were analysed by flow cytometry. The frequency of Tfh cells in the joint tissue of collagen-induced arthritis (CIA) mice was examined by flow cytometry. The mRNA expression of Tfh cell transcription factors and functional molecules such as B-cell lymphoma 6 (Bcl-6), B lymphocyte maturation protein 1 (Blimp-1), IL-6, IL-21, IL-12 and IFNγ in the joints of CIA mice were detected by real time PCR (RT-PCR). RESULTS: Adiponectin receptor 1 (AdipoR1) expression was detected on the surface of Tfh cells. However, in the present study, we did not find that AD has a direct effect on Tfh cell generation in vitro. Nonetheless, AD-stimulated RA FLSs could promote Tfh cell generation, predominantly via IL-6 production. And this upregulated effect was partially abolished upon neutralising IL-6. Finally, intraarticular injection of AD aggravated synovial inflammation with increased frequency of Tfh cells in the joints of AD-treated CIA mice. CONCLUSIONS: Our study demonstrated that AD-stimulated RA FLSs promote Tfh cell generation, which is mainly mediated by the secretion of soluble factor IL-6. This finding reveals a novel mechanism for AD in RA pathogenesis.


Assuntos
Adiponectina , Artrite Reumatoide , Interleucina-6 , Sinoviócitos , Linfócitos T Auxiliares-Indutores , Adiponectina/fisiologia , Animais , Artrite Reumatoide/metabolismo , Bovinos , Fibroblastos , Humanos , Interleucina-6/metabolismo , Leucócitos Mononucleares , Camundongos , Linfócitos T Auxiliares-Indutores/fisiologia
15.
Curr Diabetes Rev ; 16(2): 95-103, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31267874

RESUMO

BACKGROUND: Adiponectin is an adipocyte-derived cytokine closely associated with obesity, altered body adipose tissue distribution, insulin resistance, and cardiovascular diseases. INTRODUCTION: Evidence from animal and human studies demonstrate that adiponectin plays an important role in the regulation of glucose and lipid metabolism. Adiponectin increases insulin sensitivity and improves systemic lipid metabolism. Although research efforts on adiponectin mostly aim towards its endocrine functions, this adipocyte-derived molecule also has profound autocrine and paracrine functions. CONCLUSION: In this review, our aim is to discuss the role of adiponectin in maintaining metabolic homeostasis and its association with cardiovascular health. The proper identification of these roles is of great importance, which has the potential to identify a wealth of novel targets for the treatment of diabetes and related cardio-metabolic diseases.


Assuntos
Adiponectina/fisiologia , Homeostase/fisiologia , Tecido Adiposo/metabolismo , Animais , Doenças Cardiovasculares/metabolismo , Comunicação Celular/fisiologia , Sistema Nervoso Central/metabolismo , Diabetes Mellitus/metabolismo , Metabolismo Energético/fisiologia , Glucose/metabolismo , Humanos , Resistência à Insulina/fisiologia , Células Secretoras de Insulina/metabolismo , Metabolismo dos Lipídeos/fisiologia , Obesidade/metabolismo
17.
Atherosclerosis ; 292: 1-9, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31731079

RESUMO

Visceral fat accumulation has a marked impact on atherosclerotic cardiovascular diseases and metabolic syndrome clustering diabetes, dyslipidemia, and hypertension. Adiponectin, an adipocyte-derived circulating protein, is a representative adipocytokine and uniquely possesses two major properties: 1) its circulating concentration is approximately 3-6 orders of magnitude greater than ordinary hormones and cytokines; 2) its concentration inversely correlates with body fat mass despite its adipocyte-specific production. Low serum levels of adiponectin correlate with cardiometabolic diseases. Extensive experimental evidence has demonstrated that adiponectin possesses multiple properties, such as anti-atherosclerotic, anti-diabetic, and anti-inflammatory activities. It has been shown to play a central role against the development of metabolic syndrome and its complications. However, even approximately 25 years after its discovery, the properties of adiponectin, including how and why it exerts multiple beneficial effects on various tissues and/or organs, remain unclear. Furthermore, the mechanisms responsible for the very high circulating concentrations of adiponectin in the bloodstream have not been elucidated. Several adiponectin-binding partners, such as AdipoR1/2, have been identified, but do not fully explain the multi-functional and beneficial properties of adiponectin. Recent advances in adiponectin research may resolve these issues. Adiponectin binds to and covers cell surfaces with T-cadherin, a unique glycosylphosphatidylinositol (GPI)-anchored cadherin. The adiponectin/T-cadherin complex enhances exosomal production and release, excreting cell-toxic products from cells, particularly in the vasculature. In this review, we discuss adiponectin and the role of the adiponectin/T-cadherin system in the maintenance of whole body homeostasis and cardiovascular protection.


Assuntos
Adiponectina/sangue , Adiponectina/fisiologia , Humanos
18.
FASEB J ; 33(12): 13617-13631, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-31585050

RESUMO

Adiponectin (APN), an adipocyte-derived adipokine, has been shown to limit lung injury originating from endothelial cell (EC) damage. Previously we reported that obese mice with low circulatory APN levels exhibited pulmonary vascular endothelial dysfunction. This study was designed to investigate the cellular and molecular mechanisms underlying the pulmonary endothelium-dependent protective effects of APN. Our results demonstrated that in APN-/- mice, there was an inherent state of endothelium mitochondrial dysfunction that could contribute to endothelial activation and increased susceptibility to LPS-induced acute lung injury (ALI). We noted that APN-/- mice showed decreased expression of mitochondrial biogenesis regulatory protein peroxisome proliferator-activated receptor γ coactivator 1-α (PGC-1α) and its downstream proteins nuclear respiratory factor 1, transcription factor A, mitochondrial, and Sirtuin (Sirt)3 and Sirt1 expression in whole lungs and in freshly isolated lung ECs from these mice at baseline and subjected to LPS-induced ALI. We further showed that treating APN-/- mice with PGC-1α activator pyrroloquinoline quinone enhances mitochondrial biogenesis and function in lung endothelium and attenuation of ALI. These results suggest that the pulmonary endothelium-protective properties of APN are mediated, at least in part, by an enhancement of mitochondrial biogenesis through a mechanism involving PGC-1α activation.-Shah, D., Torres, C., Bhandari, V. Adiponectin deficiency induces mitochondrial dysfunction and promotes endothelial activation and pulmonary vascular injury.


Assuntos
Adiponectina/deficiência , Endotélio Vascular/patologia , Inflamassomos , Lesão Pulmonar/etiologia , Erros Inatos do Metabolismo/complicações , Mitocôndrias/patologia , Lesões do Sistema Vascular/etiologia , Adiponectina/fisiologia , Animais , Endotélio Vascular/metabolismo , Lipopolissacarídeos/toxicidade , Lesão Pulmonar/metabolismo , Lesão Pulmonar/patologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Camundongos Obesos , Mitocôndrias/metabolismo , Proteína 3 que Contém Domínio de Pirina da Família NLR/genética , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Biogênese de Organelas , Lesões do Sistema Vascular/metabolismo , Lesões do Sistema Vascular/patologia
19.
Reproduction ; 158(5): 429-440, 2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-31518996

RESUMO

Adiponectin (ADIPOQ, encoded by Adipoq) is an important white adipose-derived adipokine linked to energy homeostasis and reproductive function. This study aims to reveal the expression and role of the adiponectin system in the ovaries under acute malnutrition. In this study, 48-h food deprivation significantly inhibited ovarian growth by suppressing cell proliferation and inducing cell apoptosis in the ovaries of gonadotrophin-primed immature mice. It was also accompanied by significantly decelerated basic metabolism (glucose, triacylglycerol and cholesterol), varied steroid hormones (follicle-stimulating hormone, luteinizing hormone and estradiol) and vanishment of the peri-ovarian fat. It is noteworthy that after acute fasting, the adiponectin levels in ovaries rather than in blood were significantly elevated. Immunohistochemical study demonstrated that adiponectin and its receptors (ADIPOR1 and ADIPOR2) primarily appeared in ovarian somatic and/or germ cells, and their protein expressions were upregulated in the ovaries from fasted mice. Further in vitro study verified that ADIPOR1/2 agonist obviously inhibited follicle-stimulating hormone-induced oocyte meiotic resumption, while the antagonist significantly enhanced the percentage of oocyte maturation in the absence of follicle-stimulating hormone. Furthermore, the build up of peri-ovarian fat under physiological status in mice showed a positive correlation with both the hypertrophy of adipocytes and growth of ovaries. Taken together, these findings indicate that the upregulation of the adiponectin system disturbs the normal female reproductive function under the malnutrition status, and it may be associated with the loss of peri-ovarian fat depots.


Assuntos
Adiponectina/fisiologia , Restrição Calórica/efeitos adversos , Jejum/fisiologia , Desnutrição/fisiopatologia , Ovário/fisiologia , Doença Aguda , Adipócitos/fisiologia , Adiponectina/farmacologia , Tecido Adiposo/metabolismo , Adiposidade/fisiologia , Animais , Metabolismo Energético/fisiologia , Feminino , Desnutrição/complicações , Desnutrição/metabolismo , Desnutrição/patologia , Camundongos , Ovário/metabolismo , Ovário/patologia , Receptores de Adiponectina/genética , Receptores de Adiponectina/metabolismo , Transdução de Sinais/efeitos dos fármacos , Transdução de Sinais/fisiologia
20.
Cells ; 8(10)2019 09 24.
Artigo em Inglês | MEDLINE | ID: mdl-31554182

RESUMO

Adiponectin is an adipokine with anti-insulin resistance and anti-inflammatory functions. It exists in serum predominantly in three multimeric complexes: the trimer, hexamer, and high-molecular-weight forms. Although recent studies indicate that adiponectin promotes wound healing in rodents, its role in the wound healing process in humans is unknown. This study investigated the expression levels of adiponectin in adipose tissue and serum of women who experienced either normal or delayed wound healing after abdominal plastic surgery. We found that obese women with delayed healing had slightly lower total adiponectin levels in their adipose tissue compared with women with normal healing rates. Among the different isoforms of adiponectin, levels of the trimer forms were significantly reduced in adipose tissue, but not the serum, of obese women with delayed healing compared to women who healed normally. This study provides clinical evidence for a potential role of low-molecular-weight oligomers of adiponectin in the wound healing process as well as implications for an autocrine and/or paracrine mechanism of adiponectin action in adipose tissues.


Assuntos
Adiponectina/fisiologia , Obesidade/fisiopatologia , Cicatrização/fisiologia , Adiponectina/sangue , Adiponectina/genética , Tecido Adiposo/metabolismo , Tecido Adiposo/patologia , Adulto , Idoso , Comunicação Autócrina/fisiologia , Estudos de Casos e Controles , Feminino , Humanos , Pessoa de Meia-Idade , Obesidade/sangue , Obesidade/complicações , Obesidade/genética , Comunicação Parácrina/fisiologia , Isoformas de Proteínas/sangue , Isoformas de Proteínas/genética , Isoformas de Proteínas/fisiologia , Fatores de Tempo , Adulto Jovem
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